Long Term Evaluation of Sarilumab in Rheumatoid Arthritis Patients (SARIL-RA-EXTEND)

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT01146652

Collaborator

Regeneron Pharmaceuticals (Industry)

2,023

Enrollment

335

Locations

Arms

126.4

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Main Study:

Primary Objective:

Assess the long term safety of sarilumab in participants with rheumatoid arthritis (RA).

Secondary Objective:

Assess the long term efficacy of sarilumab in participants with RA.

Sub-Study:

This phase 3, open label sub-study was aimed to assess the usability of PFS-S when used by participants with moderate or severe RA, or their professional or non-professional healthcare providers in an unsupervised real-world situation. To mimic the real-world practice, the sub-study was incorporated into the LTS11210 study without additional visits compared to the scheduled visits in the main study. The duration of this sub-study was 12 weeks.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: SAR153191 (REGN88)	Phase 3

Detailed Description

The maximum duration of the study was up to 523 weeks:

Up to 1-week of screening, if any.
At least 264 weeks of open label treatment phase and up to 516 weeks as maximum.
6-week post-treatment follow-up as required per protocol.

Study Design

Study Type:

Interventional

Actual Enrollment :

2023 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multi-center, Uncontrolled Extension Study Evaluating Efficacy and Safety of SAR153191 in Patients With Active Rheumatoid Arthritis (RA)

Actual Study Start Date :

Jun 21, 2010

Actual Primary Completion Date :

Dec 31, 2020

Actual Study Completion Date :

Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD) Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Drug: SAR153191 (REGN88) Pharmaceutical form: solution Route of administration: subcutaneous
Experimental: Sarilumab monotherapy Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).	Drug: SAR153191 (REGN88) Pharmaceutical form: solution Route of administration: subcutaneous

Arm

Intervention/Treatment

Experimental: Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)

Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.

Drug: SAR153191 (REGN88)

Pharmaceutical form: solution Route of administration: subcutaneous

Experimental: Sarilumab monotherapy

Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).

Drug: SAR153191 (REGN88)

Pharmaceutical form: solution Route of administration: subcutaneous

Outcome Measures

Primary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [From first dose (i.e., Day 1 of study LTS11210) up to 60 days after last dose (maximum duration: up to 523 weeks)]
An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal product and which did not necessarily have to have a causal relationship with the treatment. An SAE was any untoward medical occurrence at any dose that: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were AEs that developed or worsened or became serious during the TEAE period (defined as the time from the first dose of the investigational medicinal product (IMP) in study LTS11210 to the last dose of the IMP +60 days).
Sub-study: Number of Participants Reported Product Technical Complaints (PTC), Product Technical Failures (PTF) and/or Failed Drug Deliveries (FDD) With Pre-filled Syringe With Safety System [From Week 24 to 36]
A PTF was defined as any product technical complaint (PTC) related to the use of the PFS-S that had a validated technical cause. FDD was defined as participant's failure to administer the full dose at a given attempt. A PTC was defined as any participant- or healthcare provider-reported complaint regarding the use of the PFS-S syringe and collected via the completion of the injection diary. The injection diary comprised specific questions: 1. Were you able to remove the cap? 2. Was the needle safety system activated?, 3. Did the safety system entirely cover the needle, and 4. Was the person who performed the injection the person who was trained by the site staff?, where each question was given the option yes/no. Participants who answered "no" for any of the questions of PTC, had PTF and/or FDD were reported in this outcome measure.
Sub-study: Number of Product Technical Complaints - Product Technical Failures With Pre-filled Syringe With Safety System [From Week 24 to 36]
A PTF was defined as any PTC (defined as any participant- or healthcare provider-reported complaint regarding the use of the PFS-S syringe and collected via the completion of the injection diary) related to the use of the PFS-S that had a validated technical cause. Number of PTF in the participants enrolled in sub-study were reported in this outcome measure.
Sub-study: Number of Failed Drug Deliveries Associated With Pre-filled Syringe With Safety System [From Week 24 to 36]
FDD was defined as participant's failure to administer the full dose at a given attempt. Number of FDD in the participants enrolled in sub-study were reported in this outcome measure.
Sub-study: Number of Product Technical Complaints With Pre-filled Syringe With Safety System [From Week 24 to 36]
A PTC was defined as any participant- or healthcare provider-reported complaint regarding the use of the PFS-S syringe and collected via the completion of the injection diary. The injection diary comprised specific questions: 1. Were you able to remove the cap? 2. Was the needle safety system activated?, 3. Did the safety system entirely cover the needle, and 4. Was the person who performed the injection the person who was trained by the site staff?, where each question was given the option yes/no. Number of PTC (based on participant's answer to "no" for any of the questions of PTC) in the participants enrolled in sub-study were reported in this outcome measure.

Secondary Outcome Measures

Percentage of Participants Achieving American College of Rheumatology 20 (ACR20) Response [At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
ACR20 response: greater than or equal to (>=) 20% improvement in both tender joint count and swollen joint count and, >=20% improvement in at least 3 of the 5 remaining ACR core measures assessments: C-reactive protein [CRP] level (mg/liter [mg/L]); participant's assessment of pain (measured on 0 [no pain] to 100 mm [worst pain] visual analog scale [VAS]); participant's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by health assessment questionnaire disability index [HAQ-DI], with scoring range of 0 [better physical function] to 3 [worst physical function]). Higher score indicated worse outcomes.
Percentage of Participants Achieving American College of Rheumatology 50 (ACR50) Response [At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
ACR50 response: >=50% improvement in both TJC and SJC, and >=50% improvement in at least 3 of the 5 remaining ACR core measures assessments: CRP level (in mg/L); participant's assessment of pain (measured on 0 [no pain] to 100 mm [worst pain] VAS); participant's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by HAQ-DI, with scoring range of 0 [better physical function] to 3 [worst physical function]). Higher score indicated worse outcomes.
Percentage of Participants Achieving American College of Rheumatology 70 (ACR70) Response [At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
ACR70 response: >=70% improvement in both TJC and SJC, and >=70% improvement in at least 3 of the 5 remaining ACR core measures assessments: CRP level (in mg/L); participant's assessment of pain (measured on 0 [no pain] to 100 mm [worst pain] VAS); participant's global assessment of disease activity (measured on 0 [no arthritis activity]to 100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by HAQ-DI, with scoring range of 0 [better physical function] to 3 [worst physical function]). Higher score indicated worse outcomes.
Percentage of Participants With Disease Activity Score for 28 Joints (DAS28) Remission [At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210]
Disease activity score based on 28 joints and C-reactive protein (DAS28-CRP) was a composite score which included 4 components: TJC with 28 joints assessed; SJC with 28 joints assessed; high-sensitivity CRP (in mg/L) and general health assessment by the participant using participant global assessment (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS). DAS28-CRP total score ranges from 0 to 10, where higher scores indicated greater disease activity. Percentage of participants with DAS28 remission were reported.
Percentage of Participants Achieving Good Response, Moderate Response or Non-response Using the European League Against Rheumatism (EULAR) Response Criteria [At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210]
DAS28-based EULAR response criteria were used to measure individual response as none, good or moderate, depending on the extent of change from baseline and level of disease activity reached. The EULAR response criteria are defined as: Good response = change from baseline of >1.2 and a present DAS28-CRP score <=3.2. Moderate response = change from baseline of >0.6 to <=1.2 and a present DAS28-CRP score <=5.1, or, change from baseline of >1.2 and present DAS28-CRP score >3.2. Non-response = change from baseline of <=0.6, or change from baseline of >0.6 to <=1.2 and present DAS28-CRP score >5.1. Scores of good and moderate were considered to indicate therapeutic response. DAS28-CRP is a composite score which included 4 components: TJC with 28 joints assessed; SJC with 28 joints assessed; high-sensitivity CRP (in mg/L) and general health assessment by participant using participant global assessment (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS.
Change From Baseline in DAS28-CRP Score at Weeks 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210 [Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210]
DAS28-CRP is a composite score which included 4 components: TJC with 28 joints assessed; SJC with 28 joints assessed; high-sensitivity CRP (in mg/L) and general health assessment by the participant using participant global assessment (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS). DAS28-CRP total score ranges from 0-10, where higher scores indicated greater disease activity. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 [Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
HAQ-DI is a standardized questionnaire used to assess the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; hygiene; reach; grip and activities. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3, where 0= no difficulty in physical function; 1= some difficulty in physical function; 2= much difficulty in physical function; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty in physical function) to 3 (extreme difficulty in physical function), where higher scores indicate more difficulty while performing daily living activities. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 0 and Week 48 of LTS11210: Campaign 1 X-ray Data - Participants From EFC11072 Part B [Baseline, Week 0 and 48 of LTS11210]
Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both joint erosions (JE) for 44 joints and joint space narrowing (JSN) for 42 joints in bilateral hand and foot joints. Total mTSS: sum of the scores from both erosion score and joint space narrowing score and ranged from 0 (normal, no progression) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Here, Baseline refers to the Baseline of initial study (EFC11072 Part B). In this outcome measure, change from initial study Baseline in 2 years X-ray data at Week 0 and 48 of LTS11210 were reported.
Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 48 and Week 96 of LTS11210: Campaign 2 X-ray Data - Participants From EFC11072 Part B [Baseline, Week 48 and 96 of LTS11210]
Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS: sum of the scores from both erosion score and joint space narrowing score and ranged from 0 (normal, no progression) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Here, Baseline refers to the Baseline of initial study (EFC11072 Part B). In this outcome measure, change from initial study (EFC11072 Part B) Baseline in 3 years X-ray data (participants with study duration of more than 48 weeks in LTS11210) at Week 48 and 96 of LTS11210 from Campaign 2 were reported.
Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 96, Week 144 and Week 192 of LTS11210: Campaign 3 X-ray Data - Participants From EFC11072 Part B [Baseline, Week 96, 144 and 192 of LTS11210]
Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS: sum of the scores from both erosion score and joint space narrowing score and ranged from 0 (normal, no progression) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Here, Baseline refers to the Baseline of initial study (EFC11072 Part B). In this outcome measure, change from initial study (EFC11072 Part B) Baseline in 5 years X-ray data (participants with study duration of more than 96 weeks in LTS11210) at Week 96, 144 and 192 of LTS11210 from Campaign 3 were reported.
Percentage of Participants With no Radiographic Progression of the Van Der Heijde Modified Total Sharp Score at Week 0 and 48 of LTS11210: Campaign 1 X-ray Data - Participants From EFC11072 Part B [Week 0 (post-dose) and 48 of LTS11210]
Radiographic no progression: defined as a change from Baseline in Van der Heijde mTSS <= 0. Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS was sum of scores from both erosion score and joint space narrowing score, ranged from 0 (normal, no progression) to 448 (worst possible total score). Increase in total score represents progression of structural damage. In this outcome measure, percentage of participants with no radiographic progression at Week 48 of LTS11210 from Campaign 1 X-ray data were reported.
Percentage of Participants With no Radiographic Progression of the Van Der Heijde Modified Total Sharp Score at Week 48 and Week 96 of LTS11210: Campaign 2 X-ray Data - Participants From EFC11072 Part B [Week 48 and 96 of LTS11210]
Radiographic no progression: defined as a change from Baseline in Van der Heijde mTSS <= 0. Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS was sum of scores from both erosion score and joint space narrowing score, ranged from 0 (normal, no progression) to 448 (worst possible total score). Increase in total score represents progression of structural damage. In this outcome measure, percentage of participants with no radiographic progression at Week 48 and 96 of LTS11210 from Campaign 2 X-ray data (participants with study duration of more than 48 weeks in LTS11210) were reported.
Percentage of Participants With no Radiographic Progression of the Van Der Heijde Modified Total Sharp Score at Week 96, 144 and 192 of LTS11210: Campaign 3 X-ray Data - Participants From EFC11072 Part B [Week 96, 144 and 192 of LTS11210]
Radiographic no progression: defined as a change from Baseline in Van der Heijde mTSS <= 0. Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS was sum of scores from both erosion score and joint space narrowing score, ranged from 0 (normal, no progression) to 448 (worst possible total score). Increase in total score represents progression of structural damage. In this outcome measure, percentage of participants with no radiographic progression at Week 96, 144 and 192 of LTS11210 from Campaign 3 X-ray data (participants with study duration more than 96 weeks in LTS11210) were reported.
Change From Baseline in Tender Joint Count (TJC) at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210 [Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210]
TJC is the sum of all tender joints based on examination of the 68 joints of the fingers, elbows, hips, knees, ankles, and toes. Total TJC ranged from 0 (best) to 68 (worst), where higher score = more severity. Change from Baseline in TJC was reported in the outcome measure. Here, Baseline refers to Baseline of initial study (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Change From Baseline in Swollen Joint Count (SJC) at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210 [Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210]
SJC is the sum of all swollen joints based on examination of the fingers, elbows, knees and toes. Total SJC ranged from 0 (best) to 66 (worst), where higher score = more severity. Change from Baseline in SJC was reported in the outcome measure. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Change From Baseline in Physician's Global Assessments of Disease Activity Visual Analogue Scale (VAS) Score at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, and 264 of LTS11210 [Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, and 264 of LTS11210]
Physician global assessment of disease activity was measured on a 100 millimeters (mm) horizontal VAS, ranging from 0 (best disease activity) to 100 (worst disease activity), where lower score = less disease activity and higher score = more disease activity. Here, Baseline refers to Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Change From Baseline in Participant Global Assessment of Disease Activity Visual Analogue Scale Score at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210 [Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210]
Participant global assessment of disease activity was measured on a 100 mm horizontal VAS, ranging from 0 (best disease activity) to 100 (worst disease activity), where lower score = less disease activity and higher score = more disease activity. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Change From Baseline in Participant's Assessment of Pain Visual Analogue Scale Score at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, and 264 of LTS11210 [Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, and 264 of LTS11210]
Participants were requested to indicate their pain intensity due to their RA on a 100 mm horizontal VAS, ranging from 0 (no pain) to 100 (worst pain), where a higher score represented more pain due to RA. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Change From Baseline in Short Form 36 (SF-36; Version 2) Physical Component Summary (PCS) Score at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, ACT11575 and EFC10832 Only [Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
SF-36 is a generic 36-item questionnaire consisting of 8 domains, measuring quality of life (QoL) covering 2 summary measures: PCS and mental component summary (MCS). PCS with 4 domains: physical functioning, role limitations due to physical problems, bodily pain, and general health; and MCS with 4 domains: vitality, social functioning, role limitations due to emotional problems, and mental health. Each domain is scored by summing the individual items, which are transformed into a score range from 0 to 100; where 0= worst QoL to 100=best QoL. PCS total score ranged from 0 to 100 with higher scores indicating better physical health. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, and EFC10832).
Change From Baseline in Short Form 36 (SF-36; Version 2) Mental Component Summary Score at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, ACT11575 and EFC10832 Only [Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
SF-36 is a generic 36-item questionnaire consisting of 8 domains, measuring quality of life (QoL) covering 2 summary measures: PCS and MCS. PCS with 4 domains: physical functioning, role limitations due to physical problems, bodily pain, and general health; and MCS with 4 domains: vitality, social functioning, role limitations due to emotional problems, and mental health. Each domain is scored by summing the individual items, which are transformed into a score range from 0 to 100; 0= worst QoL to 100=best QoL. MCS total score ranged from 0 to 100 with higher scores indicating better physical and mental health. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, and EFC10832).
Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Total Score at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210-Participants From EFC11072, ACT11575 and EFC10832 Only [Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
The FACIT-F is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0 to 4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. The sum of all responses resulted in the FACIT-Fatigue total score ranged from 0 to 52, where higher score = lower level of fatigue and indicates better QoL. A positive change from baseline score indicates an improvement. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, and EFC10832).
Change From Baseline in Sleep Visual Analogue Scale Score at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, and ACT11575 Only [Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
Rheumatoid arthritis (RA), like other chronic illness, is associated with sleep disturbances and is linked to pain, mood, and disease activity. The effect of sarilumab on sleep was assessed on a on 100 mm horizontal VAS scale, ranging from 0 (sleep is not a problem) to 100 (sleep is a major problem), where higher score = more sleep disturbances. Here, Baseline refers to the Baseline of initial studies (EFC11072, and ACT11575).
Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Due to RA at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072 and ACT11575 Only [Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
WPAI assesses work productivity and impairment. It is 6-item questionnaire used to assess degree to which RA affected work productivity and regular activities over past 7 days. Questions were: Q1 = currently employed; Q2 = hours missed due to RA; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree problem affected productivity while working (0 to 10 scale, with higher numbers indicated less productivity); Q6 = degree problem affected regular activities (0 to 10 scale, with higher numbers indicated greater impairment). The percent work time missed due to RA was a subscale and calculated as: 100*Q2/(Q2+Q4) for those who were currently employed. Subscale score was expressed as impairment percentage (range:0 to 100%) where higher numbers indicate greater impairment and less productivity. Here, Baseline refers to Baseline of initial studies (EFC11072 and ACT11575).
Change From Baseline in Work Productivity and Activity Impairment: Percent Impairment While Working Due to RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, and ACT11575 Only [Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
WPAI assesses work productivity and impairment. It is 6-item questionnaire used to assess degree to which RA affected work productivity and regular activities over past 7 days. Questions were: Q1 = currently employed; Q2 = hours missed due to RA; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree problem affected productivity while working (0 to 10 scale, with higher numbers = less productivity); Q6 = degree problem affected regular activities (0 to 10 scale, with higher numbers = greater impairment). Percentage impairment while working due to RA was subscale and calculated as: 10*Q5 for those who were currently employed and actually worked in past 7 days. Subscale score=expressed as impairment percentage (range:0 to 100%), where higher numbers=greater impairment and less productivity. Here, Baseline refers to the Baseline of initial studies (EFC11072 and ACT11575).
Change From Baseline in Work Productivity and Activity Impairment: Percent Overall Work Impairment Due to RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, and ACT11575 Only [Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
WPAI assesses work productivity and impairment. It is 6-item questionnaire used to assess degree to which RA affected work productivity and regular activities over past 7 days. Questions were: Q1 = currently employed; Q2 = hours missed due to RA; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree problem affected productivity while working (0 to 10 scale, with higher numbers indicated less productivity); Q6 = degree problem affected regular activities (0 10 scale, with higher numbers indicated greater impairment). Percent overall work impairment due to RA was subscale and calculated as: 100*Q2/(Q2+Q4)+100*[(1- Q2/(Q2+Q4))*(Q5/10)] for those who were currently employed . Subscale score = expressed as impairment percentage (range: 0 to 100%) where higher numbers indicate greater impairment. Here, Baseline refers to Baseline of initial studies (EFC11072 and ACT11575).
Change From Baseline in Work Productivity and Activity Impairment: Percent Activity Impairment Due to RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, and ACT11575 Only [Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
WPAI assesses work productivity and impairment. It is 6-item questionnaire used to assess degree to which RA affected work productivity and regular activities over past 7 days. Questions were: Q1 = currently employed; Q2 = hours missed due to RA; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree problem affected productivity while working (0 to 10 scale, with higher numbers indicated less productivity); Q6 = degree problem affected regular activities (0 10 scale, with higher numbers indicated greater impairment). Percent activity impairment due to RA was a subscale and calculated as: 10*Q6 for all respondents. Subscale score=expressed as impairment percentage (range: 0 to 100%) where higher numbers indicate greater impairment. Here, Baseline refers to Baseline of initial studies (EFC11072 and ACT11575).
Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Work Days Missed Due to Arthritis - Participants From EFC10832 Only [Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with arthritis over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from Baseline in number of work days missed in the last month due to arthritis by the participant was reported in the outcome measure. Here, Baseline refers to the Baseline of initial study (EFC10832).
Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Days With Work Productivity Reduced by >=50% Due to Arthritis - Participants From EFC10832 Only [Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from Baseline in number of work days with reduced productivity by >= 50% in the last month by the participant was reported in the outcome measure. Here, Baseline refers to the Baseline of initial study (EFC10832).
Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Arthritis Interference With Work Productivity - Participants From EFC10832 Only [Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity was measured on a scale that ranged from 0 (no interference) to 10 (complete interference), where higher scores indicated more interference. Here, Baseline refers to the Baseline of initial study (EFC10832).
Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: House Work Days Missed Due to Arthritis - Participants From EFC10832 Only [Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
'The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from baseline in number of days with no household work/household work missed in the last month by the participants was reported. Here, Baseline refers to the Baseline of initial study (EFC10832).
Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Days With Household Work Productivity Reduced by >=50% Due to Arthritis - Participants From EFC10832 Only [Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from baseline in number of days with reduced household work productivity by >= 50% in the last month by the participants was reported. Here, Baseline refers to the Baseline of initial study (EFC10832).
Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Days With Family/Social/Leisure Activities Missed Due to Arthritis - Participants From EFC10832 Only [Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from baseline in number of days missed of family/social/leisure activities in the last month by the participants was reported. Here, Baseline refers to the Baseline of initial study (EFC10832).
Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Days With Outside Help Hired Due to Arthritis- Participants From EFC10832 Only [Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from baseline in number of days with outside help hired in the last month by the participant was reported. Here, Baseline refers to the Baseline of initial study (EFC10832).
Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Arthritis Interference With Household Work Productivity - Participants From EFC10832 Only [Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210]
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranged from 0 (no interference) to 10 (complete interference), where higher scores indicated more interference. Here, Baseline refers to the Baseline of initial study (EFC10832).
Sub-study: Number of Participants Who Reported Adverse Events Related to Pre-filled Syringe With Safety System [From Week 24 to 36]
AEs related to PFS-S included PTC-related AEs, device-related AEs, or AEs of injection site reaction. In this outcome measure, only PTC-related AEs, device-related AEs, or AEs of injection site reaction assessed during the sub-study were reported. TEAEs and SAEs reported during the sub-study were included in the main study data and no separate data collection and analysis was performed, as pre-planned in the protocol .

