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

ID: NCT02332590
Status: Active, not recruiting
Phase: Phase 3
Start Date: February 01, 2015
First Submitted: January 05, 2015
Last Updated: February 22, 2018
Results: Available
Success Rate: 86%
Organization: Sanofi
Sponsors & Collaborators: Sanofi, Regeneron Pharmaceuticals
Location: Chile, Czechia, Germany, Hungary, Israel, Korea, Republic of, Peru, Poland, Romania, Russian Federation, South Africa, Spain, Ukraine, United Kingdom, United States
Conditions: Rheumatoid Arthritis
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for 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.

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.
Condition or disease Intervention/treatment Phase

Rheumatoid Arthritis

Drug: Sarilumab
Other Names
SAR153191 REGN88
Drug: Adalimumab
Other Names
Humira
Drug: Placebo (for sarilumab)
Other Names
Drug: Placebo (for adalimumab)
Other Names
Phase 3

Tracking Information

First Submitted DateJanuary 05, 2015
Last Update Posted DateFebruary 22, 2018
Start DateFebruary 01, 2015
Anticipated Completion DateDecember 01, 2020
Primary Completion DateJanuary 01, 2016
Results First Submitted DateMay 24, 2017
Received Results Disposit DateDecember 07, 2016

Current Primary Outcome Measures

  • Change From Baseline in Disease Activity Score for 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 24 [Time Frame: Baseline, Week 24]

    DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the American College of Rheumatology (ACR) rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (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.

Original Primary Outcome Measures

  • 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); General health (GH) assessment by the participant assessed from the American College of Rheumatology (ACR) rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (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.

Current Secondary Outcome Measures

  • Percentage of Participants Achieving Clinical Remission Score (DAS28-ESR <2.6) at Week 24 [Time Frame: 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.

  • Percentage of Participants Achieving ACR50 Criteria at Week 24 [Time Frame: 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 health] - 3 [worst health]). 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.

  • Percentage of Participants Achieving ACR70 Criteria at Week 24 [Time Frame: 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 health] - 3 [worst health]). 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.

  • Percentage of Participants Achieving ACR20 Criteria at Week 24 [Time Frame: 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 health] - 3 [worst health]). 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.

  • Change From Baseline in HAQ-DI at Week 24 [Time Frame: 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.

  • Change From Baseline in Short-Form-36 (SF-36) - Physical Component Summary (PCS) Score at Week 24 [Time Frame: 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.

  • Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24 [Time Frame: 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 range 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.

  • Change From Baseline in SF-36 - Mental Health Component Summary Score at Week 24 [Time Frame: 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.

  • Change From Baseline in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP Score) at Week 24 [Time Frame: 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.

  • Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP <2.6) at Week 24 [Time Frame: 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.

  • Percentage of Participants Achieving Low Disease Activity (DAS28-ESR < 3.2) at Week 24 [Time Frame: 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.

  • Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Remission (CDAI ≤2.8) at Week 24 [Time Frame: 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 disease activity (in cm), and physician's global assessment (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.

  • Change From Baseline in CDAI at Week 24 [Time Frame: 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 disease activity (in cm), and physician's global assessment of disease 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.

  • Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) Scores at Week 24 [Time Frame: 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 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.

  • Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) at Week 24 [Time Frame: 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 and calculated 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.

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

  • Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to Arthritis [Time Frame: 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.

  • Change From Baseline in WPS-RA at Week 24: Arthritis Interference With Work Productivity [Time Frame: 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.

  • Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to Arthritis [Time Frame: 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.

  • Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to Arthritis [Time Frame: 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.

  • Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to Arthritis [Time Frame: 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.

  • Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to Arthritis [Time Frame: 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.

  • Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity [Time Frame: 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.

  • Change From Baseline in Morning Stiffness VAS at Week 24 [Time Frame: 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.

  • Change From Baseline in Individual ACR Component - TJC and SJC at Week 24 [Time Frame: 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.

  • Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 24 [Time Frame: 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.

  • Change From Baseline in Individual ACR Component - CRP Level at Week 24 [Time Frame: 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 was considered a non-specific "marker" for RA. A reduction level indicates improvement. LS mean and SE at Week 24 were obtained using MMRM approach.

  • Change From Baseline in Individual ACR Component- ESR Level at Week 24 [Time Frame: 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.

  • Sarilumab Exposure Assessed by Trough Serum Sarilumab Concentrations [Time Frame: Over time, maximum to Week 306]

  • Number of Participants With Adverse Events [Time Frame: Over time, maximum to Week 306]

  • Clinically Significant Changes in Laboratory Values: Hematology, Clinical Chemistry, and Urinalysis [Time Frame: Over time, maximum to Week 306]

  • Clinically Significant Changes in ECG [Time Frame: Over time, maximum to Week 306]

  • Clinically Significant Changes in Vital Signs [Time Frame: Over time, maximum to Week 306]

  • Measurement of Anti-Drug Antibody (ADA) Levels [Time Frame: Over time, maximum to Week 306]

Original Secondary Outcome Measures

  • Measurement of Anti-Drug Antibody (ADA) Levels

  • Clinically Significant Changes in Vital Signs

  • Clinically Significant Changes in ECG

  • Clinically Significant Changes in Laboratory Values: Hematology, Clinical Chemistry, and Urinalysis

  • Number of Participants With Adverse Events

  • Sarilumab Exposure Assessed by Trough Serum Sarilumab Concentrations

  • 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.

