Comparing The Effectiveness And Safety Of 2 Doses Of An Experimental Drug, CP-690,550, To Methotrexate (MTX) In Patients With Rheumatoid Arthritis Who Have Not Previously Received MTX

• Drug: CP-690,550
  
  Oral tablets administered at a dose of 5 mg BID for 24 months
• Drug: CP-690,550
  
  Oral tablets administered at a dose of 10 mg BID for 24 months
• Drug: Disease-modifying antirheumatic drug
  
  Oral capsules,administered as 10 mg per week for 4 weeks titrated to 15 mg per week for 4 weeks, then titrated to 20 mg week for 24 months
  Other Name: DMARD, MTX

• Experimental: 5 mg BID CP-690,550
  
  Intervention: Drug: CP-690,550
• Experimental: 10 mg BID CP-690,550
  
  Intervention: Drug: CP-690,550
• Active Comparator: methotrexate
  
  Intervention: Drug: Disease-modifying antirheumatic drug

• Fleischmann RM, Huizinga TW, Kavanaugh AF, Wilkinson B, Kwok K, DeMasi R, van Vollenhoven RF. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis. RMD Open. 2016 Jul 26;2(2):e000262. doi: 10.1136/rmdopen-2016-000262. eCollection 2016.
• Fleischmann R, Strand V, Wilkinson B, Kwok K, Bananis E. Relationship between clinical and patient-reported outcomes in a phase 3 trial of tofacitinib or MTX in MTX-naïve patients with rheumatoid arthritis. RMD Open. 2016 Apr 26;2(1):e000232. doi: 10.1136/rmdopen-2015-000232. eCollection 2016.
• Cohen S, Radominski SC, Gomez-Reino JJ, Wang L, Krishnaswami S, Wood SP, Soma K, Nduaka CI, Kwok K, Valdez H, Benda B, Riese R. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Nov;66(11):2924-37. doi: 10.1002/art.38779.
• Lee EB, Fleischmann R, Hall S, Wilkinson B, Bradley JD, Gruben D, Koncz T, Krishnaswami S, Wallenstein GV, Zang C, Zwillich SH, van Vollenhoven RF; ORAL Start Investigators. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med. 2014 Jun 19;370(25):2377-86. doi: 10.1056/NEJMoa1310476.

Inclusion Criteria:

• Adults with moderate to severe RA (Rheumatoid Arthritis) who have not been treated with methotrexate.
• Diagnosis of RA based on the American College of Rheumatology 1987 revised criteria.
• Active disease as defined by both >=6 tender or painful joints on motion and >= 6 joints swollen; and either an erythrocyte sedimentation rate (ESR) > 28 mm or a C-reactive protein (CRP) concentration > 7 mg/dL

Exclusion Criteria:

• Blood dyscrasias including confirmed: Hemoglobin <9 g/dL or Hematocrit <30%; White blood cell count <3.0 x 109/L; Absolute neutrophil count <1.2 x 109/L; Platelet count <100 x 109/L
• History of any other rheumatic autoimmune disease other than Sjogren's syndrome
• No malignancy or history of malignancy
• History of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 6 months prior to the first dose of study drug
• No chronic liver disease, recent or active hepatitis or other contraindication to methotrexate therapy