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

INTERVENTION: Product Name: Sarilumab Product Code: SAR153191 Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed INN: Sarilumab Current Sponsor code: SAR153191 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 131.6‐ Pharmaceutical form of the placebo: Solution for injection in pre‐filled syringe Route of administration of the placebo: Subcutaneous use Product Name: Sarilumab Product Code: SAR153191 Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed INN: Sarilumab Current Sponsor code: SAR153191 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 175‐ Pharmaceutical form of the placebo: Solution for injection in pre‐filled syringe Route of administration of the placebo: Subcutaneous use CONDITION: Rheumatoid Arthritis ; MedDRA version: 15.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 ‐ Musculoskeletal and connective tissue disorders Therapeutic area: Diseases [C] ‐ Musculoskeletal Diseases [C05] PRIMARY OUTCOME: Main Objective: To demonstrate that sarilumab added to disease modifying anti‐rheumatic drugs (DMARDs) is effective for: ; • reduction of signs and symptoms at week 24 and ; • improvement of physical function over 24 weeks ; in patients with active rheumatoid arthritis (RA) who are inadequate responders or intolerant to tumor necrosis factor alpha (TNF‐a) antagonists ; Primary end point(s): The percentage of patients who achieved at least 20% improvement in the American College of Rheumatology (ACR) criteria; Change in physical function as measured by the average of change from baseline in the health assessment questionnaire‐disability index (HAQ‐DI) from Wk 8 to Wk 24 Secondary Objective: The secondary objectives are to investigate the effects of SAR153191 (REGN88) when added to DMARD therapy, in patients with active RA who are inadequate responders or intolerant to TNF‐a antagonists, for:; • reduction of signs and symptoms at 12 weeks,; • improvement in physical function at 12 weeks, ; • improvement in disease activity as measured by other ACR derived components at Weeks 12 and 24, and; • improvement in quality of life as measured by patient reported outcomes (PROs) at intermediate visits and Week 24.; To assess the safety of sarilumab in this population.; To assess the exposure of sarilumab added to DMARD therapy in this population.; Timepoint(s) of evaluation of this end point: At Week 24 SECONDARY OUTCOME: Secondary end point(s): 1‐ Percentage of patients achieving American College of Rheumatology (ACR) 20/50/70 criteria ; ; 2‐ Percentage of patients achieving American College of Rheumatology (ACR) 50/70 criteria ; ; 3‐ Changes from baseline in disease activity score (DAS) 28 ; ; 4‐ Disease activity score (DAS) 28 remission rate ; ; 5‐ Change from baseline in short form (SF)‐36 domains ; ; 6‐ Change from baseline in the Rheumatoid Arthritis‐Work Productivity Survey (WPS‐RA) items ; ; 7‐ Change from baseline in the Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT‐fatigue) ; ; 8‐ Change from baseline in European Qouality of Life‐5 dimension (EQ‐5D) ; ; 9‐ Change from baseline in rheumatoid arthritis impact of disease (RAID) scores ; ; 10‐ Change from baseline in each individual ACR component ; Timepoint(s) of evaluation of this end point: 1‐ At Week 12 ; 2‐ At Week 24 ; 3 to 10‐ At Week 12 and Week 24 ; ACR Class I‐III functional status, based on 1991 revised criteria TNF‐blockers may include, but are not limited to, etanercept, infliximab, adalimumab, golimumab and/or certolizumab. INCLUSION CRITERIA: Diagnosis of rheumatoid arthritis =6 months duration, according to the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) 2010 Rheumatoid Arthritis Classification Criteria Anti‐TNF therapy failures, defined by the investigator as patients with an inadequate clinical response, after being treated for at least 3 consecutive months, and/or intolerance to at least 1 anti‐TNF blocker(s), resulting in or requiring their discontinuation: Moderate‐to‐severely active rheumatoid arthritis. Continuous treatment with one or a combination of DMARDs (except for simultaneous combination use of leflunomide and methotrexate) for at least 12 weeks prior to baseline and on a stable dose(s) for at least 6 weeks prior to screening: Methotrexate –