To Evaluate The Effect Of SAR153191 (REGN88) Added To Other RA Drugs In Patients With RA Who Are Not Responding To Or Intolerant Of Anti-TNF Therapy (SARIL-RA-TARGET)

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01709578
• Collaborator: Regeneron Pharmaceuticals (Industry)
• Enrollment: 546
• Locations: 196
• Arms: 3
• Duration (Months): 28.9
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Primary Objective:

To demonstrate that sarilumab added to disease modifying anti-rheumatic drugs (DMARDs) were effective for:

• reduction of signs and symptoms at Week 24 and

• improvement of physical function at Week 12

in participants with active rheumatoid arthritis (RA) who were inadequate responders or intolerant to tumor necrosis factor alpha (TNF-α) antagonists.

Secondary Objectives:

The secondary objectives were to investigate the effects of SAR153191 (REGN88) when added to DMARD therapy, in participants with active RA who were inadequate responders or intolerant to

TNF-α antagonists, for:

• Reduction of signs and symptoms at Week 12;

• Improvement in physical function at Week 24;

• Improvement in disease activity score as measured by other American College of Rheumatology (ACR) derived components at Weeks 12 and 24;

• Improvement in quality of life as measured by participant reported outcomes (PROs) at intermediate visits and Week 24.

To assess the exposure of sarilumab added to DMARD therapy in this population.

To assess the safety of sarilumab in this population.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Sarilumab; Drug: placebo; Drug: hydroxychloroquine; Drug: methotrexate; Drug: sulfasalazine; Drug: leflunomide	Phase 3

Detailed Description

Total study duration was up to 34 weeks: screening up to 28 days, treatment phase of 24 weeks, and post-treatment follow-up of 6 weeks.

After completion of the treatment phase of this study, participant were eligible to enter a long term safety study (LTS11210) for active treatment with SAR153191 (REGN88).

Study Design

• Study Type: Interventional
• Actual Enrollment: 546 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing the Efficacy and Safety of Sarilumab Added to Non-biologic DMARD Therapy in Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF-α Antagonists
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo q2w Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.	Drug: placebo; Pharmaceutical form:solution Route of administration: subcutaneous; Drug: hydroxychloroquine; Dispensed according to the local practice.; Drug: methotrexate; Dispensed according to the local practice.; Drug: sulfasalazine; Dispensed according to the local practice.; Drug: leflunomide; Dispensed according to the local practice.
Experimental: Sarilumab 150 mg q2w Sarilumab 150 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.	Drug: Sarilumab; Pharmaceutical form:solution Route of administration: subcutaneous; Other Names: SAR153191 REGN88 ; Drug: hydroxychloroquine; Dispensed according to the local practice.; Drug: methotrexate; Dispensed according to the local practice.; Drug: sulfasalazine; Dispensed according to the local practice.; Drug: leflunomide; Dispensed according to the local practice.
Experimental: Sarilumab 200 mg q2w Sarilumab 200 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.	Drug: Sarilumab; Pharmaceutical form:solution Route of administration: subcutaneous; Other Names: SAR153191 REGN88 ; Drug: hydroxychloroquine; Dispensed according to the local practice.; Drug: methotrexate; Dispensed according to the local practice.; Drug: sulfasalazine; Dispensed according to the local practice.; Drug: leflunomide; Dispensed according to the local practice.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24 [Week 24]

   ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant (C-reactive Protein levels [CRP]); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by (health assessment questionnaire disability index [HAQ-DI]). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR.

2. Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 [Baseline, Week 12]

   Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. Least-squares (LS) means and standard errors (SE) at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.

Secondary Outcome Measures

1. Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24 [Baseline, Week 24]

   DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the ACR rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (VAS). Marker of inflammation assessed by the high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28 score provides a number indicating the current disease activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS28-CRP score as a covariate.

2. Percentage of Participants Achieving ACR50 Criteria at Week 24 [Week 24]

   ACR responses are assessed with a composite rating scale that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR.

3. Percentage of Participants Achieving ACR70 Criteria at Week 24 [Week 24]

   ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.

4. Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24 [Week 24]

   DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.

5. Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 [Baseline, Week 24]

   CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: TJC (28 joints), SJC (28 joints), Participant's Global Assessment of Disease Activity VAS (in cm), and Physician's Global Assessment of Disease VAS (in cm). Total scores ranges from 0 to 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline CDAI as a covariate.

6. Change From Baseline in HAQ-DI at Week 24 [Baseline, Week 24]

   Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.

7. Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24 [Baseline, Week 24]

   SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: PCS and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS had 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS had 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 by MMRM with treatment,region,number of previous anti TNFs,visit,and treatment-by-visit interaction as fixed effects and baseline SF-36 (PCS) as a covariate.

8. Change From Baseline in SF-36 MCS at Week 24 [Baseline, Week 24]

   SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 MCS as a covariate.

9. Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24 [Baseline, Week 24]

   The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.

10. Change From Baseline in Morning Stiffness VAS at Week 24 [Baseline, Week 24]

    RA is associated with stiffness of joints, especially in the morning after prolonged stationery state. The degree of stiffness can be an indicator of disease severity. The severity of morning stiffness was assessed on a VAS scale from 0 mm (no problem) to 100 mm (major problem). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline Morning Stiffness as a covariate.

11. Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA [Baseline, Week 24]

    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). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

12. Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA [Baseline, Week 24]

    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). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

13. Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity [Baseline, Week 24]

    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 is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

14. Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA [Baseline, Week 24]

    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). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

15. Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA [Baseline, Week 24]

    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). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

16. Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA [Baseline, Week 24]

    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). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

17. Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA [Baseline, Week 24]

    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). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

18. Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity [Baseline, Week 24]

    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 ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

19. Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24 [Baseline, Week 24]

    RAID is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 numerical rating scales (NRS) questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicate worse status and lower indicate not affected. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID as a covariate.

20. Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24 [Baseline, Week 24]

    The EQ-5D-3L is a standardized, generic measure of health outcome. It was designed for self-completion by participants. It was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L Scores as a covariate.

21. Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 [Week 12]

    ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.

22. Change From Baseline in DAS28-CRP at Week 12 [Baseline, Week 12]

    DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS score as a covariate.

23. Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP <2.6) at Week 12 [Week 12]

    DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.

24. Change From Baseline in SF-36 at Week 12 [Baseline, Week 12]

    SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 as a covariate.

25. Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA [Baseline, Week 12]

    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). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

26. Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA [Baseline, Week 12]

    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). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

27. Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity [Baseline, Week 12]

    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 ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

28. Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA [Baseline, Week 12]

    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). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

29. Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA [Baseline, Week 12]

    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). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

30. Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA [Baseline, Week 12]

    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). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

31. Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA [Baseline, Week 12]

    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). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

32. Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity [Baseline, Week 12]

    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 ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

33. Change From Baseline in the FACIT-fatigue at Week 12 [Baseline, Week 12]

    The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.

34. Change From Baseline in EQ-5D-3L VAS Scores at Week 12 [Baseline, Week 12]

    The EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. The EQ-5D was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L scores as a covariate.

35. Change From Baseline in RAID Scores at Week 12 [Baseline, Week 12]

    RAID score is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 NRS questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicates worse status and lower indicates not affected. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID scores as a covariate.

36. Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 [Baseline, Week 12 and Week 24]

    ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI & CRP. 68 joints were assessed for tenderness (TJC scoring 0-68) and 66 joints for swelling (SJC scoring 0-66). The 66 SJC evaluated the following joints: temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, interphalangeal of thumb, distal interphalangeal, proximal interphalangeal, knee, ankle mortise, ankle tarsus, metatarsophalangeal, interphalangeal of great toe, and proximal/distal interphalangeal of the toes. The TJC examined hip joints, in addition to the joints assessed for SJC. Increase in number of tender joints/swollen joints indicated severity. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.

37. Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24 [Baseline, Week 12 and Week 24]

    ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & CRP. Physician global VAS & participant global VAS was done by 100 mm non-anchored VAS, from no arthritis (0) activity to maximal arthritis (100) activity. Pain VAS by 100 mm VAS ranging from 0 "no pain" to 100 "worst pain". LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.

38. Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24 [Baseline, Week 12 and Week 24]

    ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & CRP. An elevated CRP level was considered a non-specific "marker" for RA. A reduction level indicates improvement. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.

39. Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24 [Baseline, Week 12 and Week 24]

    ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI & CRP. HAQ-DI consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

Diagnosis of RA ≥6 months duration, according to the ACR /European League against Rheumatism (EULAR) 2010 RA Classification Criteria

ACR Class I-III functional status, based on 1991 revised criteria

Anti-TNF therapy failures, defined by the investigator as participants with an inadequate clinical response, after being treated for at least 3 consecutive months, and/or intolerance to at least 1 anti-TNF blocker(s), resulting in or requiring their discontinuation:

• TNF-blockers included, but were not limited to, etanercept, infliximab, adalimumab, golimumab and/or certolizumab

Moderate-to-severely active RA

Continuous treatment with one or a combination of DMARDs (except for simultaneous combination use of leflunomide and methotrexate) for at least 12 weeks prior to baseline and on a stable dose(s) for at least 6 weeks prior to screening:

• Methotrexate - 6 to 25 mg/week orally or parenterally

• Leflunomide - 10 to 20 mg orally daily

• Sulfasalazine - 1000 to 3000 mg orally daily

• Hydroxychloroquine - 200 to 400 mg orally daily

Exclusion criteria:

Participants <18 years of age or legal adult age

Past history of, or current, autoimmune or inflammatory systemic or localized joint disease(s) other than RA

History of juvenile idiopathic arthritis or arthritis onset prior to age 16

Severe active systemic RA, including but not limited to vasculitis, pulmonary fibrosis, and/or Felty's syndrome.

Treatment with anti-TNF agents, as follows:

• Within 28 days prior to the baseline visit - etanercept

• Within 42 days prior to the baseline visit - infliximab, adalimumab, golimumab, certolizumab pegol

Treatment with previous RA-directed biologic agents with other than TNF antagonist mechanisms:

Within 28 days prior to the randomization (baseline) visit - anakinra Within 42 days prior to the randomization (baseline) visit - abatacept

Within 6 months prior to the randomization (baseline) visit - any cell depleting agents including but not limited to rituximab without a normal lymphocyte and cluster of differentiation (CD) 19+ lymphocyte count

Treatment with any DMARD other than those allowed per protocol and limited to the maximum specified dosage within 12 weeks prior to baseline

Treatment with prednisone >10 mg or equivalent per day, or change in dosage within 4 weeks prior to baseline visit

Any parenteral or intra-articular glucocorticoid injection within 4 weeks prior to baseline

Prior treatment with anti-interleukin (IL) -6 or IL-6 receptor antagonist therapies, including tocilizumab or sarilumab, participation in a prior study of sarilumab, irrespective of treatment arm

Prior treatment with a Janus kinase inhibitor (such as tofacitinib)

New treatment or dose-adjustment to ongoing medication for dyslipidemia within 6 weeks prior to randomization, ie, stable dose for at least 6 weeks prior to randomization

Participation in any clinical research study evaluating another investigational drug or therapy within 5 half-lives or 60 days of first investigational medicinal product (IMP) administration, whichever was longer

History of alcohol or drug abuse within 5 years prior to the screening visit

Participants with a history of malignancy other than adequately-treated carcinoma in-situ of the cervix, nonmetastatic squamous cell or basal cell carcinoma of the skin, within 5 years prior to the randomization (baseline) visit. Nonmalignant lymphoproliferative disorders were also excluded

