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Efficacy and Safety of Sarilumab and Adalimumab Monotherapy in Patients With Rheumatoid Arthritis (SARIL-RA-MONARCH)

Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT02332590
Collaborator
Regeneron Pharmaceuticals (Industry)
369
Enrollment
86
Locations
2
Arms
71
Actual Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective:

To demonstrate that sarilumab monotherapy was superior to adalimumab monotherapy with respect to signs and symptoms as assessed by disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) in participants with active rheumatoid arthritis (RA) who were either intolerant of, or considered inappropriate candidates for continued treatment with methotrexate (MTX), or after at least 12 weeks of continued treatment with MTX, were determined to be inadequate responders.

Secondary Objectives:

To demonstrate that sarilumab monotherapy was superior to adalimumab monotherapy in participants with active RA who were either intolerant of, or considered inappropriate candidates for continued treatment with MTX, or after at least 12 weeks of continued treatment with MTX, were determined to be inadequate responders, with respect to:

  • Reduction of signs and symptoms of RA.

  • Improvement in quality of life assessed by participant reported outcome questionnaires.

Assessment of the safety and tolerability of sarilumab monotherapy (including immunogenicity) throughout the study.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Total study duration was up to 310 weeks: Up to a 4 week screening period, 24 week randomized double-blind treatment phase, 276-week open-label extension, and 6 weeks post-treatment final study visit.

Study Design

Study Type:
Interventional
Actual Enrollment :
369 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
During the OLE period of this study, all participants received sarilumab 200 mg or 150 mg q2w via prefilled syringe.During the OLE period of this study, all participants received sarilumab 200 mg or 150 mg q2w via prefilled syringe.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Parallel-group Study Assessing the Efficacy and Safety of Sarilumab Monotherapy Versus Adalimumab Monotherapy in Patients With Rheumatoid Arthritis
Actual Study Start Date :
Jan 28, 2015
Actual Primary Completion Date :
Jan 20, 2016
Actual Study Completion Date :
Dec 29, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Adalimumab 40 mg/Sarilumab 200 mg

Adalimumab 40 milligrams (mg) subcutaneous (SC) injection in combination with placebo for sarilumab every 2 weeks (q2w) for 24 weeks during the double-blind (DB) period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (less than [<] 20% improvement from baseline in tender joint count [TJC] and swollen joint count [SJC] for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in open label extension (OLE) period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).

Drug: Adalimumab
Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC
Other Names:
  • Humira

    • Drug: Placebo (for sarilumab)
    Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC
    Experimental: Sarilumab 200 mg/Sarilumab 200 mg

    Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).

    Drug: Sarilumab
    Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC
    Other Names:
  • SAR153191
  • REGN88

    • Drug: Placebo (for adalimumab)
    Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC

    Outcome Measures

    Primary Outcome Measures

    1. DB Period: Change From Baseline in Disease Activity Score for 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 24 [Baseline, Week 24]

      DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR and RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Least square (LS) mean and standard error (SE) at Week 24 were obtained using Mixed-effect model with repeated measures (MMRM) approach.

    Secondary Outcome Measures

    1. DB Period: Percentage of Participants Achieving Clinical Remission Score (DAS28-ESR <2.6) at Week 24 [Week 24]

      DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Participants who discontinued treatment prior to Week 24 were analyzed as non-responders.

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

      ACR responses are assessed with a composite rating scale of the ACR that includes 7 variables: TJC (68 joints); SJC (66 joints); levels of an acute phase reactant (C-reactive protein [CRP] level); participant's assessment of pain (measured on 0 [no pain]-100 mm [worst pain] VAS); participant's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by Health Assessment Questionnaire - Disability Index [HAQ-DI], with scoring range of 0 [better physical function] - 3 [worst physical function]). 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. Participants were analyzed as non-responders from the time they discontinued treatment.

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

      ACR responses are assessed with a composite rating scale of the ACR that includes 7 variables: TJC (68 joints); SJC (66 joints); levels of an acute phase reactant (CRP level); participant's assessment of pain (measured on 0 [no pain]-100 mm [worst pain] VAS); participant's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by HAQ-DI, with scoring range of 0 [better physical function] - 3 [worst physical function]). ACR70 was 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. Participants were analyzed as non-responders from the time they discontinued treatment.

    4. DB Period: Percentage of Participants Achieving ACR20 Criteria at Week 24 [Week 24]

      ACR responses are assessed with a composite rating scale of the ACR that includes 7 variables: TJC (68 joints); SJC (66 joints); levels of an acute phase reactant (CRP level); participant's assessment of pain (measured on 0 [no pain]-100 mm [worst pain] VAS); participant's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by HAQ-DI, with scoring range of 0 [better physical function] - 3 [worst physical function]). ACR20 was 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. Participants were analyzed as non-responders from the time they discontinued treatment.

    5. DB Period: 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 or 3 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 24 were obtained using MMRM approach.

    6. DB Period: Change From Baseline in Short-Form-36 (SF-36) - Physical Component Summary (PCS) Score at Week 24 [Baseline, Week 24]

      SF-36 is a generic 36-item questionnaire consisting of 8 sub-scales, measures health-related quality of life (HRQL) in the last 4 weeks covering 2 summary measures: PCS and mental component summary (MCS). PCS with 4 sub-scales: physical function, role limitations due to physical problems, pain, and general health perception; and MCS with 4 sub-scales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a sub-scale 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 sub-scale give the sub-scale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Both PCS and MCS range from 0-100 with higher scores indicating better physical and mental health. LS mean and SE at Week 24 by MMRM approach.

    7. DB Period: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24 [Baseline, Week 24]

      The FACIT-F 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 ranged from 0 to 52, where higher score corresponds to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 by MMRM approach.

    8. DB Period: Change From Baseline in SF-36 - Mental Health Component Summary Score at Week 24 [Baseline, Week 24]

      SF-36 is a generic 36-item questionnaire consisting of 8 sub-scales, measures HRQL in the last 4 weeks covering 2 summary measures: PCS and MCS. PCS with 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception; and MCS with 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 sub-scale give the sub-scale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Both PCS and MCS range from 0-100 with higher scores indicating better physical and mental health. LS mean and SE at Week 24 by MMRM approach.

    9. DB Period: Change From Baseline in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP Score) at Week 24 [Baseline, Week 24]

      DAS28-CRP is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28-CRP score provides a number indicating the current disease activity of the RA. DAS28-CRP total score ranges from 2-10. A DAS28-CRP score above 5.1 means high disease activity, whereas a DAS28-CRP score below 3.2 indicates low disease activity and a DAS28-CRP score below 2.6 means disease remission. LS mean and SE at Week 24 were obtained using MMRM approach.

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

      DAS28-CRP is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment 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-CRP score provides a number indicating the current disease activity of the RA. DAS28-CRP total score ranges from 2-10. A DAS28-CRP score above 5.1 means high disease activity, whereas a DAS28-CRP score below 3.2 indicates low disease activity and a DAS28-CRP score below 2.6 means disease remission. Participants were analyzed as non-responders from the time they discontinued treatment.

    11. DB Period: Percentage of Participants Achieving Low Disease Activity (DAS28-ESR < 3.2) at Week 24 [Week 24]

      DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Participants were analyzed as non-responders from the time they discontinued treatment.

    12. DB Period: Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Remission (CDAI ≤2.8) at Week 24 [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: SJC (28 joints), TJC (28 joints), participant's global assessment of disease activity (in cm), and physician's global assessment of disease activity (in cm). Total score ranges from 0 to 76 with a lower score indicating less disease activity. Participants were analyzed as non-responders from the time they discontinued treatment.

    13. DB Period: Change From Baseline in 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: SJC (28 joints), TJC (28 joints), participant's global assessment of disease activity (in cm), and physician's global assessment of disease activity (VAS in cm). Total score ranges from 0 to 76 with a lower score indicating less disease activity. A negative change in CDAI score indicates an improvement in disease activity and a positive change in score indicates a worsening of disease activity. LS means and SE at Week 24 were obtained using MMRM approach.

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

      EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. EQ-5D was specifically included to address concerns regarding the health economic impact of RA. EQ-5D-3L comprises of 5 questions on mobility, self-care, pain/discomfort, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems). The 5-dimensional 3-level systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-3L-VAS records the participant's self-rated health on a vertical VAS that allows the participants to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained using MMRM approach.

    15. DB Period: Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) 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. Each NRS is assessed as a number between 0 and 10 that corresponds to the 7 domains. The values for each of these domains are weighed by participant assessment of relative importance and combined in a single score with a total score range of 0 (not affected, very good) to 10 (most affected). LS mean and SE at Week 24 were obtained using MMRM approach.

    16. DB Period: Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to Arthritis [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 is interviewer-administered and 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 using MMRM approach.

    17. DB Period: Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to Arthritis [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 is interviewer-administered and 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 participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.

    18. DB Period: Change From Baseline in WPS-RA at Week 24: Arthritis 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 is interviewer-administered and 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 24 were obtained using MMRM approach.

    19. DB Period: Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to Arthritis [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 is interviewer-administered and 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 participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.

    20. DB Period: Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by >= 50% Due to Arthritis [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 is interviewer-administered and 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 participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.

    21. DB Period: Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to Arthritis [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 is interviewer-administered and 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 participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.

    22. DB Period: Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to Arthritis [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 is interviewer-administered and 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 using MMRM approach.

    23. DB Period: 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 is interviewer-administered and 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 using MMRM approach.

    24. DB Period: 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 using MMRM approach.

    25. DB Period: Change From Baseline in Individual ACR Component - TJC and SJC at Week 24 [Baseline, Week 24]

      ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). 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 24 were obtained using MMRM approach.

    26. DB Period: Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 24 [Baseline, Week 24]

      ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). Physician global VAS & participant global VAS was done on 100 mm horizontal anchored VAS, ranging from 0 "no arthritis activity" to 100 "maximal arthritis activity" and Pain VAS on 100 mm VAS, ranging from 0 "no pain" to 100 "worst pain". LS mean and SE at Week 24 were obtained using MMRM approach.

    27. DB Period: Change From Baseline in Individual ACR Component - CRP Level at Week 24 [Baseline, Week 24]

      ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). An elevated CRP level is considered a non-specific "marker" for RA. A decrease indicates improvement. LS mean and SE at Week 24 were obtained using MMRM approach.

    28. DB Period: Change From Baseline in Individual ACR Component- ESR Level at Week 24 [Baseline, Week 24]

      ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). The ESR is a blood test that can reveal inflammatory activity. Inflammation can cause the cells to clump together. The farther the red blood cells have descended, the greater the inflammatory response. LS mean and SE at Week 24 were obtained using MMRM approach.

    29. DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [From Week 0 to Week 24]

      Adverse event (AE) was defined as any untoward medical occurrence in participant who received investigational medicinal product (IMP) and did not necessarily had to have causal relationship with treatment. All reported AEs are TEAEs developed/worsened during 'on treatment period' (time from first dose of study drug up to day before first dose of open-label treatment for participants who completed 24-week randomized//DB treatment). SAEs were AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or a medically important event.

    30. OLE Period: Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events [From end of Week 24 (Baseline of OLE Period) up to last dose in OLE + 6 weeks of follow up (i.e. up to Week 306)]

      AE was defined as any untoward medical occurrence in participant who received IMP and did not necessarily had to have causal relationship with treatment. All reported AEs are TEAEs developed/worsened during 'on treatment period' (from end of week 24 [Baseline of OLE Period] up to last dose in OLE period + 6 weeks [follow-up], regardless of unplanned intermittent discontinuations). SAEs were AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or a medically important event.

