Leflunomide + Methotrexate in Rheumatoid Arthritis

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.