Cyclosporine A in rheumatoid arthritis: Randomized, placebo controlled dose finding study

Objective. To determine the lowest effective starting dose and residual ben efit of cyclosporine A (CSA) in patients with rheumatoid arthritis (RA) ref ractory 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 1.5 (n = 93) 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 fo r 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, Ex aminer Global Assessment, Pain/Tender Joint Count and Index, Swollen Joint Count, and the "Ability at this moment" part of a modified Health Assessmen t 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 occurre d between 8 and 12 weeks of therapy; average CSA dose escalation resulted i n CSA 2.85 mg/kg/day by Week 16; benefit was not maintained during post-the rapy observation and 7 patients discontinued the study because of an advers e event. Adverse events were common in all groups and included gastrointest inal discomfort, hypertension, and increased creatinine. Adverse events rem itted 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 w hen compared to placebo. Adverse events were mostly manageable. CSA was an effective therapy for patients with RA who had failed at least one second l ine agent.