Clinical Trial to Evaluate the Efficacy and Safety of Infliximab Treatment on Rheumatoid Arthritis (RA)

The purpose of this study is to compare the effectiveness of Infliximab plus methotrexate (MTX) in treatment of RA patients with moderate disease versus RA patients with severe disease and to compare the efficacy and the safety of the MTX subgroups.

This is an open label (both physician and patient know the name of the study drug), multi-center study comparing the American College of Rheumatology (ACR) scores of patients with moderate Rheumatoid Arthritis (RA) to those RA patients with severe disease while being treated with infliximab and methotrexate (MTX). Moderate RA is defined as having a score greater than 3.2, but less than 5.1 on the Disease Activity Score 28 and severe RA is defined as having a score greater than 5.1 on the Disease Activity Score 28). Change in the Disease Activity Score (DAS) at week 26 will be utilized to determine effectiveness. The following are used to evaluate the severity of RA: ACR measures improvement in tender or swollen joints by assessing several parameters. DAS evaluates RA activity by looking at several parameters including the number of swollen and tender joints and the VAS (which measures the patient's own assessment of their pain). About 220 patients with RA will be recruited in this study. Patients will receive infliximab 3mg/kg intravenous infusion (drug given into a vein) at weeks 0, 2, 6, 14 and 22 along with a stable dose of MTX capsules. Patients will be evaluated using the ACR criteria. Any patient ending study early will be followed for Adverse Events (AE) and Serious Adverse Events (SAE) up to 4 weeks following the last dose of study drug. Patients will have a follow-up visit on Week 26 to evaluate safety assessments. Primary Outcome Measure is the percentage of patients obtaining ACR20, ACR50 and ACR70 response at week 26. The Secondary Outcome Measures include the change in DAS and individual components of the ACR score (number of joints with swelling and tenderness, joint pain and swelling, each item of the Visual Analog Score (VAS), and results of laboratory evaluation) between the baseline visit and at week 26. Other Outcomes Measures are to compare the ACR20, ACR50 and ACR70 responses in the MTX subgroups at week 26. Safety evaluations (AE reporting, labs, vital signs, etc) will be performed. Infliximab is administered as an intravenous injection (directly into the vein) on weeks 0, 2, 6, 14, 22. The dosage is 3mg/kg infused over no less than 2 hours. MTX is taken orally, in doses of 7.5 - 20 mg/week (equal to the dose used prior to participation in the study)

Inclusion Criteria:

• Subjects who are capable of providing informed consent, which must be obtained prior to any study-related procedures
• Those who have a definitive diagnosis of RA based on the criteria of American College of Rheumatology in 1987
• Patients must have been on MTX for 12 weeks with the dose having been stable for at least 4 weeks prior to study entry
• Patients using oral corticosteroids, must have been on a stable dose of prednisone <10mg/day or its equivalent for at least 4 weeks prior to screening or if currently not using corticosteroids, the patient must not have received corticosteroids for at least 4 weeks prior to screening
• Moderate to severe RA (DAS28>3.2)

Exclusion Criteria:

• Patient who has a known hypersensitivity to human immunoglobulin proteins or other components of infliximab
• Patient who has a history of receiving infliximab or any other monoclonal antibody
• Patient who is in stage IV RA evaluated by X-ray
• Patients who are suffering tuberculosis
• Female patient who is pregnant or breast-feeding
• Female patient or male patient's wife who plans to become pregnant during this study and within 6 months after completion of this study.