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria :

Main study:

Participants with RA who were previously randomized in the sarilumab RA clinical program:

e.g., the EFC11072 study, ACT11575 study, EFC10832 study, SFY13370, and EFC13752 study.

Sub-study:

Participants enrolled in the LTS11210 study who were receiving either sarilumab 200mg q2w PFS or sarilumab 150mg q2w PFS and who were able and willing to participate in this sub-study.

Participants who had been enrolled in the main study for at least 24 weeks. Participants must sign a sub-study written informed consent prior to any sub-study related procedure.

Exclusion criteria:

Main study:

Participants with any adverse event (AE) led to permanent study drug discontinuation from a prior study.

Participants with an abnormality(ies) or AEs that per investigator judgment would adversely affect participation of the participant in the study.

Sub-study: There are no additional exclusion criteria to those defined in main study.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840070	Anniston	Alabama	United States	36207
2	Investigational Site Number 840138	Birmingham	Alabama	United States	35205
3	Investigational Site Number 840152	Huntsville	Alabama	United States	35801
4	Investigational Site Number 840072	Gilbert	Arizona	United States	85234
5	Investigational Site Number 840141	Glendale	Arizona	United States	85304
6	Investigational Site Number 840134	Fullerton	California	United States	92835
7	Investigational Site Number 840008	La Jolla	California	United States	92093
8	Investigational Site Number 840135	San Diego	California	United States	92120
9	Investigational Site Number 840021	Santa Maria	California	United States	94354
10	Investigational Site Number 840100	Stanford	California	United States	94305
11	Investigational Site Number 840049	Upland	California	United States	91786
12	Investigational Site Number 840151	Colorado Springs	Colorado	United States	80903
13	Investigational Site Number 840130	Lewes	Delaware	United States	19958
14	Investigational Site Number 840153	Aventura	Florida	United States	33180
15	Investigational Site Number 840050	Clearwater	Florida	United States	35765
16	Investigational Site Number 840033	Fort Lauderdale	Florida	United States	33309
17	Investigational Site Number 840041	Gainesville	Florida	United States	32608
18	Investigational Site Number 840067	Jupiter	Florida	United States	33458
19	Investigational Site Number 840048	Miami	Florida	United States	33155
20	Investigational Site Number 840024	Naples	Florida	United States	34102
21	Investigational Site Number 840006	Orlando	Florida	United States	32806
22	Investigational Site Number 840128	Ormond Beach	Florida	United States	32174
23	Investigational Site Number 840063	Palm Harbor	Florida	United States	34684
24	Investigational Site Number 840155	Palm Harbor	Florida	United States	34684
25	Investigational Site Number 840060	Sarasota	Florida	United States	34239
26	Investigational Site Number 840140	Tampa	Florida	United States	33614
27	Investigational Site Number 840126	Vero Beach	Florida	United States	32960
28	Investigational Site Number 840003	Atlanta	Georgia	United States	30322
29	Investigational Site Number 840028	Decatur	Georgia	United States	30033
30	Investigational Site Number 840027	Marietta	Georgia	United States	30060
31	Investigational Site Number 840018	Idaho Falls	Idaho	United States	83404
32	Investigational Site Number 840046	Chicago	Illinois	United States	60612
33	Investigational Site Number 840052	Kansas City	Kansas	United States	66160-7321
34	Investigational Site Number 840230	Elizabethtown	Kentucky	United States	42701
35	Investigational Site Number 840015	Lexington	Kentucky	United States	40504
36	Investigational Site Number 840120	Baton Rouge	Louisiana	United States	70809
37	Investigational Site Number 840109	Lake Charles	Louisiana	United States	70601
38	Investigational Site Number 840055	Frederick	Maryland	United States	21702
39	Investigational Site Number 840013	Wheaton	Maryland	United States	20902
40	Investigational Site Number 840154	Boston	Massachusetts	United States	02115
41	Investigational Site Number 840150	Lansing	Michigan	United States	48910
42	Investigational Site Number 840137	Saint Clair Shores	Michigan	United States	48081
43	Investigational Site Number 840112	Lincoln	Nebraska	United States	68516
44	Investigational Site Number 840026	Freehold	New Jersey	United States	07728
45	Investigational Site Number 840115	Lake Success	New York	United States	11042
46	Investigational Site Number 840056	New York	New York	United States	10003
47	Investigational Site Number 840043	New York	New York	United States	11201
48	Investigational Site Number 840106	Orchard Park	New York	United States	14127
49	Investigational Site Number 840118	Smithtown	New York	United States	11787
50	Investigational Site Number 840116	Wilmington	North Carolina	United States	28401
51	Investigational Site Number 840233	Minot	North Dakota	United States	58701
52	Investigational Site Number 840002	Oklahoma City	Oklahoma	United States	73103
53	Investigational Site Number 840127	Oklahoma City	Oklahoma	United States	73103
54	Investigational Site Number 840011	Tulsa	Oklahoma	United States	74104
55	Investigational Site Number 840065	Tulsa	Oklahoma	United States	74135
56	Investigational Site Number 840010	Bethlehem	Pennsylvania	United States	18015
57	Investigational Site Number 840009	Duncansville	Pennsylvania	United States	16635
58	Investigational Site Number 840062	Reading	Pennsylvania	United States	19611
59	Investigational Site Number 840058	Columbia	South Carolina	United States	29204
60	Investigational Site Number 840016	North Charleston	South Carolina	United States	29406
61	Investigational Site Number 840025	Jackson	Tennessee	United States	38305
62	Investigational Site Number 840059	Memphis	Tennessee	United States	38119
63	Investigational Site Number 840032	Amarillo	Texas	United States	79124
64	Investigational Site Number 840038	Austin	Texas	United States	78705
65	Investigational Site Number 840001	Dallas	Texas	United States	75231
66	Investigational Site Number 840022	Dallas	Texas	United States	75235
67	Investigational Site Number 840012	Dallas	Texas	United States	75390
68	Investigational Site Number 840129	Houston	Texas	United States	77074
69	Investigational Site Number 840069	Lubbock	Texas	United States	79424
70	Investigational Site Number 840074	Mesquite	Texas	United States	75150
71	Investigational Site Number 840020	Nassau Bay	Texas	United States	77058
72	Investigational Site Number 840103	San Antonio	Texas	United States	78217
73	Investigational Site Number 840036	Spokane	Washington	United States	99204
74	Investigational Site Number 840061	Tacoma	Washington	United States	98405
75	Investigational Site Number 840124	Clarksburg	West Virginia	United States	26301
76	Investigational Site Number 032006	Caba		Argentina	C1015ABO
77	Investigational Site Number 032007	Caba		Argentina	C1055AAF
78	Investigational Site Number 032008	Caba		Argentina	C1428DZF
79	Investigational Site Number 032019	Capital Federal		Argentina	1180
80	Investigational Site Number 032016	Capital Federal		Argentina	1425
81	Investigational Site Number 032002	Cordoba		Argentina	X5004BAL
82	Investigational Site Number 032020	Cordoba		Argentina	X5016KEH
83	Investigational Site Number 032003	Córdoba		Argentina
84	Investigational Site Number 032017	La Plata		Argentina	B1902
85	Investigational Site Number 032012	Mar Del Plata		Argentina	B7600FZN
86	Investigational Site Number 032011	Quilmes		Argentina	B1878DVB
87	Investigational Site Number 032010	Ramos Mejia		Argentina	B1704ETD
88	Investigational Site Number 032001	Rosario		Argentina	2000
89	Investigational Site Number 032013	Rosario		Argentina	S2000PBJ
90	Investigational Site Number 032015	San Fernando		Argentina	1646
91	Investigational Site Number 032005	San Miguel De Tucuman		Argentina	4000
92	Investigational Site Number 032004	San Miguel De Tucuman		Argentina	T4000AXL
93	Investigational Site Number 032009	Zarate		Argentina	B2800DGH
94	Investigational Site Number 036003	Camperdown		Australia	2050
95	Investigational Site Number 036012	Fitzroy		Australia	3065
96	Investigational Site Number 036010	Garran		Australia	2605
97	Investigational Site Number 036004	Heidelberg West		Australia	3081
98	Investigational Site Number 036001	Maroochydore		Australia	4558
99	Investigational Site Number 036014	Victoria Park		Australia	6100
100	Investigational Site Number 036007	Woodville		Australia	5011
101	Investigational Site Number 040001	Graz		Austria	8036
102	Investigational Site Number 112002	Minsk		Belarus	220037
103	Investigational Site Number 112001	Minsk		Belarus	220116
104	Investigational Site Number 056010	Leuven		Belgium	3000
105	Investigational Site Number 076001	Curitiba		Brazil	80060-240
106	Investigational Site Number 076006	Goiania		Brazil	74110-120
107	Investigational Site Number 076010	Juiz De Fora		Brazil	36010-570
108	Investigational Site Number 076004	Porto Alegre		Brazil	90610-000
109	Investigational Site Number 076005	Rio De Janeiro		Brazil	20551-030
110	Investigational Site Number 076015	Rio De Janeiro		Brazil	22271-100
111	Investigational Site Number 076011	Salvador		Brazil	40050-410
112	Investigational Site Number 076002	Sao Paulo		Brazil	04039-901
113	Investigational Site Number 076003	Sao Paulo		Brazil	04266-010
114	Investigational Site Number 076013	Vitoria		Brazil	29055 450
115	Investigational Site Number 124003	Mississauga		Canada	L5M 2V8
116	Investigational Site Number 124002	St. Catharines		Canada	L2N 7E4
117	Investigational Site Number 124005	Toronto		Canada	M5T 2S8
118	Investigational Site Number 124009	Trois-Rivières		Canada	G8Z 1Y2
119	Investigational Site Number 124104	Victoria		Canada	V8V 3P9
120	Investigational Site Number 124012	Winnipeg		Canada	R3A 1M3
121	Investigational Site Number 152005	Osorno		Chile	5311092
122	Investigational Site Number 152012	Santiago		Chile	7500922
123	Investigational Site Number 152002	Santiago		Chile	7501126
124	Investigational Site Number 152011	Santiago		Chile	7510186
125	Investigational Site Number 152009	Santiago		Chile	8207257
126	Investigational Site Number 152001	Santiago		Chile	8360156
127	Investigational Site Number 152013	Santiago		Chile	8360156
128	Investigational Site Number 152008	Santiago		Chile
129	Investigational Site Number 152014	Talca		Chile
130	Investigational Site Number 152015	Temuco IX Region		Chile	4790928
131	Investigational Site Number 152004	Valdivia		Chile	5090146
132	Investigational Site Number 152006	Vina Del Mar		Chile
133	Investigational Site Number 152007	Viña Del Mar		Chile	2520997
134	Investigational Site Number 170005	Barranquilla		Colombia	080020399
135	Investigational Site Number 170004	Barranquilla		Colombia	99999
136	Investigational Site Number 170001	Bogota		Colombia	110221042
137	Investigational Site Number 170008	Bogota		Colombia	111211626
138	Investigational Site Number 170006	Bogotá		Colombia	11011
139	Investigational Site Number 170003	Bogotá		Colombia	111211191
140	Investigational Site Number 170007	Bucaramanga		Colombia	680003288
141	Investigational Site Number 170009	Bucaramanga		Colombia	680003
142	Investigational Site Number 203009	Liberec		Czechia	46063
143	Investigational Site Number 203004	Ostrava		Czechia	702 00
144	Investigational Site Number 203034	Pardubice		Czechia	53002
145	Investigational Site Number 203001	Praha 2		Czechia	12850
146	Investigational Site Number 203007	Praha 2		Czechia	12850
147	Investigational Site Number 203011	Praha 2		Czechia	12850
148	Investigational Site Number 203010	Praha 4		Czechia	140 00
149	Investigational Site Number 203002	Uherske Hradiste		Czechia	686 01
150	Investigational Site Number 203006	Zlin		Czechia	760 01
151	Investigational Site Number 218003	Cuenca		Ecuador	010204
152	Investigational Site Number 218001	Guayaquil		Ecuador	090109
153	Investigational Site Number 218002	Quito		Ecuador	170524
154	Investigational Site Number 233001	Tallinn		Estonia	10128
155	Investigational Site Number 233010	Tallinn		Estonia	10138
156	Investigational Site Number 233002	Tallinn		Estonia	13419
157	Investigational Site Number 246001	Helsinki		Finland	00290
158	Investigational Site Number 246002	Hyvinkää		Finland	05800
159	Investigational Site Number 246003	Pori		Finland	28100
160	Investigational Site Number 246010	Riihimäki		Finland	11120
161	Investigational Site Number 276011	Bad Nauheim		Germany	61231
162	Investigational Site Number 276010	Berlin		Germany	10117
163	Investigational Site Number 276007	Berlin		Germany	12161
164	Investigational Site Number 276008	Berlin		Germany	12163
165	Investigational Site Number 276014	Berlin		Germany	14059
166	Investigational Site Number 276018	Deggingen		Germany	73326
167	Investigational Site Number 276015	Halle/Saale		Germany	06108
168	Investigational Site Number 276005	Hamburg		Germany	22081
169	Investigational Site Number 276013	Hamburg		Germany	22147
170	Investigational Site Number 276001	Herne		Germany	44649
171	Investigational Site Number 276016	Leipzig		Germany	04103
172	Investigational Site Number 276017	München		Germany	80336
173	Investigational Site Number 276021	Osnabrück		Germany	49074
174	Investigational Site Number 276020	Tübingen		Germany	72076
175	Investigational Site Number 276019	Zerbst		Germany	39261
176	Investigational Site Number 300002	Heraklion		Greece	71110
177	Investigational Site Number 300003	Thessaloniki		Greece	54636
178	Investigational Site Number 300005	Thessaloniki		Greece	57010
179	Investigational Site Number 320002	Guatemala City		Guatemala	01009
180	Investigational Site Number 320003	Guatemala City		Guatemala	01011
181	Investigational Site Number 320001	Guatemala		Guatemala	9090
182	Investigational Site Number 348006	Budapest		Hungary	1023
183	Investigational Site Number 348014	Budapest		Hungary	1027
184	Investigational Site Number 348025	Budapest		Hungary	1027
185	Investigational Site Number 348022	Budapest		Hungary	1036
186	Investigational Site Number 348010	Debrecen		Hungary	4031
187	Investigational Site Number 348003	Debrecen		Hungary	4032
188	Investigational Site Number 348021	Esztergom		Hungary	2500
189	Investigational Site Number 348013	Györ		Hungary	9025
190	Investigational Site Number 348009	Szolnok		Hungary	5000
191	Investigational Site Number 348015	Szombathely		Hungary	9700
192	Investigational Site Number 348004	Székesfehérvár		Hungary	8000
193	Investigational Site Number 348005	Sátoraljaújhely		Hungary	3980
194	Investigational Site Number 376001	Haifa		Israel	31048
195	Investigational Site Number 376010	Haifa		Israel	31096
196	Investigational Site Number 376011	Tel Aviv		Israel	64239
197	Investigational Site Number 376002	Tel Hashomer		Israel	52621
198	Investigational Site Number 380005	Genova		Italy	16132
199	Investigational Site Number 410014	Anyang-Si		Korea, Republic of	431-070
200	Investigational Site Number 410006	Busan		Korea, Republic of	602-739
201	Investigational Site Number 410004	Daegu		Korea, Republic of	700-721
202	Investigational Site Number 410017	Daejeon		Korea, Republic of	301-721
203	Investigational Site Number 410005	Daejeon		Korea, Republic of	302-799
204	Investigational Site Number 410010	Gwangju		Korea, Republic of	61469
205	Investigational Site Number 410001	Incheon		Korea, Republic of	21565
206	Investigational Site Number 410009	Incheon		Korea, Republic of	400-711
207	Investigational Site Number 410011	Jeonju		Korea, Republic of	561-712
208	Investigational Site Number 410007	Seoul		Korea, Republic of	03080
209	Investigational Site Number 410012	Seoul		Korea, Republic of	04763
210	Investigational Site Number 410016	Seoul		Korea, Republic of	120-752
211	Investigational Site Number 410003	Seoul		Korea, Republic of	150-713
212	Investigational Site Number 410008	Suwon		Korea, Republic of	443-721
213	Investigational Site Number 440001	Kaunas		Lithuania	50009
214	Investigational Site Number 440006	Klaipeda		Lithuania	LT-92288
215	Investigational Site Number 440002	Vilnius		Lithuania	LT-08661
216	Investigational Site Number 440007	Vilnius		Lithuania	LT-08661
217	Investigational Site Number 458001	Ipoh		Malaysia	30990
218	Investigational Site Number 458002	Kuching		Malaysia	94300
219	Investigational Site Number 484023	Chihuahua		Mexico	31000
220	Investigational Site Number 484008	Durango		Mexico	34080
221	Investigational Site Number 484018	Guadalajara		Mexico	44620
222	Investigational Site Number 484002	Guadalajara		Mexico	44690
223	Investigational Site Number 484035	Leon		Mexico	37000
224	Investigational Site Number 484009	Merida		Mexico	97000
225	Investigational Site Number 484007	Metepec		Mexico	52140
226	Investigational Site Number 484010	Mexicali		Mexico	21200
227	Investigational Site Number 484003	Mexico City		Mexico	6726
228	Investigational Site Number 484019	Monterrey		Mexico	64000
229	Investigational Site Number 484020	Monterrey		Mexico	64000
230	Investigational Site Number 484005	Monterrey		Mexico	64460
231	Investigational Site Number 484004	Mérida		Mexico	97070
232	Investigational Site Number 484001	México, D.F.		Mexico	11850
233	Investigational Site Number 484017	México		Mexico	06700
234	Investigational Site Number 484021	Queretaro		Mexico	76000
235	Investigational Site Number 528010	Amsterdam		Netherlands	1056 AB
236	Investigational Site Number 554004	Christchurch		New Zealand	8002
237	Investigational Site Number 554011	Nelson		New Zealand	7010
238	Investigational Site Number 554007	Otahuhu		New Zealand	2025
239	Investigational Site Number 554002	Rotorua		New Zealand	3010
240	Investigational Site Number 554001	Timaru		New Zealand	7910
241	Investigational Site Number 604001	Lima		Peru	021
242	Investigational Site Number 604010	Lima		Peru	14
243	Investigational Site Number 604008	Lima		Peru	34
244	Investigational Site Number 604009	Lima		Peru	LIMA 01
245	Investigational Site Number 604006	Lima		Peru	LIMA 11
246	Investigational Site Number 604012	Lima		Peru	LIMA 11
247	Investigational Site Number 604013	Lima		Peru	LIMA 13
248	Investigational Site Number 604007	Lima		Peru	LIMA 33
249	Investigational Site Number 604005	Lima		Peru	LIMA 41
250	Investigational Site Number 608003	Cebu City		Philippines	6000
251	Investigational Site Number 608001	Manila		Philippines	1008
252	Investigational Site Number 616014	Bialystok		Poland	15-099
253	Investigational Site Number 616002	Bialystok		Poland	15-351
254	Investigational Site Number 616003	Bialystok		Poland	15-879
255	Investigational Site Number 616019	Bydgoszcz		Poland	85-168
256	Investigational Site Number 616054	Bytom		Poland	41-902
257	Investigational Site Number 616015	Elblag		Poland	82-300
258	Investigational Site Number 616001	Krakow		Poland	30-510
259	Investigational Site Number 616005	Lublin		Poland	20-582
260	Investigational Site Number 616030	Lublin		Poland	20-954
261	Investigational Site Number 616018	Poznan		Poland	61-397
262	Investigational Site Number 616016	Szczecin		Poland	71-252
263	Investigational Site Number 616006	Torun		Poland	87-100
264	Investigational Site Number 616031	Warszawa		Poland	01-518
265	Investigational Site Number 616004	Warszawa		Poland	02-118
266	Investigational Site Number 616017	Warszawa		Poland	02-653
267	Investigational Site Number 616020	Wroclaw		Poland	50-556
268	Investigational Site Number 616012	Wroclaw		Poland	52-416
269	Investigational Site Number 620002	Lisboa		Portugal	1050-034
270	Investigational Site Number 642006	Braila		Romania	810019
271	Investigational Site Number 642010	Bucharest		Romania	011171
272	Investigational Site Number 642021	Bucuresti		Romania	010584
273	Investigational Site Number 642001	Bucuresti		Romania	010976
274	Investigational Site Number 642020	Bucuresti		Romania	020125
275	Investigational Site Number 642002	Bucuresti		Romania	020983
276	Investigational Site Number 642005	Galati		Romania	800578
277	Investigational Site Number 643006	Kemerovo		Russian Federation	650000
278	Investigational Site Number 643017	Kemerovo		Russian Federation	650066
279	Investigational Site Number 643020	Moscow		Russian Federation	115404
280	Investigational Site Number 643001	Moscow		Russian Federation	115522
281	Investigational Site Number 643002	Moscow		Russian Federation	117997
282	Investigational Site Number 643021	Moscow		Russian Federation	119049
283	Investigational Site Number 643004	Moscow		Russian Federation	119333
284	Investigational Site Number 643012	Moscow		Russian Federation	121359
285	Investigational Site Number 643031	Moscow		Russian Federation	121374
286	Investigational Site Number 643030	Moscow		Russian Federation	125284
287	Investigational Site Number 643009	Novosibirsk		Russian Federation	630099
288	Investigational Site Number 643016	Ryazan		Russian Federation	390026
289	Investigational Site Number 643008	Saint-Petersburg		Russian Federation	192242
290	Investigational Site Number 643010	Samara		Russian Federation	443095
291	Investigational Site Number 643011	Saratov		Russian Federation	410053
292	Investigational Site Number 643007	St-Petersburg		Russian Federation	190068
293	Investigational Site Number 643032	St-Petersburg		Russian Federation	191186
294	Investigational Site Number 643014	St-Petersburg		Russian Federation	196247
295	Investigational Site Number 643013	Ufa		Russian Federation	450005
296	Investigational Site Number 710011	Cape Town		South Africa	7405
297	Investigational Site Number 710007	Cape Town		South Africa	7500
298	Investigational Site Number 710009	Cape Town		South Africa	8001
299	Investigational Site Number 710003	Durban		South Africa	4001
300	Investigational Site Number 710002	Durban		South Africa	4091
301	Investigational Site Number 710001	Johannesburg		South Africa	2013
302	Investigational Site Number 710004	Kempton Park		South Africa	1619
303	Investigational Site Number 710005	Pretoria		South Africa	0002
304	Investigational Site Number 710006	Pretoria		South Africa	0084
305	Investigational Site Number 710010	Stellenbosch		South Africa	7600
306	Investigational Site Number 724016	Barakaldo		Spain	48903
307	Investigational Site Number 724015	Barcelona		Spain	08034
308	Investigational Site Number 724014	Cádiz		Spain	11009
309	Investigational Site Number 724009	La Coruña		Spain	15006
310	Investigational Site Number 724001	Málaga		Spain	29010
311	Investigational Site Number 724011	Sabadell		Spain	08208
312	Investigational Site Number 724012	Santiago De Compostela		Spain	15705
313	Investigational Site Number 724013	Santiago De Compostela		Spain	15706
314	Investigational Site Number 724022	Sevilla		Spain	41010
315	Investigational Site Number 724007	Sevilla		Spain	41071
316	Investigational Site Number 752002	Uppsala		Sweden	751 85
317	Investigational Site Number 158006	Taichung		Taiwan	40201
318	Investigational Site Number 158002	Taoyuan County		Taiwan	33305
319	Investigational Site Number 764001	Bangkok		Thailand	10400
320	Investigational Site Number 764003	Bangkok		Thailand	10700
321	Investigational Site Number 792008	Gaziantep		Turkey	27310
322	Investigational Site Number 804003	Dnipro		Ukraine	49047
323	Investigational Site Number 804010	Kharkiv		Ukraine	61058
324	Investigational Site Number 804013	Kharkiv		Ukraine	61176
325	Investigational Site Number 804014	Kyiv		Ukraine	01103
326	Investigational Site Number 804004	Kyiv		Ukraine	03680
327	Investigational Site Number 804027	Kyiv		Ukraine	03680
328	Investigational Site Number 804005	Lviv		Ukraine	79010
329	Investigational Site Number 804006	Simferopol		Ukraine	95017
330	Investigational Site Number 804011	Vinnytsya		Ukraine	21018
331	Investigational Site Number 804009	Zaporizhzhya		Ukraine	69600
332	Investigational Site Number 826004	Doncaster		United Kingdom	DN2 5LT
333	Investigational Site Number 826006	Edinburgh		United Kingdom	EH4 2XU
334	Investigational Site Number 826002	Leytonstone		United Kingdom	E11 1NR
335	Investigational Site Number 826005	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