    31. DB Period: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) - Hematological Parameters [From Week 0 to Week 24]

      Criteria for potentially clinically significant laboratory abnormalities included: Hemoglobin (Hb): less than or equal to (<=) 115 grams per liter (g/L) (Male), <= 95 g/L (Female); greater than or equal to (>=) 185 g/L (18.5 g/dL) (Male), >= 165 g/L (16.5 g/dL) (Female); Decrease From Baseline (DFB) = 20 g/L (2 g/dL). Hematocrit: <= 0.37 volume/volume (v/v) (Male); <= 0.32 v/v (F); >= 0.55 v/v (Male); >= 0.5 v/v (Female). Red Blood Cells (RBCs): >=6 Tera/ liter (L). Platelets: < 50 Giga/L, 50 - 100 Giga/L, >= 700 Giga/L. White blood cells (WBC): < 3.0 Giga/L (Non-Black); < 2.0 Giga/L (Black), >= 16.0 Giga/L. Neutrophils: < 1.0 Giga/L, < 1.5 Giga/L (Non-Black); < 1.0 Giga/L (Black). Lymphocytes: < 0.5 Giga/L, >= 0.5 Giga/L - lower limit of normal (LLN), > 4.0 Giga/L. Monocytes: > 0.7 Giga/L. Basophils: > 0.1 Giga/L. Eosinophils: > 0.5 Giga/L or > upper limit of normal (ULN) (if ULN >= 0.5 Giga/L).

    32. OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Hematological Parameters [From end of Week 24 (Baseline of OLE Period) up to Week 300]

      Criteria for potentially clinically significant laboratory abnormalities included: Hb: <=115 g/L (Male), <= 95 g/L (Female); >=185 g/L (18.5 g/dL) (Male), >= 165 g/L (16.5 g/dL) (Female); DFB >= 20 g/L (2 g/dL). Hematocrit: <= 0.37 v/v (Male); <= 0.32 v/v (Female); >= 0.55 v/v (Male); >= 0.5 v/v (Female). RBCs: >=6 Tera/ L. Platelets: < 50 Giga/L, >=50 - 100 Giga/L, >= 700 Giga/L. WBC: < 3.0 Giga/L (Non-Black); < 2.0 Giga/L (Black), >= 16.0 Giga/L. Neutrophils: < 1.0 Giga/L, < 1.5 Giga/L (Non-Black); < 1.0 Giga/L (Black). Lymphocytes: < 0.5 Giga/L, >= 0.5 Giga/L - LLN, > 4.0 Giga/L. Monocytes: > 0.7 Giga/L. Basophils: > 0.1 Giga/L. Eosinophils: > 0.5 Giga/L or > ULN (if ULN >= 0.5 Giga/L).

    33. DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function Tests [From Week 0 to Week 24]

      Criteria for potentially clinically significant abnormalities: Alanine Aminotransferase (ALT): >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN. Aspartate aminotransferase (AST): >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN. Alkaline phosphatase: >1.5 ULN. Total bilirubin (TBILI): >1.5 ULN; >2 ULN. Conjugated bilirubin (CBILI): >1.5 ULN. Unconjugated bilirubin: >1.5 ULN, >2 ULN. ALT >3 ULN and TBILI >2 ULN. CBILI >35% TBILI and TBILI >1.5 ULN. Albumin: <=25 g/L.

    34. OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function Tests [From end of Week 24 (Baseline of OLE Period) up to Week 300]

      Criteria for potentially clinically significant abnormalities: ALT: >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN. AST: >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN. Alkaline phosphatase: >1.5 ULN. TBILI: >1.5 ULN; >2 ULN. CBILI: >1.5 ULN. Unconjugated bilirubin: >1.5 ULN, >2 ULN. ALT >3 ULN and TBILI >2 ULN. CBILI >35% TBILI and TBILI >1.5 ULN. Albumin: <=25 g/L.

    35. DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters [From Week 0 to Week 24]

      Criteria for potentially clinically significant abnormalities: Glucose: <=3.9 millimole/liter (mmol/L) and <LLN; >=11.1 mmol/L (unfasted [unfas]) or >=7 mmol/L (fasted [fas]). Hemoglobin A1c (HbA1c): >8%. Total cholesterol: >=6.2 mmol/L; >=7.74 mmol/L. LDL cholesterol: >=4.1 mmol/L; >=4.9 mmol/L. Triglycerides: >=4.6 mmol/L; >=5.6 mmol/L.

    36. OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters [From end of Week 24 (Baseline of OLE Period) up to Week 300]

      Criteria for potentially clinically significant abnormalities: Glucose: <=3.9 mmol/L and <LLN; >=11.1 mmol/L (unfas) or >=7 mmol/L (fas). HbA1c: >8%. Total cholesterol: >=6.2 mmol/L; >=7.74 mmol/L. LDL cholesterol: >=4.1 mmol/L; >=4.9 mmol/L. Triglycerides: >=4.6 mmol/L; >=5.6 mmol/L.

    37. DB Period: Number of Participants With Different Post-baseline Categories of High-density Lipoprotein (HDL) [From Week 0 to Week 24]

      Number of participants with different post-baseline status of HDL: < 40 mg/dL, 40 - < 60 mg/dL, >= 60 mg/dL, is reported here.

    38. OLE Period: Number of Participants With Different Post-baseline Categories of High-density Lipoprotein [From end of Week 24 (Baseline of OLE Period) up to Week 300]

      Number of participants with different post-baseline status of HDL: < 40 mg/dL, 40 - < 60 mg/dL, >=60 mg/dL, is reported here.

    39. DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function [From Week 0 to Week 24]

      Criteria for potentially clinically significant abnormalities: Creatinine: >=150 micromol/L (adults); >=30% change from baseline, >=100% change from baseline. Creatinine clearance: <15 mL/min; >=15 to <30 mL/min; >=30 to <60 mL/min; >=60 to <90 mL/min. Blood urea nitrogen: >=17 mmol/L. Uric acid: <120 micromol/L; >408 micromol/L.

    40. OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function [From end of Week 24 (Baseline of OLE Period) up to Week 300]

      Criteria for potentially clinically significant abnormalities: Creatinine: >=150 micromol/L (adults); >=30% change from baseline, >=100% change from baseline. Creatinine clearance: <15 mL/min; >=15 to <30 mL/min; >=30 to <60 mL/min; >=60 to <90 mL/min. Blood urea nitrogen: >=17 mmol/L. Uric acid: <120 micromol/L; >408 micromol/L.

    41. DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Urinalysis [From Week 0 to Week 24]

      Criteria with potentially clinically significant urine abnormalities: pH: <= 4.6; pH: >= 8.0.

    42. OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Urinalysis [From end of Week 24 (Baseline of OLE Period) up to Week 300]

      Criteria with potentially clinically significant urine abnormalities: pH: <= 4.6; pH: >= 8.0.

    43. DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Electrolytes [From Week 0 to Week 24]

      Criteria for potentially clinically significant abnormalities: Sodium: <=129 mmol/L; >=160 mmol/L. Potassium: <3 mmol/L; >=5.5 mmol/L. Chloride: <80 mmol/L; >115 mmol/L.

    44. OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Electrolytes [From end of Week 24 (Baseline of OLE Period) up to Week 300]

      Criteria for potentially clinically significant abnormalities: Sodium: <=129 mmol/L; >=160 mmol/L. Potassium: <3 mmol/L; >=5.5 mmol/L. Chloride: <80 mmol/L; >115 mmol/L.

    45. DB Period: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities [From Week 0 to Week 24]

      Criteria for potentially clinically significant ECG abnormalities: Heart rate (HR): <50 beats per minute (bpm); <50 bpm and DFB >=20 bpm; <40 bpm; <40 bpm and DFB >=20 bpm; <30 bpm; <30 bpm and DFB >=20 bpm; >90 bpm; >=90 bpm and increase from baseline (IFB) >=20 bpm; >100 bpm; >=100 bpm and IFB >=20 bpm; >120 bpm; >=120 bpm and IFB >=20 bpm. PR Interval: >200 millisecond (ms); >200 ms and IFB >=25%; >220 ms; >220 ms and IFB >=25%; >240 ms; >240 ms and IFB >=25%. QRS Interval: >110 ms; >110 ms and IFB >=25%; >120 ms; >120 ms and IFB >=25%. QT Interval: >500 ms. QTc Bazett (QTc B): >450 ms; >480 ms; >500 ms; IFB >30 and <=60 ms; IFB >60 ms. QTc Fridericia (QTc F): >450 ms; >480 ms; >500 ms; IFB >30 and <=60 ms; IFB >60 ms.

    46. OLE Period: Number of Participants With Potentially Clinically Significant Electrocardiogram Abnormalities [From end of Week 24 (Baseline of OLE Period) up to Week 300]

      Criteria for potentially clinically significant ECG abnormalities: HR: <50 bpm; <50 bpm and DFB >=20 bpm; <40 bpm; <40 bpm and DFB >=20 bpm; <30 bpm; <30 bpm and DFB >=20 bpm; >90 bpm; >=90 bpm and IFB >=20 bpm; >100 bpm; >=100 bpm and IFB >=20 bpm; >120 bpm; >=120 bpm and IFB >=20 bpm. PR Interval: >200 ms; >200 ms and IFB >=25%; >220 ms; >220 ms and IFB >=25%; >240 ms; >240 ms and IFB >=25%. QRS Interval: >110 ms; >110 ms and IFB >=25%; >120 ms; >120 ms and IFB >=25%. QT Interval: >500 ms. QTc B: >450 ms; >480 ms; >500 ms; IFB >30 and <=60 ms; IFB >60 ms. QTc F: >450 ms; >480 ms; >500 ms; IFB >30 and <=60 ms; IFB >60 ms.

    47. DB Period: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities [From Week 0 to Week 24]

      Criteria for potentially clinically significant vital sign abnormalities: Systolic blood pressure (SBP) supine: <=95 mmHg and DFB>=20 mmHg; >=160 mmHg and IFB >=20 mmHg. Diastolic blood pressure (DBP) supine: <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB >=10 mmHg. SBP (Orthostatic): <=-20 mmHg. DBP (Orthostatic): <=-10 mmHg. HR supine: <=50 bpm and DFB >=20 bpm; >=120 bpm and IFB >=20 bpm. Weight: >=5% DFB; >=5% IFB.

    48. OLE Period: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities [From end of Week 24 (Baseline of OLE Period) up to Week 300]

      Criteria for potentially clinically significant vital sign abnormalities: SBP supine: <=95 mmHg and DFB >=20 mmHg; >=160 mmHg and IFB >=20 mmHg. DBP supine: <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB >=10 mmHg. SBP (Orthostatic): <=-20 mmHg. DBP (Orthostatic): <=-10 mmHg. HR supine: <=50 bpm and DFB >=20 bpm; >=120 bpm and IFB >=20 bpm. Weight: >=5% DFB; >=5% IFB.

    49. DB Period: Number of Participants With Treatment-emergent and Treatment-boosted Anti-drug Antibody (ADA) Response [From Week 0 to Week 24]

      Anti-drug antibody response was categorized as: Treatment emergent and Treatment-boosted. Treatment emergent ADAs was defined as a participant with no positive assay response at baseline but with a positive assay response during the TEAE period. Treatment boosted ADAs: defined as participants with a positive ADA assay response at baseline and with at least a 4-fold increase in titer compared to baseline during the TEAE period. TEAE period: time from first dose of study drug up to day before first dose of open-label treatment for participants who completed 24-week randomized/DB treatment.

    50. Number of Participants With Treatment-emergent and Treatment-boosted Anti-drug Antibody Response During Entire Treatment-emergent Adverse Event Period [From Week 0 up to last dose in OLE + 6 weeks of follow-up (i.e. up to Week 306)]

      Anti-drug antibody response was categorized as: Treatment emergent and Treatment-boosted. Treatment emergent ADAs was defined as a participant with no positive assay response at baseline but with a positive assay response during the entire TEAE period. Treatment boosted ADAs: defined as participants with a positive ADA assay response at baseline and with at least a 4-fold increase in titer compared to baseline during the entire TEAE period. Entire TEAE period: last OLE dose - first DB dose date + 6 weeks (follow-up), regardless of unplanned intermittent discontinuations.

    51. DB Period: Pharmacokinetics: Serum Trough (Pre-dose) Concentrations of Functional Sarilumab [Pre-dose at Week 0 (Baseline), 2, 4, 12, 16, 20, and 24]

      Data for this outcome measure was not planned to be collected and analyzed for "Adalimumab 40 mg/Sarilumab 200 mg" arm.

    52. OLE Period: Pharmacokinetics: Serum Trough (Pre-dose) Concentrations of Functional Sarilumab [Pre-dose at Week 24 (Baseline of OLE period), 36, 48, 60, 84, 108, 132, 156, 180, 204, 228, 252, 276, 300 and 306]

    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 greater than or equal to (>=)3 months duration.