Participants with active tuberculosis or latent tuberculosis infection

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 840142	Phoenix	Arizona	United States	85037
4	Investigational Site Number 840134	Fullerton	California	United States	92835
5	Investigational Site Number 840141	Glendale	California	United States	85304
6	Investigational Site Number 840111	La Jolla	California	United States	92037
7	Investigational Site Number 840135	San Diego	California	United States	92120
8	Investigational Site Number 840021	Santa Maria	California	United States	94354
9	Investigational Site Number 840100	Stanford	California	United States	94305
10	Investigational Site Number 840049	Upland	California	United States	91786
11	Investigational Site Number 840131	Whittier	California	United States	90606
12	Investigational Site Number 840201	Denver	Colorado	United States	80230
13	Investigational Site Number 840130	Lewes	Delaware	United States	19958
14	Investigational Site Number 840125	DeBary	Florida	United States	32713
15	Investigational Site Number 840048	Miami	Florida	United States	33155
16	Investigational Site Number 840024	Naples	Florida	United States	34102
17	Investigational Site Number 840006	Orlando	Florida	United States	32806
18	Investigational Site Number 840128	Ormond Beach	Florida	United States	32174
19	Investigational Site Number 840063	Palm Harbor	Florida	United States	34684
20	Investigational Site Number 840060	Sarasota	Florida	United States	34239
21	Investigational Site Number 840140	Tampa	Florida	United States	33614
22	Investigational Site Number 840126	Vero Beach	Florida	United States	32960
23	Investigational Site Number 840018	Idaho Falls	Idaho	United States	83404
24	Investigational Site Number 840110	Meridian	Idaho	United States	83642
25	Investigational Site Number 840052	Kansas City	Kansas	United States	66160-7321
26	Investigational Site Number 840015	Lexington	Kentucky	United States	40504
27	Investigational Site Number 840120	Baton Rouge	Louisiana	United States	70809
28	Investigational Site Number 840109	Lake Charles	Louisiana	United States	70601
29	Investigational Site Number 840055	Frederick	Maryland	United States	21702
30	Investigational Site Number 840150	Lansing	Michigan	United States	48910
31	Investigational Site Number 840137	Saint Clair Shores	Michigan	United States	48081
32	Investigational Site Number 840037	Tupelo	Mississippi	United States	38801
33	Investigational Site Number 840112	Lincoln	Nebraska	United States	68516
34	Investigational Site Number 840106	Orchard Park	New York	United States	14127
35	Investigational Site Number 840121	Rochester	New York	United States	14609
36	Investigational Site Number 840115	Roslyn	New York	United States	11576
37	Investigational Site Number 840118	Smithtown	New York	United States	11787
38	Investigational Site Number 840139	Syracuse	New York	United States	13210
39	Investigational Site Number 840123	Charlotte	North Carolina	United States	28210
40	Investigational Site Number 840116	Wilmington	North Carolina	United States	28401
41	Investigational Site Number 840127	Oklahoma City	Oklahoma	United States	73103
42	Investigational Site Number 840011	Tulsa	Oklahoma	United States	74104
43	Investigational Site Number 840009	Duncansville	Pennsylvania	United States	16635
44	Investigational Site Number 840117	Pittsburgh	Pennsylvania	United States	15213
45	Investigational Site Number 840062	Reading	Pennsylvania	United States	19611
46	Investigational Site Number 840058	Columbia	South Carolina	United States	29204
47	Investigational Site Number 840025	Jackson	Tennessee	United States	38305
48	Investigational Site Number 840059	Memphis	Tennessee	United States	38119
49	Investigational Site Number 840132	Austin	Texas	United States	78731
50	Investigational Site Number 840022	Dallas	Texas	United States	75235
51	Investigational Site Number 840114	El Paso	Texas	United States	79902
52	Investigational Site Number 840133	Houston	Texas	United States	77008
53	Investigational Site Number 840129	Houston	Texas	United States	77074
54	Investigational Site Number 840074	Mesquite	Texas	United States	75150
55	Investigational Site Number 840036	Spokane	Washington	United States	99204
56	Investigational Site Number 840124	Clarksburg	West Virginia	United States	26301
57	Investigational Site Number 032015	Buenos Aires		Argentina	32015
58	Investigational Site Number 032008	Buenos Aires		Argentina	C1428DZF
59	Investigational Site Number 032019	Caba		Argentina	1180
60	Investigational Site Number 032006	Caba		Argentina	C1015ABO
61	Investigational Site Number 032016	Capital Federal		Argentina	1425
62	Investigational Site Number 032020	Cordoba		Argentina	X5119XAA
63	Investigational Site Number 032017	La Plata		Argentina
64	Investigational Site Number 032010	Ramos Mejia		Argentina	B1704ETD
65	Investigational Site Number 032013	Rosario		Argentina	S2000PBJ
66	Investigational Site Number 032004	San Miguel De Tucuman		Argentina	T4000AXL
67	Investigational Site Number 032009	Zarate		Argentina	B2800DGH
68	Investigational Site Number 036014	Victoria Park		Australia	6100
69	Investigational Site Number 040004	Stockerau		Austria	2000
70	Investigational Site Number 040003	Wien		Austria	1090
71	Investigational Site Number 076001	Curitiba		Brazil	80060-240
72	Investigational Site Number 076016	Curitiba		Brazil
73	Investigational Site Number 076006	Goiania		Brazil	74110-120
74	Investigational Site Number 076010	Juiz De Fora		Brazil	36010-570
75	Investigational Site Number 076005	Rio De Janeiro		Brazil	20551-030
76	Investigational Site Number 076015	Rio De Janeiro		Brazil	22271-100
77	Investigational Site Number 124005	Toronto		Canada	M5T 2S8
78	Investigational Site Number 124009	Trois-Rivières		Canada	G8Z 1Y2
79	Investigational Site Number 124104	Victoria		Canada	V8V 3P9
80	Investigational Site Number 152015	Temuco		Chile
81	Investigational Site Number 170001	Bogota		Colombia
82	Investigational Site Number 170012	Bogota		Colombia
83	Investigational Site Number 170006	Bogotá		Colombia
84	Investigational Site Number 170007	Bucaramanga		Colombia
85	Investigational Site Number 170009	Bucaramanga		Colombia
86	Investigational Site Number 170014	Chia		Colombia
87	Investigational Site Number 170019	Medellin		Colombia
88	Investigational Site Number 203008	Hostivice		Czechia	233 01
89	Investigational Site Number 203004	Ostrava		Czechia	702 00
90	Investigational Site Number 203007	Praha 2		Czechia	12850
91	Investigational Site Number 203002	Uherske Hradiste		Czechia	686 01
92	Investigational Site Number 203006	Zlin		Czechia	76001
93	Investigational Site Number 218003	Cuenca		Ecuador