Sanofi
Regeneron Pharmaceuticals

Investigators

Study Director: Clinical Sciences and Operations, Sanofi

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT01146652

Other Study ID Numbers:

LTS11210
2010-019262-86

First Posted:

Jun 17, 2010

Last Update Posted:

Mar 28, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Additional relevant MeSH terms:

Arthritis

Arthritis, Rheumatoid

Study Results

Participant Flow

Recruitment Details

Participants who completed any of studies EFC11072 (NCT01061736), ACT11575 ( NCT01217814), EFC10832 (NCT01709578), SFY13370 (NCT01768572), EFC13752 (NCT02121210) were eligible for enrollment in LTS11210 (named as main study). A total of 2023 participants were enrolled between 21 June 2010 and 04 May 2015. From Week 24 of LTS11210, willing participants were enrolled in a 12-week sub-study (part of main study only) to assess usability of pre-filled syringe with safety system (PFS-S).

Pre-assignment Detail

Participants had been exposed to sarilumab for 12 weeks if they were initially randomized in EFC11072 Part A or ACT11575; for up to 52 weeks if initially randomized in EFC11072 Part B; for up to 24 weeks if initially randomized in EFC10832; or for 24 weeks if initially randomized in SFY13370 or EFC13752. Participant's end-of-treatment visit in initial study corresponded to initial visit in study LTS11210.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Period Title: Overall Study
STARTED	1912	111
Treated	1910	111
Enrolled in the Sub-study	110	14
Discontinued From the Sub-study	1	2
Switched Back to Main Study	108	13
COMPLETED	961	66
NOT COMPLETED	951	45

Baseline Characteristics

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy	Total Title
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Overall Participants	1912	111	2023
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.1 (11.8)	52.9 (13.1)	52.2 (11.9)
Sex: Female, Male (Count of Participants)
Female	1550 81.1%	88 79.3%	1638 81%
Male	362 18.9%	23 20.7%	385 19%
Race/Ethnicity, Customized (Count of Participants)
Caucasian/White	1639 85.7%	108 97.3%	1747 86.4%
Black	48 2.5%	1 0.9%	49 2.4%
Asian/Oriental	69 3.6%	1 0.9%	70 3.5%
Other	156 8.2%	1 0.9%	157 7.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description	An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal product and which did not necessarily have to have a causal relationship with the treatment. An SAE was any untoward medical occurrence at any dose that: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were AEs that developed or worsened or became serious during the TEAE period (defined as the time from the first dose of the investigational medicinal product (IMP) in study LTS11210 to the last dose of the IMP +60 days).
Time Frame	From first dose (i.e., Day 1 of study LTS11210) up to 60 days after last dose (maximum duration: up to 523 weeks)

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population which included all enrolled participants who had received at least one dose of the study treatment in LTS11210.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Measure Participants	1910	111
Any TEAE	1760 92.1%	98 88.3%
Any TE SAE	617 32.3%	27 24.3%

2. Primary Outcome

Title	Sub-study: Number of Participants Reported Product Technical Complaints (PTC), Product Technical Failures (PTF) and/or Failed Drug Deliveries (FDD) With Pre-filled Syringe With Safety System
Description	A PTF was defined as any product technical complaint (PTC) related to the use of the PFS-S that had a validated technical cause. FDD was defined as participant's failure to administer the full dose at a given attempt. A PTC was defined as any participant- or healthcare provider-reported complaint regarding the use of the PFS-S syringe and collected via the completion of the injection diary. The injection diary comprised specific questions: 1. Were you able to remove the cap? 2. Was the needle safety system activated?, 3. Did the safety system entirely cover the needle, and 4. Was the person who performed the injection the person who was trained by the site staff?, where each question was given the option yes/no. Participants who answered "no" for any of the questions of PTC, had PTF and/or FDD were reported in this outcome measure.
Time Frame	From Week 24 to 36

Outcome Measure Data

Analysis Population Description
Analysis was performed on all participants who were enrolled in the sub-study.

Arm/Group Title	PFS-S Sarilumab 150 mg q2w	PFS-S Sarilumab 200 mg q2w	PFS-S Sarilumab 200 to 150 mg q2w
Arm/Group Description	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 150 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PFS-S.	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 200 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PFS-S.	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 200 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PF-S. The dose might be reduced to 150 mg q2w due to neutropenia, thrombocytopenia, or an increase in liver enzymes.
Measure Participants	25	98	1
PFS-S-associated PTF	0 0%	0 0%	0 0%
PFS-S-associated FDD	0 0%	5 4.5%	0 0%
PFS-S-associated PTC	0 0%	5 4.5%	0 0%

3. Primary Outcome

Title	Sub-study: Number of Product Technical Complaints - Product Technical Failures With Pre-filled Syringe With Safety System
Description	A PTF was defined as any PTC (defined as any participant- or healthcare provider-reported complaint regarding the use of the PFS-S syringe and collected via the completion of the injection diary) related to the use of the PFS-S that had a validated technical cause. Number of PTF in the participants enrolled in sub-study were reported in this outcome measure.
Time Frame	From Week 24 to 36

Outcome Measure Data

Analysis Population Description
Analysis was performed on all participants who were enrolled in the sub-study.

Arm/Group Title	PFS-S Sarilumab 150 mg q2w	PFS-S Sarilumab 200 mg q2w	PFS-S Sarilumab 200 to 150 mg q2w
Arm/Group Description	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 150 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PFS-S.	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 200 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PFS-S.	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 200 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PF-S. The dose might be reduced to 150 mg q2w due to neutropenia, thrombocytopenia, or an increase in liver enzymes.
Measure Participants	25	98	1
Number [PTF]	0	0	0

4. Primary Outcome

Title	Sub-study: Number of Failed Drug Deliveries Associated With Pre-filled Syringe With Safety System
Description	FDD was defined as participant's failure to administer the full dose at a given attempt. Number of FDD in the participants enrolled in sub-study were reported in this outcome measure.
Time Frame	From Week 24 to 36

Outcome Measure Data

Analysis Population Description
Analysis was performed on all participants who were enrolled in the sub-study.

Arm/Group Title	PFS-S Sarilumab 150 mg q2w	PFS-S Sarilumab 200 mg q2w	PFS-S Sarilumab 200 to 150 mg q2w
Arm/Group Description	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 150 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PFS-S.	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 200 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PFS-S.	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 200 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PF-S. The dose might be reduced to 150 mg q2w due to neutropenia, thrombocytopenia, or an increase in liver enzymes.
Measure Participants	25	98	1
Number [FDD]	0	5	0

5. Primary Outcome

Title	Sub-study: Number of Product Technical Complaints With Pre-filled Syringe With Safety System
Description	A PTC was defined as any participant- or healthcare provider-reported complaint regarding the use of the PFS-S syringe and collected via the completion of the injection diary. The injection diary comprised specific questions: 1. Were you able to remove the cap? 2. Was the needle safety system activated?, 3. Did the safety system entirely cover the needle, and 4. Was the person who performed the injection the person who was trained by the site staff?, where each question was given the option yes/no. Number of PTC (based on participant's answer to "no" for any of the questions of PTC) in the participants enrolled in sub-study were reported in this outcome measure.
Time Frame	From Week 24 to 36

Outcome Measure Data

Analysis Population Description
Analysis was performed on all participants who were enrolled in the sub-study.

Arm/Group Title	PFS-S Sarilumab 150 mg q2w	PFS-S Sarilumab 200 mg q2w	PFS-S Sarilumab 200 to 150 mg q2w
Arm/Group Description	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 150 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PFS-S.	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 200 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PFS-S.	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 200 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PF-S. The dose might be reduced to 150 mg q2w due to neutropenia, thrombocytopenia, or an increase in liver enzymes.
Measure Participants	25	98	1
Number [PTC]	0	5	0

6. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 20 (ACR20) Response
Description	ACR20 response: greater than or equal to (>=) 20% improvement in both tender joint count and swollen joint count and, >=20% improvement in at least 3 of the 5 remaining ACR core measures assessments: C-reactive protein [CRP] level (mg/liter [mg/L]); participant's assessment of pain (measured on 0 [no pain] to 100 mm [worst pain] visual analog scale [VAS]); participant's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by health assessment questionnaire disability index [HAQ-DI], with scoring range of 0 [better physical function] to 3 [worst physical function]). Higher score indicated worse outcomes.
Time Frame	At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population which included participants who had at least 1 dose of study treatment in LTS11210. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Measure Participants	1898	111
Week 0	69.4 3.6%	82.0 73.9%
Week 4	77.8 4.1%	85.8 77.3%
Week 8	80.2 4.2%	92.5 83.3%
Week 12	80.3 4.2%	91.7 82.6%
Week 24	82.9 4.3%	88.1 79.4%
Week 36	82.8 4.3%	91.7 82.6%
Week 48	82.9 4.3%	85.0 76.6%
Week 60	84.6 4.4%	93.2 84%
Week 72	84.4 4.4%	94.1 84.8%
Week 84	84.5 4.4%	94.7 85.3%
Week 96	85.2 4.5%	91.3 82.3%
Week 120	84.9 4.4%	90.9 81.9%
Week 144	86.4 4.5%	94.0 84.7%
Week 168	86.0 4.5%	90.1 81.2%
Week 192	85.7 4.5%	89.3 80.5%
Week 216	87.1 4.6%	89.2 80.4%
Week 240	86.4 4.5%	91.9 82.8%
Week 264	88.5 4.6%	90.2 81.3%

7. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 50 (ACR50) Response
Description	ACR50 response: >=50% improvement in both TJC and SJC, and >=50% improvement in at least 3 of the 5 remaining ACR core measures assessments: CRP level (in mg/L); participant's assessment of pain (measured on 0 [no pain] to 100 mm [worst pain] VAS); participant's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by HAQ-DI, with scoring range of 0 [better physical function] to 3 [worst physical function]). Higher score indicated worse outcomes.
Time Frame	At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Measure Participants	1897	111
Week 0	43.4 2.3%	58.6 52.8%
Week 4	51.3 2.7%	59.3 53.4%
Week 8	55.1 2.9%	59.0 53.2%
Week 12	58.1 3%	66.7 60.1%
Week 24	60.5 3.2%	64.2 57.8%
Week 36	62.1 3.2%	64.2 57.8%
Week 48	62.4 3.3%	69.2 62.3%
Week 60	63.2 3.3%	68.9 62.1%
Week 72	64.8 3.4%	71.3 64.2%
Week 84	63.6 3.3%	73.4 66.1%
Week 96	65.3 3.4%	71.7 64.6%
Week 120	65.6 3.4%	73.6 66.3%
Week 144	65.7 3.4%	70.2 63.2%
Week 168	66.2 3.5%	70.0 63.1%
Week 192	68.4 3.6%	70.7 63.7%
Week 216	69.0 3.6%	75.7 68.2%
Week 240	68.3 3.6%	79.7 71.8%
Week 264	69.6 3.6%	71.7 64.6%

8. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 70 (ACR70) Response
Description	ACR70 response: >=70% improvement in both TJC and SJC, and >=70% improvement in at least 3 of the 5 remaining ACR core measures assessments: CRP level (in mg/L); participant's assessment of pain (measured on 0 [no pain] to 100 mm [worst pain] VAS); participant's global assessment of disease activity (measured on 0 [no arthritis activity]to 100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by HAQ-DI, with scoring range of 0 [better physical function] to 3 [worst physical function]). Higher score indicated worse outcomes.
Time Frame	At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Measure Participants	1901	111
Week 0	22.9 1.2%	32.4 29.2%
Week 4	27.8 1.5%	31.5 28.4%
Week 8	32.1 1.7%	36.2 32.6%
Week 12	34.1 1.8%	43.0 38.7%
Week 24	38.7 2%	37.4 33.7%
Week 36	40.2 2.1%	40.4 36.4%
Week 48	40.6 2.1%	43.8 39.5%
Week 60	41.6 2.2%	45.6 41.1%
Week 72	42.1 2.2%	49.0 44.1%
Week 84	41.8 2.2%	52.1 46.9%
Week 96	43.4 2.3%	55.4 49.9%
Week 120	42.9 2.2%	56.8 51.2%
Week 144	44.7 2.3%	50.0 45%
Week 168	45.6 2.4%	51.3 46.2%
Week 192	47.9 2.5%	53.9 48.6%
Week 216	46.8 2.4%	62.0 55.9%
Week 240	47.9 2.5%	60.8 54.8%
Week 264	48.8 2.6%	58.3 52.5%

