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)

A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing the Efficacy and Safety of Sarilumab Added to Non-biologic DMARD Therapy in Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF-α Antagonists

Primary Objective:

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

• reduction of signs and symptoms at Week 24 and
• improvement of physical function at Week 12

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

Secondary Objectives:

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

• Reduction of signs and symptoms at Week 12;
• Improvement in physical function at Week 24;
• Improvement in disease activity score as measured by other American College of Rheumatology (ACR) derived components at Weeks 12 and 24;
• Improvement in quality of life as measured by participant reported outcomes (PROs) at intermediate visits and Week 24.

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

To assess the safety of sarilumab in this population.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: placebo; Drug: hydroxychloroquine; Drug: methotrexate; Drug: sulfasalazine; Drug: leflunomide; Drug: Sarilumab

Detailed Description

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

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

• Study Type: Interventional
• Enrollment (Actual): 546
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 32015
    • Investigational Site Number 032015
  • Buenos Aires, Argentina, C1428DZF
    • Investigational Site Number 032008
  • Caba, Argentina, C1015ABO
    • Investigational Site Number 032006
  • Caba, Argentina, 1180
    • Investigational Site Number 032019
  • Capital Federal, Argentina, 1425
    • Investigational Site Number 032016
  • Cordoba, Argentina, X5119XAA
    • Investigational Site Number 032020
  • La Plata, Argentina
    • Investigational Site Number 032017
  • Ramos Mejia, Argentina, B1704ETD
    • Investigational Site Number 032010
  • Rosario, Argentina, S2000PBJ
    • Investigational Site Number 032013
  • San Miguel De Tucuman, Argentina, T4000AXL
    • Investigational Site Number 032004
  • Zarate, Argentina, B2800DGH
    • Investigational Site Number 032009
• Australia
  • Victoria Park, Australia, 6100
    • Investigational Site Number 036014
• Austria
  • Stockerau, Austria, 2000
    • Investigational Site Number 040004
  • Wien, Austria, 1090
    • Investigational Site Number 040003
• Brazil
  • Curitiba, Brazil, 80060-240
    • Investigational Site Number 076001
  • Curitiba, Brazil
    • Investigational Site Number 076016
  • Goiania, Brazil, 74110-120
    • Investigational Site Number 076006
  • Juiz De Fora, Brazil, 36010-570
    • Investigational Site Number 076010
  • Rio De Janeiro, Brazil, 20551-030
    • Investigational Site Number 076005
  • Rio De Janeiro, Brazil, 22271-100
    • Investigational Site Number 076015
• Canada
  • Toronto, Canada, M5T 2S8
    • Investigational Site Number 124005
  • Trois-Rivières, Canada, G8Z 1Y2
    • Investigational Site Number 124009
  • Victoria, Canada, V8V 3P9
    • Investigational Site Number 124104
• Chile
  • Temuco, Chile
    • Investigational Site Number 152015
• Colombia
  • Bogota, Colombia
    • Investigational Site Number 170001
  • Bogota, Colombia
    • Investigational Site Number 170012
  • Bogotá, Colombia
    • Investigational Site Number 170006
  • Bucaramanga, Colombia
    • Investigational Site Number 170007
  • Bucaramanga, Colombia
    • Investigational Site Number 170009
  • Chia, Colombia
    • Investigational Site Number 170014
  • Medellin, Colombia
    • Investigational Site Number 170019
• Czechia
  • Hostivice, Czechia, 233 01
    • Investigational Site Number 203008
  • Ostrava, Czechia, 702 00
    • Investigational Site Number 203004
  • Praha 2, Czechia, 12850
    • Investigational Site Number 203007
  • Uherske Hradiste, Czechia, 686 01
    • Investigational Site Number 203002
  • Zlin, Czechia, 76001
    • Investigational Site Number 203006
• Ecuador
  • Cuenca, Ecuador
    • Investigational Site Number 218003
  • Guayaquil, Ecuador, 0593
    • Investigational Site Number 218001