94	Investigational Site Number 218001	Guayaquil		Ecuador	0593
95	Investigational Site Number 218002	Quito		Ecuador	0593
96	Investigational Site Number 276011	Bad Nauheim		Germany	61231
97	Investigational Site Number 276010	Berlin		Germany	10117
98	Investigational Site Number 276001	Berlin		Germany	12305
99	Investigational Site Number 276014	Berlin		Germany	14059
100	Investigational Site Number 276018	Deggingen		Germany	73326
101	Investigational Site Number 276004	Erlangen		Germany	91054
102	Investigational Site Number 276015	Halle/Saale		Germany	06108
103	Investigational Site Number 276013	Hamburg		Germany	22147
104	Investigational Site Number 276016	Leipzig		Germany	04103
105	Investigational Site Number 276017	München		Germany	80336
106	Investigational Site Number 276021	Osnabrück		Germany	49074
107	Investigational Site Number 276020	Tübingen		Germany	72076
108	Investigational Site Number 276019	Zerbst		Germany	39261
109	Investigational Site Number 300002	Heraklion		Greece	71110
110	Investigational Site Number 300005	Thessaloniki		Greece	57010
111	Investigational Site Number 320002	Guatemala City		Guatemala	01009
112	Investigational Site Number 320003	Guatemala City		Guatemala	01011
113	Investigational Site Number 320001	Guatemala City		Guatemala	09090
114	Investigational Site Number 348022	Budapest		Hungary	1036
115	Investigational Site Number 348003	Debrecen		Hungary	4032
116	Investigational Site Number 348004	Veszprém		Hungary	8200
117	Investigational Site Number 348017	Veszprém		Hungary	8200
118	Investigational Site Number 376001	Haifa		Israel	31048
119	Investigational Site Number 376003	Petach Tikva		Israel	49100
120	Investigational Site Number 376002	Tel Hashomer		Israel	52621
121	Investigational Site Number 380011	Catania		Italy	95122
122	Investigational Site Number 380002	Firenze		Italy	50139
123	Investigational Site Number 380005	Genova		Italy	16132
124	Investigational Site Number 380014	Milano		Italy	20157
125	Investigational Site Number 380013	Udine		Italy	33100
126	Investigational Site Number 410017	Daejeon		Korea, Republic of	301-721
127	Investigational Site Number 410016	Seoul		Korea, Republic of	120-752
128	Investigational Site Number 440005	Kaunas		Lithuania	LT-50009
129	Investigational Site Number 440006	Klaipeda		Lithuania	LT-92288
130	Investigational Site Number 440007	Vilnius		Lithuania	LT-08661
131	Investigational Site Number 484023	Chihuahua		Mexico	31020
132	Investigational Site Number 484018	Guadalajara		Mexico	44620
133	Investigational Site Number 484002	Guadalajara		Mexico	44690
134	Investigational Site Number 484024	Guadalajara		Mexico
135	Investigational Site Number 484010	Mexicali		Mexico	21200
136	Investigational Site Number 484019	Monterrey		Mexico	64000
137	Investigational Site Number 484020	Monterrey		Mexico	64000
138	Investigational Site Number 484005	Monterrey		Mexico	64460
139	Investigational Site Number 484017	México		Mexico	06700
140	Investigational Site Number 484021	Queretaro		Mexico	76178
141	Investigational Site Number 554005	Hamilton		New Zealand	3204
142	Investigational Site Number 554011	Nelson		New Zealand	7010
143	Investigational Site Number 554007	Otahuhu		New Zealand	2025
144	Investigational Site Number 554001	Timaru		New Zealand	7910
145	Investigational Site Number 554006	Wellington		New Zealand	6021
146	Investigational Site Number 604010	Lima		Peru	14
147	Investigational Site Number 604009	Lima		Peru	LIMA 01
148	Investigational Site Number 604006	Lima		Peru	LIMA 11
149	Investigational Site Number 604012	Lima		Peru	LIMA 11
150	Investigational Site Number 604013	Lima		Peru	LIMA 13
151	Investigational Site Number 604001	Lima		Peru	Lima 21
152	Investigational Site Number 604008	Lima		Peru	LIMA 27
153	Investigational Site Number 604007	Lima		Peru	Lima 33
154	Investigational Site Number 604005	Lima		Peru	LIMA 41
155	Investigational Site Number 604014	Lima		Peru	LIMA 41
156	Investigational Site Number 616014	Bialystok		Poland	15-099
157	Investigational Site Number 616019	Bydgoszcz		Poland	85-168
158	Investigational Site Number 616015	Elblag		Poland	82-300
159	Investigational Site Number 616018	Poznan		Poland	61-397
160	Investigational Site Number 616016	Szczecin		Poland	71-252
161	Investigational Site Number 616004	Warszawa		Poland	02-118
162	Investigational Site Number 616017	Warszawa		Poland	02-653
163	Investigational Site Number 616020	Wroclaw		Poland	50-556
164	Investigational Site Number 620002	Lisboa		Portugal	1050-034
165	Investigational Site Number 620004	Lisboa		Portugal	1649-035
166	Investigational Site Number 620007	Ponte De Lima		Portugal
167	Investigational Site Number 642001	Bucuresti		Romania	010976
168	Investigational Site Number 642012	Bucuresti		Romania	020475
169	Investigational Site Number 642002	Bucuresti		Romania	020983
170	Investigational Site Number 642014	Iasi		Romania	700661
171	Investigational Site Number 643001	Moscow		Russian Federation	115522
172	Investigational Site Number 643021	Moscow		Russian Federation	119049
173	Investigational Site Number 643022	Novosibirsk		Russian Federation	630091
174	Investigational Site Number 643008	Saint-Petersburg		Russian Federation	192242
175	Investigational Site Number 643010	Samara		Russian Federation	443095
176	Investigational Site Number 703001	Kosice		Slovakia	040 11
177	Investigational Site Number 724016	Barakaldo		Spain	48903
178	Investigational Site Number 724015	Barcelona		Spain	08034
179	Investigational Site Number 724014	Cadiz		Spain	1009
180	Investigational Site Number 724009	La Coruña		Spain	15006
181	Investigational Site Number 724001	Málaga		Spain	29009
182	Investigational Site Number 724011	Sabadell		Spain	08208
183	Investigational Site Number 724017	Santiago De Compostela		Spain	15702
184	Investigational Site Number 724013	Santiago De Compostela		Spain	15706
185	Investigational Site Number 724007	Sevilla		Spain	41071
186	Investigational Site Number 158005	Kaohsiung		Taiwan	81346
187	Investigational Site Number 158006	Taipei		Taiwan	402
188	Investigational Site Number 158002	Taoyuan County		Taiwan	33305
189	Investigational Site Number 792007	Edirne		Turkey	22030
190	Investigational Site Number 792008	Gaziantep		Turkey	27310
191	Investigational Site Number 792009	Samsun		Turkey
192	Investigational Site Number 804013	Kharkiv		Ukraine	61176
193	Investigational Site Number 804014	Kyiv		Ukraine	01103
194	Investigational Site Number 804027	Kyiv		Ukraine	03680
195	Investigational Site Number 804011	Vinnytsia		Ukraine	21018
196	Investigational Site Number 804009	Zaporizhzhya		Ukraine	69600