  • 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 was considered a non-specific "marker" for RA. A reduction level indicates improvement. LS mean and SE at Week 24 were obtained using MMRM approach.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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 and calculated 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.

  • 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 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.

  • 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 disease activity (in cm), and physician’s global assessment of disease 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.

  • 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 disease activity (in cm), and physician’s global assessment (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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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 range 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.

  • 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.

  • 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.

  • 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 health] - 3 [worst health]). 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.

  • 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 health] - 3 [worst health]). 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.

  • 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 health] - 3 [worst health]). 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.

  • 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.

Study Design

Brief TitleEfficacy and Safety of Sarilumab and Adalimumab Monotherapy in Patients With Rheumatoid Arthritis (SARIL-RA-MONARCH)
Official TitleA Randomized, Double-blind, Parallel-group Study Assessing the Efficacy and Safety of Sarilumab Monotherapy Versus Adalimumab Monotherapy in Patients With Rheumatoid Arthritis
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.

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 TypeInterventional
Study PhasePhase 3
Estimated Enrollment
369
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Quadruple
Primary Purpose
Treatment
Conditions
Rheumatoid Arthritis
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Sarilumab

Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC

Other Names
SAR153191
REGN88
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

Other Names
Drug: Placebo (for adalimumab)

Pharmaceutical form:solution for injection in pre-filled syringe; Route of administration: SC

Other Names
Study Groups/Cohorts
Adalimumab 40 mg
Adalimumab 40 mg subcutaneous (SC) injection in combination with placebo for sarilumab every 2 weeks (q2w) for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (<20% improvement from baseline tender joint count [TJC] and swollen joint count [SJC] for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.

Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.

Study Arms
Active Comparator Adalimumab 40 mg
Adalimumab 40 mg subcutaneous (SC) injection in combination with placebo for sarilumab every 2 weeks (q2w) for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (<20% improvement from baseline tender joint count [TJC] and swollen joint count [SJC] for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.
Drug : Adalimumab
Pharmaceutical form:solution for injection in pre-filled syringe; Route of administration: SC

Active Comparator Adalimumab 40 mg
Adalimumab 40 mg subcutaneous (SC) injection in combination with placebo for sarilumab every 2 weeks (q2w) for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (<20% improvement from baseline tender joint count [TJC] and swollen joint count [SJC] for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.
Drug : Placebo (for sarilumab)
Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC

Experimental Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.
Drug : Placebo (for adalimumab)
Pharmaceutical form:solution for injection in pre-filled syringe; Route of administration: SC

Experimental Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.
Drug : Sarilumab
Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC

Arm Intervention/Treatment
Active Comparator Adalimumab 40 mg
Adalimumab 40 mg subcutaneous (SC) injection in combination with placebo for sarilumab every 2 weeks (q2w) for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (<20% improvement from baseline tender joint count [TJC] and swollen joint count [SJC] for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.
Drug : Adalimumab
Active Comparator Adalimumab 40 mg
Adalimumab 40 mg subcutaneous (SC) injection in combination with placebo for sarilumab every 2 weeks (q2w) for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (<20% improvement from baseline tender joint count [TJC] and swollen joint count [SJC] for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.
Drug : Placebo (for sarilumab)
Experimental Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.
Drug : Placebo (for adalimumab)
Experimental Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.
Drug : Sarilumab

Recruitment Information

Recruitment Status:Active, not recruiting
Enrollment369
Completion DateDecember 01, 2020
Eligibility Criteria: Inclusion criteria:
- Diagnosis of RA ≥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 mm/H, and DAS28-ESR >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.
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
Chile
Czechia
Germany
Hungary
Israel
Korea, Republic of
Peru
Poland
Romania
Russian Federation
South Africa
Spain
Ukraine
United Kingdom
United States
Czech Republic
France

Administrative Information

NCT Number:NCT02332590
Other Study ID Numbers
EFC14092
2014-002541-22
U1111-1160-6154
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
Investigators
Study Director
Clinical Sciences & Operations
Sanofi

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 86 centers in 15 countries. A total of 540 participants were screened between 28 January 2015 and 09 July 2015, 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 Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized in 1:1 ratio (Adalimumab 40 mg every 2 weeks [q2w]: Sarilumab 200 mg q2w) and treated for 24 weeks. Completers are those participants who completed 24 weeks randomized treatment.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg subcutaneous (SC) injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (<20% improvement from baseline tender joint count [TJC] and swollen joint count [SJC] for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.