  • Quito, Ecuador, 0593
    • Investigational Site Number 218002
• Germany
  • Bad Nauheim, Germany, 61231
    • Investigational Site Number 276011
  • Berlin, Germany, 10117
    • Investigational Site Number 276010
  • Berlin, Germany, 14059
    • Investigational Site Number 276014
  • Berlin, Germany, 12305
    • Investigational Site Number 276001
  • Deggingen, Germany, 73326
    • Investigational Site Number 276018
  • Erlangen, Germany, 91054
    • Investigational Site Number 276004
  • Halle/Saale, Germany, 06108
    • Investigational Site Number 276015
  • Hamburg, Germany, 22147
    • Investigational Site Number 276013
  • Leipzig, Germany, 04103
    • Investigational Site Number 276016
  • München, Germany, 80336
    • Investigational Site Number 276017
  • Osnabrück, Germany, 49074
    • Investigational Site Number 276021
  • Tübingen, Germany, 72076
    • Investigational Site Number 276020
  • Zerbst, Germany, 39261
    • Investigational Site Number 276019
• Greece
  • Heraklion, Greece, 71110
    • Investigational Site Number 300002
  • Thessaloniki, Greece, 57010
    • Investigational Site Number 300005
• Guatemala
  • Guatemala City, Guatemala, 01009
    • Investigational Site Number 320002
  • Guatemala City, Guatemala, 01011
    • Investigational Site Number 320003
  • Guatemala City, Guatemala, 09090
    • Investigational Site Number 320001
• Hungary
  • Budapest, Hungary, 1036
    • Investigational Site Number 348022
  • Debrecen, Hungary, 4032
    • Investigational Site Number 348003
  • Veszprém, Hungary, 8200
    • Investigational Site Number 348004
  • Veszprém, Hungary, 8200
    • Investigational Site Number 348017
• Israel
  • Haifa, Israel, 31048
    • Investigational Site Number 376001
  • Petach Tikva, Israel, 49100
    • Investigational Site Number 376003
  • Tel Hashomer, Israel, 52621
    • Investigational Site Number 376002
• Italy
  • Catania, Italy, 95122
    • Investigational Site Number 380011
  • Firenze, Italy, 50139
    • Investigational Site Number 380002
  • Genova, Italy, 16132
    • Investigational Site Number 380005
  • Milano, Italy, 20157
    • Investigational Site Number 380014
  • Udine, Italy, 33100
    • Investigational Site Number 380013
• Korea, Republic of
  • Daejeon, Korea, Republic of, 301-721
    • Investigational Site Number 410017
  • Seoul, Korea, Republic of, 120-752
    • Investigational Site Number 410016
• Lithuania
  • Kaunas, Lithuania, LT-50009
    • Investigational Site Number 440005
  • Klaipeda, Lithuania, LT-92288
    • Investigational Site Number 440006
  • Vilnius, Lithuania, LT-08661
    • Investigational Site Number 440007
• Mexico
  • Chihuahua, Mexico, 31020
    • Investigational Site Number 484023
  • Guadalajara, Mexico, 44620
    • Investigational Site Number 484018
  • Guadalajara, Mexico, 44690
    • Investigational Site Number 484002
  • Guadalajara, Mexico
    • Investigational Site Number 484024
  • Mexicali, Mexico, 21200
    • Investigational Site Number 484010
  • Monterrey, Mexico, 64000
    • Investigational Site Number 484019
  • Monterrey, Mexico, 64000
    • Investigational Site Number 484020
  • Monterrey, Mexico, 64460
    • Investigational Site Number 484005
  • México, Mexico, 06700
    • Investigational Site Number 484017
  • Queretaro, Mexico, 76178
    • Investigational Site Number 484021
• New Zealand
  • Hamilton, New Zealand, 3204
    • Investigational Site Number 554005
  • Nelson, New Zealand, 7010
    • Investigational Site Number 554011
  • Otahuhu, New Zealand, 2025
    • Investigational Site Number 554007
  • Timaru, New Zealand, 7910
    • Investigational Site Number 554001
  • Wellington, New Zealand, 6021
    • Investigational Site Number 554006
• Peru
  • Lima, Peru, 14
    • Investigational Site Number 604010
  • Lima, Peru, LIMA 01
    • Investigational Site Number 604009
  • Lima, Peru, LIMA 11
    • Investigational Site Number 604006
  • Lima, Peru, LIMA 11
    • Investigational Site Number 604012
  • Lima, Peru, LIMA 13
    • Investigational Site Number 604013
  • Lima, Peru, Lima 33
    • Investigational Site Number 604007
  • Lima, Peru, Lima 41
    • Investigational Site Number 604005