    • American College of Rheumatology (ACR) Class I-III functional status.

    • Active RA was defined as:

    At least 6 of 66 swollen joints and 8 of 68 tender joints, high sensitivity C-reactive protein (hs-CRP) >=8 mg/L or ESR >=28 millimeter per hour (mm/H), and DAS28-ESR greater than (>) 5.1.

    • Participants as per Investigator judgment were either intolerant of, or considered inappropriate candidates for continued treatment with MTX, or after at least 12 weeks of continued treatment with MTX, or inadequate responders treated with an adequate MTX dose for at least 12 weeks.
    Exclusion criteria:

    • Age <18 years or the legal age of consent in the country of the study site, whichever was higher.

    • Current treatment with disease-modifying antirheumatic drug (DMARDs)/immunosuppressive agents including MTX, cyclosporine, mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine or hydroxychloroquine within 2 weeks prior to the baseline (Randomization Visit) or azathioprine, cyclophosphamide within 12 weeks prior to baseline (Randomization Visit) or leflunomide within 8 weeks prior to the Randomization Visit, or 4 weeks after cholestyramine washout.

    • Treatment with any prior biologic agent, including anti-interleukin 6 (IL-6), IL-6 receptor (IL-6R) antagonists, and prior treatment with a Janus kinase inhibitor.

    • Use of parenteral corticosteroids or intra-articular corticosteroids within 4 weeks prior to screening.

    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 840407 Covina California United States 91723
    2 Investigational Site Number 840400 Long Beach California United States 90808
    3 Investigational Site Number 840141 Whittier California United States 90606
    4 Investigational Site Number 840130 Lewes Delaware United States 19958
    5 Investigational Site Number 840229 Coral Gables Florida United States 33134
    6 Investigational Site Number 840128 Ormond Beach Florida United States 32174
    7 Investigational Site Number 840403 Saint Petersburg Florida United States 33708
    8 Investigational Site Number 840140 Tampa Florida United States 33614
    9 Investigational Site Number 840073 Cumberland Maryland United States 21502
    10 Investigational Site Number 840202 Hagerstown Maryland United States 21740
    11 Investigational Site Number 840232 Flint Michigan United States 48504
    12 Investigational Site Number 840112 Lincoln Nebraska United States 68516
    13 Investigational Site Number 840402 Charlotte North Carolina United States 28210
    14 Investigational Site Number 840406 Hickory North Carolina United States 28601
    15 Investigational Site Number 840404 Middleburg Heights Ohio United States 44130
    16 Investigational Site Number 840127 Oklahoma City Oklahoma United States 73103
    17 Investigational Site Number 840074 Mesquite Texas United States 75150
    18 Investigational Site Number 152005 Osorno Chile 5311092
    19 Investigational Site Number 152001 Puerto Varas Chile
    20 Investigational Site Number 152002 Santiago Chile 7501126
    21 Investigational Site Number 152050 Santiago Chile 8207257
    22 Investigational Site Number 152014 Talca Chile
    23 Investigational Site Number 152015 Temuco IX Region Chile 4790928
    24 Investigational Site Number 152007 Viña Del Mar Chile
    25 Investigational Site Number 203033 Praha 11 Czechia 14800
    26 Investigational Site Number 203001 Praha 2 Czechia 12850
    27 Investigational Site Number 203030 Praha 4 Czechia
    28 Investigational Site Number 203002 Uherske Hradiste Czechia 686 01
    29 Investigational Site Number 276058 Köln Germany 50937
    30 Investigational Site Number 276021 Osnabrück Germany 49074
    31 Investigational Site Number 348025 Budapest Hungary 1027
    32 Investigational Site Number 348020 Budapest Hungary 1033
    33 Investigational Site Number 348022 Budapest Hungary 1036
    34 Investigational Site Number 348024 Szombathely Hungary 9700
    35 Investigational Site Number 348023 Veszprém Hungary 8200
    36 Investigational Site Number 376032 Ashkelon Israel 78278
    37 Investigational Site Number 376031 Haifa Israel 34362
    38 Investigational Site Number 376030 Ramat Gan Israel 52621
    39 Investigational Site Number 376011 Tel Aviv Israel 64239
    40 Investigational Site Number 410005 Daegu Korea, Republic of 42601
    41 Investigational Site Number 410004 Daejeon Korea, Republic of 35233
    42 Investigational Site Number 410006 Seoul Korea, Republic of 01830
    43 Investigational Site Number 410001 Seoul Korea, Republic of 03080
    44 Investigational Site Number 604003 Lima Peru LIMA 27
    45 Investigational Site Number 604005 Lima Peru LIMA 41
    46 Investigational Site Number 604022 Lima Peru Lima29
    47 Investigational Site Number 616056 Bytom Poland 41-902
    48 Investigational Site Number 616015 Elblag Poland
    49 Investigational Site Number 616005 Lublin Poland 20-582
    50 Investigational Site Number 616030 Lublin Poland 20-954
    51 Investigational Site Number 616055 Nadarzyn Poland 05-830
    52 Investigational Site Number 616018 Poznan Poland 61-397
    53 Investigational Site Number 616016 Szczecin Poland 71-252
    54 Investigational Site Number 616004 Warszawa Poland 02-118
    55 Investigational Site Number 616031 Warszawa Poland 03-291
    56 Investigational Site Number 642006 Braila Romania 810019
    57 Investigational Site Number 642010 Bucharest Romania 011172
    58 Investigational Site Number 642001 Bucuresti Romania 010976
    59 Investigational Site Number 642002 Bucuresti Romania 020983
    60 Investigational Site Number 642005 Galati Romania 800578
    61 Investigational Site Number 643006 Kemerovo Russian Federation 650000
    62 Investigational Site Number 643020 Moscow Russian Federation 115404
    63 Investigational Site Number 643001 Moscow Russian Federation 115522
    64 Investigational Site Number 643031 Moscow Russian Federation 121374
    65 Investigational Site Number 643030 Moscow Russian Federation 125284
    66 Investigational Site Number 643008 Saint-Petersburg Russian Federation 192242
    67 Investigational Site Number 643011 Saratov Russian Federation 410053
    68 Investigational Site Number 710011 Cape Town South Africa 7405
    69 Investigational Site Number 710007 Cape Town South Africa 7500
    70 Investigational Site Number 710004 Kempton Park South Africa 1619
    71 Investigational Site Number 724003 Barakaldo Spain 48903
    72 Investigational Site Number 724011 Barcelona / Sabadell Spain 08208
    73 Investigational Site Number 724015 Barcelona Spain 08034
    74 Investigational Site Number 724001 Málaga Spain 29010
    75 Investigational Site Number 724012 Santiago De Compostela Spain 15705
    76 Investigational Site Number 724007 Sevilla Spain 41009
    77 Investigational Site Number 804029 Ivano-Frankivsk Ukraine 76018
    78 Investigational Site Number 804048 Kharkiv Ukraine 61058
    79 Investigational Site Number 804014 Kyiv Ukraine 01103
    80 Investigational Site Number 804047 Kyiv Ukraine 02125
    81 Investigational Site Number 804037 Lutsk Ukraine 43005
    82 Investigational Site Number 804046 Lviv Ukraine 79010
    83 Investigational Site Number 804049 Poltava Ukraine 36011
    84 Investigational Site Number 804011 Vinnitsya Ukraine 21018
    85 Investigational Site Number 804043 Vinnitsya Ukraine 21100
    86 Investigational Site Number 826001 Leytonstone United Kingdom E11 1NR

    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:
    NCT02332590
    Other Study ID Numbers:
    • EFC14092
    • 2014-002541-22
    • U1111-1160-6154
    First Posted:
    Jan 7, 2015
    Last Update Posted:
    Mar 28, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:
    Arthritis
    Arthritis, Rheumatoid
    Adalimumab

    Study Results

    Participant Flow

    Recruitment Details The study was conducted at 86 centers in 15 countries. A total of 540 participants were involved in the study from 28 January 2015 to 29-December-2020, of whom 369 participants were randomized and 171 were screen failures. Screen failures were mainly due to exclusion criteria met and inclusion criteria not met.
    Pre-assignment Detail Participants were randomized in 1:1 ratio (Adalimumab 40 milligrams (mg) every 2 weeks [q2w]: Sarilumab 200 mg q2w) and treated for 24 weeks in double-blind (DB) period of the study. Out of 321 participants who completed DB period, 320 participants entered the open label extension (OLE) period of the study.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg subcutaneous (SC) injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (less than [<] 20% improvement from baseline in tender joint count [TJC] and swollen joint count [SJC] for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Period Title: DB Period (up to 24 Weeks)
    STARTED 185 184
    Treated 184 184
    COMPLETED 156 165
    NOT COMPLETED 29 19
    Period Title: DB Period (up to 24 Weeks)
    STARTED 155 165
    COMPLETED 108 120
    NOT COMPLETED 47 45

    Baseline Characteristics

    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg Total
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Total of all reporting groups
    Overall Participants 185 184 369
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    53.6
    (11.9)
    50.9
    (12.6)
    52.2
    (12.3)
    Sex: Female, Male (Count of Participants)
    Female
    150
    81.1%
    157
    85.3%
    307
    83.2%
    Male
    35
    18.9%
    27
    14.7%
    62
    16.8%
    Race/Ethnicity, Customized (Count of Participants)
    Caucasian/White
    164
    88.6%
    171
    92.9%
    335
    90.8%
    Black
    3
    1.6%
    1
    0.5%
    4
    1.1%
    Asian/Oriental
    9
    4.9%
    2
    1.1%
    11
    3%
    Other
    9
    4.9%
    10
    5.4%
    19
    5.1%
    Disease Activity Score 28 based on erythrocyte sedimentation rate (DAS28-ESR) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    6.76
    (0.83)
    6.83
    (0.76)
    6.80
    (0.80)