Participant Flow: Overall

Adalimumab 40 mgSarilumab 200 mg
184184
Started185184
Completed156165
Not Completed2919
Adverse Event1511
Lack of Efficacy42
Other than specified above65
Poor compliance to protocol31
Randomized but not treated10

Baseline Characteristics

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Not Available

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants completed 24 weeks treatment period had the option to continue in open-label treatment period and received sarilumab 200 mg q2w until commercial availability of sarilumab in the country or maximum of 276 weeks.
Total
Total of all reporting groups

Baseline Measures

Adalimumab 40 mgSarilumab 200 mgTotal
Overall Participants Analyzed
Units: Participants
Participants Analyzed
185184369
185184369
Age
Units: years - Mean (Standard Deviation)
Participants Analyzed
185184369
53.6 (11.9)50.9 (12.6)52.2 (12.3)
Sex: Female, Male
Units: Participants - Count of Participants
Participants Analyzed
185184369
Female150157307
Male352762

Outcome Measures

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

Measure Type
Primary
Measure Title
Change From Baseline in Disease Activity Score for 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 24
Measure Description
DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the American College of Rheumatology (ACR) rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population included all participants. Number of participants analyzed = participants with DAS28-ESR assessment at both baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
163165
Change From Baseline in Disease Activity Score for 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 24
Units: units on a scale - Least Squares Mean (Standard Error)
-2.20 (0.106)-3.28 (0.105)

Statistical Analysis

Groups
All Groups
Statistical Test Type
Superiority
Statistical Method
Mixed Models Analysis
P Value
<0.00010
LS Mean Difference
-1.07700
95% Confidence Interval
-1.36100 to -0.79300
  1. Additional details about the analysis, such as null hypothesis and power calculation
    Not Available
  2. Details of power calculation, definition of non-inferiority margin, and other key parameters
    Not Available
  3. Other relevant method information, such as adjustments or degrees of freedom
    Not Available
  4. Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance
    Threshold for significance at 0.05 level.
  5. Other relevant estimation information
    Sarilumab 200 mg vs. Adalimumab 40 mg

2. Secondary: Percentage of Participants Achieving Clinical Remission Score (DAS28-ESR <2.6) at Week 24

Measure Type
Secondary
Measure Title
Percentage of Participants Achieving Clinical Remission Score (DAS28-ESR <2.6) at Week 24
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
185184
Percentage of Participants Achieving Clinical Remission Score (DAS28-ESR <2.6) at Week 24
Units: percentage of participants - Number
7.026.6

Statistical Analysis

Groups
All Groups
Statistical Test Type
Superiority
Statistical Method
Cochran-Mantel-Haenszel
P Value
<0.00010
Odds Ratio (OR)
4.87900
95% Confidence Interval
2.53600 to 9.38900
  1. Additional details about the analysis, such as null hypothesis and power calculation
    Not Available
  2. Details of power calculation, definition of non-inferiority margin, and other key parameters
    Not Available
  3. Other relevant method information, such as adjustments or degrees of freedom
    Not Available
  4. Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance
    Threshold for significance at 0.05 level.
  5. Other relevant estimation information
    Sarilumab 200 mg vs. Adalimumab 40 mg

3. Secondary: Percentage of Participants Achieving ACR50 Criteria at Week 24

Measure Type
Secondary
Measure Title
Percentage of Participants Achieving ACR50 Criteria at Week 24
Measure 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 health] - 3 [worst health]). 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
185184
Percentage of Participants Achieving ACR50 Criteria at Week 24
Units: percentage of participants - Number
29.745.7

Statistical Analysis

Groups
All Groups
Statistical Test Type
Superiority
Statistical Method
Cochran-Mantel-Haenszel
P Value
0.00170
Odds Ratio (OR)
1.97600
95% Confidence Interval
1.28900 to 3.02800
  1. Additional details about the analysis, such as null hypothesis and power calculation
    Not Available
  2. Details of power calculation, definition of non-inferiority margin, and other key parameters
    Not Available
  3. Other relevant method information, such as adjustments or degrees of freedom
    Not Available
  4. Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance
    Threshold for significance at 0.05 level.
  5. Other relevant estimation information
    Sarilumab 200 mg vs. Adalimumab 40 mg

4. Secondary: Percentage of Participants Achieving ACR70 Criteria at Week 24

Measure Type
Secondary
Measure Title
Percentage of Participants Achieving ACR70 Criteria at Week 24
Measure 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 health] - 3 [worst health]). 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
185184
Percentage of Participants Achieving ACR70 Criteria at Week 24
Units: percentage of participants - Number
11.923.4

Statistical Analysis

Groups
All Groups
Statistical Test Type
Superiority
Statistical Method
Cochran-Mantel-Haenszel
P Value
0.00360
Odds Ratio (OR)
2.28600
95% Confidence Interval
1.30000 to 4.02000
  1. Additional details about the analysis, such as null hypothesis and power calculation
    Not Available
  2. Details of power calculation, definition of non-inferiority margin, and other key parameters
    Not Available
  3. Other relevant method information, such as adjustments or degrees of freedom
    Not Available
  4. Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance
    Threshold for significance at 0.05 level.
  5. Other relevant estimation information
    Sarilumab 200 mg vs. Adalimumab 40 mg

5. Secondary: Percentage of Participants Achieving ACR20 Criteria at Week 24

Measure Type
Secondary
Measure Title
Percentage of Participants Achieving ACR20 Criteria at Week 24
Measure 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 health] - 3 [worst health]). 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
185184
Percentage of Participants Achieving ACR20 Criteria at Week 24
Units: percentage of participants - Number
58.471.7