Sponsors and Collaborators

• Sanofi
• Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT01709578
• Other Study ID Numbers: EFC10832; U1111-1115-8466; 2011-003538-16
• First Posted: Oct 18, 2012
• Last Update Posted: Aug 8, 2017
• Last Verified: Jul 1, 2017

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Hydroxychloroquine; Sulfasalazine; Methotrexate; Leflunomide

Study Results

Participant Flow

Recruitment Details	The study was conducted at 240 centers in 27 countries. A total of 1224 participants were screened between 29 October 2012 and 7 August 2014, of whom 546 participants were randomized and 678 were screen failures. Screen failures were mainly due to failure to meet inclusion criteria.
Pre-assignment Detail	Participants were randomized 1:1:1 (placebo q2w : sarilumab 150 mg q2w : sarilumab 200 mg q2w) via a centralized randomization system using an interactive voice response system stratified by region and number of previous anti- tumor necrosis factor (TNF) therapy (1 versus >1).

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab subcutaneous (SC) injection once every 2 weeks (q2w) was added to one or a combination of the nonbiologic disease modifying antirheumatic drug (DMARD) for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Period Title: Overall Study
STARTED	181	181	184
COMPLETED	101	125	133
NOT COMPLETED	80	56	51

Baseline Characteristics

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w	Total
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Total of all reporting groups
Overall Participants	181	181	184	546
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.9 (12.4)	54.0 (11.7)	52.9 (12.9)	52.9 (12.4)
Sex: Female, Male (Count of Participants)
Female	154 85.1%	142 78.5%	151 82.1%	447 81.9%
Male	27 14.9%	39 21.5%	33 17.9%	99 18.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24
Description	ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant (C-reactive Protein levels [CRP]); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by (health assessment questionnaire disability index [HAQ-DI]). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all randomized participants.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	181	181	184
Number [percentage of participants]	33.7 18.6%	55.8 30.8%	60.9 33.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 150 mg q2w
	Comments	A hierarchical testing procedure was used to control type I error rate at 0.05 and handle multiple endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.025 level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.025 level
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.711
	Confidence Interval	(2-Sided) 95%; 1.730 to 4.247
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 150 mg q2w vs Placebo q2w

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 200 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.025 level
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.284
	Confidence Interval	(2-Sided) 95%; 2.108 to 5.115
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 200 mg q2w vs Placebo q2w

2. Primary Outcome

Title	Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12
Description	Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. Least-squares (LS) means and standard errors (SE) at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = number of participants with HAQ-DI assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	170	165	171
Least Squares Mean (Standard Error) [units on a scale]	-0.26 (0.043)	-0.46 (0.044)	-0.47 (0.043)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 150 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments	Threshold for significance at 0.025 level
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.202
	Confidence Interval	(2-Sided) 95%; -0.318 to -0.086
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 150 mg q2w vs Placebo q2w

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 200 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments	Threshold for significance at 0.025 level
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.210
	Confidence Interval	(2-Sided) 95%; -0.325 to -0.095
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 200 mg q2w vs Placebo q2w

3. Secondary Outcome

Title	Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24
Description	DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the ACR rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (VAS). Marker of inflammation assessed by the high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28 score provides a number indicating the current disease activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS28-CRP score as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = number of participants with DAS28--CRP Score assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	99	126	136
Least Squares Mean (Standard Error) [units on a scale]	-1.38 (0.119)	-2.35 (0.111)	-2.82 (0.108)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 150 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.025 level
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.971
	Confidence Interval	(2-Sided) 95%; -1.283 to -0.658
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 150 mg q2w vs Placebo q2w

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 200 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.025 level
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.444
	Confidence Interval	(2-Sided) 95%; -1.752 to -1.135
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 200 mg q2w vs Placebo q2w

4. Secondary Outcome

Title	Percentage of Participants Achieving ACR50 Criteria at Week 24
Description	ACR responses are assessed with a composite rating scale that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	181	181	184
Number [Percentage of participants]	18.2 10.1%	37.0 20.4%	40.8 22.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 150 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.025 level
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.958
	Confidence Interval	(2-Sided) 95%; 1.764 to 4.959
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 150 mg q2w vs Placebo q2w

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 200 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance was 0.025 level
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.374
	Confidence Interval	(2-Sided) 95%; 2.045 to 5.566
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 200 mg q2w vs Placebo q2w