    Outcome Measures

    1. Primary Outcome
    Title DB Period: Change From Baseline in Disease Activity Score for 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 24
    Description DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR and RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Least square (LS) mean and standard error (SE) at Week 24 were obtained using Mixed-effect model with repeated measures (MMRM) approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all participants. Overall Number of Participants Analyzed = participants with DAS28-ESR assessment at both baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 163 165
    Least Squares Mean (Standard Error) [units on a scale]
    -2.20
    (0.106)
    -3.28
    (0.105)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg/Sarilumab 200 mg, Sarilumab 200 mg/Sarilumab 200 mg
    Comments Analysis was performed using MMRM approach with treatment, region, visits, and treatment-by-visit interaction as fixed effects and baseline DAS28-ESR score as a continuous covariate. Hierarchical testing procedure was used to control overall alpha error rate at 0.05 level and handle multiple endpoint analyses. Testing was then performed sequentially in order endpoints are reported. Hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Threshold for significance at 0.05 level.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -1.077
    Confidence Interval (2-Sided) 95%
    -1.361 to -0.793
    Parameter Dispersion Type:
    Value:
    Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
    2. Secondary Outcome
    Title DB Period: Percentage of Participants Achieving Clinical Remission Score (DAS28-ESR <2.6) at Week 24
    Description DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Participants who discontinued treatment prior to Week 24 were analyzed as non-responders.
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT Population.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 185 184
    Number [percentage of participants]
    7.0
    3.8%
    26.6
    14.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg/Sarilumab 200 mg, Sarilumab 200 mg/Sarilumab 200 mg
    Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel method stratified by region.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Threshold for significance at 0.05 level.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.879
    Confidence Interval (2-Sided) 95%
    2.536 to 9.389
    Parameter Dispersion Type:
    Value:
    Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
    3. Secondary Outcome
    Title DB Period: Percentage of Participants Achieving ACR50 Criteria at Week 24
    Description ACR responses are assessed with a composite rating scale of the ACR that includes 7 variables: TJC (68 joints); SJC (66 joints); levels of an acute phase reactant (C-reactive protein [CRP] level); participant's assessment of pain (measured on 0 [no pain]-100 mm [worst pain] VAS); participant's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by Health Assessment Questionnaire - Disability Index [HAQ-DI], with scoring range of 0 [better physical function] - 3 [worst physical function]). 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. Participants were analyzed as non-responders from the time they discontinued treatment.
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT Population.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 185 184
    Number [percentage of participants]
    29.7
    16.1%
    45.7
    24.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg/Sarilumab 200 mg, Sarilumab 200 mg/Sarilumab 200 mg
    Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel method stratified by region.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0017
    Comments Threshold for significance at 0.05 level.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.976
    Confidence Interval (2-Sided) 95%
    1.289 to 3.028
    Parameter Dispersion Type:
    Value:
    Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
    4. Secondary Outcome
    Title DB Period: Percentage of Participants Achieving ACR70 Criteria at Week 24
    Description ACR responses are assessed with a composite rating scale of the ACR that includes 7 variables: TJC (68 joints); SJC (66 joints); levels of an acute phase reactant (CRP level); participant's assessment of pain (measured on 0 [no pain]-100 mm [worst pain] VAS); participant's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by HAQ-DI, with scoring range of 0 [better physical function] - 3 [worst physical function]). ACR70 was 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. Participants were analyzed as non-responders from the time they discontinued treatment.
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT Population.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 185 184
    Number [percentage of participants]
    11.9
    6.4%
    23.4
    12.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg/Sarilumab 200 mg, Sarilumab 200 mg/Sarilumab 200 mg
    Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel method stratified by region.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0036
    Comments Threshold for significance at 0.05 level.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.286
    Confidence Interval (2-Sided) 95%
    1.300 to 4.020
    Parameter Dispersion Type:
    Value:
    Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
    5. Secondary Outcome
    Title DB Period: Percentage of Participants Achieving ACR20 Criteria at Week 24
    Description ACR responses are assessed with a composite rating scale of the ACR that includes 7 variables: TJC (68 joints); SJC (66 joints); levels of an acute phase reactant (CRP level); participant's assessment of pain (measured on 0 [no pain]-100 mm [worst pain] VAS); participant's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by HAQ-DI, with scoring range of 0 [better physical function] - 3 [worst physical function]). ACR20 was 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. Participants were analyzed as non-responders from the time they discontinued treatment.
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 185 184
    Number [percentage of participants]
    58.4
    31.6%
    71.7
    39%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg/Sarilumab 200 mg, Sarilumab 200 mg/Sarilumab 200 mg
    Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel method stratified by region.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0074
    Comments Threshold for significance 0.05 level.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.800
    Confidence Interval (2-Sided) 95%
    1.168 to 2.773
    Parameter Dispersion Type:
    Value:
    Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
    6. Secondary Outcome
    Title DB Period: Change From Baseline in HAQ-DI at Week 24
    Description Physical function was assessed by HAQ-DI. It consisted of at least 2 or 3 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 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with HAQ-DI assessment at both baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 158 165
    Least Squares Mean (Standard Error) [units on a scale]
    -0.43
    (0.045)
    -0.61
    (0.045)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg/Sarilumab 200 mg, Sarilumab 200 mg/Sarilumab 200 mg
    Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using MMRM approach with treatment, region, visits, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI score as a continuous covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0037
    Comments Threshold for significance at 0.05 level.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.182
    Confidence Interval (2-Sided) 95%
    -0.305 to -0.059
    Parameter Dispersion Type:
    Value:
    Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
    7. Secondary Outcome
    Title DB Period: Change From Baseline in Short-Form-36 (SF-36) - Physical Component Summary (PCS) Score at Week 24
    Description SF-36 is a generic 36-item questionnaire consisting of 8 sub-scales, measures health-related quality of life (HRQL) in the last 4 weeks covering 2 summary measures: PCS and mental component summary (MCS). PCS with 4 sub-scales: physical function, role limitations due to physical problems, pain, and general health perception; and MCS with 4 sub-scales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a sub-scale 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 sub-scale give the sub-scale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Both PCS and MCS range from 0-100 with higher scores indicating better physical and mental health. LS mean and SE at Week 24 by MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with SF-36 PCS score assessment at both baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 157 159
    Least Squares Mean (Standard Error) [units on a scale]
    6.09
    (0.555)
    8.74
    (0.555)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg/Sarilumab 200 mg, Sarilumab 200 mg/Sarilumab 200 mg
    Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using MMRM approach with treatment, region, visits, and treatment-by-visit interaction as fixed effects and baseline SF-36 PCS score as a continuous covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0006
    Comments Threshold for significance at 0.05 level.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 2.650
    Confidence Interval (2-Sided) 95%
    1.147 to 4.153
    Parameter Dispersion Type:
    Value:
    Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
    8. Secondary Outcome
    Title DB Period: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24
    Description The FACIT-F 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 ranged from 0 to 52, where higher score corresponds to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 by MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with FACIT-F score assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 158 165
    Least Squares Mean (Standard Error) [units on a scale]
    8.41
    (0.709)
    10.18
    (0.701)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adalimumab 40 mg/Sarilumab 200 mg, Sarilumab 200 mg/Sarilumab 200 mg
    Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using MMRM approach with treatment, region, visits, and treatment-by-visit interaction as fixed effects and baseline FACIT-F score as a continuous covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0689
    Comments Threshold for significance at 0.05 level.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 1.768
    Confidence Interval (2-Sided) 95%
    -0.137 to 3.674
    Parameter Dispersion Type:
    Value:
    Estimation Comments Sarilumab 200 mg vs. Adalimumab 40 mg
    9. Secondary Outcome
    Title DB Period: Change From Baseline in SF-36 - Mental Health Component Summary Score at Week 24
    Description SF-36 is a generic 36-item questionnaire consisting of 8 sub-scales, measures HRQL in the last 4 weeks covering 2 summary measures: PCS and MCS. PCS with 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception; and MCS with 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 sub-scale give the sub-scale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Both PCS and MCS range from 0-100 with higher scores indicating better physical and mental health. LS mean and SE at Week 24 by MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with SF-36 - mental health component summary score assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 157 159
    Least Squares Mean (Standard Error) [units on a scale]
    6.83
    (0.774)
    7.86
    (0.773)
    10. Secondary Outcome
    Title DB Period: Change From Baseline in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP Score) at Week 24
    Description DAS28-CRP is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28-CRP score provides a number indicating the current disease activity of the RA. DAS28-CRP total score ranges from 2-10. A DAS28-CRP score above 5.1 means high disease activity, whereas a DAS28-CRP score below 3.2 indicates low disease activity and a DAS28-CRP score below 2.6 means disease remission. LS mean and SE at Week 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with DAS28-CRP score assessment at both baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 156 163
    Least Squares Mean (Standard Error) [units on a scale]
    -1.97
    (0.094)
    -2.86
    (0.093)
    11. Secondary Outcome
    Title DB Period: Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP <2.6) at Week 24
    Description DAS28-CRP is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment 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-CRP score provides a number indicating the current disease activity of the RA. DAS28-CRP total score ranges from 2-10. A DAS28-CRP score above 5.1 means high disease activity, whereas a DAS28-CRP score below 3.2 indicates low disease activity and a DAS28-CRP score below 2.6 means disease remission. Participants were analyzed as non-responders from the time they discontinued treatment.
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 185 184
    Number [percentage of participants]
    13.5
    7.3%
    34.2
    18.6%
    12. Secondary Outcome
    Title DB Period: Percentage of Participants Achieving Low Disease Activity (DAS28-ESR < 3.2) at Week 24
    Description DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Participants were analyzed as non-responders from the time they discontinued treatment.
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT Population.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 185 184
    Number [percentage of participants]
    14.1
    7.6%
    42.9
    23.3%
    13. Secondary Outcome
    Title DB Period: Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Remission (CDAI ≤2.8) 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: SJC (28 joints), TJC (28 joints), participant's global assessment of disease activity (in cm), and physician's global assessment of disease activity (in cm). Total score ranges from 0 to 76 with a lower score indicating less disease activity. Participants were analyzed as non-responders from the time they discontinued treatment.
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 185 184
    Number [percentage of participants]
    2.7
    1.5%
    7.1
    3.9%
    14. Secondary Outcome
    Title DB Period: Change From Baseline in 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: SJC (28 joints), TJC (28 joints), participant's global assessment of disease activity (in cm), and physician's global assessment of disease activity (VAS in cm). Total score ranges from 0 to 76 with a lower score indicating less disease activity. A negative change in CDAI score indicates an improvement in disease activity and a positive change in score indicates a worsening of disease activity. LS means and SE at Week 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with CDAI assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 158 165
    Least Squares Mean (Standard Error) [units on a scale]
    -25.20
    (0.842)
    -28.94
    (0.834)
    15. Secondary Outcome
    Title DB Period: Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) Scores at Week 24
    Description EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. EQ-5D was specifically included to address concerns regarding the health economic impact of RA. EQ-5D-3L comprises of 5 questions on mobility, self-care, pain/discomfort, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems). The 5-dimensional 3-level systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-3L-VAS records the participant's self-rated health on a vertical VAS that allows the participants to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with EQ-5D-3L score assessment both at baseline and Week 24. Here, Number Analyzed = participants with available data for specified category for each arm, respectively.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 156 164
    EQ-5D Single index utility score
    0.26
    (0.019)
    0.32
    (0.019)
    EQ-5D VAS
    19.94
    (1.720)
    24.22
    (1.686)
    16. Secondary Outcome
    Title DB Period: Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) 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. Each NRS is assessed as a number between 0 and 10 that corresponds to the 7 domains. The values for each of these domains are weighed by participant assessment of relative importance and combined in a single score with a total score range of 0 (not affected, very good) to 10 (most affected). LS mean and SE at Week 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with RAID assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 157 161
    Least Squares Mean (Standard Error) [units on a scale]
    -2.30
    (0.168)
    -3.08
    (0.168)
    17. Secondary Outcome
    Title DB Period: Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to Arthritis
    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 is interviewer-administered and 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 using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 60 70
    Least Squares Mean (Standard Error) [days]
    0.05
    (0.611)
    -0.28
    (0.547)
    18. Secondary Outcome
    Title DB Period: Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to Arthritis
    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 is interviewer-administered and 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 participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 60 70
    Least Squares Mean (Standard Error) [days]
    -3.50
    (0.525)
    -3.74
    (0.456)
    19. Secondary Outcome
    Title DB Period: Change From Baseline in WPS-RA at Week 24: Arthritis 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 is interviewer-administered and 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 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT Population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 60 69
    Least Squares Mean (Standard Error) [units on a scale]
    -2.510
    (0.3470)
    -2.919
    (0.3073)
    20. Secondary Outcome
    Title DB Period: Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to Arthritis
    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 is interviewer-administered and 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 participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 163 169
    Least Squares Mean (Standard Error) [days]
    -4.22
    (0.405)
    -5.49
    (0.400)
    21. Secondary Outcome
    Title DB Period: Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by >= 50% Due to Arthritis
    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 is interviewer-administered and 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 participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 163 169
    Least Squares Mean (Standard Error) [days]
    -4.87
    (0.451)
    -6.70
    (0.445)
    22. Secondary Outcome
    Title DB Period: Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to Arthritis
    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 is interviewer-administered and 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 participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 163 169
    Least Squares Mean (Standard Error) [days]
    -3.33
    (0.376)
    -4.14
    (0.371)
    23. Secondary Outcome
    Title DB Period: Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to Arthritis
    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 is interviewer-administered and 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 using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed =participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 163 168
    Least Squares Mean (Standard Error) [days]
    -2.57
    (0.401)
    -3.43
    (0.398)
    24. Secondary Outcome
    Title DB Period: 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 is interviewer-administered and 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 using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 163 168
    Least Squares Mean (Standard Error) [units on a scale]
    -2.605
    (0.2110)
    -3.276
    (0.2099)
    25. Secondary Outcome
    Title DB Period: 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 using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with morning stiffness VAS assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 156 165
    Least Squares Mean (Standard Error) [mm]
    -29.29
    (1.970)
    -35.08
    (1.947)
    26. Secondary Outcome
    Title DB Period: Change From Baseline in Individual ACR Component - TJC and SJC at Week 24
    Description ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). 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 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with TJC and SJC assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 158 166
    TJC
    -16.45
    (0.781)
    -18.23
    (0.772)
    SJC
    -12.20
    (0.450)
    -13.44
    (0.444)
    27. Secondary Outcome
    Title DB Period: Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 24
    Description ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). Physician global VAS & participant global VAS was done on 100 mm horizontal anchored VAS, ranging from 0 "no arthritis activity" to 100 "maximal arthritis activity" and Pain VAS on 100 mm VAS, ranging from 0 "no pain" to 100 "worst pain". LS mean and SE at Week 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with individual ACR components assessment both at baseline and Week 24. Here, Number Analyzed = participants with available data for specified category for each arm, respectively.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 158 166
    Physician global VAS
    -37.80
    (1.431)
    -45.33
    (1.414)
    Participant global VAS
    -24.82
    (1.752)
    -33.30
    (1.731)
    Pain VAS
    -27.41
    (1.802)
    -36.19
    (1.776)
    28. Secondary Outcome
    Title DB Period: Change From Baseline in Individual ACR Component - CRP Level at Week 24
    Description ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). An elevated CRP level is considered a non-specific "marker" for RA. A decrease indicates improvement. LS mean and SE at Week 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with CRP assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 156 164
    Least Squares Mean (Standard Error) [mg/L]
    -2.91
    (1.461)
    -17.01
    (1.431)
    29. Secondary Outcome
    Title DB Period: Change From Baseline in Individual ACR Component- ESR Level at Week 24
    Description ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). The ESR is a blood test that can reveal inflammatory activity. Inflammation can cause the cells to clump together. The farther the red blood cells have descended, the greater the inflammatory response. LS mean and SE at Week 24 were obtained using MMRM approach.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    ITT population. Number of participants analyzed = participants with ESR assessment both at baseline and Week 24.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 163 166
    Least Squares Mean (Standard Error) [mm/hr]
    -12.74
    (1.398)
    -32.11
    (1.388)
    30. Secondary Outcome
    Title DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
    Description Adverse event (AE) was defined as any untoward medical occurrence in participant who received investigational medicinal product (IMP) and did not necessarily had to have causal relationship with treatment. All reported AEs are TEAEs developed/worsened during 'on treatment period' (time from first dose of study drug up to day before first dose of open-label treatment for participants who completed 24-week randomized//DB treatment). SAEs were AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or a medically important event.
    Time Frame From Week 0 to Week 24