Statistical Analysis

Groups
All Groups
Statistical Test Type
Superiority
Statistical Method
Cochran-Mantel-Haenszel
P Value
0.00740
Odds Ratio (OR)
1.80000
95% Confidence Interval
1.16800 to 2.77300
  1. Additional details about the analysis, such as null hypothesis and power calculation
    Not Available
  2. Details of power calculation, definition of non-inferiority margin, and other key parameters
    Not Available
  3. Other relevant method information, such as adjustments or degrees of freedom
    Not Available
  4. Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance
    Threshold for significance 0.05 level.
  5. Other relevant estimation information
    Sarilumab 200 mg vs. Adalimumab 40 mg

6. Secondary: Change From Baseline in HAQ-DI at Week 24

Measure Type
Secondary
Measure Title
Change From Baseline in HAQ-DI at Week 24
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with HAQ-DI assessment at both baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
158165
Change From Baseline in HAQ-DI at Week 24
Units: units on a scale - Least Squares Mean (Standard Error)
-0.43 (0.045)-0.61 (0.045)

Statistical Analysis

Groups
All Groups
Statistical Test Type
Superiority
Statistical Method
Mixed Models Analysis
P Value
0.00370
LS Mean Difference
-0.18200
95% Confidence Interval
-0.30500 to -0.05900
  1. Additional details about the analysis, such as null hypothesis and power calculation
    Not Available
  2. Details of power calculation, definition of non-inferiority margin, and other key parameters
    Not Available
  3. Other relevant method information, such as adjustments or degrees of freedom
    Not Available
  4. Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance
    Threshold for significance at 0.05 level.
  5. Other relevant estimation information
    Sarilumab 200 mg vs. Adalimumab 40 mg

7. Secondary: Change From Baseline in Short-Form-36 (SF-36) - Physical Component Summary (PCS) Score at Week 24

Measure Type
Secondary
Measure Title
Change From Baseline in Short-Form-36 (SF-36) - Physical Component Summary (PCS) Score at Week 24
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with SF-36 PCS score assessment at both baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
157159
Change From Baseline in Short-Form-36 (SF-36) - Physical Component Summary (PCS) Score at Week 24
Units: units on a scale - Least Squares Mean (Standard Error)
6.09 (0.555)8.74 (0.555)

Statistical Analysis

Groups
All Groups
Statistical Test Type
Superiority
Statistical Method
Mixed Models Analysis
P Value
0.00060
LS Mean Difference
2.65000
95% Confidence Interval
1.14700 to 4.15300
  1. Additional details about the analysis, such as null hypothesis and power calculation
    Not Available
  2. Details of power calculation, definition of non-inferiority margin, and other key parameters
    Not Available
  3. Other relevant method information, such as adjustments or degrees of freedom
    Not Available
  4. Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance
    Threshold for significance at 0.05 level.
  5. Other relevant estimation information
    Sarilumab 200 mg vs. Adalimumab 40 mg

8. Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24

Measure Type
Secondary
Measure Title
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24
Measure 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 range 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with FACIT-F score assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
158165
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24
Units: units on a scale - Least Squares Mean (Standard Error)
8.41 (0.709)10.18 (0.701)

Statistical Analysis

Groups
All Groups
Statistical Test Type
Superiority
Statistical Method
Mixed Models Analysis
P Value
0.06890
LS Mean Difference
1.76800
95% Confidence Interval
-0.13700 to 3.67400
  1. Additional details about the analysis, such as null hypothesis and power calculation
    Not Available
  2. Details of power calculation, definition of non-inferiority margin, and other key parameters
    Not Available
  3. Other relevant method information, such as adjustments or degrees of freedom
    Not Available
  4. Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance
    Threshold for significance at 0.05 level.
  5. Other relevant estimation information
    Sarilumab 200 mg vs. Adalimumab 40 mg

9. Secondary: Change From Baseline in SF-36 - Mental Health Component Summary Score at Week 24

Measure Type
Secondary
Measure Title
Change From Baseline in SF-36 - Mental Health Component Summary Score at Week 24
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with SF-36 - mental health component summary score assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
157159
Change From Baseline in SF-36 - Mental Health Component Summary Score at Week 24
Units: units on a scale - Least Squares Mean (Standard Error)
6.83 (0.774)7.86 (0.773)

10. Secondary: Change From Baseline in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP Score) at Week 24

Measure Type
Secondary
Measure Title
Change From Baseline in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP Score) at Week 24
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with DAS28-CRP score assessment at both baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
156163
Change From Baseline in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP Score) at Week 24
Units: units on a scale - Least Squares Mean (Standard Error)
-1.97 (0.094)-2.86 (0.093)

11. Secondary: Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP <2.6) at Week 24

Measure Type
Secondary
Measure Title
Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP <2.6) at Week 24
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
185184
Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP <2.6) at Week 24
Units: percentage of participants - Number
13.534.2

