The effectiveness and toxicity of cyclosporin A in rheumatoid arthritis: Longitudinal analysis of a population-based registry

Objective, To determine factors associated with response or toxicity to cyc losporin A (CSA) in a population-based inception cohort with rheumatoid art hritis (RA). Methods. Prospectively collected longitudinal measures including tender joi nt count (JC), duration of morning stiffness (MS), systolic and diastolic b lood pressure (SBP, DBP), and serum creatinine (SCr) were modeled using gen eralized estimating equations. Survival methods were used to estimate CSA c ontinuation time and its determinants. Results. Of 133 patients (75% female, median RA duration 13 years), 37 disc ontinued CSA because of ineffectiveness (19) or because of toxicity (18) in cluding increased SCr in 10, hypertension in 4, infections in 3, and gingiv al hyperplasia in 1. Patients remained on CSA a median of 75 months (95% co nfidence interval [Cl] 38-112). Those receiving concomitant methotrexate (M TX) were more than 4 times as likely to continue on CSA therapy (hazard rat io 0.22, 95% CI 0.10-0.94). A lower final JC was predicted by a longer CSA treatment duration (relative risk [RR] 0.99 per month, 95% CI 0.98-0.99) an d concomitant MTX therapy (RR 0.79, 95% Cl 0.63-0.99); decreased MS was pre dicted only by longer CSA treatment duration (reduction of 2.0 minutes per month, 95% Cl 1.1-3.0). Each previous disease-modifying antirheumatic drug (DMARD) exposure predicted a rise in SCr (35 mu mole/liter, 95% CI 22-48), SBP (7.2 mm Hg, 95% CI 2.7-11.7), and DBP (3.8 nun Hg, 95% Cl 3.0-6.4). Conclusions. Combination CSA/MTX prolongs therapy and reduces JC. Long-term CSA treatment was fairly well tolerated. Previous DMARD use appears to be a determinant for the development of toxicity.