Effects of Tofacitinib (CP-690,550) on Magnetic Resonance Imaging (MRI)- Assessed Joint Structure In Early Rheumatoid Arthritis (RA)

• Drug: Tasocitinib plus Methotrexate
  
  Tofacitinib (CP 690,550) 10 mg BID, tablets + methotrexate (MTX) 10 mg/wk to 20 mg/wk, titrated over 2 months
• Drug: Tofacitinib plus placebo methotrexate
  
  Tofacitinib (CP-90,550) 10 mg BID, tablets. Placebo to match methotrexate (MTX) capsules titrated as in Treatment Arm 1.
• Drug: Placebo tofacitinib plus Methotrexate
  
  Methotrexate (MTX) 10 mg/wk to 20 mg/wk, capsules, titrated over 2 months. Placebo in tablets to match tofacitinib

• Experimental: Tofacitinib (CP 690,550) 10 mg BID plus MTX
  
  Intervention: Drug: Tasocitinib plus Methotrexate
• Experimental: Tofacitinib (CP-690,550) 10 mg BID, tablet plus placebo MTX
  
  Intervention: Drug: Tofacitinib plus placebo methotrexate
• Active Comparator: Placebo tofacitinib (CP-690,55) plus MTX 10 mg/wk to 20 mg/wk
  
  Intervention: Drug: Placebo tofacitinib plus Methotrexate

• Conaghan PG, Østergaard M, Troum O, Bowes MA, Guillard G, Wilkinson B, Xie Z, Andrews J, Stein A, Chapman D, Koenig A. Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis. Arthritis Res Ther. 2019 Oct 21;21(1):214. doi: 10.1186/s13075-019-2000-1.
• Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Thirunavukkarasu K, DeMasi R, Geier J, Kwok K, Wang L, Riese R, Wollenhaupt J. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31.
• Conaghan PG, Østergaard M, Bowes MA, Wu C, Fuerst T, van der Heijde D, Irazoque-Palazuelos F, Soto-Raices O, Hrycaj P, Xie Z, Zhang R, Wyman BT, Bradley JD, Soma K, Wilkinson B. Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques. Ann Rheum Dis. 2016 Jun;75(6):1024-33. doi: 10.1136/annrheumdis-2015-208267. Epub 2016 Jan 25.
• 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.

Inclusion Criteria:

• Adult patients with moderate to severe early rheumatoid arthritis (< 2 years) who are methotrexate and biologic disease modifying antirheumatic drug naive.

Exclusion Criteria:

• Pregnant or lactating patients;
• Patients with renal or hepatic impairment or other severe or progressing disease;
• Patients with contraindication to magnetic resonance imaging with gadolinium contrast.