12. Secondary: Percentage of Participants Achieving Low Disease Activity (DAS28-ESR < 3.2) at Week 24

Measure Type
Secondary
Measure Title
Percentage of Participants Achieving Low Disease Activity (DAS28-ESR < 3.2) at Week 24
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
185184
Percentage of Participants Achieving Low Disease Activity (DAS28-ESR < 3.2) at Week 24
Units: percentage of participants - Number
14.142.9

13. Secondary: Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Remission (CDAI ≤2.8) at Week 24

Measure Type
Secondary
Measure Title
Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Remission (CDAI ≤2.8) at Week 24
Measure 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 disease activity (in cm), and physician’s global assessment (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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
185184
Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Remission (CDAI ≤2.8) at Week 24
Units: percentage of participants - Number
2.77.1

14. Secondary: Change From Baseline in CDAI at Week 24

Measure Type
Secondary
Measure Title
Change From Baseline in CDAI at Week 24
Measure 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 disease activity (in cm), and physician’s global assessment of disease 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with CDAI assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
158165
Change From Baseline in CDAI at Week 24
Units: units on a scale - Least Squares Mean (Standard Error)
-25.20 (0.842)-28.94 (0.834)

15. Secondary: Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) Scores at Week 24

Measure Type
Secondary
Measure Title
Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) Scores at Week 24
Measure Description
EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. EQ-5D 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
156164
Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) Scores at Week 24
Units: units on a scale - Least Squares Mean (Standard Error)
EQ-5D Single index utility score0.26 (0.019)0.32 (0.019)
EQ-5D VAS19.94 (1.720)24.22 (1.686)

16. Secondary: Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) at Week 24

Measure Type
Secondary
Measure Title
Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) at Week 24
Measure 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 and calculated 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with RAID assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
157161
Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) at Week 24
Units: units on a scale - Least Squares Mean (Standard Error)
-2.30 (0.168)-3.08 (0.168)

17. Secondary: Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to Arthritis

Measure Type
Secondary
Measure Title
Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to Arthritis
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
6070
Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to Arthritis
Units: days - Least Squares Mean (Standard Error)
0.05 (0.611)-0.28 (0.547)

18. Secondary: Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to Arthritis

Measure Type
Secondary
Measure Title
Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to Arthritis
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
6070
Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to Arthritis
Units: days - Least Squares Mean (Standard Error)
-3.50 (0.525)-3.74 (0.456)

19. Secondary: Change From Baseline in WPS-RA at Week 24: Arthritis Interference With Work Productivity

Measure Type
Secondary
Measure Title
Change From Baseline in WPS-RA at Week 24: Arthritis Interference With Work Productivity
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
6069
Change From Baseline in WPS-RA at Week 24: Arthritis Interference With Work Productivity
Units: units on a scale - Least Squares Mean (Standard Error)
-2.510 (0.3470)-2.919 (0.3073)

20. Secondary: Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to Arthritis

Measure Type
Secondary
Measure Title
Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to Arthritis
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
163169
Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to Arthritis
Units: days - Least Squares Mean (Standard Error)
-4.22 (0.405)-5.49 (0.400)

21. Secondary: Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to Arthritis

Measure Type
Secondary
Measure Title
Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to Arthritis
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
163169
Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to Arthritis
Units: days - Least Squares Mean (Standard Error)
-4.87 (0.451)-6.70 (0.445)

22. Secondary: Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to Arthritis

Measure Type
Secondary
Measure Title
Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to Arthritis
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
163169
Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to Arthritis
Units: days - Least Squares Mean (Standard Error)
-3.33 (0.376)-4.14 (0.371)

23. Secondary: Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to Arthritis

Measure Type
Secondary
Measure Title
Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to Arthritis
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed =participants with WPS-RA: Individual items assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
163168
Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to Arthritis
Units: days - Least Squares Mean (Standard Error)
-2.57 (0.401)-3.43 (0.398)

24. Secondary: Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity

Measure Type
Secondary
Measure Title
Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with WPS-RA: Individual items assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
163168
Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity
Units: units on a scale - Least Squares Mean (Standard Error)
-2.605 (0.2110)-3.276 (0.2099)

25. Secondary: Change From Baseline in Morning Stiffness VAS at Week 24

Measure Type
Secondary
Measure Title
Change From Baseline in Morning Stiffness VAS at Week 24
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with morning stiffness VAS assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
156165
Change From Baseline in Morning Stiffness VAS at Week 24
Units: mm - Least Squares Mean (Standard Error)
-29.29 (1.970)-35.08 (1.947)

26. Secondary: Change From Baseline in Individual ACR Component - TJC and SJC at Week 24

Measure Type
Secondary
Measure Title
Change From Baseline in Individual ACR Component - TJC and SJC at Week 24
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with TJC and SJC assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
158166
Change From Baseline in Individual ACR Component - TJC and SJC at Week 24
Units: joints - Least Squares Mean (Standard Error)
SJC-12.20 (0.450)-13.44 (0.444)
TJC-16.45 (0.781)-18.23 (0.772)

