COMBINATION THERAPY WITH CYCLOSPORINE AND METHOTREXATE IN SEVERE RHEUMATOID-ARTHRITIS

Background. Patients with severe rheumatoid arthritis who are treated with methotrexate frequently have only partial improvement. Methods. I n a six-month randomized, double-blind trial, we compared combination therapy with cyclosporine (2.5 to 5 mg per kilogram of body weight per day) and methotrexate (at the maximal tolerated dose) with methotrexa te and placebo in 148 patients with rheumatoid arthritis who had resid ual inflammation and disability despite partial but substantial respon ses to prior methotrexate treatment. The primary outcome measure was t he change in the number of tender joints. Results. As compared with th e placebo group, the patients in the treatment group had a net improve ment in the tender-joint count of 25 percent, or 4.8 joints (95 percen t confidence interval, 0.7 to 8.9; P=0.02), and in the swollen-joint c ount of 25 percent, or 3.8 joints (95 percent confidence interval, 1.3 to 6.3; P=0.005); improvement in overall disease activity as assessed by the physician (19 percent, P<0.001) and the patient (21 per cent, P<0.001); and improvement in joint pain (23 percent, P=0.04) and in th e degree of disability (26 percent, P<0.001). Thirty-six patients (48 percent) in the cyclosporine group and 12 patients (16 percent) in the placebo group (P<0.001) met the 1993 criteria for improvement of the American College of Rheumatology (more than 20 percent improvement in the numbers of both swollen and tender joints and improvement in three of five other variables). Serum creatinine concentrations increased b y a mean of 0.14+/-0.27 mg per deciliter (12+/-24 mmol per liter) in t he cyclosporine group and by 0.05+/-0.19 mg per deciliter (4+/-17 mmol per liter) in the placebo group (P=0.02). Conclusions. Patients with severe rheumatoid arthritis and only partial responses to methotrexate had clinically important improvement after combination therapy with c yclosporine and methotrexate. Side effects were not substantially incr eased. Long-term follow-up of patients treated with this combination i s needed.