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/efficacy 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 and remained stable thereafter. The C-reactive protein decreased from 43 U/ml at entry to 22 U/ml (p < 0.0001) at 12 months. Forty-four percent of the patients and 47% of the physicians judged the efficacy as good or very good. The median number of adverse events/patient was 3 but most adverse events were either not clinically important or disappeared after dose reduction. Gastrointestinal (GI) intolerance and nephrotoxicity (> 30% increase in serum creatinine) each occurred in 50% of the patients. GI intolerance was transient in 80% of the patients but accounted for 50% of the premature discontinuations for toxicity. Nephrotoxicity persisted in the 50% of the patients in whom it occurred, despite dose reduction. The mean serum creatinine rose from 70 (13) mumol/l at entry to 86 (23) mumol/l at 12 months (23% increase; p < 0.0001), and this increase had been entirely reached after 3 months. Variables that could significantly predict the occurrence of nephrotoxicity could not be identified.

CONCLUSION

CsA can be safely and effectively administered to patients with RA for a duration of at least 12 months. An acceptable renal function at entry, close monitoring of the serum creatinine concentration and dose reductions when appropriate are prerequisities.