  • Lima, Peru, Lima 21
    • Investigational Site Number 604001
  • Lima, Peru, LIMA 27
    • Investigational Site Number 604008
  • Lima, Peru, LIMA 41
    • Investigational Site Number 604014
• Poland
  • Bialystok, Poland, 15-099
    • Investigational Site Number 616014
  • Bydgoszcz, Poland, 85-168
    • Investigational Site Number 616019
  • Elblag, Poland, 82-300
    • Investigational Site Number 616015
  • Poznan, Poland, 61-397
    • Investigational Site Number 616018
  • Szczecin, Poland, 71-252
    • Investigational Site Number 616016
  • Warszawa, Poland, 02-118
    • Investigational Site Number 616004
  • Warszawa, Poland, 02-653
    • Investigational Site Number 616017
  • Wroclaw, Poland, 50-556
    • Investigational Site Number 616020
• Portugal
  • Lisboa, Portugal, 1649-035
    • Investigational Site Number 620004
  • Lisboa, Portugal, 1050-034
    • Investigational Site Number 620002
  • Ponte De Lima, Portugal
    • Investigational Site Number 620007
• Romania
  • Bucuresti, Romania, 010976
    • Investigational Site Number 642001
  • Bucuresti, Romania, 020983
    • Investigational Site Number 642002
  • Bucuresti, Romania, 020475
    • Investigational Site Number 642012
  • Iasi, Romania, 700661
    • Investigational Site Number 642014
• Russian Federation
  • Moscow, Russian Federation, 115522
    • Investigational Site Number 643001
  • Moscow, Russian Federation, 119049
    • Investigational Site Number 643021
  • Novosibirsk, Russian Federation, 630091
    • Investigational Site Number 643022
  • Saint-Petersburg, Russian Federation, 192242
    • Investigational Site Number 643008
  • Samara, Russian Federation, 443095
    • Investigational Site Number 643010
• Slovakia
  • Kosice, Slovakia, 040 11
    • Investigational Site Number 703001
• Spain
  • Barakaldo, Spain, 48903
    • Investigational Site Number 724016
  • Barcelona, Spain, 08034
    • Investigational Site Number 724015
  • Cadiz, Spain, 1009
    • Investigational Site Number 724014
  • La Coruña, Spain, 15006
    • Investigational Site Number 724009
  • Málaga, Spain, 29009
    • Investigational Site Number 724001
  • Sabadell, Spain, 08208
    • Investigational Site Number 724011
  • Santiago De Compostela, Spain, 15706
    • Investigational Site Number 724013
  • Santiago De Compostela, Spain, 15702
    • Investigational Site Number 724017
  • Sevilla, Spain, 41071
    • Investigational Site Number 724007
• Taiwan
  • Kaohsiung, Taiwan, 81346
    • Investigational Site Number 158005
  • Taipei, Taiwan, 402
    • Investigational Site Number 158006
  • Taoyuan County, Taiwan, 33305
    • Investigational Site Number 158002
• Turkey
  • Edirne, Turkey, 22030
    • Investigational Site Number 792007
  • Gaziantep, Turkey, 27310
    • Investigational Site Number 792008
  • Samsun, Turkey
    • Investigational Site Number 792009
• Ukraine
  • Kharkiv, Ukraine, 61176
    • Investigational Site Number 804013
  • Kyiv, Ukraine, 01103
    • Investigational Site Number 804014
  • Kyiv, Ukraine, 03680
    • Investigational Site Number 804027
  • Vinnytsia, Ukraine, 21018
    • Investigational Site Number 804011
  • Zaporizhzhya, Ukraine, 69600
    • Investigational Site Number 804009
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Investigational Site Number 840070
    • Birmingham, Alabama, United States, 35205
      • Investigational Site Number 840138
  • Arizona
    • Phoenix, Arizona, United States, 85037
      • Investigational Site Number 840142
  • California
    • Fullerton, California, United States, 92835
      • Investigational Site Number 840134
    • Glendale, California, United States, 85304
      • Investigational Site Number 840141
    • La Jolla, California, United States, 92037
      • Investigational Site Number 840111
    • San Diego, California, United States, 92120
      • Investigational Site Number 840135
    • Santa Maria, California, United States, 94354
      • Investigational Site Number 840021
    • Stanford, California, United States, 94305
      • Investigational Site Number 840100
    • Upland, California, United States, 91786
      • Investigational Site Number 840049
    • Whittier, California, United States, 90606