5. Secondary Outcome

Title	Percentage of Participants Achieving ACR70 Criteria at Week 24
Description	ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	181	181	184
Number [Percentage of participants]	7.2 4%	19.9 11%	16.3 8.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 150 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	Threshold for significance at 0.025 level
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.607
	Confidence Interval	(2-Sided) 95%; 1.774 to 7.332
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 150 mg q2w vs Placebo q2w

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 200 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0056
	Comments	Threshold for significance at 0.025 level
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.653
	Confidence Interval	(2-Sided) 95%; 1.308 to 5.383
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 200 mg q2w vs Placebo q2w

6. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24
Description	DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	181	181	184
Number [Percentage of participants]	7.2 4%	24.9 13.8%	28.8 15.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 150 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.025 level
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.622
	Confidence Interval	(2-Sided) 95%; 2.339 to 9.132
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 150 mg q2w vs Placebo q2w

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 200 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.025 level
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.801
	Confidence Interval	(2-Sided) 95%; 2.948 to 11.413
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 200 mg q2w vs Placebo q2w

7. Secondary Outcome

Title	Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
Description	CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: TJC (28 joints), SJC (28 joints), Participant's Global Assessment of Disease Activity VAS (in cm), and Physician's Global Assessment of Disease VAS (in cm). Total scores ranges from 0 to 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline CDAI as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed=number of participants with CDAI assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	100	127	136
Least Squares Mean (Standard Error) [units on a scale]	-16.35 (1.195)	-23.65 (1.136)	-26.08 (1.109)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 150 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.025 level
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-7.306
	Confidence Interval	(2-Sided) 95%; -10.444 to -4.167
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 150 mg q2w vs Placebo q2w

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 200 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.025 level
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-9.727
	Confidence Interval	(2-Sided) 95%; -12.833 to -6.622
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 200 mg q2w vs Placebo q2w

8. Secondary Outcome

Title	Change From Baseline in HAQ-DI at Week 24
Description	Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = number of participants with HAQ-DI assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	101	127	136
Least Squares Mean (Standard Error) [units on a scale]	-0.34 (0.051)	-0.52 (0.049)	-0.58 (0.048)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 150 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0078
	Comments	Threshold for significance was 0.025 level
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.183
	Confidence Interval	(2-Sided) 95%; -0.318 to -0.048
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 150 mg q2w vs Placebo q2w

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 200 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments	Threshold for significance was 0.025 level
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.242
	Confidence Interval	(2-Sided) 95%; -0.376 to -0.109
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 200 mg q2w vs Placebo q2w

9. Secondary Outcome

Title	Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24
Description	SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: PCS and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS had 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS had 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 by MMRM with treatment,region,number of previous anti TNFs,visit,and treatment-by-visit interaction as fixed effects and baseline SF-36 (PCS) as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with SF-36 PCS assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	99	123	134
Least Squares Mean (Standard Error) [units on a scale]	4.40 (0.692)	7.65 (0.653)	8.48 (0.630)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 150 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments	Threshold for significance at 0.025 level
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.250
	Confidence Interval	(2-Sided) 95%; 1.450 to 5.049
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 150 mg q2w vs Placebo q2w

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 200 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.025 level
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.075
	Confidence Interval	(2-Sided) 95%; 2.305 to 5.846
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 200 mg q2w vs Placebo q2w

10. Secondary Outcome

Title	Change From Baseline in SF-36 MCS at Week 24
Description	SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 MCS as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed=participants with SF-36 MCS assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	99	123	134
Least Squares Mean (Standard Error) [units on a scale]	4.74 (0.902)	6.26 (0.848)	6.76 (0.817)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 150 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2026
	Comments	Threshold for significance at 0.025 level
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.515
	Confidence Interval	(2-Sided) 95%; -0.818 to 3.848
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 150 mg q2w vs Placebo q2w

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Sarilumab 200 mg q2w
	Comments	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0854
	Comments	Threshold for significance at 0.025 level
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.013
	Confidence Interval	(2-Sided) 95%; -0.282 to 4.309
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sarilumab 200 mg q2w vs Placebo q2w

11. Secondary Outcome

Title	Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24
Description	The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of Participants analyzed = number of participants with FACIT-fatigue score assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	98	126	136
Least Squares Mean (Standard Error) [units on a scale]	6.82 (0.863)	9.86 (0.802)	10.06 (0.778)

12. Secondary Outcome

Title	Change From Baseline in Morning Stiffness VAS at Week 24
Description	RA is associated with stiffness of joints, especially in the morning after prolonged stationery state. The degree of stiffness can be an indicator of disease severity. The severity of morning stiffness was assessed on a VAS scale from 0 mm (no problem) to 100 mm (major problem). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline Morning Stiffness as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = number of participants with morning stiffness VAS assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	101	127	136
Least Squares Mean (Standard Error) [mm]	-21.66 (2.390)	-32.30 (2.213)	-33.79 (2.148)

13. Secondary Outcome

Title	Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA
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). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed=participants with WPS-RA individual items assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	32	43	45
Least Squares Mean (Standard Error) [Days]	-2.01 (0.458)	-2.87 (0.438)	-3.19 (0.447)

14. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA
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). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	32	43	45
Least Squares Mean (Standard Error) [Days]	-3.64 (0.589)	-4.26 (0.521)	-4.34 (0.535)

15. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity
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 is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	32	42	45
Least Squares Mean (Standard Error) [units on a scale]	-1.632 (0.4186)	-2.422 (0.3719)	-2.727 (0.3700)

16. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA
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). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	101	126	133
Least Squares Mean (Standard Error) [Days]	-3.50 (0.590)	-6.13 (0.551)	-6.18 (0.537)

17. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA
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). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	101	125	133
Least Squares Mean (Standard Error) [Days]	-3.36 (0.632)	-4.60 (0.591)	-4.88 (0.574)

18. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA
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). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	101	127	133
Least Squares Mean (Standard Error) [Days]	-1.97 (0.479)	-3.51 (0.446)	-4.12 (0.435)

19. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA
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). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	101	126	133
Least Squares Mean (Standard Error) [Days]	-1.60 (0.567)	-3.87 (0.536)	-3.86 (0.523)

20. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity
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 ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	100	126	132
Least Squares Mean (Standard Error) [units on a scale]	-1.970 (0.2438)	-3.096 (0.2238)	-3.269 (0.2186)

21. Secondary Outcome

Title	Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24
Description	RAID is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 numerical rating scales (NRS) questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicate worse status and lower indicate not affected. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = number of participants with RAID score assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	99	126	136
Least Squares Mean (Standard Error) [units on a scale]	-1.80 (0.203)	-2.55 (0.189)	-2.80 (0.183)

22. Secondary Outcome

Title	Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24
Description	The EQ-5D-3L is a standardized, generic measure of health outcome. It was designed for self-completion by participants. It was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L Scores as a covariate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = number of participants with EQ-5D-3L score assessment at both baseline and Week 24.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	96	126	133
Least Squares Mean (Standard Error) [units on a scale]	14.85 (2.098)	20.06 (1.891)	18.40 (1.842)

23. Secondary Outcome

Title	Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12
Description	ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	181	181	184
ACR20	37.6 20.8%	54.1 29.9%	62.5 34%
ACR50	13.3 7.3%	30.4 16.8%	33.2 18%
ACR70	2.2 1.2%	13.8 7.6%	14.7 8%

24. Secondary Outcome

Title	Change From Baseline in DAS28-CRP at Week 12
Description	DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS score as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = number of participants with DAS28-CRP- Score assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	168	163	169
Least Squares Mean (Standard Error) [units on a scale]	-0.97 (0.104)	-2.13 (0.105)	-2.45 (0.103)

25. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP <2.6) at Week 12
Description	DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	181	181	184
Number [Percentage of participants]	3.9 2.2%	17.1 9.4%	17.9 9.7%

26. Secondary Outcome

Title	Change From Baseline in SF-36 at Week 12
Description	SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed=participants with SF-36 assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	169	160	165
Physical Component Summary Score at Week 12	3.74 (0.582)	6.93 (0.596)	6.84 (0.584)
Mental Component Summary Score at Week 12	3.50 (0.738)	5.14 (0.758)	6.47 (0.741)

27. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA
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). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed=participants with WPS-RA individual items assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	54	54	56
Least Squares Mean (Standard Error) [Days]	-1.20 (0.581)	-1.97 (0.571)	-2.98 (0.585)

28. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA
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). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	54	54	56
Least Squares Mean (Standard Error) [Days]	-1.69 (0.784)	-4.24 (0.773)	-3.20 (0.785)

29. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity
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 ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	53	54	56
Least Squares Mean (Standard Error) [units on a scale]	-1.043 (0.3803)	-1.924 (0.3742)	-1.873 (0.3764)

30. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA
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). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	170	164	169
Least Squares Mean (Standard Error) [Days]	-2.10 (0.551)	-5.52 (0.563)	-5.54 (0.553)

31. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA
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). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	169	163	169
Least Squares Mean (Standard Error) [Days]	-2.60 (0.576)	-3.97 (0.587)	-3.98 (0.575)

32. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA
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). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	170	164	169
Least Squares Mean (Standard Error) [Days]	-2.23 (0.433)	-2.53 (0.442)	-3.26 (0.434)

33. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA
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). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	170	164	169
Least Squares Mean (Standard Error) [Days]	-0.77 (0.558)	-3.07 (0.570)	-2.94 (0.560)

34. Secondary Outcome

Title	Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity
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 ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	169	164	167
Least Squares Mean (Standard Error) [units on a scale]	-1.210 (0.2428)	-2.772 (0.2474)	-2.404 (0.2443)

35. Secondary Outcome

Title	Change From Baseline in the FACIT-fatigue at Week 12
Description	The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of Participants analyzed = number of participants with FACIT-fatigue score assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	169	165	172
Least Squares Mean (Standard Error) [units on a scale]	5.56 (0.721)	8.02 (0.729)	9.45 (0.714)

36. Secondary Outcome

Title	Change From Baseline in EQ-5D-3L VAS Scores at Week 12
Description	The EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. The EQ-5D was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L scores as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = number of participants with EQ-5D-3L score assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	167	163	171
Least Squares Mean (Standard Error) [units on a scale]	8.39 (1.699)	17.16 (1.720)	15.23 (1.680)

37. Secondary Outcome

Title	Change From Baseline in RAID Scores at Week 12
Description	RAID score is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 NRS questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicates worse status and lower indicates not affected. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID scores as a covariate.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = number of participants with RAID score assessment at both baseline and Week 12.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	167	162	171
Mean (Standard Error) [units on a scale]	-1.34 (0.163)	-2.27 (0.165)	-2.47 (0.161)

38. Secondary Outcome

Title	Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24
Description	ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI & CRP. 68 joints were assessed for tenderness (TJC scoring 0-68) and 66 joints for swelling (SJC scoring 0-66). The 66 SJC evaluated the following joints: temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, interphalangeal of thumb, distal interphalangeal, proximal interphalangeal, knee, ankle mortise, ankle tarsus, metatarsophalangeal, interphalangeal of great toe, and proximal/distal interphalangeal of the toes. The TJC examined hip joints, in addition to the joints assessed for SJC. Increase in number of tender joints/swollen joints indicated severity. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number analyzed = number of participants with TJC and SJC assessments at both baseline and specified time points.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	181	181	184
TJC at week 12	-8.55 (0.959)	-13.74 (0.975)	-14.87 (0.954)
SJC at week 12	-6.75 (0.687)	-10.54 (0.698)	-10.59 (0.684)
TJC at week 24	-10.55 (1.060)	-14.44 (1.017)	-16.95 (0.992)
SJC at week 24	-8.19 (0.721)	-11.56 (0.691)	-11.94 (0.674)