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (DB period) which consisted of all randomized participants who received at least one dose of study medication analyzed according to the treatment they have actually received.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 184 184
    TEAEs
    117
    63.2%
    118
    64.1%
    SAEs
    13
    7%
    9
    4.9%
    31. Secondary Outcome
    Title OLE Period: Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events
    Description AE was defined as any untoward medical occurrence in participant who received IMP and did not necessarily had to have causal relationship with treatment. All reported AEs are TEAEs developed/worsened during 'on treatment period' (from end of week 24 [Baseline of OLE Period] up to last dose in OLE period + 6 weeks [follow-up], regardless of unplanned intermittent discontinuations). SAEs were AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or a medically important event.
    Time Frame From end of Week 24 (Baseline of OLE Period) up to last dose in OLE + 6 weeks of follow up (i.e. up to Week 306)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (OLE period) which included all randomized participants who continued OLE period and received at least one dose of the study medication during OLE period, analyzed according to the treatment they have actually received.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 155 165
    TEAE
    135
    73%
    143
    77.7%
    SAE
    31
    16.8%
    25
    13.6%
    32. Secondary Outcome
    Title DB Period: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) - Hematological Parameters
    Description Criteria for potentially clinically significant laboratory abnormalities included: Hemoglobin (Hb): less than or equal to (<=) 115 grams per liter (g/L) (Male), <= 95 g/L (Female); greater than or equal to (>=) 185 g/L (18.5 g/dL) (Male), >= 165 g/L (16.5 g/dL) (Female); Decrease From Baseline (DFB) = 20 g/L (2 g/dL). Hematocrit: <= 0.37 volume/volume (v/v) (Male); <= 0.32 v/v (F); >= 0.55 v/v (Male); >= 0.5 v/v (Female). Red Blood Cells (RBCs): >=6 Tera/ liter (L). Platelets: < 50 Giga/L, 50 - 100 Giga/L, >= 700 Giga/L. White blood cells (WBC): < 3.0 Giga/L (Non-Black); < 2.0 Giga/L (Black), >= 16.0 Giga/L. Neutrophils: < 1.0 Giga/L, < 1.5 Giga/L (Non-Black); < 1.0 Giga/L (Black). Lymphocytes: < 0.5 Giga/L, >= 0.5 Giga/L - lower limit of normal (LLN), > 4.0 Giga/L. Monocytes: > 0.7 Giga/L. Basophils: > 0.1 Giga/L. Eosinophils: > 0.5 Giga/L or > upper limit of normal (ULN) (if ULN >= 0.5 Giga/L).
    Time Frame From Week 0 to Week 24

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (DB Period). Here, 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 184 184
    Hb:<=115 g/L, <=95 g/L
    12
    6.5%
    7
    3.8%
    Hb: >=185 g/L, >=165 g/L
    0
    0%
    1
    0.5%
    Hb: DFB >=20 g/L
    5
    2.7%
    5
    2.7%
    Hematocrit: <= 0.37 v/v; <=0.32 v/v
    21
    11.4%
    10
    5.4%
    Hematocrit: >=0.55 v/v; >=0.5 v/v
    1
    0.5%
    3
    1.6%
    RBCs: >=6 Tera/L
    0
    0%
    1
    0.5%
    Platelets: < 50 Giga/L
    0
    0%
    1
    0.5%
    Platelets: 50 - 100 Giga/L
    0
    0%
    0
    0%
    Platelets: >= 700 Giga/L
    1
    0.5%
    0
    0%
    WBC: < 3.0 Giga/L (Non-Black); < 2.0 Giga/L (Black)
    1
    0.5%
    32
    17.4%
    WBC: >= 16.0 Giga/L
    8
    4.3%
    5
    2.7%
    Neutrophils: < 1.0 Giga/L
    2
    1.1%
    19
    10.3%
    Neutrophils: < 1.5 Giga/L (Non-Black); < 1.0 Giga/L (Black)
    7
    3.8%
    50
    27.2%
    Lymphocytes: < 0.5 Giga/L
    2
    1.1%
    2
    1.1%
    Lymphocytes: >= 0.5 Giga/L - LLN
    8
    4.3%
    21
    11.4%
    Lymphocytes: > 4.0 Giga/L
    17
    9.2%
    6
    3.3%
    Monocytes: > 0.7 Giga/L
    46
    24.9%
    38
    20.7%
    Basophils: > 0.1 Giga/L
    53
    28.6%
    37
    20.1%
    Eosinophils: > 0.5 Giga/L or > ULN (if ULN >= 0.5 Giga/L)
    4
    2.2%
    9
    4.9%
    33. Secondary Outcome
    Title OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Hematological Parameters
    Description Criteria for potentially clinically significant laboratory abnormalities included: Hb: <=115 g/L (Male), <= 95 g/L (Female); >=185 g/L (18.5 g/dL) (Male), >= 165 g/L (16.5 g/dL) (Female); DFB >= 20 g/L (2 g/dL). Hematocrit: <= 0.37 v/v (Male); <= 0.32 v/v (Female); >= 0.55 v/v (Male); >= 0.5 v/v (Female). RBCs: >=6 Tera/ L. Platelets: < 50 Giga/L, >=50 - 100 Giga/L, >= 700 Giga/L. WBC: < 3.0 Giga/L (Non-Black); < 2.0 Giga/L (Black), >= 16.0 Giga/L. Neutrophils: < 1.0 Giga/L, < 1.5 Giga/L (Non-Black); < 1.0 Giga/L (Black). Lymphocytes: < 0.5 Giga/L, >= 0.5 Giga/L - LLN, > 4.0 Giga/L. Monocytes: > 0.7 Giga/L. Basophils: > 0.1 Giga/L. Eosinophils: > 0.5 Giga/L or > ULN (if ULN >= 0.5 Giga/L).
    Time Frame From end of Week 24 (Baseline of OLE Period) up to Week 300

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (OLE Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 154 165
    Hb:<=115 g/L, <=95 g/L
    8
    4.3%
    5
    2.7%
    Hb: >=185 g/L, >=165 g/L
    3
    1.6%
    3
    1.6%
    Hb: DFB >=20 g/L
    13
    7%
    13
    7.1%
    Hematocrit: <= 0.37 v/v; <=0.32 v/v
    12
    6.5%
    14
    7.6%
    Hematocrit: >=0.55 v/v; >=0.5 v/v
    5
    2.7%
    8
    4.3%
    RBCs: >=6 Tera/L
    3
    1.6%
    2
    1.1%
    Platelets: < 50 Giga/L
    0
    0%
    0
    0%
    Platelets: >=50 - 100 Giga/L
    4
    2.2%
    4
    2.2%
    Platelets: >= 700 Giga/L
    2
    1.1%
    1
    0.5%
    WBC: < 3.0 Giga/L (Non-Black); < 2.0 Giga/L (Black)
    34
    18.4%
    46
    25%
    WBC: >= 16.0 Giga/L
    11
    5.9%
    7
    3.8%
    Neutrophils: < 1.0 Giga/L
    24
    13%
    25
    13.6%
    Neutrophils: < 1.5 Giga/L (Non-Black); < 1.0 Giga/L (Black)
    62
    33.5%
    69
    37.5%
    Lymphocytes: < 0.5 Giga/L
    2
    1.1%
    3
    1.6%
    Lymphocytes: >= 0.5 Giga/L - LLN
    28
    15.1%
    42
    22.8%
    Lymphocytes: > 4.0 Giga/L
    15
    8.1%
    7
    3.8%
    Monocytes: > 0.7 Giga/L
    48
    25.9%
    43
    23.4%
    Basophils: > 0.1 Giga/L
    78
    42.2%
    70
    38%
    Eosinophils: > 0.5 Giga/L or > ULN (if ULN >= 0.5 Giga/L)
    11
    5.9%
    14
    7.6%
    34. Secondary Outcome
    Title DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function Tests
    Description Criteria for potentially clinically significant abnormalities: Alanine Aminotransferase (ALT): >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN. Aspartate aminotransferase (AST): >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN. Alkaline phosphatase: >1.5 ULN. Total bilirubin (TBILI): >1.5 ULN; >2 ULN. Conjugated bilirubin (CBILI): >1.5 ULN. Unconjugated bilirubin: >1.5 ULN, >2 ULN. ALT >3 ULN and TBILI >2 ULN. CBILI >35% TBILI and TBILI >1.5 ULN. Albumin: <=25 g/L.
    Time Frame From Week 0 to Week 24

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (DB Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 183 184
    ALT >1 ULN and <=1.5 ULN
    22
    11.9%
    36
    19.6%
    ALT >1.5 ULN and <=3 ULN
    17
    9.2%
    26
    14.1%
    ALT >3 ULN and <=5 ULN
    3
    1.6%
    5
    2.7%
    ALT >5 ULN and <=10 ULN
    1
    0.5%
    1
    0.5%
    ALT >10 ULN and <=20 ULN
    1
    0.5%
    0
    0%
    ALT >20 ULN
    0
    0%
    0
    0%
    AST >1 ULN and <=1.5 ULN
    16
    8.6%
    22
    12%
    AST >1.5 ULN and <=3 ULN
    7
    3.8%
    13
    7.1%
    AST >3 ULN and <=5 ULN
    3
    1.6%
    2
    1.1%
    AST >5 ULN and <=10 ULN
    0
    0%
    0
    0%
    AST >10 ULN and <=20 ULN
    1
    0.5%
    0
    0%
    AST >20 ULN
    0
    0%
    0
    0%
    Alkaline Phosphatase >1.5 ULN
    6
    3.2%
    2
    1.1%
    TBILI >1.5 ULN
    1
    0.5%
    7
    3.8%
    TBILI >2 ULN
    0
    0%
    2
    1.1%
    CBILI >1.5 ULN
    0
    0%
    0
    0%
    Unconjugated Bilirubin >1.5 ULN
    5
    2.7%
    13
    7.1%
    Unconjugated Bilirubin >2 ULN
    1
    0.5%
    7
    3.8%
    ALT> 3 ULN and TBILI >2 ULN
    0
    0%
    0
    0%
    CBILI >35% TBILI and TBILI >1.5 ULN
    0
    0%
    0
    0%
    Albumin <=25 g/L
    0
    0%
    0
    0%
    35. Secondary Outcome
    Title OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function Tests
    Description Criteria for potentially clinically significant abnormalities: ALT: >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN. AST: >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN. Alkaline phosphatase: >1.5 ULN. TBILI: >1.5 ULN; >2 ULN. CBILI: >1.5 ULN. Unconjugated bilirubin: >1.5 ULN, >2 ULN. ALT >3 ULN and TBILI >2 ULN. CBILI >35% TBILI and TBILI >1.5 ULN. Albumin: <=25 g/L.
    Time Frame From end of Week 24 (Baseline of OLE Period) up to Week 300