      • Investigational Site Number 840131
  • Colorado
    • Denver, Colorado, United States, 80230
      • Investigational Site Number 840201
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Investigational Site Number 840130
  • Florida
    • DeBary, Florida, United States, 32713
      • Investigational Site Number 840125
    • Miami, Florida, United States, 33155
      • Investigational Site Number 840048
    • Naples, Florida, United States, 34102
      • Investigational Site Number 840024
    • Orlando, Florida, United States, 32806
      • Investigational Site Number 840006
    • Ormond Beach, Florida, United States, 32174
      • Investigational Site Number 840128
    • Palm Harbor, Florida, United States, 34684
      • Investigational Site Number 840063
    • Sarasota, Florida, United States, 34239
      • Investigational Site Number 840060
    • Tampa, Florida, United States, 33614
      • Investigational Site Number 840140
    • Vero Beach, Florida, United States, 32960
      • Investigational Site Number 840126
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Investigational Site Number 840018
    • Meridian, Idaho, United States, 83642
      • Investigational Site Number 840110
  • Kansas
    • Kansas City, Kansas, United States, 66160-7321
      • Investigational Site Number 840052
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Investigational Site Number 840015
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Investigational Site Number 840120
    • Lake Charles, Louisiana, United States, 70601
      • Investigational Site Number 840109
  • Maryland
    • Frederick, Maryland, United States, 21702
      • Investigational Site Number 840055
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Investigational Site Number 840150
    • Saint Clair Shores, Michigan, United States, 48081
      • Investigational Site Number 840137
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Investigational Site Number 840037
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Investigational Site Number 840112
  • New York
    • Orchard Park, New York, United States, 14127
      • Investigational Site Number 840106
    • Rochester, New York, United States, 14609
      • Investigational Site Number 840121
    • Roslyn, New York, United States, 11576
      • Investigational Site Number 840115
    • Smithtown, New York, United States, 11787
      • Investigational Site Number 840118
    • Syracuse, New York, United States, 13210
      • Investigational Site Number 840139
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Investigational Site Number 840123
    • Wilmington, North Carolina, United States, 28401
      • Investigational Site Number 840116
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Investigational Site Number 840127
    • Tulsa, Oklahoma, United States, 74104
      • Investigational Site Number 840011
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Investigational Site Number 840009
    • Pittsburgh, Pennsylvania, United States, 15213
      • Investigational Site Number 840117
    • Reading, Pennsylvania, United States, 19611
      • Investigational Site Number 840062
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • Investigational Site Number 840058
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Investigational Site Number 840025
    • Memphis, Tennessee, United States, 38119
      • Investigational Site Number 840059
  • Texas
    • Austin, Texas, United States, 78731
      • Investigational Site Number 840132
    • Dallas, Texas, United States, 75235
      • Investigational Site Number 840022
    • El Paso, Texas, United States, 79902
      • Investigational Site Number 840114
    • Houston, Texas, United States, 77074
      • Investigational Site Number 840129
    • Houston, Texas, United States, 77008
      • Investigational Site Number 840133
    • Mesquite, Texas, United States, 75150
      • Investigational Site Number 840074
  • Washington
    • Spokane, Washington, United States, 99204
      • Investigational Site Number 840036
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • Investigational Site Number 840124