39. Secondary Outcome

Title	Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24
Description	ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & CRP. Physician global VAS & participant global VAS was done by 100 mm non-anchored VAS, from no arthritis (0) activity to maximal arthritis (100) activity. Pain VAS by 100 mm VAS ranging from 0 "no pain" to 100 "worst pain". LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number analyzed = number of participants with individual ACR components assessment at both baseline and specified time points.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	181	181	184
Physician global VAS at week 12	-22.74 (1.744)	-33.64 (1.775)	-35.44 (1.740)
Participant global VAS at week 12	-13.75 (1.807)	-25.28 (1.836)	-27.38 (1.803)
Pain VAS at week 12	-15.13 (1.908)	-26.93 (1.933)	-30.56 (1.901)
Physician global VAS at week 24	-28.55 (1.806)	-40.65 (1.695)	-43.22 (1.646)
Participant global VAS at week 24	-19.76 (2.171)	-29.59 (2.046)	-31.28 (1.997)
Pain VAS at week 24	-21.27 (2.250)	-31.90 (2.086)	-33.65 (2.037)

40. Secondary Outcome

Title	Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24
Description	ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & CRP. An elevated CRP level was considered a non-specific "marker" for RA. A reduction level indicates improvement. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number analyzed = number of participants with CRP assessment at both baseline and specified time points.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	181	181	184
CRP at week 12	-3.63 (1.436)	-15.08 (1.452)	-22.98 (1.432)
CRP at week 24	-3.60 (1.556)	-15.24 (1.457)	-23.27 (1.421)

41. Secondary Outcome

Title	Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24
Description	ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI & CRP. HAQ-DI consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Number analyzed = number of participants with HAQ-DI assessment at both baseline and specified time points.

Arm/Group Title	Placebo q2w	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Measure Participants	181	181	184
HAQ-DI at week 12	-0.26 (0.043)	-0.46 (0.044)	-0.47 (0.043)
HAQ-DI at week 24	-0.34 (0.051)	-0.52 (0.049)	-0.58 (0.048)

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Arm/Group Title	Placebo q2w		Sarilumab 150 mg q2w		Sarilumab 200 mg q2w
Arm/Group Description	Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.		Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.		Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
All Cause Mortality
	Placebo q2w		Sarilumab 150 mg q2w		Sarilumab 200 mg q2w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo q2w		Sarilumab 150 mg q2w		Sarilumab 200 mg q2w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/181 (3.3%)		6/181 (3.3%)		10/184 (5.4%)
Blood and lymphatic system disorders
Anaemia	1/181 (0.6%)		0/181 (0%)		0/184 (0%)
Neutropenia	0/181 (0%)		1/181 (0.6%)		1/184 (0.5%)
Cardiac disorders
Acute myocardial infarction	0/181 (0%)		0/181 (0%)		1/184 (0.5%)
Atrioventricular block second degree	0/181 (0%)		0/181 (0%)		1/184 (0.5%)
Endocarditis noninfective	0/181 (0%)		0/181 (0%)		1/184 (0.5%)
Gastrointestinal disorders
Gastric ulcer haemorrhage	0/181 (0%)		1/181 (0.6%)		0/184 (0%)
Inguinal hernia	0/181 (0%)		0/181 (0%)		1/184 (0.5%)
Hepatobiliary disorders
Mixed liver injury	1/181 (0.6%)		0/181 (0%)		0/184 (0%)
Infections and infestations
Bacteraemia	1/181 (0.6%)		0/181 (0%)		0/184 (0%)
Bronchitis	1/181 (0.6%)		0/181 (0%)		0/184 (0%)
Cellulitis	1/181 (0.6%)		1/181 (0.6%)		1/184 (0.5%)
Osteomyelitis	0/181 (0%)		1/181 (0.6%)		0/184 (0%)
Pneumonia	0/181 (0%)		0/181 (0%)		1/184 (0.5%)
Injury, poisoning and procedural complications
Ankle fracture	1/181 (0.6%)		0/181 (0%)		0/184 (0%)
Post procedural haemorrhage	0/181 (0%)		0/181 (0%)		1/184 (0.5%)
Road traffic accident	1/181 (0.6%)		0/181 (0%)		0/184 (0%)
Investigations
Neutrophil count decreased	0/181 (0%)		0/181 (0%)		1/184 (0.5%)
Transaminases increased	0/181 (0%)		0/181 (0%)		1/184 (0.5%)
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder	0/181 (0%)		0/181 (0%)		1/184 (0.5%)
Intervertebral disc protrusion	0/181 (0%)		1/181 (0.6%)		0/184 (0%)
Rheumatoid arthritis	1/181 (0.6%)		0/181 (0%)		0/184 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ureteric cancer	1/181 (0.6%)		0/181 (0%)		0/184 (0%)
Nervous system disorders
Ischaemic stroke	0/181 (0%)		0/181 (0%)		1/184 (0.5%)
Syncope	0/181 (0%)		1/181 (0.6%)		0/184 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/181 (0%)		1/181 (0.6%)		0/184 (0%)
Vascular disorders
Venous thrombosis limb	0/181 (0%)		0/181 (0%)		1/184 (0.5%)
Other (Not Including Serious) Adverse Events
	Placebo q2w		Sarilumab 150 mg q2w		Sarilumab 200 mg q2w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/181 (14.4%)		60/181 (33.1%)		57/184 (31%)
Blood and lymphatic system disorders
Neutropenia	2/181 (1.1%)		23/181 (12.7%)		22/184 (12%)
General disorders
Injection site erythema	0/181 (0%)		11/181 (6.1%)		7/184 (3.8%)
Infections and infestations
Nasopharyngitis	9/181 (5%)		11/181 (6.1%)		7/184 (3.8%)
Urinary tract infection	12/181 (6.6%)		6/181 (3.3%)		13/184 (7.1%)
Investigations
Alanine aminotransferase increased	2/181 (1.1%)		5/181 (2.8%)		10/184 (5.4%)
Metabolism and nutrition disorders
Hypertriglyceridaemia	3/181 (1.7%)		11/181 (6.1%)		5/184 (2.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.