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (OLE Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 154 165
    ALT >1 ULN and <=1.5 ULN
    41
    22.2%
    36
    19.6%
    ALT >1.5 ULN and <=3 ULN
    31
    16.8%
    34
    18.5%
    ALT >3 ULN and <=5 ULN
    11
    5.9%
    10
    5.4%
    ALT >5 ULN and <=10 ULN
    1
    0.5%
    6
    3.3%
    ALT >10 ULN and <=20 ULN
    0
    0%
    2
    1.1%
    ALT >20 ULN
    1
    0.5%
    1
    0.5%
    AST >1 ULN and <=1.5 ULN
    25
    13.5%
    39
    21.2%
    AST >1.5 ULN and <=3 ULN
    23
    12.4%
    17
    9.2%
    AST >3 ULN and <=5 ULN
    2
    1.1%
    7
    3.8%
    AST >5 ULN and <=10 ULN
    2
    1.1%
    2
    1.1%
    AST >10 ULN and <=20 ULN
    0
    0%
    0
    0%
    AST >20 ULN
    0
    0%
    1
    0.5%
    Alkaline Phosphatase >1.5 ULN
    0
    0%
    1
    0.5%
    TBILI >1.5 ULN
    11
    5.9%
    6
    3.3%
    TBILI >2 ULN
    3
    1.6%
    1
    0.5%
    CBILI >1.5 ULN
    0
    0%
    0
    0%
    Unconjugated Bilirubin >1.5 ULN
    21
    11.4%
    22
    12%
    Unconjugated Bilirubin >2 ULN
    11
    5.9%
    10
    5.4%
    ALT> 3 ULN and TBILI >2 ULN
    1
    0.5%
    0
    0%
    CBILI >35% TBILI and TBILI >1.5 ULN
    0
    0%
    0
    0%
    Albumin <=25 g/L
    0
    0%
    0
    0%
    36. Secondary Outcome
    Title DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters
    Description Criteria for potentially clinically significant abnormalities: Glucose: <=3.9 millimole/liter (mmol/L) and <LLN; >=11.1 mmol/L (unfasted [unfas]) or >=7 mmol/L (fasted [fas]). Hemoglobin A1c (HbA1c): >8%. Total cholesterol: >=6.2 mmol/L; >=7.74 mmol/L. LDL cholesterol: >=4.1 mmol/L; >=4.9 mmol/L. Triglycerides: >=4.6 mmol/L; >=5.6 mmol/L.
    Time Frame From Week 0 to Week 24

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (DB Period). Here, 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 184 184
    Glucose <=3.9 mmol/L and <LLN
    10
    5.4%
    8
    4.3%
    Glucose >=11.1 mmol/L (unfas) or >=7 mmol/L (fas)
    17
    9.2%
    12
    6.5%
    HbA1c >8%
    3
    1.6%
    3
    1.6%
    Total Cholesterol >=6.2 mmol/L
    52
    28.1%
    88
    47.8%
    Total Cholesterol >=7.74 mmol/L
    15
    8.1%
    14
    7.6%
    LDL Cholesterol >=4.1 mmol/L
    35
    18.9%
    59
    32.1%
    LDL Cholesterol >=4.9 mmol/L
    18
    9.7%
    20
    10.9%
    Triglycerides >=4.6 mmol/L
    4
    2.2%
    8
    4.3%
    Triglycerides >=5.6 mmol/L
    3
    1.6%
    6
    3.3%
    37. Secondary Outcome
    Title OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters
    Description Criteria for potentially clinically significant abnormalities: Glucose: <=3.9 mmol/L and <LLN; >=11.1 mmol/L (unfas) or >=7 mmol/L (fas). HbA1c: >8%. Total cholesterol: >=6.2 mmol/L; >=7.74 mmol/L. LDL cholesterol: >=4.1 mmol/L; >=4.9 mmol/L. Triglycerides: >=4.6 mmol/L; >=5.6 mmol/L.
    Time Frame From end of Week 24 (Baseline of OLE Period) up to Week 300

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (OLE Period). Here, 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 155 165
    Glucose <=3.9 mmol/L and <LLN
    5
    2.7%
    6
    3.3%
    Glucose >=11.1 mmol/L (unfas) or >=7 mmol/L (fas)
    20
    10.8%
    14
    7.6%
    HbA1c >8%
    2
    1.1%
    2
    1.1%
    Total Cholesterol >=6.2 mmol/L
    77
    41.6%
    69
    37.5%
    Total Cholesterol >=7.74 mmol/L
    22
    11.9%
    19
    10.3%
    LDL Cholesterol >=4.1 mmol/L
    57
    30.8%
    48
    26.1%
    LDL Cholesterol >=4.9 mmol/L
    25
    13.5%
    16
    8.7%
    Triglycerides >=4.6 mmol/L
    13
    7%
    6
    3.3%
    Triglycerides >=5.6 mmol/L
    4
    2.2%
    6
    3.3%
    38. Secondary Outcome
    Title DB Period: Number of Participants With Different Post-baseline Categories of High-density Lipoprotein (HDL)
    Description Number of participants with different post-baseline status of HDL: < 40 mg/dL, 40 - < 60 mg/dL, >= 60 mg/dL, is reported here.
    Time Frame From Week 0 to Week 24

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (DB Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 181 184
    HDL: < 40 mg/dL
    5
    2.7%
    7
    3.8%
    HDL: 40 - < 60 mg/dL
    57
    30.8%
    45
    24.5%
    HDL: >=60 mg/dL
    119
    64.3%
    132
    71.7%
    39. Secondary Outcome
    Title OLE Period: Number of Participants With Different Post-baseline Categories of High-density Lipoprotein
    Description Number of participants with different post-baseline status of HDL: < 40 mg/dL, 40 - < 60 mg/dL, >=60 mg/dL, is reported here.
    Time Frame From end of Week 24 (Baseline of OLE Period) up to Week 300

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (OLE Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 153 165
    HDL: < 40 mg/dL
    7
    3.8%
    5
    2.7%
    HDL: 40 - < 60 mg/dL
    52
    28.1%
    49
    26.6%
    HDL: >=60 mg/dL
    94
    50.8%
    111
    60.3%
    40. Secondary Outcome
    Title DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function
    Description Criteria for potentially clinically significant abnormalities: Creatinine: >=150 micromol/L (adults); >=30% change from baseline, >=100% change from baseline. Creatinine clearance: <15 mL/min; >=15 to <30 mL/min; >=30 to <60 mL/min; >=60 to <90 mL/min. Blood urea nitrogen: >=17 mmol/L. Uric acid: <120 micromol/L; >408 micromol/L.
    Time Frame From Week 0 to Week 24

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (DB Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 183 184
    Creatinine >=150 micromol/L (Adults)
    0
    0%
    3
    1.6%
    Creatinine >=30% change from baseline
    19
    10.3%
    23
    12.5%
    Creatinine >=100% change from baseline
    0
    0%
    1
    0.5%
    Creatinine Clearance <15 mL/min
    0
    0%
    0
    0%
    Creatinine clearance >=15 to <30 mL/min
    0
    0%
    1
    0.5%
    Creatinine clearance >=30 to <60 mL/min
    21
    11.4%
    22
    12%
    Creatinine clearance >=60 to <90 mL/min
    74
    40%
    65
    35.3%
    Blood Urea Nitrogen >=17 mmol/L
    0
    0%
    2
    1.1%
    Uric acid <120 micromol/L
    4
    2.2%
    3
    1.6%
    Uric acid >408 micromol/L
    25
    13.5%
    35
    19%
    41. Secondary Outcome
    Title OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function
    Description Criteria for potentially clinically significant abnormalities: Creatinine: >=150 micromol/L (adults); >=30% change from baseline, >=100% change from baseline. Creatinine clearance: <15 mL/min; >=15 to <30 mL/min; >=30 to <60 mL/min; >=60 to <90 mL/min. Blood urea nitrogen: >=17 mmol/L. Uric acid: <120 micromol/L; >408 micromol/L.
    Time Frame From end of Week 24 (Baseline of OLE Period) up to Week 300

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (OLE Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 154 165
    Creatinine >=150 micromol/L (Adults)
    2
    1.1%
    2
    1.1%
    Creatinine >=30% change from baseline
    63
    34.1%
    62
    33.7%
    Creatinine >=100% change from baseline
    5
    2.7%
    1
    0.5%
    Creatinine Clearance <15 mL/min
    0
    0%
    0
    0%
    Creatinine clearance >=15 to <30 mL/min
    1
    0.5%
    0
    0%
    Creatinine clearance >=30 to <60 mL/min
    34
    18.4%
    24
    13%
    Creatinine clearance >=60 to <90 mL/min
    66
    35.7%
    81
    44%
    Blood Urea Nitrogen >=17 mmol/L
    1
    0.5%
    3
    1.6%
    Uric acid <120 micromol/L
    2
    1.1%
    3
    1.6%
    Uric acid >408 micromol/L
    44
    23.8%
    43
    23.4%
    42. Secondary Outcome
    Title DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Urinalysis
    Description Criteria with potentially clinically significant urine abnormalities: pH: <= 4.6; pH: >= 8.0.
    Time Frame From Week 0 to Week 24

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (DB period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 87 85
    pH <= 4.6
    0
    0%
    0
    0%
    pH >= 8.0
    0
    0%
    0
    0%
    43. Secondary Outcome
    Title OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Urinalysis
    Description Criteria with potentially clinically significant urine abnormalities: pH: <= 4.6; pH: >= 8.0.
    Time Frame From end of Week 24 (Baseline of OLE Period) up to Week 300

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (OLE Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 105 109
    pH <= 4.6
    0
    0%
    0
    0%
    pH >= 8.0
    0
    0%
    1
    0.5%
    44. Secondary Outcome
    Title DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Electrolytes
    Description Criteria for potentially clinically significant abnormalities: Sodium: <=129 mmol/L; >=160 mmol/L. Potassium: <3 mmol/L; >=5.5 mmol/L. Chloride: <80 mmol/L; >115 mmol/L.
    Time Frame From Week 0 to Week 24

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (DB Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 183 184
    Sodium <=129 mmol/L
    1
    0.5%
    1
    0.5%
    Sodium >=160 mmol/L
    0
    0%
    0
    0%
    Potassium <3 mmol/L
    3
    1.6%
    0
    0%
    Potassium >=5.5 mmol/L
    0
    0%
    0
    0%
    Chloride <80 mmol/L
    0
    0%
    0
    0%
    Chloride >115 mmol/L
    0
    0%
    1
    0.5%
    45. Secondary Outcome
    Title OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Electrolytes
    Description Criteria for potentially clinically significant abnormalities: Sodium: <=129 mmol/L; >=160 mmol/L. Potassium: <3 mmol/L; >=5.5 mmol/L. Chloride: <80 mmol/L; >115 mmol/L.
    Time Frame From end of Week 24 (Baseline of OLE Period) up to Week 300