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

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

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

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

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

Moderate-to-severely active RA

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

• Methotrexate - 6 to 25 mg/week orally or parenterally
• Leflunomide - 10 to 20 mg orally daily
• Sulfasalazine - 1000 to 3000 mg orally daily
• Hydroxychloroquine - 200 to 400 mg orally daily

Exclusion criteria:

Participants <18 years of age or legal adult age

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

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

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

Treatment with anti-TNF agents, as follows:

• Within 28 days prior to the baseline visit - etanercept
• Within 42 days prior to the baseline visit - infliximab, adalimumab, golimumab, certolizumab pegol

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

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

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

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

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

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

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

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

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

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

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

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

Participants with active tuberculosis or latent tuberculosis infection

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24	ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant (C-reactive Protein levels [CRP]); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by (health assessment questionnaire disability index [HAQ-DI]). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR.	Week 24
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12	Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. Least-squares (LS) means and standard errors (SE) at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24	DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the ACR rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (VAS). Marker of inflammation assessed by the high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28 score provides a number indicating the current disease activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS28-CRP score as a covariate.	Baseline, Week 24
Percentage of Participants Achieving ACR50 Criteria at Week 24	ACR responses are assessed with a composite rating scale that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR.	Week 24
Percentage of Participants Achieving ACR70 Criteria at Week 24	ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.	Week 24
Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24	DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.	Week 24
Change From Baseline in Clinical Disease Activity Index (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: TJC (28 joints), SJC (28 joints), Participant's Global Assessment of Disease Activity VAS (in cm), and Physician's Global Assessment of Disease VAS (in cm). Total scores ranges from 0 to 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline CDAI as a covariate.	Baseline, Week 24
Change From Baseline in HAQ-DI at Week 24	Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.	Baseline, Week 24
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24	SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: PCS and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS had 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS had 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 by MMRM with treatment,region,number of previous anti TNFs,visit,and treatment-by-visit interaction as fixed effects and baseline SF-36 (PCS) as a covariate.	Baseline, Week 24
Change From Baseline in SF-36 MCS at Week 24	SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 MCS as a covariate.	Baseline, Week 24
Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24	The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.	Baseline, Week 24
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 from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline Morning Stiffness as a covariate.	Baseline, Week 24
Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 24
Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 24
Change From Baseline in WPS-RA at Week 24: RA 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 was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 24
Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 24
Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 24
Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 24
Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 24
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 was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 24
Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores 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. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicate worse status and lower indicate not affected. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID as a covariate.	Baseline, Week 24
Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24	The EQ-5D-3L is a standardized, generic measure of health outcome. It was designed for self-completion by participants. It was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L Scores as a covariate.	Baseline, Week 24
Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12	ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.	Week 12
Change From Baseline in DAS28-CRP at Week 12	DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS score as a covariate.	Baseline, Week 12
Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP <2.6) at Week 12	DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.	Week 12
Change From Baseline in SF-36 at Week 12	SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 as a covariate.	Baseline, Week 12
Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 12
Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 12
Change From Baseline in WPS-RA at Week 12: RA 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 was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 12
Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 12
Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 12
Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 12
Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA	The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 12
Change From Baseline in WPS-RA at Week 12: 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 was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.	Baseline, Week 12
Change From Baseline in the FACIT-fatigue at Week 12	The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.	Baseline, Week 12
Change From Baseline in EQ-5D-3L VAS Scores at Week 12	The EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. The EQ-5D was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L scores as a covariate.	Baseline, Week 12
Change From Baseline in RAID Scores at Week 12	RAID score is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 NRS questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicates worse status and lower indicates not affected. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID scores as a covariate.	Baseline, Week 12
Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24	ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI & CRP. 68 joints were assessed for tenderness (TJC scoring 0-68) and 66 joints for swelling (SJC scoring 0-66). The 66 SJC evaluated the following joints: temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, interphalangeal of thumb, distal interphalangeal, proximal interphalangeal, knee, ankle mortise, ankle tarsus, metatarsophalangeal, interphalangeal of great toe, and proximal/distal interphalangeal of the toes. The TJC examined hip joints, in addition to the joints assessed for SJC. Increase in number of tender joints/swollen joints indicated severity. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.	Baseline, Week 12 and Week 24
Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24	ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & CRP. Physician global VAS & participant global VAS was done by 100 mm non-anchored VAS, from no arthritis (0) activity to maximal arthritis (100) activity. Pain VAS by 100 mm VAS ranging from 0 "no pain" to 100 "worst pain". LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.	Baseline, Week 12 and Week 24
Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24	ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & CRP. An elevated CRP level was considered a non-specific "marker" for RA. A reduction level indicates improvement. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.	Baseline, Week 12 and Week 24
Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24	ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI & CRP. HAQ-DI consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.	Baseline, Week 12 and Week 24

