This 4 arm study will compare the safety and efficacy, with regard to reduction of signs and symptoms, of P38 Inhibitor (4) (50, 150 or 300mg po qd) monotherapy versus methotrexate monotherapy in adult patients with active rheumatoid arthritis. Patients will be randomized to receive one of 3 doses of P38 Inhibitor (4) or methotrexate. The anticipated time on study treatment is <3 months, and the target sample size is 100-500 individuals.

Inclusion Criteria:

• adult patients >18 years of age, with active RA;
• receiving treatment for RA on an outpatient basis;
• females of child-bearing potential, or nonsterilized males with partners of child-bearing potential, must use reliable contraception during, and for 4 weeks after, the study.

Exclusion Criteria:

• major surgery within 8 weeks prior to screening;
• rheumatic autoimmune disease or inflammatory joint disease other than RA;
• treatment with methotrexate within 8 weeks of baseline;
• concurrent use of DMARDs, including anti-TNF or other biologic therapy for RA.