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (OLE Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 154 165
    Sodium <=129 mmol/L
    3
    1.6%
    0
    0%
    Sodium >=160 mmol/L
    0
    0%
    0
    0%
    Potassium <3 mmol/L
    2
    1.1%
    2
    1.1%
    Potassium >=5.5 mmol/L
    6
    3.2%
    7
    3.8%
    Chloride <80 mmol/L
    1
    0.5%
    0
    0%
    Chloride >115 mmol/L
    0
    0%
    0
    0%
    46. Secondary Outcome
    Title DB Period: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities
    Description Criteria for potentially clinically significant ECG abnormalities: Heart rate (HR): <50 beats per minute (bpm); <50 bpm and DFB >=20 bpm; <40 bpm; <40 bpm and DFB >=20 bpm; <30 bpm; <30 bpm and DFB >=20 bpm; >90 bpm; >=90 bpm and increase from baseline (IFB) >=20 bpm; >100 bpm; >=100 bpm and IFB >=20 bpm; >120 bpm; >=120 bpm and IFB >=20 bpm. PR Interval: >200 millisecond (ms); >200 ms and IFB >=25%; >220 ms; >220 ms and IFB >=25%; >240 ms; >240 ms and IFB >=25%. QRS Interval: >110 ms; >110 ms and IFB >=25%; >120 ms; >120 ms and IFB >=25%. QT Interval: >500 ms. QTc Bazett (QTc B): >450 ms; >480 ms; >500 ms; IFB >30 and <=60 ms; IFB >60 ms. QTc Fridericia (QTc F): >450 ms; >480 ms; >500 ms; IFB >30 and <=60 ms; IFB >60 ms.
    Time Frame From Week 0 to Week 24

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (DB Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 163 162
    HR <50 bpm
    4
    2.2%
    5
    2.7%
    HR <50 bpm and DFB >=20 bpm
    0
    0%
    0
    0%
    HR <40 bpm
    0
    0%
    0
    0%
    HR <40 bpm and DFB >=20 bpm
    0
    0%
    0
    0%
    HR <30 bpm
    0
    0%
    0
    0%
    HR <30 bpm and DFB >=20 bpm
    0
    0%
    0
    0%
    HR >90 bpm
    11
    5.9%
    2
    1.1%
    HR >=90 bpm and IFB >=20 bpm
    5
    2.7%
    1
    0.5%
    HR >100 bpm
    2
    1.1%
    1
    0.5%
    HR >=100 bpm and IFB >=20 bpm
    2
    1.1%
    0
    0%
    HR >120 bpm
    0
    0%
    0
    0%
    HR >=120 bpm and IFB >=20 bpm
    0
    0%
    0
    0%
    PR Interval >200 ms
    11
    5.9%
    5
    2.7%
    PR Interval >200 ms and IFB >=25%
    1
    0.5%
    0
    0%
    PR Interval >220 ms
    4
    2.2%
    1
    0.5%
    PR Interval >220 ms and IFB >=25%
    0
    0%
    0
    0%
    PR Interval >240 ms
    1
    0.5%
    1
    0.5%
    PR Interval >240 ms and IFB >=25%
    0
    0%
    0
    0%
    QRS Interval >110 ms
    3
    1.6%
    9
    4.9%
    QRS Interval >110 ms and IFB >=25%
    0
    0%
    0
    0%
    QRS Interval >120 ms
    1
    0.5%
    2
    1.1%
    QRS Interval >120 ms and IFB >=25%
    0
    0%
    0
    0%
    QT Interval >500 ms
    0
    0%
    1
    0.5%
    QTc B >450 ms
    16
    8.6%
    7
    3.8%
    QTc B >480 ms
    2
    1.1%
    0
    0%
    QTc B >500 ms
    0
    0%
    0
    0%
    QTc B IFB >30 and <=60 ms
    11
    5.9%
    5
    2.7%
    QTc B IFB >60 ms
    0
    0%
    0
    0%
    QTc F>450 ms
    7
    3.8%
    5
    2.7%
    QTc F>480 ms
    0
    0%
    0
    0%
    QTc F>500 ms
    0
    0%
    0
    0%
    QTc F IFB >30 and <=60 ms
    9
    4.9%
    3
    1.6%
    QTc F IFB >60 ms
    0
    0%
    0
    0%
    47. Secondary Outcome
    Title OLE Period: Number of Participants With Potentially Clinically Significant Electrocardiogram Abnormalities
    Description Criteria for potentially clinically significant ECG abnormalities: HR: <50 bpm; <50 bpm and DFB >=20 bpm; <40 bpm; <40 bpm and DFB >=20 bpm; <30 bpm; <30 bpm and DFB >=20 bpm; >90 bpm; >=90 bpm and IFB >=20 bpm; >100 bpm; >=100 bpm and IFB >=20 bpm; >120 bpm; >=120 bpm and IFB >=20 bpm. PR Interval: >200 ms; >200 ms and IFB >=25%; >220 ms; >220 ms and IFB >=25%; >240 ms; >240 ms and IFB >=25%. QRS Interval: >110 ms; >110 ms and IFB >=25%; >120 ms; >120 ms and IFB >=25%. QT Interval: >500 ms. QTc B: >450 ms; >480 ms; >500 ms; IFB >30 and <=60 ms; IFB >60 ms. QTc F: >450 ms; >480 ms; >500 ms; IFB >30 and <=60 ms; IFB >60 ms.
    Time Frame From end of Week 24 (Baseline of OLE Period) up to Week 300

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (OLE Period). Here, 'overall number analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 154 163
    HR <50 bpm
    10
    5.4%
    19
    10.3%
    HR <50 bpm and DFB >=20 bpm
    0
    0%
    3
    1.6%
    HR <40 bpm
    1
    0.5%
    1
    0.5%
    HR <40 bpm and DFB >=20 bpm
    0
    0%
    1
    0.5%
    HR <30 bpm
    0
    0%
    0
    0%
    HR <30 bpm and DFB >=20 bpm
    0
    0%
    0
    0%
    HR >90 bpm
    16
    8.6%
    11
    6%
    HR >=90 bpm and IFB >=20 bpm
    7
    3.8%
    6
    3.3%
    HR >100 bpm
    3
    1.6%
    3
    1.6%
    HR >=100 bpm and IFB >=20 bpm
    2
    1.1%
    1
    0.5%
    HR >120 bpm
    0
    0%
    0
    0%
    HR >=120 bpm and IFB >=20 bpm
    0
    0%
    0
    0%
    PR Interval >200 ms
    17
    9.2%
    14
    7.6%
    PR Interval >200 ms and IFB >=25%
    6
    3.2%
    3
    1.6%
    PR Interval >220 ms
    8
    4.3%
    6
    3.3%
    PR Interval >220 ms and IFB >=25%
    4
    2.2%
    3
    1.6%
    PR Interval >240 ms
    2
    1.1%
    2
    1.1%
    PR Interval >240 ms and IFB >=25%
    2
    1.1%
    1
    0.5%
    QRS Interval >110 ms
    8
    4.3%
    18
    9.8%
    QRS Interval >110 ms and IFB >=25%
    2
    1.1%
    1
    0.5%
    QRS Interval >120 ms
    3
    1.6%
    7
    3.8%
    QRS Interval >120 ms and IFB >=25%
    1
    0.5%
    0
    0%
    QT Interval >500 ms
    2
    1.1%
    2
    1.1%
    QTc B >450 ms
    35
    18.9%
    33
    17.9%
    QTc B >480 ms
    3
    1.6%
    30
    16.3%
    QTc B >500 ms
    1
    0.5%
    1
    0.5%
    QTc B IFB >30 and <=60 ms
    18
    9.7%
    23
    12.5%
    QTc B IFB >60 ms
    3
    1.6%
    2
    1.1%
    QTc F>450 ms
    16
    8.6%
    16
    8.7%
    QTc F>480 ms
    3
    1.6%
    2
    1.1%
    QTc F>500 ms
    0
    0%
    1
    0.5%
    QTc F IFB >30 and <=60 ms
    19
    10.3%
    19
    10.3%
    QTc F IFB >60 ms
    4
    2.2%
    3
    1.6%
    48. Secondary Outcome
    Title DB Period: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities
    Description Criteria for potentially clinically significant vital sign abnormalities: Systolic blood pressure (SBP) supine: <=95 mmHg and DFB>=20 mmHg; >=160 mmHg and IFB >=20 mmHg. Diastolic blood pressure (DBP) supine: <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB >=10 mmHg. SBP (Orthostatic): <=-20 mmHg. DBP (Orthostatic): <=-10 mmHg. HR supine: <=50 bpm and DFB >=20 bpm; >=120 bpm and IFB >=20 bpm. Weight: >=5% DFB; >=5% IFB.
    Time Frame From Week 0 to Week 24

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (DB Period). Here, 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 184 184
    SBP (supine) <=95 mmHg and DFB >=20 mmHg
    4
    2.2%
    3
    1.6%
    SBP (supine) >=160 mmHg and IFB >=20 mmHg
    4
    2.2%
    5
    2.7%
    DBP (supine) <=45 mmHg and DFB >=10 mmHg
    1
    0.5%
    1
    0.5%
    DBP (supine) >=110 mmHg and IFB >=10 mmHg
    1
    0.5%
    1
    0.5%
    SBP (orthostatic) <=-20 mmHg
    13
    7%
    10
    5.4%
    DBP (orthostatic) <=-10 mmHg
    20
    10.8%
    27
    14.7%
    HR (supine) <=50 bpm and DFB >= 20 bpm
    2
    1.1%
    1
    0.5%
    HR (supine) >=120 bpm and IFB >=20 bpm
    1
    0.5%
    0
    0%
    Weight >=5% DFB
    12
    6.5%
    6
    3.3%
    Weight >=5% IFB
    21
    11.4%
    23
    12.5%
    49. Secondary Outcome
    Title OLE Period: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities
    Description Criteria for potentially clinically significant vital sign abnormalities: SBP supine: <=95 mmHg and DFB >=20 mmHg; >=160 mmHg and IFB >=20 mmHg. DBP supine: <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB >=10 mmHg. SBP (Orthostatic): <=-20 mmHg. DBP (Orthostatic): <=-10 mmHg. HR supine: <=50 bpm and DFB >=20 bpm; >=120 bpm and IFB >=20 bpm. Weight: >=5% DFB; >=5% IFB.
    Time Frame From end of Week 24 (Baseline of OLE Period) up to Week 300

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population (OLE Period). Here, 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 155 165
    SBP (supine) <=95 mmHg and DFB >=20 mmHg
    3
    1.6%
    9
    4.9%
    SBP (supine) >=160 mmHg and IFB >=20 mmHg
    10
    5.4%
    11
    6%
    DBP (supine) <=45 mmHg and DFB >=10 mmHg
    0
    0%
    0
    0%
    DBP (supine) >=110 mmHg and IFB >=10 mmHg
    1
    0.5%
    2
    1.1%
    SBP (orthostatic) <=-20 mmHg
    24
    13%
    32
    17.4%
    DBP (orthostatic) <=-10 mmHg
    41
    22.2%
    46
    25%
    HR (supine) <=50 bpm and DFB >= 20 bpm
    3
    1.6%
    0
    0%
    HR (supine) >=120 bpm and IFB >=20 bpm
    0
    0%
    0
    0%
    Weight >=5% DFB
    44
    23.8%
    51
    27.7%
    Weight >=5% IFB
    82
    44.3%
    87
    47.3%
    50. Secondary Outcome
    Title DB Period: Number of Participants With Treatment-emergent and Treatment-boosted Anti-drug Antibody (ADA) Response
    Description Anti-drug antibody response was categorized as: Treatment emergent and Treatment-boosted. Treatment emergent ADAs was defined as a participant with no positive assay response at baseline but with a positive assay response during the TEAE period. Treatment boosted ADAs: defined as participants with a positive ADA assay response at baseline and with at least a 4-fold increase in titer compared to baseline during the TEAE period. TEAE period: time from first dose of study drug up to day before first dose of open-label treatment for participants who completed 24-week randomized/DB treatment.
    Time Frame From Week 0 to Week 24