27. Secondary: Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 24

Measure Type
Secondary
Measure Title
Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 24
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
158166
Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 24
Units: mm - Least Squares Mean (Standard Error)
Pain VAS-27.41 (1.802)-36.19 (1.776)
Participant global VAS-24.82 (1.752)-33.30 (1.731)
Physician global VAS-37.80 (1.431)-45.33 (1.414)

28. Secondary: Change From Baseline in Individual ACR Component - CRP Level at Week 24

Measure Type
Secondary
Measure Title
Change From Baseline in Individual ACR Component - CRP Level at Week 24
Measure 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 was considered a non-specific "marker" for RA. A reduction level indicates improvement. LS mean and SE at Week 24 were obtained using MMRM approach.
Time Frame
Baseline, Week 24

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with CRP assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
156164
Change From Baseline in Individual ACR Component - CRP Level at Week 24
Units: mg/L - Least Squares Mean (Standard Error)
-2.91 (1.461)-17.01 (1.431)

29. Secondary: Change From Baseline in Individual ACR Component- ESR Level at Week 24

Measure Type
Secondary
Measure Title
Change From Baseline in Individual ACR Component- ESR Level at Week 24
Measure 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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Number of participants analyzed = participants with ESR assessment both at baseline and Week 24.

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Outcome Measures

Adalimumab 40 mgSarilumab 200 mg
Participants Analyzed
Units: Participants
163166
Change From Baseline in Individual ACR Component- ESR Level at Week 24
Units: mm/hr - Least Squares Mean (Standard Error)
-12.74 (1.398)-32.11 (1.388)

30. Secondary: Sarilumab Exposure Assessed by Trough Serum Sarilumab Concentrations

Measure Type
Secondary
Measure Title
Sarilumab Exposure Assessed by Trough Serum Sarilumab Concentrations
Measure Description
Not Available
Time Frame
Over time, maximum to Week 306

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Not Available

31. Secondary: Number of Participants With Adverse Events

Measure Type
Secondary
Measure Title
Number of Participants With Adverse Events
Measure Description
Not Available
Time Frame
Over time, maximum to Week 306

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Not Available

32. Secondary: Clinically Significant Changes in Laboratory Values: Hematology, Clinical Chemistry, and Urinalysis

Measure Type
Secondary
Measure Title
Clinically Significant Changes in Laboratory Values: Hematology, Clinical Chemistry, and Urinalysis
Measure Description
Not Available
Time Frame
Over time, maximum to Week 306

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Not Available

33. Secondary: Clinically Significant Changes in ECG

Measure Type
Secondary
Measure Title
Clinically Significant Changes in ECG
Measure Description
Not Available
Time Frame
Over time, maximum to Week 306

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Not Available

34. Secondary: Clinically Significant Changes in Vital Signs

Measure Type
Secondary
Measure Title
Clinically Significant Changes in Vital Signs
Measure Description
Not Available
Time Frame
Over time, maximum to Week 306

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Not Available

35. Secondary: Measurement of Anti-Drug Antibody (ADA) Levels

Measure Type
Secondary
Measure Title
Measurement of Anti-Drug Antibody (ADA) Levels
Measure Description
Not Available
Time Frame
Over time, maximum to Week 306

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Not Available

Serious Adverse Events

Time Frame
All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 24 regardless of seriousness or relationship to study drug.
Additional Description
Reported AEs are treatment-emergent AEs 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 treatment and time from first dose of study drug up to last dose date of study drug + 60 days for participants who discontinued 24-week randomized treatment). Safety population consisted of all randomized participants who received ≥1 dose or part of a dose of study drug.
Frequency Threshold0% (Threshold above which other adverse events are reported)

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Serious Adverse Events

Adalimumab 40 mgSarilumab 200 mg
Total, serious adverse events
No. of participants affected / at risk12/184 (0.00%)9/184 (0.00%)
Neutropenia
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Cardiac failure acute
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Coronary artery dissection
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Papillary muscle rupture
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Small intestinal obstruction
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Serum sickness
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Arthritis bacterial
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Bursitis infective
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Mastitis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Respiratory tract infection
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Accidental overdose
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Concussion
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Periorbital haematoma
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Wound
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Alanine aminotransferase increased
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Arthritis
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Back pain
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Intervertebral disc protrusion
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Lumbar spinal stenosis
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Basal cell carcinoma
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Cerebral ischaemia
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Cerebrovascular accident
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Demyelinating polyneuropathy
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Multiple sclerosis
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Syncope
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Pulmonary embolism
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Haematoma
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)

Other Adverse Events

Time Frame
All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 24 regardless of seriousness or relationship to study drug.
Additional Description
Reported AEs are treatment-emergent AEs 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 treatment and time from first dose of study drug up to last dose date of study drug + 60 days for participants who discontinued 24-week randomized treatment). Safety population consisted of all randomized participants who received ≥1 dose or part of a dose of study drug.
Frequency Threshold0% (Threshold above which other adverse events are reported)

Reporting Groups

TitleDescription
Adalimumab 40 mg
Adalimumab 40 mg SC injection in combination with placebo for sarilumab q2w for 24 weeks during randomized treatment period. The dosing frequency of adalimumab may be adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.
Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during randomized treatment period. The dosing frequency of placebo for adalimumab may be adjusted to qw dosing in case of participants with inadequate response (<20% improvement from baseline TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23.

