Efficacy of Remicade in the Treatment of Active Rheumatoid Arthritis Despite Methotrexate (Study P03027)

Study Overview
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Brief Summary
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This is an open-label program of Remicade in the treatment of patients with active rheumatoid arthritis (RA) despite treatment with methotrexate (MTX) to determine the onset of efficacy of infliximab.

Official Title
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Onset of Efficacy of Anti-TNF Chimeric Monoclonal Antibody (Remicade) in the Treatment of Patients With Active Rheumatoid Arthritis Despite Methotrexate Treatment

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Biological: Infliximab (Remicade)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women, >=18 to <=75 years of age. Diagnosis of RA according to the revised 1987 criteria of the American Rheumatism Association (Arnett et al., 1988). The disease should have been diagnosed at least 6 months prior to Screening. Patients have active disease, in the opinion of the physician, despite the concomitant use of DMARDS. Evidence of active disease may include any of the following: 6 or more swollen or tender joints; and 2 of the following Morning stiffness >45 minutes C-reactive protein >2.0 mg/L ESR >28 mm/h Patients must have been using oral or parenteral MTX for at least 2 months with no break(s) in treatment of more than 2 weeks total during this period. Patients must have been on a stable dose of >=7.5 mg/wk (IM, SQ, PO) for at least 8 weeks prior to Screening. Men and women of childbearing potential must be using adequate birth control measures (abstinence, oral contraceptives, IUD, barrier method with spermicide or, surgical sterilization) and should continue such precautions for 6 months after receiving the last infusion. Patients must be on a stable dose of folic acid prophylaxis for at least 4 weeks prior to Screening. Patients using oral corticosteroids or NSAIDs, must have been on a stable dose for at least 4 weeks prior to Screening, and must continue during the treatment period. If currently not using corticosteroids or NSAIDs, the patient must have not received corticosteroids or NASIDs for at least 4 weeks prior to Screening. Patients must be able to adhere to the program visit schedule and other protocol requirements. Patients must be capable of giving informed consent and the consent must have been obtained prior to any screening procedures. Exclusion Criteria: Pregnant women, nursing mothers or a planned pregnancy within 1.5 years of enrollment Patients who are incapacitated, largely or wholly bedridden or confined to a wheelchair, and who have little or no ability for self-care. Patients who have any current systemic inflammatory condition with signs and symptoms that might confound the evaluations of benefit from the Remicade therapy, eg, Lyme disease, or a rheumatic disease other than RA. Use of DMARDS other than MTX within 4 weeks prior to Screening. Use of intra-articular, IM, or IV. corticosteroids (including IM ACTH) within 4 weeks prior to Screening. Prior administration any other therapeutic agent targeted at reducing TNF (eg, Etanercept, pentoxifylline, thalidomide or anti-CD4+ antibody) within the previous 6 months. Treatment with any investigational drug within the previous 6 months. A history of known allergies to murine proteins. Serious infections, such as hepatitis, pneumonia, pyelonephritis in the previous 3 months. Less serious infections in the previous 3 months, such as acute upper respiratory tract infection (colds) or uncomplicated urinary tract infection need not be considered exclusions at the discretion of the treating physician. History of opportunistic infections such as herpes zoster within 2 months of Screening. Evidence of active CMV, active pneumocystis carinii, drug resistant atypical mycobacterium, etc. Documented HIV infection. Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic or cerebral disease. Any currently known malignancy or pre-malignant lesions or any history of malignancy within the past 5 years. Patients with alcoholism, alcoholic liver disease, or other chronic liver disease. Patients with a positive PPD within 3 months and chest X-Ray suggestive of active TB or a previous exposure to TB. Patients with CHF, even if asymptomatic or not requiring medication must be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Remicade in the treatment of patients with active RA despite treatment with MTX. | Biological: Infliximab (Remicade)<br>* Infliximab 3 mg/kg infusions at Weeks 0, 2, and 6. All patients will continue to receive the same dose of MTX they were receiving at entry throughout the subsequent treatment period.<br>* Other names: SCH 215596;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define the onset of efficacy of infliximab in patients with active RA, using the validated SF-36 questionnaire. |  | After the first 2 weeks of treatment. |