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on ADA population which consisted of all participants who had signed informed consent and had been allocated to a randomized treatment; received at least 1 dose or part of a dose of IMP with at least 1 post-dose, evaluable ADA sample. Data for this outcome measure was not planned to be collected and analyzed for Adalimumab 40 mg/Sarilumab 200 mg arm.
    Arm/Group Title Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 184
    Treatment-emergent ADA
    13
    7%
    Treatment-boosted ADA
    0
    0%
    51. Secondary Outcome
    Title Number of Participants With Treatment-emergent and Treatment-boosted Anti-drug Antibody Response During Entire Treatment-emergent Adverse Event Period
    Description Anti-drug antibody response was categorized as: Treatment emergent and Treatment-boosted. Treatment emergent ADAs was defined as a participant with no positive assay response at baseline but with a positive assay response during the entire TEAE period. Treatment boosted ADAs: defined as participants with a positive ADA assay response at baseline and with at least a 4-fold increase in titer compared to baseline during the entire TEAE period. Entire TEAE period: last OLE dose - first DB dose date + 6 weeks (follow-up), regardless of unplanned intermittent discontinuations.
    Time Frame From Week 0 up to last dose in OLE + 6 weeks of follow-up (i.e. up to Week 306)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on immunogenicity population which consisted of all participants who received at least 1 dose or part of a dose of IMP with at least 1 post-dose, evaluable ADA sample.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 150 163
    Treatment-emergent ADAs
    11
    5.9%
    11
    6%
    Treatment-boosted ADAs
    0
    0%
    0
    0%
    52. Secondary Outcome
    Title DB Period: Pharmacokinetics: Serum Trough (Pre-dose) Concentrations of Functional Sarilumab
    Description Data for this outcome measure was not planned to be collected and analyzed for "Adalimumab 40 mg/Sarilumab 200 mg" arm.
    Time Frame Pre-dose at Week 0 (Baseline), 2, 4, 12, 16, 20, and 24

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Pharmacokinetics population (DB period) which consisted of all randomized Sarilumab participants who received at least 1 dose of IMP with at least one post-dose, non-missing concentration of functional Sarilumab in serum concentration value. Here, 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 184
    Baseline
    0.00
    (0.00)
    Week 2
    5566.03
    (4843.57)
    Week 4
    11209.64
    (8202.70)
    Week 12
    21355.19
    (14805.63)
    Week 16
    23143.39
    (16508.71)
    Week 20
    25252.43
    (17319.04)
    Week 24
    24233.10
    (17581.72)
    53. Secondary Outcome
    Title OLE Period: Pharmacokinetics: Serum Trough (Pre-dose) Concentrations of Functional Sarilumab
    Description
    Time Frame Pre-dose at Week 24 (Baseline of OLE period), 36, 48, 60, 84, 108, 132, 156, 180, 204, 228, 252, 276, 300 and 306

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Pharmacokinetics population (OLE period) which consisted of all participants from the randomized population who received at least 1 dose of IMP with at least one post-dose, non-missing serum sarilumab concentration. Here, 'number analyzed' = participants with available data for each specified category and '0' denotes that no participant was available for the assessment at the specified timepoint.
    Arm/Group Title Adalimumab 40 mg/Sarilumab 200 mg Sarilumab 200 mg/Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during the DB period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (< 20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300). Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
    Measure Participants 150 163
    Week 24 (Baseline of OLE period)
    109.38
    (1237.44)
    24403.72
    (17588.31)
    Week 36
    18952.69
    (15125.86)
    26006.07
    (19194.79)
    Week 48
    21911.87
    (17926.01)
    25571.16
    (18958.00)
    Week 60
    21583.82
    (17594.87)
    24005.78
    (18541.46)
    Week 84
    23230.92
    (18274.09)
    23873.23
    (19794.57)
    Week 108
    20405.02
    (15553.02)
    21023.55
    (17792.89)
    Week 132
    20814.89
    (17848.70)
    20021.53
    (18580.91)
    Week 156
    23604.11
    (19660.31)
    22423.29
    (18757.11)
    Week 180
    18611.01
    (16417.46)
    21856.85
    (18612.43)
    Week 204
    17982.66
    (16640.61)
    18244.96
    (16383.47)
    Week 228
    19451.40
    (17694.09)
    18315.19
    (17525.62)
    Week 252
    19663.10
    (16020.11)
    19224.47
    (16964.41)
    Week 276
    19071.00
    (18425.13)
    17014.75
    (16207.18)
    Week 300
    9260.00
    (8683.27)
    Week 306 (Follow-up)
    1237.01
    (2856.88)
    2280.98
    (7909.71)

    Adverse Events

    Time Frame All Adverse Events (AEs) were collected from up to Week 24 in DB period and from end of Week 24 (Baseline of OLE Period) up to Week 306 in OLE Period regardless of seriousness or relationship to study drug.
    Adverse Event Reporting Description Reported AEs are treatment-emergent AEs developed/worsened during 'on treatment period' (DB: time from first dose of study drug up to day before first dose of open-label treatment; OLE: from end of Week 24 [Baseline of OLE Period] up to last dose in OLE + 6 weeks [follow-up]). Analyzed on Safety population. For OLE, data was reported for pooled population (all participants received Sarilumab).
    Arm/Group Title DB Period - Adalimumab 40 mg DB Period - Sarilumab 200 mg OLE Period - Sarilumab 200 mg
    Arm/Group Description Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during DB period. The dosing frequency of adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. All participants who completed 24 weeks DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to maximum of additional 276 weeks (i.e. up to Week 300).
    All Cause Mortality
    DB Period - Adalimumab 40 mg DB Period - Sarilumab 200 mg OLE Period - Sarilumab 200 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/184 (0%) 1/184 (0.5%) 8/320 (2.5%)
    Serious Adverse Events
    DB Period - Adalimumab 40 mg DB Period - Sarilumab 200 mg OLE Period - Sarilumab 200 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 13/184 (7.1%) 9/184 (4.9%) 56/320 (17.5%)
    Blood and lymphatic system disorders
    Anaemia 0/184 (0%) 0/184 (0%) 2/320 (0.6%)
    Blood loss anaemia 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Neutropenia 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Cardiac disorders
    Acute myocardial infarction 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Atrial fibrillation 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Atrial flutter 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Cardiac failure acute 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Cardiomyopathy 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Coronary artery disease 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Papillary muscle rupture 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Sinus node dysfunction 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Endocrine disorders
    Thyroid mass 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Eye disorders
    Cataract 0/184 (0%) 0/184 (0%) 2/320 (0.6%)
    Uveitis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Gastrointestinal disorders
    Duodenal ulcer haemorrhage 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Inguinal hernia 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Intestinal obstruction 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Large intestine polyp 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Pancreatic necrosis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Pancreatitis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Pancreatitis acute 0/184 (0%) 0/184 (0%) 2/320 (0.6%)
    Small intestinal obstruction 1/184 (0.5%) 0/184 (0%) 0/320 (0%)
    General disorders
    Non-cardiac chest pain 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Hepatobiliary disorders
    Biliary obstruction 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Cholelithiasis 0/184 (0%) 0/184 (0%) 4/320 (1.3%)
    Cholestasis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Hepatic haematoma 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Immune system disorders
    Serum sickness 1/184 (0.5%) 0/184 (0%) 0/320 (0%)
    Infections and infestations
    Arthritis bacterial 1/184 (0.5%) 0/184 (0%) 0/320 (0%)
    Bone abscess 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Bullous erysipelas 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Bursitis infective 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Epididymitis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Erysipelas 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Mastitis 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Osteomyelitis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Peritonitis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Pharyngotonsillitis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Pneumonia 0/184 (0%) 0/184 (0%) 5/320 (1.6%)
    Upper respiratory tract infection 1/184 (0.5%) 0/184 (0%) 0/320 (0%)
    Urinary tract infection 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Vestibular neuronitis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Injury, poisoning and procedural complications
    Accidental overdose 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Ankle fracture 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Concussion 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Head injury 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Lumbar vertebral fracture 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Periorbital haematoma 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Rib fracture 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Investigations
    Alanine aminotransferase increased 1/184 (0.5%) 0/184 (0%) 0/320 (0%)
    Hepatic enzyme increased 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Musculoskeletal and connective tissue disorders
    Arthritis 1/184 (0.5%) 0/184 (0%) 0/320 (0%)
    Back pain 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Intervertebral disc protrusion 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Lumbar spinal stenosis 1/184 (0.5%) 0/184 (0%) 1/320 (0.3%)
    Osteoarthritis 1/184 (0.5%) 0/184 (0%) 5/320 (1.6%)
    Rheumatoid arthritis 0/184 (0%) 0/184 (0%) 3/320 (0.9%)
    Spinal stenosis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Spondylolisthesis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 1/184 (0.5%) 0/184 (0%) 0/320 (0%)
    Chronic lymphocytic leukaemia 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Lung adenocarcinoma stage IV 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Lung squamous cell carcinoma stage II 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Malignant melanoma 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Malignant mesenteric neoplasm 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Metastases to peritoneum 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Ureteric cancer metastatic 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Yolk sac tumour site unspecified 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Nervous system disorders
    Cerebral ischaemia 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Cerebrovascular accident 1/184 (0.5%) 0/184 (0%) 1/320 (0.3%)
    Demyelinating polyneuropathy 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Headache 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Intracranial aneurysm 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Multiple sclerosis 1/184 (0.5%) 0/184 (0%) 0/320 (0%)
    Subarachnoid haemorrhage 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Syncope 1/184 (0.5%) 0/184 (0%) 1/320 (0.3%)
    Product Issues
    Device defective 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Device dislocation 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Renal and urinary disorders
    Nephrolithiasis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Ureterolithiasis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Reproductive system and breast disorders
    Cervical dysplasia 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Uterovaginal prolapse 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Vaginal prolapse 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary alveolar haemorrhage 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Pulmonary embolism 1/184 (0.5%) 0/184 (0%) 1/320 (0.3%)
    Skin and subcutaneous tissue disorders
    Panniculitis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Stevens-Johnson syndrome 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Vascular disorders
    Aortic dissection 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Haematoma 0/184 (0%) 1/184 (0.5%) 0/320 (0%)
    Iliac artery occlusion 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Iliac artery stenosis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Peripheral ischaemia 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Thrombophlebitis 0/184 (0%) 0/184 (0%) 1/320 (0.3%)
    Other (Not Including Serious) Adverse Events
    DB Period - Adalimumab 40 mg DB Period - Sarilumab 200 mg OLE Period - Sarilumab 200 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 62/184 (33.7%) 79/184 (42.9%) 220/320 (68.8%)
    Blood and lymphatic system disorders
    Neutropenia 1/184 (0.5%) 25/184 (13.6%) 59/320 (18.4%)
    Gastrointestinal disorders
    Diarrhoea 6/184 (3.3%) 5/184 (2.7%) 20/320 (6.3%)
    General disorders
    Injection site erythema 7/184 (3.8%) 14/184 (7.6%) 26/320 (8.1%)
    Infections and infestations
    Bronchitis 7/184 (3.8%) 12/184 (6.5%) 41/320 (12.8%)
    Nasopharyngitis 14/184 (7.6%) 11/184 (6%) 60/320 (18.8%)
    Upper respiratory tract infection 7/184 (3.8%) 3/184 (1.6%) 36/320 (11.3%)
    Urinary tract infection 4/184 (2.2%) 5/184 (2.7%) 30/320 (9.4%)
    Injury, poisoning and procedural complications
    Accidental overdose 11/184 (6%) 5/184 (2.7%) 39/320 (12.2%)
    Investigations
    Alanine aminotransferase increased 6/184 (3.3%) 7/184 (3.8%) 23/320 (7.2%)
    Musculoskeletal and connective tissue disorders
    Back pain 3/184 (1.6%) 3/184 (1.6%) 21/320 (6.6%)
    Rheumatoid arthritis 7/184 (3.8%) 3/184 (1.6%) 21/320 (6.6%)
    Nervous system disorders
    Headache 12/184 (6.5%) 7/184 (3.8%) 17/320 (5.3%)
    Vascular disorders
    Hypertension 3/184 (1.6%) 4/184 (2.2%) 28/320 (8.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

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

    Results Point of Contact

    Name/Title Trial Transparency Team
    Organization Sanofi
    Phone 800-633-1610 ext 6#
    Email Contact-US@sanofi.com
    Responsible Party:
    Sanofi
    ClinicalTrials.gov Identifier:
    NCT02332590
    Other Study ID Numbers:
    • EFC14092
    • 2014-002541-22
    • U1111-1160-6154
    First Posted:
    Jan 7, 2015
    Last Update Posted:
    Mar 28, 2022
    Last Verified:
    Mar 1, 2022