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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Randomized, Double-blind, Parallel-group Study Assessing the Efficacy and Safety of Sarilumab Monotherapy Versus Adalimumab Monotherapy in Patients With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Sarilumab
* Drug: Adalimumab
* Drug: Placebo (for sarilumab)
* Drug: Placebo (for adalimumab)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: During the OLE period of this study, all participants received sarilumab 200 mg or 150 mg q2w via prefilled syringe.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Adalimumab 40 mg/Sarilumab 200 mg<br>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<br>* Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC<br>* Other names: Humira;Drug: Placebo (for sarilumab)<br>* Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC<br>|
| Experimental: Sarilumab 200 mg/Sarilumab 200 mg<br>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<br>* Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC<br>* Other names: REGN88;Drug: Placebo (for adalimumab)<br>* Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DB Period: Change From Baseline in Disease Activity Score for 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) Score at 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. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DB Period: Percentage of Participants Achieving Clinical Remission Score (DAS28-ESR <2.6) at 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. | Week 24 | 
| DB Period: Percentage of Participants Achieving ACR50 Criteria at 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. | Week 24 | 
| DB Period: Percentage of Participants Achieving ACR70 Criteria at 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. | Week 24 | 
| DB Period: Percentage of Participants Achieving ACR20 Criteria at 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. | Week 24 | 
| DB Period: Change From Baseline in HAQ-DI at 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in Short-Form-36 (SF-36) - Physical Component Summary (PCS) Score at 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in SF-36 - Mental Health Component Summary Score at 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP Score) at 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. | Baseline, Week 24 | 
| DB Period: Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP <2.6) at 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. | Week 24 | 
| DB Period: Percentage of Participants Achieving Low Disease Activity (DAS28-ESR < 3.2) at 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. | Week 24 | 
| DB Period: Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Remission (CDAI ≤2.8) at 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. | Week 24 | 
| DB Period: Change From Baseline in CDAI at 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) Scores at 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) at 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to Arthritis | 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to Arthritis | 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in WPS-RA at Week 24: Arthritis Interference With Work Productivity | 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to Arthritis | 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by >= 50% Due to Arthritis | 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to Arthritis | 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to Arthritis | 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity | 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in Morning Stiffness VAS at 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in Individual ACR Component - TJC and SJC at 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in Individual ACR Component - CRP Level at 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. | Baseline, Week 24 | 
| DB Period: Change From Baseline in Individual ACR Component- ESR Level at 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. | Baseline, Week 24 | 
| DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | 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. | From Week 0 to Week 24 | 
| OLE Period: Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events | 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. | 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) | 
| DB Period: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) - Hematological Parameters | 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). | From Week 0 to Week 24 | 
| OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Hematological Parameters | 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). | From end of Week 24 (Baseline of OLE Period) up to Week 300 | 
| DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function Tests | 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. | From Week 0 to Week 24 | 
| OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function Tests | 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. | From end of Week 24 (Baseline of OLE Period) up to Week 300 | 
| DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters | 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. | From Week 0 to Week 24 | 
| OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters | 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. | From end of Week 24 (Baseline of OLE Period) up to Week 300 | 
| DB Period: Number of Participants With Different Post-baseline Categories of High-density Lipoprotein (HDL) | Number of participants with different post-baseline status of HDL: < 40 mg/dL, 40 - < 60 mg/dL, >= 60 mg/dL, is reported here. | From Week 0 to Week 24 | 
| OLE Period: Number of Participants With Different Post-baseline Categories of High-density Lipoprotein | Number of participants with different post-baseline status of HDL: < 40 mg/dL, 40 - < 60 mg/dL, >=60 mg/dL, is reported here. | From end of Week 24 (Baseline of OLE Period) up to Week 300 | 
| DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function | 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. | From Week 0 to Week 24 | 
| OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function | 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. | From end of Week 24 (Baseline of OLE Period) up to Week 300 | 
| DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Urinalysis | Criteria with potentially clinically significant urine abnormalities: pH: <= 4.6; pH: >= 8.0. | From Week 0 to Week 24 | 
| OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Urinalysis | Criteria with potentially clinically significant urine abnormalities: pH: <= 4.6; pH: >= 8.0. | From end of Week 24 (Baseline of OLE Period) up to Week 300 | 
| DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Electrolytes | 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. | From Week 0 to Week 24 | 
| OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Electrolytes | 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. | From end of Week 24 (Baseline of OLE Period) up to Week 300 | 
| DB Period: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities | 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. | From Week 0 to Week 24 | 
| OLE Period: Number of Participants With Potentially Clinically Significant Electrocardiogram Abnormalities | 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. | From end of Week 24 (Baseline of OLE Period) up to Week 300 | 
| DB Period: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities | 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. | From Week 0 to Week 24 | 
| OLE Period: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities | 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. | From end of Week 24 (Baseline of OLE Period) up to Week 300 | 
| DB Period: Number of Participants With Treatment-emergent and Treatment-boosted Anti-drug Antibody (ADA) Response | 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. | From Week 0 to Week 24 | 
| Number of Participants With Treatment-emergent and Treatment-boosted Anti-drug Antibody Response During Entire Treatment-emergent Adverse Event Period | 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. | From Week 0 up to last dose in OLE + 6 weeks of follow-up (i.e. up to Week 306) | 
| DB Period: Pharmacokinetics: Serum Trough (Pre-dose) Concentrations of Functional Sarilumab | Data for this outcome measure was not planned to be collected and analyzed for Adalimumab 40 mg/Sarilumab 200 mg arm. | Pre-dose at Week 0 (Baseline), 2, 4, 12, 16, 20, and 24 | 
| 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 |