Cyclosporine combined with another basic drug for the management of rheumatoid arthritis

Abstract The aim of this study was to assess the efficacy of combined treatment with cyclosporine A and another disease-modifying anti-rheumatic drug in patients with monotherapy-resistant rheumatoid arthritis, to find the minimal effective doses of combined drugs, to determine the frequency and type of side-effects, and to analyze causes for drug withdrawal. The study was performed in two groups of rheumatoid arthritis patients diagnosed according to ACR criteria who presented with symptoms of active inflammatory disease in spite of six-month-long treatment with full dose of at least one drug. Patients previously treated with cyclosporine A, with poorly controlled hypertension, and kidney failure were excluded from the study. At the beginning of the study, all patients were on 15 mg prednizone and 1-3 basic drugs. In group I (n = 36 patients), monotherapy was combined with an increasing dose of cyclosporine A (from 1.5-2 to the maximal dose of 5 mg/kg/day). Disease activity was determined according to modified ACR criteria. Improvement was observed in 30 patients (83.3%). Improvement was significant in 5 patients (13.9%), moderate in 11 (30.5%), and slight in 14 (38.9%). No improvement was observed in 6 patients (16.7%). The effective dose was 100-400 mg/day (mean 180.5 mg/day or 2,5-3,0 mg/kg/day). Treatment was terminated in 72.2% of patients, mostly because of side-effects (36.1%). In 16.7% of patients, the cause for termination was lack of early improvement or late recurrence. In group II (n = 11 patients), leflunomide 20 mg/day was added to the previous treatment. Disease activity was estimated according to DAS 28 scale. Combined treatment with cyclosporine A and leflunomide was effective in 43.3% of patients. It was demonstrated that cyclosporine A in combination therapy may cause improvement in patients resistant to other basic drugs. Its effective dose is approx. 2.5-3.0 mg/kg/day. Side-effects requiring drug withdrawal were present in one-fourth of patients and together with non-effective therapy were the most common cause for drug withdrawal. However, it must be emphasized that patients who were qualified to this study had a severe course of the disease resistant to other therapies. In this context, our combination therapy deserves attention.