9. Secondary Outcome

Title	Percentage of Participants With Disease Activity Score for 28 Joints (DAS28) Remission
Description	Disease activity score based on 28 joints and C-reactive protein (DAS28-CRP) was a composite score which included 4 components: TJC with 28 joints assessed; SJC with 28 joints assessed; high-sensitivity CRP (in mg/L) and general health assessment by the participant using participant global assessment (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS). DAS28-CRP total score ranges from 0 to 10, where higher scores indicated greater disease activity. Percentage of participants with DAS28 remission were reported.
Time Frame	At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category and "0" in the number analyzed field denotes that data were not planned to be collected and analyzed for the specified time-points in the respective groups.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Measure Participants	1873	110
Week 0	30.4 1.6%	46.4 41.8%
Week 4	39.2 2.1%	51.9 46.8%
Week 8	44.6 2.3%	49.5 44.6%
Week 12	47.9 2.5%	55.0 49.5%
Week 24	50.6 2.6%	59.6 53.7%
Week 36	51.7 2.7%	59.6 53.7%
Week 48	53.7 2.8%	56.1 50.5%
Week 60	56.5 3%	61.8 55.7%
Week 72	55.8 2.9%	68.3 61.5%
Week 84	55.8 2.9%	70.5 63.5%
Week 96	57.0 3%	71.7 64.6%
Week 120	59.2 3.1%	73.9 66.6%
Week 144	59.3 3.1%	72.3 65.1%
Week 168	59.7 3.1%	70.4 63.4%
Week 192	62.1 3.2%	67.1 60.5%
Week 216	63.6 3.3%	71.2 64.1%
Week 240	61.6 3.2%	82.2 74.1%
Week 264	64.4 3.4%	75.8 68.3%
Week 288	68.7 3.6%	73.1 65.9%
Week 312	69.0 3.6%	85.7 77.2%
Week 336	72.2 3.8%
Week 360	71.7 3.8%
Week 384	71.6 3.7%
Week 408	69.8 3.7%
Week 432	76.4 4%
Week 456	72.7 3.8%
Week 480	76.9 4%
Week 504	73.1 3.8%
Week 516	50.0 2.6%

10. Secondary Outcome

Title	Percentage of Participants Achieving Good Response, Moderate Response or Non-response Using the European League Against Rheumatism (EULAR) Response Criteria
Description	DAS28-based EULAR response criteria were used to measure individual response as none, good or moderate, depending on the extent of change from baseline and level of disease activity reached. The EULAR response criteria are defined as: Good response = change from baseline of >1.2 and a present DAS28-CRP score <=3.2. Moderate response = change from baseline of >0.6 to <=1.2 and a present DAS28-CRP score <=5.1, or, change from baseline of >1.2 and present DAS28-CRP score >3.2. Non-response = change from baseline of <=0.6, or change from baseline of >0.6 to <=1.2 and present DAS28-CRP score >5.1. Scores of good and moderate were considered to indicate therapeutic response. DAS28-CRP is a composite score which included 4 components: TJC with 28 joints assessed; SJC with 28 joints assessed; high-sensitivity CRP (in mg/L) and general health assessment by participant using participant global assessment (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS.
Time Frame	At Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category and "0" in the number analyzed field denotes that data was not planned to be collected and analyzed for the specified time-points in the respective groups.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Measure Participants	1872	110
Week 0: Good response	44.7 2.3%	60.9 54.9%
Week 0: Moderate response	40.3 2.1%	30.9 27.8%
Week 0: None response	15.0 0.8%	8.2 7.4%
Week 4: Good response	57.2 3%	69.8 62.9%
Week 4: Moderate response	36.2 1.9%	26.4 23.8%
Week 4:None response	6.6 0.3%	3.8 3.4%
Week 8: Good response	62.3 3.3%	68.6 61.8%
Week 8: Moderate response	31.7 1.7%	27.6 24.9%
Week 8: None response	6.0 0.3%	3.8 3.4%
Week 12: Good response	64.1 3.4%	74.3 66.9%
Week 12: Moderate response	30.6 1.6%	22.9 20.6%
Week 12: None response	5.2 0.3%	2.8 2.5%
Week 24: Good response	66.6 3.5%	73.4 66.1%
Week 24: Moderate response	28.9 1.5%	24.8 22.3%
Week 24: None response	4.5 0.2%	1.8 1.6%
Week 36: Good response	67.9 3.6%	71.6 64.5%
Week 36: Moderate response	27.0 1.4%	24.8 22.3%
Week 36: None response	5.1 0.3%	3.7 3.3%
Week 48: Good response	68.1 3.6%	72.0 64.9%
Week 48: Moderate response	27.4 1.4%	24.3 21.9%
Week 48: None response	4.5 0.2%	3.7 3.3%
Week 60: Good response	71.1 3.7%	68.6 61.8%
Week 60: Moderate response	24.6 1.3%	29.4 26.5%
Week 60: None response	4.2 0.2%	2.0 1.8%
Week 72: Good response	70.0 3.7%	81.2 73.2%
Week 72: Moderate response	26.0 1.4%	16.8 15.1%
Week 72: None response	4.0 0.2%	2.0 1.8%
Week 84: Good response	71.3 3.7%	84.2 75.9%
Week 84: Moderate response	24.2 1.3%	14.7 13.2%
Week 84: None response	4.6 0.2%	1.1 1%
Week 96: Good response	72.6 3.8%	76.1 68.6%
Week 96: Moderate response	23.3 1.2%	21.7 19.5%
Week 96: None response	4.1 0.2%	2.2 2%
Week 120: Good response	73.5 3.8%	80.7 72.7%
Week 120: Moderate response	22.3 1.2%	17.0 15.3%
Week 120: None response	4.2 0.2%	2.3 2.1%
Week 144: Good response	73.3 3.8%	86.7 78.1%
Week 144: Moderate response	22.8 1.2%	13.3 12%
Week 144: None response	3.9 0.2%	0 0%
Week 168: Good response	74.5 3.9%	84.0 75.7%
Week 168: Moderate response	20.6 1.1%	16.0 14.4%
Week 168: None response	4.9 0.3%	0 0%
Week 192: Good response	75.6 4%	81.6 73.5%
Week 192: Moderate response	20.6 1.1%	13.2 11.9%
Week 192: None response	3.8 0.2%	5.3 4.8%
Week 216: Good response	75.9 4%	80.8 72.8%
Week 216: Moderate response	20.5 1.1%	17.8 16%
Week 216: None response	3.6 0.2%	1.4 1.3%
Week 240: Good response	78.6 4.1%	89.0 80.2%
Week 240: Moderate response	17.5 0.9%	9.6 8.6%
Week 240: None response	3.8 0.2%	1.4 1.3%
Week 264: Good response	76.7 4%	83.9 75.6%
Week 264: Moderate response	20.2 1.1%	16.1 14.5%
Week 264: None response	3.1 0.2%	0 0%
Week 288: Good response	82.4 4.3%	80.8 72.8%
Week 288: Moderate response	15.2 0.8%	19.2 17.3%
Week 288: None response	2.4 0.1%	0 0%
Week 312: Good response	81.5 4.3%	100 90.1%
Week 312: Moderate response	16.3 0.9%	0 0%
Week 312: None response	2.1 0.1%	0 0%
Week 336: Good response	83.0 4.3%
Week 336: Moderate response	14.6 0.8%
Week 336: None response	2.4 0.1%
Week 360: Good response	83.3 4.4%
Week 360: Moderate response	15.1 0.8%
Week 360: None response	1.7 0.1%
Week 384: Good response	86.2 4.5%
Week 384: Moderate response	12.9 0.7%
Week 384: None response	0.9 0%
Week 408: Good response	81.9 4.3%
Week 408: Moderate response	16.1 0.8%
Week 408: None response	2.0 0.1%
Week 432: Good response	85.8 4.5%
Week 432: Moderate response	14.2 0.7%
Week 432: None response	0 0%
Week 456: Good response	87.3 4.6%
Week 456: Moderate response	12.7 0.7%
Week 456: None response	0 0%
Week 480: Good response	79.5 4.2%
Week 480: Moderate response	17.9 0.9%
Week 480: None response	2.6 0.1%
Week 504: Good response	92.3 4.8%
Week 504: Moderate response	7.7 0.4%
Week 504: None response	0 0%
Week 516: Good response	100 5.2%
Week 516: Moderate response	0 0%
Week 516: None response	0 0%

11. Secondary Outcome

Title	Change From Baseline in DAS28-CRP Score at Weeks 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210
Description	DAS28-CRP is a composite score which included 4 components: TJC with 28 joints assessed; SJC with 28 joints assessed; high-sensitivity CRP (in mg/L) and general health assessment by the participant using participant global assessment (measured on 0 [no arthritis activity] to 100 mm [maximal arthritis activity] VAS). DAS28-CRP total score ranges from 0-10, where higher scores indicated greater disease activity. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Time Frame	Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category and "0" in the number analyzed field denotes that data was not planned to be collected and analyzed for the specified time-points in the respective groups.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Measure Participants	1872	110
Week 0	-2.50 (1.52)	-2.99 (1.42)
Week 4	-2.98 (1.38)	-3.18 (1.31)
Week 8	-3.12 (1.41)	-3.21 (1.26)
Week 12	-3.19 (1.41)	-3.28 (1.29)
Week 24	-3.28 (1.41)	-3.43 (1.21)
Week 36	-3.31 (1.43)	-3.35 (1.23)
Week 48	-3.35 (1.42)	-3.36 (1.35)
Week 60	-3.41 (1.41)	-3.50 (1.28)
Week 72	-3.41 (1.42)	-3.61 (1.24)
Week 84	-3.40 (1.45)	-3.70 (1.19)
Week 96	-3.46 (1.43)	-3.59 (1.32)
Week 120	-3.49 (1.45)	-3.72 (1.20)
Week 144	-3.51 (1.41)	-3.79 (1.29)
Week 168	-3.52 (1.45)	-3.66 (1.30)
Week 192	-3.55 (1.43)	-3.61 (1.48)
Week 216	-3.59 (1.43)	-3.71 (1.24)
Week 240	-3.57 (1.44)	-3.90 (1.35)
Week 264	-3.64 (1.39)	-3.92 (1.36)
Week 288	-3.80 (1.38)	-4.38 (1.33)
Week 312	-3.86 (1.34)	-5.62 (0.86)
Week 336	-3.86 (1.34)
Week 360	-3.93 (1.34)
Week 384	-3.99 (1.36)
Week 408	-3.85 (1.44)
Week 432	-4.11 (1.35)
Week 456	-4.01 (1.14)
Week 480	-3.69 (1.47)
Week 504	-3.76 (1.24)
Week 516	-3.76 (2.32)

12. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210
Description	HAQ-DI is a standardized questionnaire used to assess the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; hygiene; reach; grip and activities. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3, where 0= no difficulty in physical function; 1= some difficulty in physical function; 2= much difficulty in physical function; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty in physical function) to 3 (extreme difficulty in physical function), where higher scores indicate more difficulty while performing daily living activities. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Time Frame	Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Measure Participants	1895	111
Week 0	-0.56 (0.63)	-0.58 (0.59)
Week 4	-0.59 (0.62)	-0.57 (0.52)
Week 8	-0.63 (0.63)	-0.63 (0.53)
Week 12	-0.65 (0.64)	-0.65 (0.57)
Week 24	-0.69 (0.65)	-0.63 (0.60)
Week 36	-0.70 (0.66)	-0.67 (0.61)
Week 48	-0.70 (0.66)	-0.63 (0.60)
Week 60	-0.70 (0.67)	-0.67 (0.50)
Week 72	-0.71 (0.66)	-0.67 (0.59)
Week 84	-0.71 (0.68)	-0.68 (0.59)
Week 96	-0.72 (0.67)	-0.69 (0.58)
Week 120	-0.74 (0.69)	-0.67 (0.55)
Week 144	-0.73 (0.70)	-0.64 (0.61)
Week 168	-0.74 (0.70)	-0.61 (0.59)
Week 192	-0.74 (0.71)	-0.65 (0.65)
Week 216	-0.75 (0.71)	-0.62 (0.69)
Week 240	-0.74 (0.72)	-0.61 (0.64)
Week 264	-0.76 (0.71)	-0.54 (0.62)

13. Secondary Outcome

Title	Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 0 and Week 48 of LTS11210: Campaign 1 X-ray Data - Participants From EFC11072 Part B
Description	Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both joint erosions (JE) for 44 joints and joint space narrowing (JSN) for 42 joints in bilateral hand and foot joints. Total mTSS: sum of the scores from both erosion score and joint space narrowing score and ranged from 0 (normal, no progression) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Here, Baseline refers to the Baseline of initial study (EFC11072 Part B). In this outcome measure, change from initial study Baseline in 2 years X-ray data at Week 0 and 48 of LTS11210 were reported.
Time Frame	Baseline, Week 0 and 48 of LTS11210

Outcome Measure Data

Analysis Population Description
Analyzed on subset of participants who previously completed study EFC11072, Part B with end of treatment X-ray evaluation. Here, 'overall number of participants analyzed' = participants from studies EFC11072 Part B evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Analysis Population Description

Analyzed on subset of participants who previously completed study EFC11072, Part B with end of treatment X-ray evaluation. Here, 'overall number of participants analyzed' = participants from studies EFC11072 Part B evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC11072 Part B
Arm/Group Description	Participants who completed EFC11072 Part B were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	856
Change at Week 0	1.05 (4.61)
Change at Week 48	1.34 (5.31)

14. Secondary Outcome

Title	Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 48 and Week 96 of LTS11210: Campaign 2 X-ray Data - Participants From EFC11072 Part B
Description	Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS: sum of the scores from both erosion score and joint space narrowing score and ranged from 0 (normal, no progression) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Here, Baseline refers to the Baseline of initial study (EFC11072 Part B). In this outcome measure, change from initial study (EFC11072 Part B) Baseline in 3 years X-ray data (participants with study duration of more than 48 weeks in LTS11210) at Week 48 and 96 of LTS11210 from Campaign 2 were reported.
Time Frame	Baseline, Week 48 and 96 of LTS11210

Outcome Measure Data

Analysis Population Description
Analyzed on subset of participants who previously completed study EFC11072, Part B with end of treatment X-ray evaluation. Here, 'overall number of participants analyzed' = participants from studies EFC11072 Part B evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Analysis Population Description

Arm/Group Title	Sarilumab + DMARD: EFC11072 Part B
Arm/Group Description	Participants who completed EFC11072 Part B were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	756
Change at Week 48	1.60 (5.96)
Change at Week 96	2.14 (7.20)

15. Secondary Outcome

Title	Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 96, Week 144 and Week 192 of LTS11210: Campaign 3 X-ray Data - Participants From EFC11072 Part B
Description	Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS: sum of the scores from both erosion score and joint space narrowing score and ranged from 0 (normal, no progression) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Here, Baseline refers to the Baseline of initial study (EFC11072 Part B). In this outcome measure, change from initial study (EFC11072 Part B) Baseline in 5 years X-ray data (participants with study duration of more than 96 weeks in LTS11210) at Week 96, 144 and 192 of LTS11210 from Campaign 3 were reported.
Time Frame	Baseline, Week 96, 144 and 192 of LTS11210

Outcome Measure Data

Analysis Population Description
Analyzed on subset of participants who previously completed study EFC11072, Part B with end of treatment X-ray evaluation. Here, 'overall number of participants analyzed' = participants from studies EFC11072 Part B evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Analysis Population Description

Arm/Group Title	Sarilumab + DMARD: EFC11072 Part B
Arm/Group Description	Participants who completed EFC11072 Part B were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	699
Change at Week 96	1.83 (7.76)
Change at Week 144	2.24 (8.43)
Change at Week 192	2.83 (9.42)

16. Secondary Outcome

Title	Percentage of Participants With no Radiographic Progression of the Van Der Heijde Modified Total Sharp Score at Week 0 and 48 of LTS11210: Campaign 1 X-ray Data - Participants From EFC11072 Part B
Description	Radiographic no progression: defined as a change from Baseline in Van der Heijde mTSS <= 0. Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS was sum of scores from both erosion score and joint space narrowing score, ranged from 0 (normal, no progression) to 448 (worst possible total score). Increase in total score represents progression of structural damage. In this outcome measure, percentage of participants with no radiographic progression at Week 48 of LTS11210 from Campaign 1 X-ray data were reported.
Time Frame	Week 0 (post-dose) and 48 of LTS11210

Outcome Measure Data

Analysis Population Description
Analyzed on subset of participants who previously completed study EFC11072, Part B with end of treatment X-ray evaluation. Here, 'overall number of participants analyzed' = participants from studies EFC11072 Part B evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC11072 Part B
Arm/Group Description	Participants who completed EFC11072 Part B were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	889
Week 0	51.9 2.7%
Week 48	51.2 2.7%

17. Secondary Outcome

Title	Percentage of Participants With no Radiographic Progression of the Van Der Heijde Modified Total Sharp Score at Week 48 and Week 96 of LTS11210: Campaign 2 X-ray Data - Participants From EFC11072 Part B
Description	Radiographic no progression: defined as a change from Baseline in Van der Heijde mTSS <= 0. Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS was sum of scores from both erosion score and joint space narrowing score, ranged from 0 (normal, no progression) to 448 (worst possible total score). Increase in total score represents progression of structural damage. In this outcome measure, percentage of participants with no radiographic progression at Week 48 and 96 of LTS11210 from Campaign 2 X-ray data (participants with study duration of more than 48 weeks in LTS11210) were reported.
Time Frame	Week 48 and 96 of LTS11210

Outcome Measure Data

Analysis Population Description
Analyzed on subset of participants who previously completed study EFC11072, Part B with end of treatment X-ray evaluation. Here, 'overall number of participants analyzed' = participants from studies EFC11072 Part B evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC11072 Part B
Arm/Group Description	Participants who completed EFC11072 Part B were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	796
Week 48	46.6 2.4%
Week 96	44.2 2.3%

18. Secondary Outcome

Title	Percentage of Participants With no Radiographic Progression of the Van Der Heijde Modified Total Sharp Score at Week 96, 144 and 192 of LTS11210: Campaign 3 X-ray Data - Participants From EFC11072 Part B
Description	Radiographic no progression: defined as a change from Baseline in Van der Heijde mTSS <= 0. Van der Heijde modified Sharp method is composite X-ray scoring system used to assess structural (joint) disease progression in RA. The method evaluates both JE for 44 joints and JSN for 42 joints in bilateral hand and foot joints. Total mTSS was sum of scores from both erosion score and joint space narrowing score, ranged from 0 (normal, no progression) to 448 (worst possible total score). Increase in total score represents progression of structural damage. In this outcome measure, percentage of participants with no radiographic progression at Week 96, 144 and 192 of LTS11210 from Campaign 3 X-ray data (participants with study duration more than 96 weeks in LTS11210) were reported.
Time Frame	Week 96, 144 and 192 of LTS11210

Outcome Measure Data

Analysis Population Description
Analyzed on subset of participants who previously completed study EFC11072, Part B with end of treatment X-ray evaluation. Here, 'overall number of participants analyzed' = participants from studies EFC11072 Part B evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC11072 Part B
Arm/Group Description	Participants who completed EFC11072 Part B were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	732
Week 96	48.6 2.5%
Week 144	46.0 2.4%
Week 192	41.8 2.2%