Other Adverse Events

Adalimumab 40 mgSarilumab 200 mg
Total, other adverse events
No. of participants affected / at risk115/184 (0.00%)116/184 (0.00%)
Anaemia
No. of participants affected / at risk0/184 (0.00%)2/184 (0.00%)
Leukopenia
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Microcytic anaemia
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Neutropenia
No. of participants affected / at risk1/184 (0.00%)25/184 (0.00%)
Atrial fibrillation
No. of participants affected / at risk0/184 (0.00%)2/184 (0.00%)
Myocardial ischaemia
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Palpitations
No. of participants affected / at risk2/184 (0.00%)1/184 (0.00%)
Vertebral artery hypoplasia
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Ear pain
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Middle ear inflammation
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Vertigo
No. of participants affected / at risk2/184 (0.00%)0/184 (0.00%)
Blepharitis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Cataract
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Conjunctival haemorrhage
No. of participants affected / at risk0/184 (0.00%)2/184 (0.00%)
Diplopia
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Dry eye
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Ulcerative keratitis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Uveitis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Visual impairment
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Abdominal pain
No. of participants affected / at risk5/184 (0.00%)0/184 (0.00%)
Abdominal pain upper
No. of participants affected / at risk1/184 (0.00%)2/184 (0.00%)
Aphthous ulcer
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Chronic gastritis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Constipation
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Diarrhoea
No. of participants affected / at risk5/184 (0.00%)5/184 (0.00%)
Dry mouth
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Dyspepsia
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Epigastric discomfort
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Gastric polyps
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Gastritis
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Gastrooesophageal reflux disease
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Inguinal hernia
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Mouth ulceration
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Nausea
No. of participants affected / at risk0/184 (0.00%)2/184 (0.00%)
Oral mucosal exfoliation
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Sensitivity of teeth
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Toothache
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Vomiting
No. of participants affected / at risk1/184 (0.00%)2/184 (0.00%)
Asthenia
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Fatigue
No. of participants affected / at risk2/184 (0.00%)2/184 (0.00%)
Generalised oedema
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Injection site discolouration
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Injection site erythema
No. of participants affected / at risk6/184 (0.00%)14/184 (0.00%)
Injection site haematoma
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Injection site oedema
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Injection site pain
No. of participants affected / at risk0/184 (0.00%)2/184 (0.00%)
Injection site pruritus
No. of participants affected / at risk0/184 (0.00%)3/184 (0.00%)
Injection site rash
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Injection site swelling
No. of participants affected / at risk1/184 (0.00%)3/184 (0.00%)
Malaise
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Non-cardiac chest pain
No. of participants affected / at risk2/184 (0.00%)0/184 (0.00%)
Oedema peripheral
No. of participants affected / at risk2/184 (0.00%)0/184 (0.00%)
Peripheral swelling
No. of participants affected / at risk0/184 (0.00%)2/184 (0.00%)
Pyrexia
No. of participants affected / at risk1/184 (0.00%)2/184 (0.00%)
Cholelithiasis
No. of participants affected / at risk2/184 (0.00%)0/184 (0.00%)
Hepatic steatosis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Allergy to arthropod bite
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Hypersensitivity
No. of participants affected / at risk0/184 (0.00%)2/184 (0.00%)
Acute sinusitis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Bronchitis
No. of participants affected / at risk7/184 (0.00%)12/184 (0.00%)
Cellulitis
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Chronic sinusitis
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Conjunctivitis
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Cystitis
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Ear infection
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Erysipelas
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Fungal infection
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Fungal skin infection
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Furuncle
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Gastric infection
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Gastroenteritis
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Gastrointestinal viral infection
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Gingivitis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Herpes dermatitis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Herpes simplex
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Herpes zoster
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Hordeolum
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Influenza
No. of participants affected / at risk2/184 (0.00%)1/184 (0.00%)
Laryngitis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Nasopharyngitis
No. of participants affected / at risk14/184 (0.00%)11/184 (0.00%)
Ophthalmic herpes zoster
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Oral candidiasis
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Oral fungal infection
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Oral herpes
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Paronychia
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Pharyngitis
No. of participants affected / at risk5/184 (0.00%)3/184 (0.00%)
Pharyngitis streptococcal
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Pulmonary tuberculosis
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Respiratory tract infection viral
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Rhinitis
No. of participants affected / at risk1/184 (0.00%)2/184 (0.00%)
Scrub typhus
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Sialoadenitis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Sinusitis
No. of participants affected / at risk0/184 (0.00%)2/184 (0.00%)
Subcutaneous abscess
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Tonsillitis
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Tonsillitis bacterial
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Tooth infection
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Tracheitis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Upper respiratory tract infection
No. of participants affected / at risk7/184 (0.00%)3/184 (0.00%)
Urinary tract infection
No. of participants affected / at risk4/184 (0.00%)5/184 (0.00%)
Viral diarrhoea
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Viral upper respiratory tract infection
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Accidental overdose
No. of participants affected / at risk11/184 (0.00%)5/184 (0.00%)
Animal bite
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Contusion
No. of participants affected / at risk2/184 (0.00%)1/184 (0.00%)
Fall
No. of participants affected / at risk3/184 (0.00%)1/184 (0.00%)