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Fleischmann R, Genovese MC, Maslova K, Leher H, Praestgaard A, Burmester GR. Long-term safety and efficacy of sarilumab over 5 years in patients with rheumatoid arthritis refractory to TNF inhibitors. Rheumatology (Oxford). 2021 Nov 3;60(11):4991-5001. doi: 10.1093/rheumatology/keab355.
• Rubbert-Roth A, Furst DE, Fiore S, Praestgaard A, Bykerk V, Bingham CO, Charles-Schoeman C, Burmester G. Association between low hemoglobin, clinical measures, and patient-reported outcomes in patients with rheumatoid arthritis: results from post hoc analyses of three phase III trials of sarilumab. Arthritis Res Ther. 2022 Aug 25;24(1):207. doi: 10.1186/s13075-022-02891-x.
• Rehberg M, Giegerich C, Praestgaard A, van Hoogstraten H, Iglesias-Rodriguez M, Curtis JR, Gottenberg JE, Schwarting A, Castaneda S, Rubbert-Roth A, Choy EHS; MOBILITY, MONARCH, TARGET, and ASCERTAIN investigators. Identification of a Rule to Predict Response to Sarilumab in Patients with Rheumatoid Arthritis Using Machine Learning and Clinical Trial Data. Rheumatol Ther. 2021 Dec;8(4):1661-1675. doi: 10.1007/s40744-021-00361-5. Epub 2021 Sep 14. Erratum In: Rheumatol Ther. 2021 Oct 29;:
• Genovese MC, Burmester GR, Hagino O, Thangavelu K, Iglesias-Rodriguez M, John GS, Gonzalez-Gay MA, Mandrup-Poulsen T, Fleischmann R. Interleukin-6 receptor blockade or TNFalpha inhibition for reducing glycaemia in patients with RA and diabetes: post hoc analyses of three randomised, controlled trials. Arthritis Res Ther. 2020 Sep 9;22(1):206. doi: 10.1186/s13075-020-02229-5.
• Genovese MC, Fleischmann R, Kivitz A, Lee EB, van Hoogstraten H, Kimura T, St John G, Mangan EK, Burmester GR. Efficacy and safety of sarilumab in combination with csDMARDs or as monotherapy in subpopulations of patients with moderately to severely active rheumatoid arthritis in three phase III randomized, controlled studies. Arthritis Res Ther. 2020 Jun 10;22(1):139. doi: 10.1186/s13075-020-02194-z.
• Gossec L, Strand V, Proudfoot C, Chen CI, Guillonneau S, Kimura T, van Hoogstraten H, Mangan E, Reaney M. Effects of Sarilumab on Rheumatoid Arthritis as Reported by Patients Using the Rheumatoid Arthritis Impact of Disease Scale. J Rheumatol. 2019 Oct;46(10):1259-1267. doi: 10.3899/jrheum.180904. Epub 2019 Mar 15.
• Fleischmann R, van Adelsberg J, Lin Y, Castelar-Pinheiro GD, Brzezicki J, Hrycaj P, Graham NM, van Hoogstraten H, Bauer D, Burmester GR. Sarilumab and Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis and Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors. Arthritis Rheumatol. 2017 Feb;69(2):277-290. doi: 10.1002/art.39944.
• Gabay C, Msihid J, Zilberstein M, Paccard C, Lin Y, Graham NMH, Boyapati A. Identification of sarilumab pharmacodynamic and predictive markers in patients with inadequate response to TNF inhibition: a biomarker substudy of the phase 3 TARGET study. RMD Open. 2018 Mar 14;4(1):e000607. doi: 10.1136/rmdopen-2017-000607. eCollection 2018.
• Strand V, Reaney M, Chen CI, Proudfoot CW, Guillonneau S, Bauer D, Mangan E, Graham NM, van Hoogstraten H, Lin Y, Pacheco-Tena C, Fleischmann R. Sarilumab improves patient-reported outcomes in rheumatoid arthritis patients with inadequate response/intolerance to tumour necrosis factor inhibitors. RMD Open. 2017 Mar 7;3(1):e000416. doi: 10.1136/rmdopen-2016-000416. eCollection 2017.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: October 15, 2012
• First Submitted That Met QC Criteria: October 16, 2012
• First Posted (Estimate): October 18, 2012

Study Record Updates

• Last Update Posted (Actual): August 8, 2017
• Last Update Submitted That Met QC Criteria: July 7, 2017
• Last Verified: July 1, 2017

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Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Reproductive Control Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate; Leflunomide; Hydroxychloroquine; Sulfasalazine
• Other Study ID Numbers: EFC10832; U1111-1115-8466 (Other Identifier: UTN); 2011-003538-16 (EudraCT Number)