19. Secondary Outcome

Title	Change From Baseline in Tender Joint Count (TJC) at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210
Description	TJC is the sum of all tender joints based on examination of the 68 joints of the fingers, elbows, hips, knees, ankles, and toes. Total TJC ranged from 0 (best) to 68 (worst), where higher score = more severity. Change from Baseline in TJC was reported in the outcome measure. Here, Baseline refers to Baseline of initial study (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Time Frame	Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category and "0" in the number analyzed field denotes that data was not planned to be collected and analyzed for the specified time-points in the respective groups.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Measure Participants	1904	111
Week 0	-16.67 (14.05)	-19.86 (12.43)
Week 4	-18.97 (13.81)	-20.13 (12.64)
Week 8	-19.72 (13.61)	-20.09 (11.73)
Week 12	-20.20 (13.89)	-20.05 (12.99)
Week 24	-20.67 (14.09)	-21.19 (12.55)
Week 36	-20.68 (14.39)	-20.60 (12.19)
Week 48	-20.95 (14.04)	-20.27 (13.54)
Week 60	-21.29 (14.06)	-20.95 (12.66)
Week 72	-21.41 (13.98)	-21.67 (12.65)
Week 84	-21.53 (14.17)	-21.36 (13.04)
Week 96	-21.65 (14.08)	-20.89 (13.50)
Week 120	-21.92 (14.20)	-20.18 (12.73)
Week 144	-22.13 (14.01)	-22.52 (13.41)
Week 168	-22.35 (14.26)	-22.42 (13.34)
Week 192	-22.62 (14.20)	-21.83 (13.79)
Week 216	-22.69 (14.28)	-22.33 (13.29)
Week 240	-22.89 (14.47)	-23.07 (14.24)
Week 264	-23.09 (14.08)	-23.66 (15.02)
Week 288	-22.59 (15.70)	-28.95 (14.79)
Week 312	-23.47 (15.23)	-43.71 (12.12)
Week 336	-23.37 (15.24)
Week 360	-24.12 (14.89)
Week 384	-24.73 (15.14)
Week 408	-24.58 (14.97)
Week 432	-25.33 (15.05)
Week 456	-24.21 (14.37)
Week 480	-21.23 (14.66)
Week 504	-23.62 (13.63)
Week 516	-24.00 (12.73)

20. Secondary Outcome

Title	Change From Baseline in Swollen Joint Count (SJC) at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210
Description	SJC is the sum of all swollen joints based on examination of the fingers, elbows, knees and toes. Total SJC ranged from 0 (best) to 66 (worst), where higher score = more severity. Change from Baseline in SJC was reported in the outcome measure. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Time Frame	Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category and "0" in the number analyzed field denotes that data was not planned to be collected and analyzed for the specified time-points in the respective groups.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Measure Participants	1904	111
Week 0	-11.36 (9.96)	-14.06 (9.65)
Week 4	-12.81 (9.77)	-14.55 (9.19)
Week 8	-13.43 (9.82)	-14.60 (9.30)
Week 12	-13.77 (10.13)	-14.58 (9.31)
Week 24	-14.28 (10.09)	-14.83 (9.64)
Week 36	-14.37 (9.99)	-14.51 (9.70)
Week 48	-14.53 (9.97)	-14.96 (9.22)
Week 60	-14.75 (10.20)	-15.54 (9.49)
Week 72	-14.76 (10.12)	-15.43 (9.67)
Week 84	-14.84 (10.16)	-15.83 (9.50)
Week 96	-15.03 (10.20)	-15.51 (10.24)
Week 120	-15.09 (10.17)	-15.77 (9.95)
Week 144	-15.18 (10.20)	-15.90 (8.57)
Week 168	-15.16 (10.30)	-15.47 (8.91)
Week 192	-15.26 (10.09)	-15.01 (9.17)
Week 216	-15.25 (9.97)	-15.72 (8.65)
Week 240	-15.43 (10.34)	-15.59 (9.08)
Week 264	-15.50 (9.79)	-16.59 (9.53)
Week 288	-14.67 (10.98)	-18.65 (8.90)
Week 312	-15.38 (10.71)	-23.57 (9.83)
Week 336	-15.51 (10.48)
Week 360	-15.96 (10.76)
Week 384	-16.42 (10.76)
Week 408	-16.30 (11.47)
Week 432	-16.62 (11.51)
Week 456	-15.64 (10.65)
Week 480	-15.43 (10.67)
Week 504	-16.21 (10.94)
Week 516	-13.00 (2.83)

21. Secondary Outcome

Title	Change From Baseline in Physician's Global Assessments of Disease Activity Visual Analogue Scale (VAS) Score at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, and 264 of LTS11210
Description	Physician global assessment of disease activity was measured on a 100 millimeters (mm) horizontal VAS, ranging from 0 (best disease activity) to 100 (worst disease activity), where lower score = less disease activity and higher score = more disease activity. Here, Baseline refers to Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Time Frame	Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Measure Participants	1903	110
Week 0	-40.51 (23.82)	-46.38 (19.17)
Week 4	-43.98 (22.03)	-47.94 (19.16)
Week 8	-45.79 (22.06)	-49.27 (18.80)
Week 12	-47.02 (22.03)	-50.20 (19.74)
Week 24	-48.39 (21.94)	-50.82 (19.99)
Week 36	-48.94 (21.72)	-51.12 (19.87)
Week 48	-49.36 (21.68)	-50.58 (21.38)
Week 60	-49.98 (21.62)	-51.40 (20.51)
Week 72	-49.91 (21.72)	-52.90 (19.40)
Week 84	-50.28 (21.42)	-55.84 (17.39)
Week 96	-50.73 (21.62)	-54.14 (18.97)
Week 120	-50.43 (21.39)	-54.33 (19.41)
Week 144	-50.84 (21.13)	-55.73 (18.04)
Week 168	-50.49 (21.65)	-53.21 (21.36)
Week 192	-50.32 (22.00)	-52.22 (22.44)
Week 216	-51.49 (21.57)	-54.67 (18.30)
Week 240	-51.00 (21.57)	-55.16 (18.82)
Week 264	-51.18 (21.24)	-55.27 (21.70)

22. Secondary Outcome

Title	Change From Baseline in Participant Global Assessment of Disease Activity Visual Analogue Scale Score at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210
Description	Participant global assessment of disease activity was measured on a 100 mm horizontal VAS, ranging from 0 (best disease activity) to 100 (worst disease activity), where lower score = less disease activity and higher score = more disease activity. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Time Frame	Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, 504 and 516 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category and "0" in the number analyzed field denotes that data was not planned to be collected and analyzed for the specified time-points in the respective groups.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Measure Participants	1904	111
Week 0	-30.51 (26.78)	-32.30 (27.55)
Week 4	-32.87 (25.60)	-33.63 (25.86)
Week 8	-34.65 (26.25)	-34.25 (25.90)
Week 12	-35.60 (26.77)	-34.24 (28.38)
Week 24	-36.91 (26.50)	-36.12 (27.82)
Week 36	-37.08 (27.18)	-37.13 (24.73)
Week 48	-37.28 (26.93)	-35.98 (28.18)
Week 60	-37.79 (27.38)	-37.82 (25.40)
Week 72	-37.90 (27.26)	-37.95 (26.53)
Week 84	-37.45 (27.82)	-40.52 (26.69)
Week 96	-38.34 (27.34)	-41.46 (26.57)
Week 120	-38.41 (27.43)	-41.67 (26.43)
Week 144	-38.91 (27.52)	-38.52 (26.40)
Week 168	-38.22 (28.26)	-37.27 (27.46)
Week 192	-39.26 (28.16)	-37.79 (32.12)
Week 216	-39.96 (27.72)	-38.72 (32.76)
Week 240	-39.54 (27.79)	-41.64 (30.13)
Week 264	-39.87 (27.31)	-37.84 (32.94)
Week 288	-43.68 (25.55)	-48.00 (33.87)
Week 312	-44.05 (26.40)	-65.71 (21.40)
Week 336	-43.42 (26.95)
Week 360	-44.56 (26.59)
Week 384	-47.19 (26.25)
Week 408	-44.97 (29.16)
Week 432	-49.77 (25.95)
Week 456	-50.40 (24.27)
Week 480	-46.65 (29.66)
Week 504	-48.89 (28.83)
Week 516	-40.50 (36.06)

23. Secondary Outcome

Title	Change From Baseline in Participant's Assessment of Pain Visual Analogue Scale Score at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, and 264 of LTS11210
Description	Participants were requested to indicate their pain intensity due to their RA on a 100 mm horizontal VAS, ranging from 0 (no pain) to 100 (worst pain), where a higher score represented more pain due to RA. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, EFC10832, SFY13370 and EFC13752).
Time Frame	Baseline, Week 0 (post-dose), 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240, and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)	Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.	Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
Measure Participants	1897	111
Week 0	-31.08 (27.45)	-37.01 (28.73)
Week 4	-34.04 (26.52)	-37.53 (27.28)
Week 8	-35.79 (26.88)	-38.14 (27.16)
Week 12	-36.46 (27.46)	-39.08 (26.79)
Week 24	-37.87 (27.07)	-38.75 (28.12)
Week 36	-37.60 (27.97)	-39.56 (25.72)
Week 48	-38.07 (28.33)	-39.41 (30.12)
Week 60	-38.46 (28.18)	-40.79 (26.20)
Week 72	-38.00 (28.54)	-42.62 (27.33)
Week 84	-38.37 (28.79)	-42.38 (28.69)
Week 96	-38.62 (28.57)	-43.73 (27.59)
Week 120	-39.29 (28.44)	-44.11 (25.69)
Week 144	-39.19 (28.21)	-41.42 (27.31)
Week 168	-39.47 (28.84)	-38.86 (29.46)
Week 192	-40.17 (28.98)	-41.25 (30.44)
Week 216	-40.25 (28.56)	-44.01 (30.27)
Week 240	-40.28 (28.44)	-43.59 (29.22)
Week 264	-41.02 (28.09)	-40.71 (29.79)

24. Secondary Outcome

Title	Change From Baseline in Short Form 36 (SF-36; Version 2) Physical Component Summary (PCS) Score at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, ACT11575 and EFC10832 Only
Description	SF-36 is a generic 36-item questionnaire consisting of 8 domains, measuring quality of life (QoL) covering 2 summary measures: PCS and mental component summary (MCS). PCS with 4 domains: physical functioning, role limitations due to physical problems, bodily pain, and general health; and MCS with 4 domains: vitality, social functioning, role limitations due to emotional problems, and mental health. Each domain is scored by summing the individual items, which are transformed into a score range from 0 to 100; where 0= worst QoL to 100=best QoL. PCS total score ranged from 0 to 100 with higher scores indicating better physical health. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, and EFC10832).
Time Frame	Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants from studies EFC11072, ACT11575 and EFC10832 evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC11072, ACT11575 and EFC10832
Arm/Group Description	Participants who completed any of the initial studies: Part A or Part B of EFC11072, ACT11575, and EFC10832 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	1367
Week 0	7.95 (8.29)
Week 12	8.84 (8.45)
Week 24	9.25 (8.59)
Week 36	9.72 (8.85)
Week 48	9.43 (8.89)
Week 60	9.64 (8.53)
Week 72	9.62 (8.78)
Week 84	9.95 (8.97)
Week 96	9.90 (8.90)
Week 120	10.18 (9.12)
Week 144	10.15 (9.18)
Week 168	10.24 (9.24)
Week 192	10.34 (9.52)
Week 216	10.15 (9.45)
Week 240	10.38 (9.21)
Week 264	10.32 (9.38)

25. Secondary Outcome

Title	Change From Baseline in Short Form 36 (SF-36; Version 2) Mental Component Summary Score at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, ACT11575 and EFC10832 Only
Description	SF-36 is a generic 36-item questionnaire consisting of 8 domains, measuring quality of life (QoL) covering 2 summary measures: PCS and MCS. PCS with 4 domains: physical functioning, role limitations due to physical problems, bodily pain, and general health; and MCS with 4 domains: vitality, social functioning, role limitations due to emotional problems, and mental health. Each domain is scored by summing the individual items, which are transformed into a score range from 0 to 100; 0= worst QoL to 100=best QoL. MCS total score ranged from 0 to 100 with higher scores indicating better physical and mental health. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, and EFC10832).
Time Frame	Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description

Arm/Group Title	Sarilumab + DMARD: EFC11072, ACT11575 and EFC10832
Arm/Group Description	Participants who completed any of the initial studies: Part A or Part B of EFC11072, ACT11575, and EFC10832 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	1367
Week 0	6.43 (10.80)
Week 12	7.15 (11.03)
Week 24	7.43 (11.15)
Week 36	7.20 (11.31)
Week 48	7.48 (11.15)
Week 60	7.43 (11.21)
Week 72	7.25 (11.24)
Week 84	7.29 (11.20)
Week 96	7.47 (11.52)
Week 120	7.69 (11.62)
Week 144	7.22 (11.60)
Week 168	7.29 (11.52)
Week 192	7.10 (11.51)
Week 216	7.20 (11.91)
Week 240	7.23 (12.03)
Week 264	7.32 (12.08)

26. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Total Score at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210-Participants From EFC11072, ACT11575 and EFC10832 Only
Description	The FACIT-F is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0 to 4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. The sum of all responses resulted in the FACIT-Fatigue total score ranged from 0 to 52, where higher score = lower level of fatigue and indicates better QoL. A positive change from baseline score indicates an improvement. Here, Baseline refers to the Baseline of initial studies (EFC11072, ACT11575, and EFC10832).
Time Frame	Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description

Arm/Group Title	Sarilumab + DMARD: EFC11072, ACT11575 and EFC10832
Arm/Group Description	Participants who completed any of the initial studies: Part A or Part B of EFC11072, ACT11575, and EFC10832 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	1651
Week 0	9.20 (10.05)
Week 12	10.26 (10.10)
Week 24	10.94 (10.31)
Week 36	10.91 (10.67)
Week 48	10.86 (10.64)
Week 60	10.97 (10.50)
Week 72	10.84 (10.68)
Week 84	10.75 (10.88)
Week 96	11.09 (10.85)
Week 120	11.18 (10.74)
Week 144	11.14 (10.86)
Week 168	11.00 (11.27)
Week 192	10.80 (11.10)
Week 216	11.12 (11.25)
Week 240	11.15 (11.21)
Week 264	10.99 (11.19)

27. Secondary Outcome

Title	Change From Baseline in Sleep Visual Analogue Scale Score at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, and ACT11575 Only
Description	Rheumatoid arthritis (RA), like other chronic illness, is associated with sleep disturbances and is linked to pain, mood, and disease activity. The effect of sarilumab on sleep was assessed on a on 100 mm horizontal VAS scale, ranging from 0 (sleep is not a problem) to 100 (sleep is a major problem), where higher score = more sleep disturbances. Here, Baseline refers to the Baseline of initial studies (EFC11072, and ACT11575).
Time Frame	Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants from studies EFC11072, and ACT11575 evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC11072, and ACT11575
Arm/Group Description	Participants who completed any of the initial studies: Part A or Part B of EFC11072, and ACT11575 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	1231
Week 0	-24.58 (30.96)
Week 12	-26.11 (30.59)
Week 24	-26.44 (30.94)
Week 36	-27.37 (31.52)
Week 48	-26.15 (31.37)
Week 60	-26.98 (31.24)
Week 72	-26.85 (32.16)
Week 84	-25.81 (31.90)
Week 96	-26.91 (31.63)
Week 120	-27.63 (32.26)
Week 144	-26.90 (31.54)
Week 168	-27.33 (33.25)
Week 192	-26.87 (32.03)
Week 216	-28.58 (31.46)
Week 240	-27.72 (33.07)
Week 264	-27.71 (32.08)

28. Secondary Outcome

Title	Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Due to RA at Week 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072 and ACT11575 Only
Description	WPAI assesses work productivity and impairment. It is 6-item questionnaire used to assess degree to which RA affected work productivity and regular activities over past 7 days. Questions were: Q1 = currently employed; Q2 = hours missed due to RA; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree problem affected productivity while working (0 to 10 scale, with higher numbers indicated less productivity); Q6 = degree problem affected regular activities (0 to 10 scale, with higher numbers indicated greater impairment). The percent work time missed due to RA was a subscale and calculated as: 100*Q2/(Q2+Q4) for those who were currently employed. Subscale score was expressed as impairment percentage (range:0 to 100%) where higher numbers indicate greater impairment and less productivity. Here, Baseline refers to Baseline of initial studies (EFC11072 and ACT11575).
Time Frame	Baseline, Week 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description

Arm/Group Title	Sarilumab + DMARD: EFC11072, and ACT11575
Arm/Group Description	Participants who completed any of the initial studies: Part A or Part B of EFC11072, and ACT11575 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	267
Week 0	-10.82 (30.64)
Week 12	-8.62 (28.67)
Week 24	-11.92 (29.33)
Week 36	-9.62 (30.08)
Week 48	-11.39 (29.92)
Week 60	-10.03 (25.74)
Week 72	-9.10 (28.14)
Week 84	-8.20 (27.06)
Week 96	-11.32 (30.28)
Week 120	-8.62 (32.95)
Week 144	-9.01 (30.16)
Week 168	-10.38 (31.48)
Week 192	-8.99 (29.24)
Week 216	-11.17 (29.35)
Week 240	-8.57 (26.11)
Week 264	-13.40 (30.57)

29. Secondary Outcome

Title	Change From Baseline in Work Productivity and Activity Impairment: Percent Impairment While Working Due to RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, and ACT11575 Only
Description	WPAI assesses work productivity and impairment. It is 6-item questionnaire used to assess degree to which RA affected work productivity and regular activities over past 7 days. Questions were: Q1 = currently employed; Q2 = hours missed due to RA; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree problem affected productivity while working (0 to 10 scale, with higher numbers = less productivity); Q6 = degree problem affected regular activities (0 to 10 scale, with higher numbers = greater impairment). Percentage impairment while working due to RA was subscale and calculated as: 10*Q5 for those who were currently employed and actually worked in past 7 days. Subscale score=expressed as impairment percentage (range:0 to 100%), where higher numbers=greater impairment and less productivity. Here, Baseline refers to the Baseline of initial studies (EFC11072 and ACT11575).
Time Frame	Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description

Arm/Group Title	Sarilumab + DMARD: EFC11072, and ACT11575
Arm/Group Description	Participants who completed any of the initial studies: Part A or Part B of EFC11072, and ACT11575 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	273
Week 0	-21.65 (27.74)
Week 12	-22.16 (26.53)
Week 24	-23.45 (26.70)
Week 36	-27.01 (27.11)
Week 48	-24.76 (26.05)
Week 60	-25.17 (25.12)
Week 72	-24.33 (27.57)
Week 84	-24.02 (27.09)
Week 96	-26.42 (27.11)
Week 120	-24.02 (27.63)
Week 144	-24.67 (28.20)
Week 168	-24.25 (28.46)
Week 192	-25.24 (26.60)
Week 216	-24.56 (27.28)
Week 240	-24.39 (26.48)
Week 264	-25.26 (27.40)

30. Secondary Outcome

Title	Change From Baseline in Work Productivity and Activity Impairment: Percent Overall Work Impairment Due to RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, and ACT11575 Only
Description	WPAI assesses work productivity and impairment. It is 6-item questionnaire used to assess degree to which RA affected work productivity and regular activities over past 7 days. Questions were: Q1 = currently employed; Q2 = hours missed due to RA; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree problem affected productivity while working (0 to 10 scale, with higher numbers indicated less productivity); Q6 = degree problem affected regular activities (0 10 scale, with higher numbers indicated greater impairment). Percent overall work impairment due to RA was subscale and calculated as: 100Q2/(Q2+Q4)+100[(1- Q2/(Q2+Q4))*(Q5/10)] for those who were currently employed . Subscale score = expressed as impairment percentage (range: 0 to 100%) where higher numbers indicate greater impairment. Here, Baseline refers to Baseline of initial studies (EFC11072 and ACT11575).
Time Frame	Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description

