Leflunomide + Methotrexate in Rheumatoid Arthritis

Study Overview
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Brief Summary
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To determine the efficacy and safety of the combination of leflunomide and methotrexate for treating active rheumatoid arthritis (RA) in an open noncomparative multicenter trial.

Official Title
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An Open-Label, Multi-Center Study to Evaluation of Leflunomide Plus Methotexate for the Treatment of Rheumatoid Arthritis in DMARDs:(Disease-Modifying Antirheumatic Drug) na¿ve or Restart (Skip DMARDs More Than 4 Weeks) Subjects.

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Leflunomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between ages of 18 and 75 years old. Female subjects must be of nonchildbearing potential (i.e., surgically sterile or at least 2 years postmenopausal) OR their participation is contingent upon the following: They are practicing a medically accepted contraceptive regimen (acceptable methods must include one of the following: systemic contraceptive, oral or implanted estrogen/progestin; diaphragm with intravaginal spermicide; cervical cap; intrauterine device; or condom with intravaginal spermicide) AND they are demonstrated not to be pregnant (by serum pregnancy test) or breast-feeding at the time of study entry AND they intend to continue the contraceptive regimen and remain not pregnant throughout the study AND they are willing to undergo pregnancy testing (serum) at screening and (urine) monthly thereafter AND they are fully informed as to the risks of entering the trial and provide written consent to enter the trial; female patients not sexually active should also be adequately informed about appropriate methods of contraception AND they agree to not get pregnant for 24 months after discontinuation of treatment with study medication or they undergo a washout procedure with cholestyramine or charcoal. Male subjects must consent to practice contraception during the study. The subject needs to have clinically diagnosed rheumatoid arthritis including diagnosis of RA by ACR criteria greater than or = to 6 months prior to enrollment active disease by ACR criteria . Men wishing to father a child should consider discontinuing use of study drug and taking cholestyramine 8 gm 3 times daily for 11 days. In addition, males should consider discontinuation of methotrexate treatment and waiting an additional three months. Active disease by ACR criteria despite methotrexate therapy for three of the following four criteria: greater than or = to 9 tender joints greater than or = to 6 swollen joints greater than or = to 45 minutes of morning stiffness ESR greater than or = to 28mm/hr Subject must remain on unchanged doses of NSAIDs for at least 4 weeks prior to study drug administration and throughout the timecourse of the study. Concomitant therapy will be permitted with corticosteroids at a dose of less than or = to 10 mg prednisone daily (or the steroid equivalent administered orally), provided the dose has been stable for at least 4 weeks prior to the study drug administration; dose must remain constant throughout the timecourse of the study. Subjects must not receive intramuscular, intra-articular or intravenous corticosteroids within 4 weeks prior to initiating study participation or during the study. Subjects must be able and willing to comply with the terms of this protocol. Informed consent must be obtained for all subjects before enrollment in the study.

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

| Intervention/Treatment |
| --- |
|Drug: Leflunomide|concomitantly leflunomide (no loading dose, 10 mg/day) and methotrexate (starting at 7.5 mg/week and titrating up to 15 mg/week) for 20 weeks.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary end point was a 20% improvement in the American College of Rheumatology criteria (ACR 20) at 20 weeks |  | 20 weeks |