Prospective Study on Intensive Early Rheumatoid Arthritis Treatment

A Phase IV Multicenter, Randomized, Double-blind Study. prospeCtive Study on Intensive Early Rheumatoid Arthritis Treatment With adalimUmab: Induction of REmission and Maintenance

Hypothesis: Early intensive treatment with anti-TNF agent plus methotrexate plus high dose prednisone may increase remission rate and may induce stable remission in Rheumatoid Arthritis Objective: to evaluate induction of remission using adalimumab, prednisone and methotrexate and maintenance of remission after discontinuation of adalimumab and prednisone

Treatment group A 0 - 6 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly + prednisone 50 mg/d tapered to 6.25 mg 6 - 12 months: Adalimumab 40 mg eow plus methotrexate 20 mg weekly group B 0 - 6 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly + placebo 6 - 12 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly

Follow up period - Open Label phase:

Patients achieving clinical remission will be than treated only with MTX and observed for another 12 months period. Patients who do not achieve clinical remission or patients who will experience a relapse of the disease will be treated according to standard of care (SOC) modalities.

Inclusion Criteria:

• Active rheumatoid arthritis diagnosed for at least 6 weeks, but no more than 1 year, according to the revised 1987 ACR criteria
• Naïve to treatment with MTX
• Swollen joint count (SJC) > 8 tender joint count (TJC) > 8
• At screening CRP > 1.5 mg/dL (15 mg/L) or ESR ≥ 28 mm/h
• ≥ 1 joint erosion or RF positivity or anti-CCP positivity
• Age 18-70 years.

Exclusion Criteria:

• Rheumatic autoimmune disease other than RA
• Functional class IV
• Any surgical procedure within 12 weeks prior to baseline or planned during the study.
• Pregnancy or breast feeding.
• Evidence of significant concomitant disease
• Primary or secondary immunodeficiency
• active infection of any kind
• History of previously untreated infection with mycobacterium tuberculosis or current treatment for same.
• History of cancer
• Any history or presence of congestive heart failure (CHF) (New York Heart Association classification for CHF: Class III or IV).
• Any history of myocardial infarction within 5 years.
• History of a severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of adalimumab or methotrexate.
• Positive serology for hepatitis B or C indicating active infection.
• Hemoglobin < 8.0 g/dL.
• Absolute neutrophil count (ANC) < 1.5 x 103/L.
• Liver function abnormality