Arm/Group Title	Sarilumab + DMARD: EFC11072, and ACT11575
Arm/Group Description	Participants who completed any of the initial studies: Part A or Part B of EFC11072, and ACT11575 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	246
Week 0	-22.84 (30.73)
Week 12	-23.13 (27.98)
Week 24	-25.39 (28.84)
Week 36	-28.13 (29.01)
Week 48	-24.72 (29.38)
Week 60	-26.44 (28.03)
Week 72	-25.06 (29.84)
Week 84	-23.62 (29.25)
Week 96	-27.06 (30.60)
Week 120	-24.15 (31.14)
Week 144	-23.97 (32.05)
Week 168	-24.59 (31.16)
Week 192	-24.77 (29.63)
Week 216	-24.54 (31.55)
Week 240	-25.05 (29.26)
Week 264	-27.10 (28.75)

31. Secondary Outcome

Title	Change From Baseline in Work Productivity and Activity Impairment: Percent Activity Impairment Due to RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210 - Participants From EFC11072, and ACT11575 Only
Description	WPAI assesses work productivity and impairment. It is 6-item questionnaire used to assess degree to which RA affected work productivity and regular activities over past 7 days. Questions were: Q1 = currently employed; Q2 = hours missed due to RA; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree problem affected productivity while working (0 to 10 scale, with higher numbers indicated less productivity); Q6 = degree problem affected regular activities (0 10 scale, with higher numbers indicated greater impairment). Percent activity impairment due to RA was a subscale and calculated as: 10*Q6 for all respondents. Subscale score=expressed as impairment percentage (range: 0 to 100%) where higher numbers indicate greater impairment. Here, Baseline refers to Baseline of initial studies (EFC11072 and ACT11575).
Time Frame	Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description

Arm/Group Title	Sarilumab + DMARD: EFC11072, and ACT11575
Arm/Group Description	Participants who completed any of the initial studies: Part A or Part B of EFC11072, and ACT11575 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	1157
Week 0	-26.47 (29.30)
Week 12	-28.02 (27.44)
Week 24	-28.76 (27.62)
Week 36	-29.71 (28.03)
Week 48	-29.11 (28.28)
Week 60	-29.81 (27.78)
Week 72	-29.61 (29.02)
Week 84	-30.28 (29.53)
Week 96	-30.28 (28.32)
Week 120	-30.42 (28.78)
Week 144	-30.29 (28.90)
Week 168	-30.64 (29.30)
Week 192	-30.88 (29.36)
Week 216	-30.36 (29.34)
Week 240	-31.12 (29.63)
Week 264	-31.97 (28.77)

32. Secondary Outcome

Title	Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Work Days Missed Due to Arthritis - Participants From EFC10832 Only
Description	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with arthritis over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from Baseline in number of work days missed in the last month due to arthritis by the participant was reported in the outcome measure. Here, Baseline refers to the Baseline of initial study (EFC10832).
Time Frame	Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants from study EFC10832 evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC10832
Arm/Group Description	Participants who completed study EFC10832 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	145
Week 0	-2.72 (6.38)
Week 12	-3.66 (6.80)
Week 24	-3.70 (6.85)
Week 36	-3.73 (7.08)
Week 48	-3.37 (7.18)
Week 60	-3.55 (6.93)
Week 72	-3.58 (7.07)
Week 84	-3.11 (8.49)
Week 96	-3.47 (7.57)
Week 120	-3.54 (7.56)
Week 144	-3.51 (6.84)
Week 168	-3.73 (7.37)
Week 192	-3.76 (7.21)
Week 216	-3.51 (7.30)
Week 240	-2.44 (6.70)
Week 264	-2.86 (5.83)

33. Secondary Outcome

Title	Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Days With Work Productivity Reduced by >=50% Due to Arthritis - Participants From EFC10832 Only
Description	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from Baseline in number of work days with reduced productivity by >= 50% in the last month by the participant was reported in the outcome measure. Here, Baseline refers to the Baseline of initial study (EFC10832).
Time Frame	Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants from study EFC10832 evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC10832
Arm/Group Description	Participants who completed study EFC10832 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	145
Week 0	-3.47 (7.64)
Week 12	-4.93 (9.22)
Week 24	-5.14 (7.67)
Week 36	-5.47 (8.41)
Week 48	-5.75 (8.14)
Week 60	-5.16 (7.96)
Week 72	-5.21 (7.74)
Week 84	-4.40 (8.27)
Week 96	-5.03 (6.91)
Week 120	-4.63 (7.47)
Week 144	-4.88 (7.53)
Week 168	-4.67 (7.06)
Week 192	-4.55 (7.25)
Week 216	-4.42 (8.01)
Week 240	-3.48 (7.56)
Week 264	-3.97 (5.02)

34. Secondary Outcome

Title	Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Arthritis Interference With Work Productivity - Participants From EFC10832 Only
Description	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity was measured on a scale that ranged from 0 (no interference) to 10 (complete interference), where higher scores indicated more interference. Here, Baseline refers to the Baseline of initial study (EFC10832).
Time Frame	Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants from study EFC10832 evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC10832
Arm/Group Description	Participants who completed study EFC10832 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	144
Week 0	-20.83 (30.51)
Week 12	-27.95 (58.67)
Week 24	-35.16 (31.45)
Week 36	-37.48 (33.72)
Week 48	-36.78 (31.58)
Week 60	-40.35 (33.19)
Week 72	-38.74 (32.73)
Week 84	-39.62 (41.56)
Week 96	-42.35 (32.19)
Week 120	-37.84 (32.32)
Week 144	-39.16 (32.28)
Week 168	-38.11 (32.25)
Week 192	-40.74 (34.96)
Week 216	-39.19 (37.00)
Week 240	-38.22 (38.24)
Week 264	-39.24 (36.09)

35. Secondary Outcome

Title	Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: House Work Days Missed Due to Arthritis - Participants From EFC10832 Only
Description	'The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from baseline in number of days with no household work/household work missed in the last month by the participants was reported. Here, Baseline refers to the Baseline of initial study (EFC10832).
Time Frame	Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants from study EFC10832 evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC10832
Arm/Group Description	Participants who completed study EFC10832 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	446
Week 0	-4.65 (9.44)
Week 12	-6.17 (10.29)
Week 24	-6.55 (9.92)
Week 36	-6.65 (10.36)
Week 48	-6.61 (10.57)
Week 60	-6.84 (10.47)
Week 72	-6.50 (10.72)
Week 84	-6.56 (10.63)
Week 96	-6.80 (10.32)
Week 120	-6.81 (10.31)
Week 144	-6.78 (10.67)
Week 168	-7.04 (10.13)
Week 192	-6.74 (10.51)
Week 216	-6.78 (10.07)
Week 240	-6.82 (10.02)
Week 264	-6.95 (10.16)

36. Secondary Outcome

Title	Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Days With Household Work Productivity Reduced by >=50% Due to Arthritis - Participants From EFC10832 Only
Description	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from baseline in number of days with reduced household work productivity by >= 50% in the last month by the participants was reported. Here, Baseline refers to the Baseline of initial study (EFC10832).
Time Frame	Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants from study EFC10832 evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC10832
Arm/Group Description	Participants who completed study EFC10832 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	445
Week 0	-4.08 (10.24)
Week 12	-5.64 (10.93)
Week 24	-6.01 (10.40)
Week 36	-6.57 (10.29)
Week 48	-7.06 (10.13)
Week 60	-7.01 (10.30)
Week 72	-6.70 (10.72)
Week 84	-6.38 (10.79)
Week 96	-7.05 (10.62)
Week 120	-7.12 (10.37)
Week 144	-6.58 (10.59)
Week 168	-6.39 (10.28)
Week 192	-6.01 (10.07)
Week 216	-6.27 (10.30)
Week 240	-6.31 (9.99)
Week 264	-6.93 (9.43)

37. Secondary Outcome

Title	Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Days With Family/Social/Leisure Activities Missed Due to Arthritis - Participants From EFC10832 Only
Description	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from baseline in number of days missed of family/social/leisure activities in the last month by the participants was reported. Here, Baseline refers to the Baseline of initial study (EFC10832).
Time Frame	Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants from study EFC10832 evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC10832
Arm/Group Description	Participants who completed study EFC10832 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	447
Week 0	-2.94 (8.34)
Week 12	-4.16 (8.38)
Week 24	-4.50 (8.42)
Week 36	-4.38 (8.88)
Week 48	-4.44 (8.51)
Week 60	-4.46 (8.31)
Week 72	-4.20 (8.52)
Week 84	-4.31 (8.30)
Week 96	-4.38 (8.03)
Week 120	-4.43 (8.01)
Week 144	-4.17 (7.90)
Week 168	-4.12 (8.16)
Week 192	-4.23 (8.17)
Week 216	-3.93 (8.03)
Week 240	-4.03 (8.26)
Week 264	-3.85 (7.65)

38. Secondary Outcome

Title	Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Days With Outside Help Hired Due to Arthritis- Participants From EFC10832 Only
Description	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Change from baseline in number of days with outside help hired in the last month by the participant was reported. Here, Baseline refers to the Baseline of initial study (EFC10832).
Time Frame	Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants from study EFC10832 evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC10832
Arm/Group Description	Participants who completed study EFC10832 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	446
Week 0	-2.92 (10.14)
Week 12	-4.24 (10.16)
Week 24	-4.12 (10.47)
Week 36	-4.28 (10.27)
Week 48	-4.58 (10.12)
Week 60	-4.21 (10.16)
Week 72	-4.00 (9.52)
Week 84	-3.81 (9.67)
Week 96	-3.90 (10.11)
Week 120	-3.90 (9.62)
Week 144	-3.91 (9.73)
Week 168	-4.14 (10.00)
Week 192	-3.93 (10.14)
Week 216	-4.19 (9.84)
Week 240	-4.12 (10.43)
Week 264	-4.05 (9.67)

39. Secondary Outcome

Title	Change From Baseline in WPS-RA at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210: Arthritis Interference With Household Work Productivity - Participants From EFC10832 Only
Description	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranged from 0 (no interference) to 10 (complete interference), where higher scores indicated more interference. Here, Baseline refers to the Baseline of initial study (EFC10832).
Time Frame	Baseline, Weeks 0 (post-dose), 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 and 264 of LTS11210

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants from study EFC10832 evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for Sarilumab Monotherapy arm, as pre-specified in protocol.

Arm/Group Title	Sarilumab + DMARD: EFC10832
Arm/Group Description	Participants who completed study EFC10832 were enrolled in LTS11210 and received sarilumab 150 mg SC qw. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.
Measure Participants	444
Week 0	-23.24 (35.09)
Week 12	-33.49 (35.76)
Week 24	-36.94 (36.75)
Week 36	-36.42 (39.35)
Week 48	-37.45 (34.85)
Week 60	-38.19 (34.55)
Week 72	-36.48 (35.37)
Week 84	-35.61 (39.69)
Week 96	-36.81 (36.04)
Week 120	-38.86 (35.22)
Week 144	-36.23 (37.52)
Week 168	-36.01 (39.84)
Week 192	-35.80 (40.99)
Week 216	-38.54 (39.81)
Week 240	-40.08 (35.68)
Week 264	-38.07 (42.39)

40. Secondary Outcome

Title	Sub-study: Number of Participants Who Reported Adverse Events Related to Pre-filled Syringe With Safety System
Description	AEs related to PFS-S included PTC-related AEs, device-related AEs, or AEs of injection site reaction. In this outcome measure, only PTC-related AEs, device-related AEs, or AEs of injection site reaction assessed during the sub-study were reported. TEAEs and SAEs reported during the sub-study were included in the main study data and no separate data collection and analysis was performed, as pre-planned in the protocol .
Time Frame	From Week 24 to 36

Outcome Measure Data

Analysis Population Description
Analysis was performed on all participants who were enrolled in the sub-study.

Arm/Group Title	PFS-S Sarilumab 150 mg q2w	PFS-S Sarilumab 200 mg q2w	PFS-S Sarilumab 200 to 150 mg q2w
Arm/Group Description	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 150 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PFS-S.	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 200 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PFS-S.	From Week 24 of main study, eligible participants entered sub-study and received sarilumab 200 mg SC q2w for 12 weeks (i.e., from main study Week 24 to Week 36) using PF-S. The dose might be reduced to 150 mg q2w due to neutropenia, thrombocytopenia, or an increase in liver enzymes.
Measure Participants	25	98	1
PTC-related AEs	0 0%	0 0%	0 0%
Device-related AEs	0 0%	0 0%	0 0%
AEs of injection site reaction	0 0%	0 0%	0 0%

Adverse Events

	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)		Sarilumab Monotherapy
Time Frame	From first dose (i.e., Day 1 of study LTS11210) of IMP to last dose of IMP + 60 days (maximum duration: up to 523 weeks)
Adverse Event Reporting Description	Reported AEs and deaths were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of the IMP to the last dose of IMP + 60 days). As pre-specified and initially planned, TEAEs and SAEs reported during the sub-study were included in the main study data and no separate analysis was done. Analysis was performed on safety population.

