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

• Change from baseline in OMERACT RAMRIS wrist joints and MCP synovitis (range 0-21) at Months 1, 6, and 12. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Change from baseline in OMERACT RAMRIS bone marrow edema (range 0 - 69) in MCP and wrist joints at Months 1, 3, and 12. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Change from baseline in OMERACT RAMRIS erosions in MCP and wrist joints, range (0-230) at all assessed time pointscentral facility. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Proportion of subjects achieving ACR 20, ACR 50 and ACR 70 at all time points. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Modified total Sharp scores, joint space narrowing and erosion scores as ascertained from posteroanterior (PA) hand and anteroposterior (AP) foot radiographs obtained at baseline, 6 and 12 months, scored by a central facility. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Proportion of subjects achieving American College of Rheumatology (ACR) responder criteria at the 20%, 50% and 70% improvement levels (ACR 20, ACR 50 and ACR 70, respectively) at all time points. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Actual and change from baseline in RA disease activity, assessed as the DAS using DAS28 3 CRP) and DAS28 4 ESR and the categorization of disease activity based on DAS at all time points. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

• Change from baseline in OMERACT RAMRIS wrist synovitis (range 0 9) at all assessed time points. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Change from baseline in OMERACT RAMRIS bone marrow edema (range 0 - 69) and erosions (MCPs 2 5 and wrist joints, range 0 230) at all assessed time points. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Modified total Sharp scores, joint space narrowing and erosion scores as ascertained from PA hand and anteroposterior AP foot radiographs obtained at baseline, 6 and 12 months, scored by a central facility. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Proportion of subjects achieving ACR 20, ACR 50 and ACR 70 at all time points. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Actual and change from baseline in disease activity, assessed as DAS28 3 CRP and DAS28 4 ESR and the categorization of disease activity based on DAS at all time points. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Incidence and severity of AEs. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
• Incidence and severity of clinical laboratory abnormalities. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Evaluation of efficacy and safety of tasocitinib (CP 690,550) for the treatment of early rheumatoid arthritis in adult patients with moderate to severe disease who are methotrexate naïve. The efficacy will be evaluated by exploring the effects on joint structure assessed by magnetic resonance imaging, x-rays and by standard clinical assessment.

• Drug: Tasocitinib plus Methotrexate
  Tasocitinib (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: Tasocitinib (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

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.