Open-Label Study Comparing Etanercept to Conventional Disease Modifying Antirheumatic Drug (DMARD) Therapy

• Biological: Phase 1: Etanercept
  
  Phase 1: prefilled syringe 50mg/ml, administered once weekly for study weeks 0 - 24
  Other Name: Enbrel
• Drug: Phase 1: Methotrexate
  
  Phase 1: oral tablet, 2.5mg, dose variable from 7.5mg to 25mg, once weekly for study weeks 0 - 24.
• Drug: Phase 2: Optional ETN, SSZ, HCQ, MTX
  

  Phase 2: All therapies are optional and may include any combination of the following: ETN, SSZ, HCQ, MTX Phase 2: Optional ETN: prefilled syringe 50mg/ml, dose variable after study week 24 to week 128.

  Phase 2: Optional SSZ: oral tablet, 0.5gm, dose variable per approved local label recommendations after study week 24 to week 128.

  Phase 2: HCQ: oral tablet, 200mg, dose variable per approved local label recommendations after study week 24 to week 128.

  Phase 2: MTX: oral tablet, 2.5mg dose variable after week 24 to week 128.

• Drug: Phase 1: Methotrexate
  
  Phase 1: oral tablet, 2.5mg dose variable from 7.5mg to 25mg, once weekly for study weeks 0 - 24.
• Drug: Phase 1: Conventiaonal DMARD
  
  Phase 1: SSZ: oral tablet, 0.5gm, dose variable per approved local label recommendations. OR Phase 1: HCQ: oral tablet, 200mg, dose variable per approved local label recommendations.

• Experimental: Phase 1 Etanercept + methotrexate
  
  Phase 1: Etanercept + methotrexate
  Interventions:
  

  • Biological: Phase 1: Etanercept
  • Drug: Phase 1: Methotrexate
  • Drug: Phase 2: Optional ETN, SSZ, HCQ, MTX
• Active Comparator: Phase 1 Conventional DMARD (SSZ or HCQ) + MTX
  
  Phase 1: Sulfasalazine (SSZ) + methotrexate (MTX) OR Phase 1: Hydrocholoquine (HCQ) + methotrexate
  Interventions:
  

  • Drug: Phase 1: Methotrexate
  • Drug: Phase 1: Conventiaonal DMARD

• Guerra Bautista G, Xavier RM, de la Vega M, Simón-Campos JA, Solano G, Pedersen RD, Vlahos B, Borlenghi C. Clinical Improvements as Predictors of Improvements in Patient-Reported Outcomes: Post Hoc Analysis of a Randomized, Open-Label Study of Etanercept in Latin American Patients with Rheumatoid Arthritis. Open Access Rheumatol. 2019 Dec 12;11:275-281. doi: 10.2147/OARRR.S228866. eCollection 2019.
• Machado DA, Guzman R, Xavier RM, Simon JA, Mele L, Shen Q, Pedersen R, Kotak S, Vlahos B. Two-Year Safety and Efficacy Experience in Patients with Methotrexate-Resistant Active Rheumatoid Arthritis Treated with Etanercept and Conventional Disease-Modifying Anti-rheumatic Drugs in the Latin American Region. Open Rheumatol J. 2016 Feb 29;10:13-25. doi: 10.2174/1874312901610010013. eCollection 2016.
• Fleischmann R, Koenig AS, Szumski A, Nab HW, Marshall L, Bananis E. Short-term efficacy of etanercept plus methotrexate vs combinations of disease-modifying anti-rheumatic drugs with methotrexate in established rheumatoid arthritis. Rheumatology (Oxford). 2014 Nov;53(11):1984-93. doi: 10.1093/rheumatology/keu235. Epub 2014 Jun 6.
• Machado DA, Guzman RM, Xavier RM, Simon JA, Mele L, Pedersen R, Ferdousi T, Koenig AS, Kotak S, Vlahos B. Open-label observation of addition of etanercept versus a conventional disease-modifying antirheumatic drug in subjects with active rheumatoid arthritis despite methotrexate therapy in the Latin American region. J Clin Rheumatol. 2014 Jan;20(1):25-33. doi: 10.1097/RHU.0000000000000055.

Inclusion Criteria:

• Diagnosis of Rheumatoid Arthritis (RA)
• Currently receiving a suboptimal response to a stable dose of methotrexate for treatment of Rheumatoid Arthritis (RA)
• Active Rheumatoid Arthritis (RA) at time of screening and baseline

Exclusion Criteria:

• Previous or current treatment with etanercept, other tumor necrosis factor-alpha inhibitors, or other biologic agents
• Concurrent treatment with a Disease Modifying Antirheumatic Drug (DMARD), other than methotrexate, at screening
• Receipt of any Disease Modifying Antirheumatic Drug (DMARD), other than methotrexate, within 3 months before screening