Arm/Group Title	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)		Sarilumab Monotherapy
Arm/Group Description	Participants who completed any of initial studies:Part A or B of EFC11072, ACT11575, EFC10832 or SFY13370 were enrolled in LTS11210 and received sarilumab 150 milligrams (mg) subcutaneously (SC) once weekly (qw). Dose could be reduced to 150 mg every 2 weeks (q2w) due to neutropenia, thrombocytopenia or increase in liver enzymes (alanine aminotransferase [ALT]). After dose regimens selection for Phase 3 studies (150 mg q2w and 200 mg q2w), participants already receiving 150 mg qw were switched to sarilumab 200 mg q2w. Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks). Participants who were already taking concomitant non-biologic DMARDs in initial study continued stable dose of one or combination of conventional synthetic DMARDs they were taking.		Participants who completed study EFC13752 were enrolled in LTS11210 and received sarilumab 200 mg q2w. Dose could be reduced to 150 mg q2w due to neutropenia, thrombocytopenia or increase in liver enzymes (ALT). Treatment duration per participant was at least 264 weeks from first study drug administration in LTS11210. Participants continued to be treated beyond 264 weeks until sarilumab was commercially available in their respective countries or until 2020, at the latest (maximum duration: 523 weeks).
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/1910 (2.6%)		3/111 (2.7%)
Serious Adverse Events
	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)		Sarilumab Monotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	617/1910 (32.3%)		27/111 (24.3%)
Blood and lymphatic system disorders
Anaemia	2/1910 (0.1%)	2	0/111 (0%)	0
Anaemia Megaloblastic	1/1910 (0.1%)	1	0/111 (0%)	0
Blood Loss Anaemia	3/1910 (0.2%)	3	0/111 (0%)	0
Bone Marrow Failure	1/1910 (0.1%)	1	0/111 (0%)	0
Febrile Neutropenia	1/1910 (0.1%)	1	0/111 (0%)	0
Iron Deficiency Anaemia	0/1910 (0%)	0	1/111 (0.9%)	1
Leukopenia	1/1910 (0.1%)	1	0/111 (0%)	0
Lymphatic Insufficiency	1/1910 (0.1%)	1	0/111 (0%)	0
Neutropenia	11/1910 (0.6%)	12	0/111 (0%)	0
Pancytopenia	4/1910 (0.2%)	4	0/111 (0%)	0
Spontaneous Haemorrhage	1/1910 (0.1%)	1	0/111 (0%)	0
Thrombocytopenia	3/1910 (0.2%)	3	0/111 (0%)	0
Cardiac disorders
Acute Coronary Syndrome	2/1910 (0.1%)	2	0/111 (0%)	0
Acute Left Ventricular Failure	1/1910 (0.1%)	1	0/111 (0%)	0
Acute Myocardial Infarction	11/1910 (0.6%)	11	0/111 (0%)	0
Angina Pectoris	3/1910 (0.2%)	3	0/111 (0%)	0
Angina Unstable	2/1910 (0.1%)	2	1/111 (0.9%)	1
Atrial Fibrillation	9/1910 (0.5%)	11	2/111 (1.8%)	3
Atrial Flutter	3/1910 (0.2%)	4	0/111 (0%)	0
Atrial Tachycardia	1/1910 (0.1%)	1	0/111 (0%)	0
Atrioventricular Block Complete	0/1910 (0%)	0	1/111 (0.9%)	1
Bradycardia	2/1910 (0.1%)	2	0/111 (0%)	0
Cardiac Failure	4/1910 (0.2%)	4	0/111 (0%)	0
Cardiac Failure Acute	1/1910 (0.1%)	1	0/111 (0%)	0
Cardiac Failure Congestive	2/1910 (0.1%)	2	0/111 (0%)	0
Cardiac Tamponade	2/1910 (0.1%)	2	0/111 (0%)	0
Cardio-Respiratory Arrest	1/1910 (0.1%)	1	0/111 (0%)	0
Cardiogenic Shock	1/1910 (0.1%)	1	0/111 (0%)	0
Cardiomyopathy	1/1910 (0.1%)	1	0/111 (0%)	0
Cardiopulmonary Failure	2/1910 (0.1%)	2	0/111 (0%)	0
Congestive Cardiomyopathy	1/1910 (0.1%)	1	0/111 (0%)	0
Coronary Artery Disease	3/1910 (0.2%)	3	0/111 (0%)	0
Coronary Artery Perforation	1/1910 (0.1%)	1	0/111 (0%)	0
Coronary Artery Stenosis	1/1910 (0.1%)	1	0/111 (0%)	0
Left Ventricular Failure	1/1910 (0.1%)	1	1/111 (0.9%)	1
Microvascular Coronary Artery Disease	2/1910 (0.1%)	2	0/111 (0%)	0
Myocardial Infarction	5/1910 (0.3%)	5	0/111 (0%)	0
Myocardial Ischaemia	4/1910 (0.2%)	4	0/111 (0%)	0
Pericarditis	1/1910 (0.1%)	1	0/111 (0%)	0
Sinus Node Dysfunction	1/1910 (0.1%)	1	0/111 (0%)	0
Supraventricular Tachycardia	2/1910 (0.1%)	2	0/111 (0%)	0
Ventricular Asystole	1/1910 (0.1%)	1	0/111 (0%)	0
Ventricular Fibrillation	1/1910 (0.1%)	1	0/111 (0%)	0
Endocrine disorders
Goitre	2/1910 (0.1%)	2	0/111 (0%)	0
Thyroiditis	1/1910 (0.1%)	1	0/111 (0%)	0
Thyroiditis Subacute	1/1910 (0.1%)	1	0/111 (0%)	0
Eye disorders
Cataract	4/1910 (0.2%)	4	0/111 (0%)	0
Central Vision Loss	1/1910 (0.1%)	1	0/111 (0%)	0
Choroiditis	1/1910 (0.1%)	1	0/111 (0%)	0
Dry Age-Related Macular Degeneration	1/1910 (0.1%)	1	0/111 (0%)	0
Macular Hole	1/1910 (0.1%)	1	0/111 (0%)	0
Neovascular Age-Related Macular Degeneration	1/1910 (0.1%)	1	0/111 (0%)	0
Optic Ischaemic Neuropathy	1/1910 (0.1%)	1	0/111 (0%)	0
Retinal Vascular Thrombosis	1/1910 (0.1%)	1	0/111 (0%)	0
Gastrointestinal disorders
Abdominal Pain	1/1910 (0.1%)	1	0/111 (0%)	0
Appendicolith	1/1910 (0.1%)	1	0/111 (0%)	0
Chronic Gastritis	0/1910 (0%)	0	1/111 (0.9%)	1
Crohn's Disease	2/1910 (0.1%)	2	0/111 (0%)	0
Diverticular Perforation	2/1910 (0.1%)	2	0/111 (0%)	0
Diverticulum Intestinal	1/1910 (0.1%)	1	0/111 (0%)	0
Diverticulum Intestinal Haemorrhagic	1/1910 (0.1%)	1	0/111 (0%)	0
Duodenal Perforation	1/1910 (0.1%)	1	0/111 (0%)	0
Enterovesical Fistula	1/1910 (0.1%)	1	0/111 (0%)	0
Femoral Hernia	1/1910 (0.1%)	1	0/111 (0%)	0
Gastric Haemorrhage	0/1910 (0%)	0	1/111 (0.9%)	1
Gastric Ulcer Perforation	1/1910 (0.1%)	1	0/111 (0%)	0
Gastritis	3/1910 (0.2%)	3	0/111 (0%)	0
Gastrointestinal Inflammation	1/1910 (0.1%)	1	0/111 (0%)	0
Gastrooesophageal Reflux Disease	1/1910 (0.1%)	1	0/111 (0%)	0
Haemorrhoidal Haemorrhage	2/1910 (0.1%)	2	0/111 (0%)	0
Haemorrhoids	1/1910 (0.1%)	1	0/111 (0%)	0
Hernial Eventration	1/1910 (0.1%)	1	0/111 (0%)	0
Hiatus Hernia	2/1910 (0.1%)	2	1/111 (0.9%)	1
Ileal Perforation	1/1910 (0.1%)	1	0/111 (0%)	0
Ileus	0/1910 (0%)	0	1/111 (0.9%)	1
Incarcerated Umbilical Hernia	1/1910 (0.1%)	1	0/111 (0%)	0
Inflammatory Bowel Disease	1/1910 (0.1%)	1	0/111 (0%)	0
Inguinal Hernia	3/1910 (0.2%)	3	0/111 (0%)	0
Intestinal Dilatation	1/1910 (0.1%)	1	0/111 (0%)	0
Intestinal Obstruction	3/1910 (0.2%)	3	0/111 (0%)	0
Irritable Bowel Syndrome	2/1910 (0.1%)	2	0/111 (0%)	0
Large Intestine Perforation	2/1910 (0.1%)	2	0/111 (0%)	0
Noninfectious Peritonitis	1/1910 (0.1%)	1	0/111 (0%)	0
Pancreatic Necrosis	1/1910 (0.1%)	1	0/111 (0%)	0
Pancreatic Pseudocyst Haemorrhage	1/1910 (0.1%)	1	0/111 (0%)	0
Pancreatitis	2/1910 (0.1%)	2	0/111 (0%)	0
Pancreatitis Acute	5/1910 (0.3%)	5	0/111 (0%)	0
Pancreatitis Necrotising	0/1910 (0%)	0	1/111 (0.9%)	1
Peritoneal Adhesions	1/1910 (0.1%)	1	0/111 (0%)	0
Rectal Haemorrhage	2/1910 (0.1%)	2	0/111 (0%)	0
Rectal Prolapse	1/1910 (0.1%)	1	0/111 (0%)	0
Small Intestinal Obstruction	2/1910 (0.1%)	5	0/111 (0%)	0
Umbilical Hernia	3/1910 (0.2%)	3	0/111 (0%)	0
Upper Gastrointestinal Haemorrhage	1/1910 (0.1%)	1	0/111 (0%)	0
General disorders
Cardiac Death	1/1910 (0.1%)	1	0/111 (0%)	0
Chills	1/1910 (0.1%)	1	0/111 (0%)	0
Death	1/1910 (0.1%)	1	0/111 (0%)	0
Multiple Organ Dysfunction Syndrome	3/1910 (0.2%)	3	0/111 (0%)	0
Non-Cardiac Chest Pain	6/1910 (0.3%)	6	0/111 (0%)	0
Pyrexia	1/1910 (0.1%)	1	0/111 (0%)	0
Sudden Death	1/1910 (0.1%)	1	0/111 (0%)	0
Hepatobiliary disorders
Bile Duct Stone	3/1910 (0.2%)	3	1/111 (0.9%)	1
Cholecystitis	9/1910 (0.5%)	9	0/111 (0%)	0
Cholecystitis Acute	3/1910 (0.2%)	3	1/111 (0.9%)	1
Cholecystitis Chronic	2/1910 (0.1%)	2	0/111 (0%)	0
Cholelithiasis	24/1910 (1.3%)	24	0/111 (0%)	0
Cholelithiasis Obstructive	1/1910 (0.1%)	1	0/111 (0%)	0
Portosplenomesenteric Venous Thrombosis	1/1910 (0.1%)	1	0/111 (0%)	0
Infections and infestations
Abdominal Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Abscess Limb	6/1910 (0.3%)	6	0/111 (0%)	0
Abscess Neck	1/1910 (0.1%)	1	0/111 (0%)	0
Abscess Oral	1/1910 (0.1%)	1	0/111 (0%)	0
Abscess Soft Tissue	2/1910 (0.1%)	2	0/111 (0%)	0
Acute Sinusitis	1/1910 (0.1%)	1	0/111 (0%)	0
Anal Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Appendicitis	4/1910 (0.2%)	4	0/111 (0%)	0
Arteriovenous Graft Site Infection	1/1910 (0.1%)	1	0/111 (0%)	0
Arthritis Bacterial	6/1910 (0.3%)	7	1/111 (0.9%)	1
Arthritis Infective	1/1910 (0.1%)	1	0/111 (0%)	0
Atypical Pneumonia	1/1910 (0.1%)	1	0/111 (0%)	0
Bacteraemia	1/1910 (0.1%)	1	0/111 (0%)	0
Bacterial Dacryocystitis	1/1910 (0.1%)	1	0/111 (0%)	0
Bartholin's Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Bone Tuberculosis	1/1910 (0.1%)	1	0/111 (0%)	0
Bronchitis	4/1910 (0.2%)	4	0/111 (0%)	0
Bronchitis Fungal	1/1910 (0.1%)	1	0/111 (0%)	0
Bullous Erysipelas	1/1910 (0.1%)	1	0/111 (0%)	0
Bursitis Infective	2/1910 (0.1%)	2	0/111 (0%)	0
Covid-19 Pneumonia	1/1910 (0.1%)	1	0/111 (0%)	0
Carbuncle	1/1910 (0.1%)	1	0/111 (0%)	0
Cellulitis	21/1910 (1.1%)	24	0/111 (0%)	0
Cellulitis Staphylococcal	3/1910 (0.2%)	3	0/111 (0%)	0
Cholecystitis Infective	1/1910 (0.1%)	1	0/111 (0%)	0
Clostridium Difficile Infection	1/1910 (0.1%)	1	2/111 (1.8%)	2
Coccidioidomycosis	1/1910 (0.1%)	1	0/111 (0%)	0
Colonic Abscess	2/1910 (0.1%)	2	0/111 (0%)	0
Dengue Fever	1/1910 (0.1%)	1	0/111 (0%)	0
Device Related Infection	1/1910 (0.1%)	1	0/111 (0%)	0
Diarrhoea Infectious	1/1910 (0.1%)	1	0/111 (0%)	0
Diverticulitis	7/1910 (0.4%)	7	1/111 (0.9%)	1
Endocarditis	2/1910 (0.1%)	2	0/111 (0%)	0
Endometritis	1/1910 (0.1%)	1	0/111 (0%)	0
Enteritis Infectious	1/1910 (0.1%)	1	0/111 (0%)	0
Epiglottitis	0/1910 (0%)	0	1/111 (0.9%)	1
Erysipelas	5/1910 (0.3%)	5	0/111 (0%)	0
Escherichia Urinary Tract Infection	1/1910 (0.1%)	1	0/111 (0%)	0
Extradural Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Gangrene	1/1910 (0.1%)	1	0/111 (0%)	0
Gas Gangrene	1/1910 (0.1%)	1	0/111 (0%)	0
Gastroenteritis	2/1910 (0.1%)	2	0/111 (0%)	0
Gastroenteritis Bacterial	1/1910 (0.1%)	1	0/111 (0%)	0
Gastroenteritis Salmonella	1/1910 (0.1%)	1	0/111 (0%)	0
Gastroenteritis Viral	1/1910 (0.1%)	1	0/111 (0%)	0
Haematoma Infection	1/1910 (0.1%)	1	0/111 (0%)	0
Herpes Ophthalmic	1/1910 (0.1%)	1	0/111 (0%)	0
Herpes Zoster	5/1910 (0.3%)	5	1/111 (0.9%)	1
Histoplasmosis Disseminated	1/1910 (0.1%)	1	0/111 (0%)	0
Infected Bite	1/1910 (0.1%)	1	0/111 (0%)	0
Infected Skin Ulcer	6/1910 (0.3%)	6	0/111 (0%)	0
Infectious Pleural Effusion	2/1910 (0.1%)	2	0/111 (0%)	0
Infective Exacerbation Of Bronchiectasis	2/1910 (0.1%)	2	0/111 (0%)	0
Infective Exacerbation Of Chronic Obstructive Airways Disease	2/1910 (0.1%)	2	0/111 (0%)	0
Large Intestine Infection	1/1910 (0.1%)	2	0/111 (0%)	0
Leptospirosis	1/1910 (0.1%)	1	0/111 (0%)	0
Liver Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Localised Infection	2/1910 (0.1%)	2	0/111 (0%)	0
Lung Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Lyme Disease	1/1910 (0.1%)	1	0/111 (0%)	0
Medical Device Site Joint Infection	3/1910 (0.2%)	3	0/111 (0%)	0
Meningitis Viral	1/1910 (0.1%)	1	0/111 (0%)	0
Meningoencephalitis Herpetic	1/1910 (0.1%)	1	0/111 (0%)	0
Muscle Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Necrotising Fasciitis	2/1910 (0.1%)	2	0/111 (0%)	0
Necrotising Soft Tissue Infection	1/1910 (0.1%)	1	0/111 (0%)	0
Ophthalmic Herpes Zoster	1/1910 (0.1%)	1	0/111 (0%)	0
Oral Candidiasis	1/1910 (0.1%)	1	0/111 (0%)	0
Osteomyelitis	6/1910 (0.3%)	6	1/111 (0.9%)	1
Osteomyelitis Acute	1/1910 (0.1%)	1	0/111 (0%)	0
Pancreas Infection	2/1910 (0.1%)	2	0/111 (0%)	0
Pelvic Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Perineal Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Peritonitis	7/1910 (0.4%)	7	0/111 (0%)	0
Pneumonia	52/1910 (2.7%)	55	1/111 (0.9%)	1
Pneumonia Chlamydial	1/1910 (0.1%)	1	0/111 (0%)	0
Pneumonia Pneumococcal	1/1910 (0.1%)	1	0/111 (0%)	0
Pneumonia Streptococcal	2/1910 (0.1%)	2	0/111 (0%)	0
Pneumonia Viral	1/1910 (0.1%)	1	0/111 (0%)	0
Post Procedural Infection	1/1910 (0.1%)	1	0/111 (0%)	0
Postoperative Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Postoperative Wound Infection	2/1910 (0.1%)	2	0/111 (0%)	0
Psoas Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Pulmonary Tuberculosis	2/1910 (0.1%)	2	0/111 (0%)	0
Pyelonephritis	3/1910 (0.2%)	3	0/111 (0%)	0
Pyelonephritis Acute	5/1910 (0.3%)	7	0/111 (0%)	0
Pyelonephritis Chronic	1/1910 (0.1%)	1	0/111 (0%)	0
Relapsing Fever	1/1910 (0.1%)	1	0/111 (0%)	0
Renal Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Respiratory Tract Infection	1/1910 (0.1%)	1	0/111 (0%)	0
Salmonellosis	1/1910 (0.1%)	1	0/111 (0%)	0
Salpingitis	1/1910 (0.1%)	1	0/111 (0%)	0
Salpingo-Oophoritis	1/1910 (0.1%)	1	0/111 (0%)	0
Sepsis	6/1910 (0.3%)	6	0/111 (0%)	0
Septic Arthritis Neisserial	1/1910 (0.1%)	1	0/111 (0%)	0
Septic Shock	6/1910 (0.3%)	6	0/111 (0%)	0
Sialoadenitis	1/1910 (0.1%)	1	0/111 (0%)	0
Sinusitis	1/1910 (0.1%)	1	0/111 (0%)	0
Soft Tissue Infection	3/1910 (0.2%)	3	0/111 (0%)	0
Staphylococcal Bacteraemia	1/1910 (0.1%)	1	0/111 (0%)	0
Staphylococcal Infection	1/1910 (0.1%)	1	0/111 (0%)	0
Staphylococcal Skin Infection	2/1910 (0.1%)	2	0/111 (0%)	0
Subcutaneous Abscess	5/1910 (0.3%)	5	0/111 (0%)	0
Subdural Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Tooth Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Tuberculosis	2/1910 (0.1%)	2	0/111 (0%)	0
Tubo-Ovarian Abscess	1/1910 (0.1%)	1	0/111 (0%)	0
Upper Respiratory Tract Infection	2/1910 (0.1%)	2	0/111 (0%)	0
Urinary Tract Infection	4/1910 (0.2%)	4	0/111 (0%)	0
Urosepsis	2/1910 (0.1%)	2	0/111 (0%)	0
Viral Myositis	1/1910 (0.1%)	1	0/111 (0%)	0
Wound Infection	2/1910 (0.1%)	2	0/111 (0%)	0
Wound Infection Staphylococcal	1/1910 (0.1%)	1	0/111 (0%)	0
Wound Sepsis	1/1910 (0.1%)	1	0/111 (0%)	0
Injury, poisoning and procedural complications
Abdominal Injury	1/1910 (0.1%)	1	0/111 (0%)	0
Accidental Overdose	1/1910 (0.1%)	1	0/111 (0%)	0
Alcohol Poisoning	1/1910 (0.1%)	1	0/111 (0%)	0
Anaemia Postoperative	1/1910 (0.1%)	1	0/111 (0%)	0
Ankle Fracture	3/1910 (0.2%)	3	0/111 (0%)	0
Bite	1/1910 (0.1%)	1	0/111 (0%)	0
Comminuted Fracture	1/1910 (0.1%)	1	0/111 (0%)	0
Craniocerebral Injury	1/1910 (0.1%)	1	0/111 (0%)	0
Dislocation Of Vertebra	1/1910 (0.1%)	2	0/111 (0%)	0
Fall	3/1910 (0.2%)	3	0/111 (0%)	0
Femoral Neck Fracture	8/1910 (0.4%)	8	0/111 (0%)	0
Femur Fracture	7/1910 (0.4%)	7	1/111 (0.9%)	1
Foot Fracture	1/1910 (0.1%)	1	0/111 (0%)	0
Fractured Sacrum	2/1910 (0.1%)	2	0/111 (0%)	0
Gastrointestinal Stoma Complication	1/1910 (0.1%)	1	0/111 (0%)	0
Gun Shot Wound	1/1910 (0.1%)	1	0/111 (0%)	0
Hip Fracture	5/1910 (0.3%)	5	0/111 (0%)	0
Humerus Fracture	5/1910 (0.3%)	5	1/111 (0.9%)	1
Incision Site Fibrosis	1/1910 (0.1%)	1	0/111 (0%)	0
Incisional Hernia	2/1910 (0.1%)	3	0/111 (0%)	0
Injury	1/1910 (0.1%)	1	0/111 (0%)	0
Joint Dislocation	2/1910 (0.1%)	2	0/111 (0%)	0
Ligament Sprain	2/1910 (0.1%)	2	0/111 (0%)	0
Lower Limb Fracture	2/1910 (0.1%)	2	0/111 (0%)	0
Multiple Injuries	1/1910 (0.1%)	1	0/111 (0%)	0
Patella Fracture	2/1910 (0.1%)	2	0/111 (0%)	0
Pelvic Fracture	2/1910 (0.1%)	3	0/111 (0%)	0
Periorbital Haematoma	1/1910 (0.1%)	1	0/111 (0%)	0
