CYCLOSPORINE IN COMMON CLINICAL-PRACTICE - AN ESTIMATION OF THE BENEFIT RISK RATIO IN PATIENTS WITH RHEUMATOID-ARTHRITIS/

Objective. To investigate in common clinical practice the toxicity/eff icacy ratio of low dose cyclosporine A (CsA) in patients with advanced rheumatoid arthritis (RA) after 12 months CsA administration. Methods . One hundred and two patients with RA were included in the study. The initial dose of CsA was 2.5 mg/kg/day, the mean maximum dose was 3.2 mg/kg/day and the dose at 12 months was 2.8 mg/kg/day. Results. Sixty- nine (68%) patients completed 12 months of treatment. Seventeen (17%) patients discontinued for lack of efficacy and 16 (16%) for toxicity ( of which 50% for gastrointestinal intolerance). The clinical efficacy variables improved significantly by 36-42% between entry and Month 6 a nd remained stable thereafter. The C-reactive protein decreased from 4 3 U/ml at entry to 22 U/ml (p <0.0001) at 12 months. Forty-four percen t of the patients and 47% of the physicians judged the efficacy as goo d or very good. The median number of adverse events/patient was 3 but most adverse events were either not clinically important or disappeare d after dose reduction. Gastrointestinal (GI) intolerance and nephroto xicity (>30% increase in serum creatinine) each occurred in 50% of the patients. GI intolerance was transient in 80% of the patients but acc ounted for 50% of the premature discontinuations for toxicity. Nephrot oxicity persisted in the 50% of the patients in whom it occurred, desp ite dose reduction. The mean serum creatinine rose from 70 (13) mu mol /l at entry to 86 (23) mu mol/l at 12 months (23% increase; p <0.0001) , and this increase had been entirely reached after 3 months. Variable s that could significantly predict the occurrence of nephrotoxicity co uld not be identified. Conclusion. CsA can be safely and effectively a dministered to patients with RA for a duration of at least 12 months. An acceptable renal function at entry, close monitoring of the serum c reatinine concentration and dose reductions when appropriate are prere quisites.