Rheumatoid Arthritis: Kopp EJ

Kremer JM, Genovese MC, Cannon GW, Caldwell JR, Cush JJ, Furst DE, Luggen ME, Keystone E, Weisman MH, Bensen WM, Kaine JL, Ruderman EM, Coleman P, Curtis DL, Kopp EJ, Kantor SM, Waltuck J, Lindsley HB, Markenson JA, Strand V, Crawford B, Fernando I, Simpson K, Bathon JM. · The Center for Rheumatology, LLP, 1367 Washington Avenue, Suite 101, Albany, NY 12206, USA. · Ann Intern Med. · Pubmed #12416946 links to  free full text

Abstract: BACKGROUND: Disease-modifying antirheumatic drugs may confer greater benefits when combined with the antimetabolite methotrexate. OBJECTIVE: To evaluate the efficacy and safety of leflunomide versus placebo when added to ongoing, stable-dose methotrexate therapy in patients with persistently active rheumatoid arthritis. DESIGN: 24-week, multicenter, randomized, double-blind, placebo-controlled trial. SETTING: 20 centers in the United States and Canada. PATIENTS: Patients with persistent rheumatoid arthritis, as defined by American College of Rheumatology (ACR) criteria, despite receiving methotrexate for at least 6 months. INTERVENTION: Leflunomide or matching placebo added to existing methotrexate therapy. MEASUREMENTS: The primary efficacy variable was the rate of achievement of 20% improvement in ACR criteria (ACR20) at the end of the study. The Health Assessment Questionnaire Disability Index was assessed at each visit, and the Medical Outcomes Study 36-Item Short Form was completed as an end point analysis. RESULTS: In the leflunomide and placebo groups, 46.2% and 19.5% of patients, respectively, met ACR20 criteria at 24 weeks (P < 0.001). Clinical improvement was demonstrated by statistically significant mean changes in individual components of the ACR20 response criteria. Discontinuation rates were similar in both treatment groups (23.1% in the leflunomide group and 24.8% in the placebo group), as were the overall incidences of adverse events (89.2% vs. 89.5%, respectively). Adverse events were predominantly mild or moderate. CONCLUSIONS: Combination therapy with leflunomide and methotrexate provides statistically significant clinical benefit in patients with active rheumatoid arthritis who are receiving methotrexate therapy. Leflunomide plus methotrexate is generally well tolerated and can be used safely with appropriate liver enzyme and hematologic monitoring.

Altman RD, Schiff M, Kopp EJ. · University of Miami, Miami Veterans Affairs Medical Center, FL 33101, USA. · J Rheumatol. · Pubmed #10529124 No free full text.

Abstract: OBJECTIVE: To determine the lowest effective starting dose and residual benefit of cyclosporine A (CSA) in patients with rheumatoid arthritis (RA) refractory to other agents. METHODS: In a double blind (masked observer), controlled, multicenter study, patients with RA started CSA 0 (placebo; n = 61), 1.5 (n = 89), or 2.5 (n = 94) mg/kg/day in a 21 week study that permitted dose escalation after 8 weeks, 1 week tapering of dose at 16 weeks, and post-therapy observation for 4 weeks. RESULTS: Patients with RA taking CSA 2.5 mg/kg/day fared better than those in the placebo or CSA 1.5 mg/kg/day groups in Patient Global Assessment, Examiner Global Assessment, Pain/Tender Joint Count and Index, Swollen Joint Count, and the "Ability at this moment" part of a modified Health Assessment Questionnaire. There was no difference in response between CSA 1.5 mg/kg/day and placebo groups. In the CSA 2.5 mg/kg/day group: improvement occurred between 8 and 12 weeks of therapy; average CSA dose escalation resulted in CSA 2.85 mg/kg/day by Week 16; benefit was not maintained during post-therapy observation and 7 patients discontinued the study because of an adverse event. Adverse events were common in all groups and included gastrointestinal discomfort, hypertension, and increased creatinine. Adverse events remitted with adjustment of dose or after washout in most patients. CONCLUSION: In RA, treatment of patients with CSA 2.5 mg/kg/day, but not 1.5 mg/kg/day, resulted in improvement of 4 of 5 primary efficacy variables when compared to placebo. Adverse events were mostly manageable. CSA was an effective therapy for patients with RA who had failed at least one second line agent.