Periprosthetic Fracture	2/1910 (0.1%)	2	0/111 (0%)	0
Periprosthetic Osteolysis	1/1910 (0.1%)	1	0/111 (0%)	0
Post Procedural Fistula	1/1910 (0.1%)	1	0/111 (0%)	0
Post Procedural Haematoma	1/1910 (0.1%)	1	0/111 (0%)	0
Post Procedural Haemorrhage	1/1910 (0.1%)	1	0/111 (0%)	0
Procedural Pain	2/1910 (0.1%)	2	0/111 (0%)	0
Procedural Shock	1/1910 (0.1%)	1	0/111 (0%)	0
Radius Fracture	2/1910 (0.1%)	2	0/111 (0%)	0
Spinal Compression Fracture	5/1910 (0.3%)	5	0/111 (0%)	0
Spinal Fracture	1/1910 (0.1%)	1	0/111 (0%)	0
Subdural Haematoma	3/1910 (0.2%)	3	0/111 (0%)	0
Tendon Rupture	5/1910 (0.3%)	5	0/111 (0%)	0
Thermal Burn	1/1910 (0.1%)	1	0/111 (0%)	0
Tibia Fracture	5/1910 (0.3%)	5	0/111 (0%)	0
Toxicity To Various Agents	1/1910 (0.1%)	1	0/111 (0%)	0
Ulna Fracture	4/1910 (0.2%)	4	0/111 (0%)	0
Investigations
Alanine Aminotransferase Increased	9/1910 (0.5%)	9	0/111 (0%)	0
Fungal Test Positive	1/1910 (0.1%)	1	0/111 (0%)	0
Hiv Test False Positive	1/1910 (0.1%)	1	0/111 (0%)	0
Neutrophil Count Decreased	1/1910 (0.1%)	1	0/111 (0%)	0
Oxygen Saturation Decreased	1/1910 (0.1%)	1	0/111 (0%)	0
Transaminases Increased	1/1910 (0.1%)	1	0/111 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/1910 (0.1%)	1	0/111 (0%)	0
Diabetes Mellitus	1/1910 (0.1%)	1	0/111 (0%)	0
Diabetes Mellitus Inadequate Control	1/1910 (0.1%)	1	0/111 (0%)	0
Diabetic Ketoacidosis	1/1910 (0.1%)	1	0/111 (0%)	0
Hyperglycaemia	1/1910 (0.1%)	1	0/111 (0%)	0
Hyperglycaemic Hyperosmolar Nonketotic Syndrome	1/1910 (0.1%)	1	0/111 (0%)	0
Hypertriglyceridaemia	2/1910 (0.1%)	2	0/111 (0%)	0
Hypoglycaemia	2/1910 (0.1%)	2	0/111 (0%)	0
Hypokalaemia	1/1910 (0.1%)	1	0/111 (0%)	0
Hyponatraemia	2/1910 (0.1%)	2	0/111 (0%)	0
Latent Autoimmune Diabetes In Adults	1/1910 (0.1%)	1	0/111 (0%)	0
Obesity	3/1910 (0.2%)	3	0/111 (0%)	0
Tumour Lysis Syndrome	1/1910 (0.1%)	1	0/111 (0%)	0
Musculoskeletal and connective tissue disorders
Ankle Deformity	1/1910 (0.1%)	1	0/111 (0%)	0
Arthralgia	2/1910 (0.1%)	2	0/111 (0%)	0
Arthritis	6/1910 (0.3%)	9	0/111 (0%)	0
Atlantoaxial Subluxation	1/1910 (0.1%)	1	0/111 (0%)	0
Back Pain	2/1910 (0.1%)	2	0/111 (0%)	0
Bone Cyst	1/1910 (0.1%)	1	0/111 (0%)	0
Bursitis	3/1910 (0.2%)	3	0/111 (0%)	0
Costochondritis	1/1910 (0.1%)	1	0/111 (0%)	0
Fasciitis	1/1910 (0.1%)	1	0/111 (0%)	0
Flank Pain	1/1910 (0.1%)	1	0/111 (0%)	0
Foot Deformity	14/1910 (0.7%)	19	0/111 (0%)	0
Hand Deformity	1/1910 (0.1%)	2	0/111 (0%)	0
Intervertebral Disc Degeneration	1/1910 (0.1%)	1	1/111 (0.9%)	1
Intervertebral Disc Disorder	2/1910 (0.1%)	2	0/111 (0%)	0
Intervertebral Disc Protrusion	3/1910 (0.2%)	3	0/111 (0%)	0
Joint Destruction	3/1910 (0.2%)	4	0/111 (0%)	0
Knee Deformity	1/1910 (0.1%)	1	0/111 (0%)	0
Lumbar Spinal Stenosis	2/1910 (0.1%)	2	0/111 (0%)	0
Osteoarthritis	45/1910 (2.4%)	52	2/111 (1.8%)	2
Osteonecrosis	3/1910 (0.2%)	3	0/111 (0%)	0
Osteoporotic Fracture	1/1910 (0.1%)	1	0/111 (0%)	0
Pathological Fracture	1/1910 (0.1%)	1	0/111 (0%)	0
Rheumatoid Arthritis	32/1910 (1.7%)	33	1/111 (0.9%)	1
Rheumatoid Nodule	1/1910 (0.1%)	1	0/111 (0%)	0
Rotator Cuff Syndrome	1/1910 (0.1%)	1	0/111 (0%)	0
Spinal Osteoarthritis	1/1910 (0.1%)	1	0/111 (0%)	0
Spinal Stenosis	4/1910 (0.2%)	4	1/111 (0.9%)	1
Spondylolisthesis	1/1910 (0.1%)	1	0/111 (0%)	0
Synovitis	2/1910 (0.1%)	2	0/111 (0%)	0
Wrist Deformity	1/1910 (0.1%)	1	0/111 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma Of Colon	1/1910 (0.1%)	1	0/111 (0%)	0
Ameloblastoma	1/1910 (0.1%)	1	0/111 (0%)	0
Anal Squamous Cell Carcinoma	1/1910 (0.1%)	1	0/111 (0%)	0
B-Cell Lymphoma	1/1910 (0.1%)	1	0/111 (0%)	0
Basal Cell Carcinoma	6/1910 (0.3%)	6	0/111 (0%)	0
Benign Neoplasm Of Thyroid Gland	1/1910 (0.1%)	1	0/111 (0%)	0
Bladder Cancer Stage Ii	1/1910 (0.1%)	1	0/111 (0%)	0
Breast Cancer	2/1910 (0.1%)	2	0/111 (0%)	0
Breast Cancer Stage Ii	1/1910 (0.1%)	1	0/111 (0%)	0
Bronchial Carcinoma	1/1910 (0.1%)	1	0/111 (0%)	0
Cervix Cancer Metastatic	1/1910 (0.1%)	1	0/111 (0%)	0
Cholesteatoma	1/1910 (0.1%)	1	0/111 (0%)	0
Clear Cell Renal Cell Carcinoma	1/1910 (0.1%)	1	0/111 (0%)	0
Colorectal Adenocarcinoma	2/1910 (0.1%)	2	0/111 (0%)	0
Colorectal Cancer Metastatic	1/1910 (0.1%)	1	0/111 (0%)	0
Eye Naevus	1/1910 (0.1%)	1	0/111 (0%)	0
Fibroadenoma Of Breast	1/1910 (0.1%)	1	0/111 (0%)	0
Fibroma	1/1910 (0.1%)	1	0/111 (0%)	0
Gallbladder Cancer Metastatic	1/1910 (0.1%)	1	0/111 (0%)	0
Invasive Ductal Breast Carcinoma	1/1910 (0.1%)	1	0/111 (0%)	0
Lung Adenocarcinoma	1/1910 (0.1%)	1	0/111 (0%)	0
Lung Cancer Metastatic	1/1910 (0.1%)	1	0/111 (0%)	0
Lung Carcinoma Cell Type Unspecified Stage Iii	1/1910 (0.1%)	1	0/111 (0%)	0
Lung Neoplasm Malignant	1/1910 (0.1%)	1	0/111 (0%)	0
Malignant Melanoma	1/1910 (0.1%)	1	0/111 (0%)	0
Metastatic Renal Cell Carcinoma	1/1910 (0.1%)	1	0/111 (0%)	0
Neoplasm Malignant	0/1910 (0%)	0	1/111 (0.9%)	1
Non-Small Cell Lung Cancer	1/1910 (0.1%)	1	0/111 (0%)	0
Ovarian Cancer	1/1910 (0.1%)	1	0/111 (0%)	0
Ovarian Germ Cell Teratoma Benign	1/1910 (0.1%)	1	0/111 (0%)	0
Papillary Thyroid Cancer	2/1910 (0.1%)	2	0/111 (0%)	0
Parathyroid Tumour Benign	1/1910 (0.1%)	1	0/111 (0%)	0
Pituitary Tumour Benign	1/1910 (0.1%)	1	0/111 (0%)	0
Pleomorphic Adenoma	1/1910 (0.1%)	1	0/111 (0%)	0
Prostate Cancer	3/1910 (0.2%)	3	0/111 (0%)	0
Prostatic Adenoma	2/1910 (0.1%)	2	0/111 (0%)	0
Rectal Cancer	1/1910 (0.1%)	1	0/111 (0%)	0
Refractory Anaemia With An Excess Of Blasts	1/1910 (0.1%)	1	0/111 (0%)	0
Renal Cell Carcinoma	1/1910 (0.1%)	1	0/111 (0%)	0
Serous Cystadenocarcinoma Ovary	1/1910 (0.1%)	1	0/111 (0%)	0
Skin Cancer	1/1910 (0.1%)	1	0/111 (0%)	0
Small Intestine Carcinoma	1/1910 (0.1%)	1	0/111 (0%)	0
Squamous Cell Carcinoma Of Skin	1/1910 (0.1%)	1	0/111 (0%)	0
Squamous Cell Carcinoma Of The Cervix	1/1910 (0.1%)	1	0/111 (0%)	0
Uterine Leiomyoma	7/1910 (0.4%)	7	0/111 (0%)	0
Nervous system disorders
Amnesia	1/1910 (0.1%)	1	0/111 (0%)	0
Carpal Tunnel Syndrome	4/1910 (0.2%)	4	0/111 (0%)	0
Cerebellar Stroke	1/1910 (0.1%)	1	0/111 (0%)	0
Cerebral Haematoma	1/1910 (0.1%)	1	0/111 (0%)	0
Cerebral Infarction	1/1910 (0.1%)	1	0/111 (0%)	0
Cerebrovascular Accident	5/1910 (0.3%)	6	0/111 (0%)	0
Cerebrovascular Insufficiency	1/1910 (0.1%)	1	0/111 (0%)	0
Depressed Level Of Consciousness	1/1910 (0.1%)	1	0/111 (0%)	0
Epilepsy	3/1910 (0.2%)	3	0/111 (0%)	0
Haemorrhage Intracranial	1/1910 (0.1%)	1	0/111 (0%)	0
Haemorrhagic Stroke	0/1910 (0%)	0	2/111 (1.8%)	2
Haemorrhagic Transformation Stroke	1/1910 (0.1%)	1	0/111 (0%)	0
Intraventricular Haemorrhage	2/1910 (0.1%)	2	0/111 (0%)	0
Ischaemic Stroke	2/1910 (0.1%)	2	1/111 (0.9%)	1
Lumbar Radiculopathy	1/1910 (0.1%)	1	0/111 (0%)	0
Migraine	1/1910 (0.1%)	1	0/111 (0%)	0
Multifocal Motor Neuropathy	1/1910 (0.1%)	1	0/111 (0%)	0
Myelopathy	1/1910 (0.1%)	1	0/111 (0%)	0
Partial Seizures	2/1910 (0.1%)	2	0/111 (0%)	0
Peripheral Sensory Neuropathy	1/1910 (0.1%)	1	0/111 (0%)	0
Radiculopathy	2/1910 (0.1%)	2	0/111 (0%)	0
Ruptured Cerebral Aneurysm	1/1910 (0.1%)	1	0/111 (0%)	0
Sciatica	1/1910 (0.1%)	1	0/111 (0%)	0
Seizure	2/1910 (0.1%)	2	0/111 (0%)	0
Subarachnoid Haemorrhage	3/1910 (0.2%)	3	0/111 (0%)	0
Syncope	4/1910 (0.2%)	4	0/111 (0%)	0
Transient Global Amnesia	1/1910 (0.1%)	1	0/111 (0%)	0
Transient Ischaemic Attack	6/1910 (0.3%)	7	0/111 (0%)	0
Vascular Headache	1/1910 (0.1%)	1	0/111 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion Missed	1/1910 (0.1%)	1	0/111 (0%)	0
Abortion Spontaneous	4/1910 (0.2%)	4	1/111 (0.9%)	1
Pregnancy	0/1910 (0%)	0	1/111 (0.9%)	1
Product Issues
Device Breakage	2/1910 (0.1%)	4	0/111 (0%)	0
Device Dislocation	1/1910 (0.1%)	1	0/111 (0%)	0
Device Loosening	1/1910 (0.1%)	1	0/111 (0%)	0
Device Malfunction	2/1910 (0.1%)	2	0/111 (0%)	0
Psychiatric disorders
Acute Psychosis	1/1910 (0.1%)	1	0/111 (0%)	0
Alcohol Abuse	1/1910 (0.1%)	1	0/111 (0%)	0
Bipolar Disorder	1/1910 (0.1%)	1	0/111 (0%)	0
Conversion Disorder	1/1910 (0.1%)	1	0/111 (0%)	0
Major Depression	2/1910 (0.1%)	2	0/111 (0%)	0
Mixed Anxiety And Depressive Disorder	1/1910 (0.1%)	2	0/111 (0%)	0
Paranoia	1/1910 (0.1%)	1	0/111 (0%)	0
Suicidal Ideation	1/1910 (0.1%)	1	0/111 (0%)	0
Suicide Attempt	1/1910 (0.1%)	1	0/111 (0%)	0
Renal and urinary disorders
Acute Kidney Injury	3/1910 (0.2%)	3	0/111 (0%)	0
Calculus Urinary	0/1910 (0%)	0	1/111 (0.9%)	1
Cystitis Haemorrhagic	1/1910 (0.1%)	1	0/111 (0%)	0
Hydronephrosis	1/1910 (0.1%)	1	0/111 (0%)	0
Nephrolithiasis	7/1910 (0.4%)	7	0/111 (0%)	0
Renal Colic	1/1910 (0.1%)	1	0/111 (0%)	0
Ureterolithiasis	2/1910 (0.1%)	2	0/111 (0%)	0
Urethral Stenosis	1/1910 (0.1%)	1	0/111 (0%)	0
Urinary Incontinence	1/1910 (0.1%)	1	0/111 (0%)	0
Reproductive system and breast disorders
Acquired Hydrocele	2/1910 (0.1%)	2	0/111 (0%)	0
Adnexa Uteri Cyst	1/1910 (0.1%)	1	0/111 (0%)	0
Benign Prostatic Hyperplasia	1/1910 (0.1%)	1	0/111 (0%)	0
Breast Enlargement	1/1910 (0.1%)	1	0/111 (0%)	0
Breast Hyperplasia	1/1910 (0.1%)	1	0/111 (0%)	0
Cervical Dysplasia	1/1910 (0.1%)	1	0/111 (0%)	0
Cervical Polyp	1/1910 (0.1%)	1	0/111 (0%)	0
Endometrial Hyperplasia	2/1910 (0.1%)	2	0/111 (0%)	0
Endometriosis	2/1910 (0.1%)	2	0/111 (0%)	0
Menometrorrhagia	1/1910 (0.1%)	1	0/111 (0%)	0
Menorrhagia	1/1910 (0.1%)	2	0/111 (0%)	0
Ovarian Cyst	4/1910 (0.2%)	4	0/111 (0%)	0
Pelvic Prolapse	1/1910 (0.1%)	1	0/111 (0%)	0
Uterine Haemorrhage	1/1910 (0.1%)	1	1/111 (0.9%)	1
Uterine Prolapse	1/1910 (0.1%)	1	0/111 (0%)	0
Vaginal Haemorrhage	1/1910 (0.1%)	1	0/111 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Oedema	1/1910 (0.1%)	1	0/111 (0%)	0
Acute Respiratory Failure	2/1910 (0.1%)	2	0/111 (0%)	0
Asthma	1/1910 (0.1%)	1	0/111 (0%)	0
Atelectasis	1/1910 (0.1%)	1	0/111 (0%)	0
Bronchial Hyperreactivity	1/1910 (0.1%)	1	0/111 (0%)	0
Chronic Obstructive Pulmonary Disease	1/1910 (0.1%)	1	0/111 (0%)	0
Diaphragmatic Abnormal Relaxation	1/1910 (0.1%)	1	0/111 (0%)	0
Dyspnoea	2/1910 (0.1%)	3	0/111 (0%)	0
Emphysema	1/1910 (0.1%)	1	0/111 (0%)	0
Epistaxis	1/1910 (0.1%)	1	0/111 (0%)	0
Idiopathic Pulmonary Fibrosis	2/1910 (0.1%)	2	0/111 (0%)	0
Interstitial Lung Disease	1/1910 (0.1%)	1	0/111 (0%)	0
Lung Infiltration	1/1910 (0.1%)	1	0/111 (0%)	0
Pleural Effusion	4/1910 (0.2%)	4	0/111 (0%)	0
Pleurisy	2/1910 (0.1%)	2	0/111 (0%)	0
Pneumonia Aspiration	1/1910 (0.1%)	1	0/111 (0%)	0
Pneumonitis	2/1910 (0.1%)	2	0/111 (0%)	0
Pneumothorax	1/1910 (0.1%)	2	0/111 (0%)	0
Pneumothorax Spontaneous	2/1910 (0.1%)	2	0/111 (0%)	0
Pulmonary Embolism	10/1910 (0.5%)	10	2/111 (1.8%)	3
Pulmonary Fibrosis	1/1910 (0.1%)	1	0/111 (0%)	0
Pulmonary Hypertension	2/1910 (0.1%)	2	0/111 (0%)	0
Pulmonary Mass	2/1910 (0.1%)	2	0/111 (0%)	0
Respiratory Failure	2/1910 (0.1%)	2	0/111 (0%)	0
Sleep Apnoea Syndrome	1/1910 (0.1%)	1	0/111 (0%)	0
Skin and subcutaneous tissue disorders
Cutaneous Lupus Erythematosus	1/1910 (0.1%)	1	0/111 (0%)	0
Decubitus Ulcer	1/1910 (0.1%)	1	0/111 (0%)	0
Dermatomyositis	1/1910 (0.1%)	1	0/111 (0%)	0
Erythema Multiforme	0/1910 (0%)	0	1/111 (0.9%)	1
Skin Necrosis	1/1910 (0.1%)	1	0/111 (0%)	0
Skin Ulcer	2/1910 (0.1%)	2	0/111 (0%)	0
Subcutaneous Emphysema	1/1910 (0.1%)	1	0/111 (0%)	0
Toxic Skin Eruption	1/1910 (0.1%)	1	0/111 (0%)	0
Social circumstances
Pregnancy Of Partner	1/1910 (0.1%)	1	0/111 (0%)	0
Vascular disorders
Accelerated Hypertension	1/1910 (0.1%)	1	0/111 (0%)	0
Aortic Embolus	1/1910 (0.1%)	1	0/111 (0%)	0
Arteriosclerosis	1/1910 (0.1%)	1	0/111 (0%)	0
Deep Vein Thrombosis	8/1910 (0.4%)	8	0/111 (0%)	0
Haematoma	2/1910 (0.1%)	2	0/111 (0%)	0
Hypertension	2/1910 (0.1%)	2	0/111 (0%)	0
Hypertensive Crisis	2/1910 (0.1%)	2	0/111 (0%)	0
Hypotension	3/1910 (0.2%)	3	0/111 (0%)	0
Hypovolaemic Shock	1/1910 (0.1%)	1	0/111 (0%)	0
Iliac Artery Embolism	1/1910 (0.1%)	1	0/111 (0%)	0
Pelvic Venous Thrombosis	1/1910 (0.1%)	1	0/111 (0%)	0
Peripheral Artery Occlusion	1/1910 (0.1%)	2	0/111 (0%)	0
Peripheral Embolism	1/1910 (0.1%)	1	0/111 (0%)	0
Peripheral Ischaemia	1/1910 (0.1%)	1	0/111 (0%)	0
Peripheral Venous Disease	1/1910 (0.1%)	1	0/111 (0%)	0
Varicose Vein	3/1910 (0.2%)	3	0/111 (0%)	0
Venous Thrombosis Limb	1/1910 (0.1%)	1	0/111 (0%)	0
Other (Not Including Serious) Adverse Events
	Sarilumab + Disease Modifying Anti-Rheumatic Drugs (DMARD)		Sarilumab Monotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1444/1910 (75.6%)		82/111 (73.9%)
Blood and lymphatic system disorders
Leukopenia	101/1910 (5.3%)	181	4/111 (3.6%)	5
Neutropenia	348/1910 (18.2%)	786	18/111 (16.2%)	64
Gastrointestinal disorders
Diarrhoea	122/1910 (6.4%)	153	2/111 (1.8%)	2
General disorders
Injection Site Erythema	111/1910 (5.8%)	751	0/111 (0%)	0
Infections and infestations
Bronchitis	215/1910 (11.3%)	301	12/111 (10.8%)	19
Influenza	124/1910 (6.5%)	160	3/111 (2.7%)	4
Nasopharyngitis	249/1910 (13%)	390	14/111 (12.6%)	26
Pharyngitis	110/1910 (5.8%)	129	4/111 (3.6%)	4
Upper Respiratory Tract Infection	303/1910 (15.9%)	574	16/111 (14.4%)	21
Urinary Tract Infection	264/1910 (13.8%)	428	14/111 (12.6%)	22
Injury, poisoning and procedural complications
Accidental Overdose	330/1910 (17.3%)	496	20/111 (18%)	22
Fall	109/1910 (5.7%)	122	3/111 (2.7%)	3
Investigations
Alanine Aminotransferase Increased	201/1910 (10.5%)	287	4/111 (3.6%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	87/1910 (4.6%)	109	9/111 (8.1%)	11
Back Pain	122/1910 (6.4%)	141	6/111 (5.4%)	6
Rheumatoid Arthritis	227/1910 (11.9%)	357	16/111 (14.4%)	31
Respiratory, thoracic and mediastinal disorders
Cough	62/1910 (3.2%)	70	7/111 (6.3%)	7
Vascular disorders
Hypertension	235/1910 (12.3%)	271	4/111 (3.6%)	5

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.

Results Point of Contact

Name/Title	Trial Transparency Team
Organization	Sanofi aventis recherche & développement
Phone	800-633-1610 ext 6#
Email	Contact-US@sanofi.com

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT01146652

Other Study ID Numbers:

LTS11210
2010-019262-86

First Posted:

Jun 17, 2010

Last Update Posted:

Mar 28, 2022

Last Verified:

Mar 1, 2022

Long Term Evaluation of Sarilumab in Rheumatoid Arthritis Patients (SARIL-RA-EXTEND)

Study Details

Study Description

Brief Summary

Main Study:

Primary Objective:

Secondary Objective:

Sub-Study:

Detailed Description

The maximum duration of the study was up to 523 weeks:

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion criteria :

Main study:

Participants with RA who were previously randomized in the sarilumab RA clinical program:

Sub-study:

Exclusion criteria:

Main study:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

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Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

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