Foot fracture
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Hand fracture
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Intentional overdose
No. of participants affected / at risk1/184 (0.00%)2/184 (0.00%)
Ligament sprain
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Limb injury
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Muscle rupture
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Post-traumatic pain
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Scratch
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Skin abrasion
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Wound
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Activated partial thromboplastin time prolonged
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Alanine aminotransferase increased
No. of participants affected / at risk6/184 (0.00%)7/184 (0.00%)
Aspartate aminotransferase increased
No. of participants affected / at risk3/184 (0.00%)1/184 (0.00%)
Blood creatinine increased
No. of participants affected / at risk0/184 (0.00%)2/184 (0.00%)
Blood lactate dehydrogenase increased
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Blood pressure increased
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Creatinine renal clearance decreased
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Electrocardiogram ST segment elevation
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Eosinophil count increased
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Haemoglobin decreased
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Hepatic enzyme increased
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Liver function test abnormal
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Neutrophil count decreased
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Transaminases increased
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Weight decreased
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
White blood cell count decreased
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Dyslipidaemia
No. of participants affected / at risk3/184 (0.00%)2/184 (0.00%)
Glucose tolerance impaired
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Hypercholesterolaemia
No. of participants affected / at risk2/184 (0.00%)0/184 (0.00%)
Hyperlipidaemia
No. of participants affected / at risk2/184 (0.00%)1/184 (0.00%)
Hypertriglyceridaemia
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Impaired fasting glucose
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Type 2 diabetes mellitus
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Arthralgia
No. of participants affected / at risk3/184 (0.00%)5/184 (0.00%)
Arthritis
No. of participants affected / at risk0/184 (0.00%)2/184 (0.00%)
Back pain
No. of participants affected / at risk3/184 (0.00%)2/184 (0.00%)
Bursitis
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Muscle spasms
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Musculoskeletal pain
No. of participants affected / at risk2/184 (0.00%)1/184 (0.00%)
Musculoskeletal stiffness
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Myalgia
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Neck pain
No. of participants affected / at risk2/184 (0.00%)1/184 (0.00%)
Osteoarthritis
No. of participants affected / at risk1/184 (0.00%)2/184 (0.00%)
Osteoporotic fracture
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Pain in extremity
No. of participants affected / at risk0/184 (0.00%)2/184 (0.00%)
Rheumatoid arthritis
No. of participants affected / at risk7/184 (0.00%)1/184 (0.00%)
Spinal osteoarthritis
No. of participants affected / at risk2/184 (0.00%)0/184 (0.00%)
Synovial cyst
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Leiomyoma
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Uterine leiomyoma
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Carotid artery disease
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Dizziness
No. of participants affected / at risk1/184 (0.00%)2/184 (0.00%)
Headache
No. of participants affected / at risk12/184 (0.00%)7/184 (0.00%)
Migraine
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Paraesthesia
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Paresis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Polyneuropathy
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Presyncope
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Radiculopathy
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Somnolence
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Vascular encephalopathy
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Depression
No. of participants affected / at risk1/184 (0.00%)3/184 (0.00%)
Grief reaction
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Insomnia
No. of participants affected / at risk2/184 (0.00%)3/184 (0.00%)
Mental disorder
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Middle insomnia
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Panic attack
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Dysuria
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Renal colic
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Renal cyst
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Dysmenorrhoea
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Bronchiectasis
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Dyspnoea
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Epistaxis
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Oropharyngeal pain
No. of participants affected / at risk1/184 (0.00%)2/184 (0.00%)
Pulmonary fibrosis
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Rhinitis allergic
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Dermatitis
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Dermatitis allergic
No. of participants affected / at risk2/184 (0.00%)2/184 (0.00%)
Dermatitis contact
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Hypersensitivity vasculitis
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Ingrowing nail
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Miliaria
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Photosensitivity reaction
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Pityriasis rosea
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Pruritus
No. of participants affected / at risk1/184 (0.00%)2/184 (0.00%)
Pruritus allergic
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Pustular psoriasis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Rash
No. of participants affected / at risk3/184 (0.00%)1/184 (0.00%)
Rash papular
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Rash pruritic
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Seborrhoeic dermatitis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Skin ulcer
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Solar dermatitis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Urticaria
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Menopause
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Tooth repair
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Aortic arteriosclerosis
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Arterial stenosis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Brachiocephalic arteriosclerosis
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)
Deep vein thrombosis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Hot flush
No. of participants affected / at risk1/184 (0.00%)1/184 (0.00%)
Hypertension
No. of participants affected / at risk4/184 (0.00%)3/184 (0.00%)
Vasculitis
No. of participants affected / at risk0/184 (0.00%)1/184 (0.00%)
Venous thrombosis limb
No. of participants affected / at risk1/184 (0.00%)0/184 (0.00%)

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.

Results Point of Contact

Name/TitleOrganizationPhoneEmail
Trial Transparency Team
Sanofi