Hotline

Cyclosporine and Methotrexate in Rheumatoid Arthritis

In a study published in the July 20 issue of the New England Journal of Medicine, investigators have reported the benef1cial effects of the combination of cyclosporine (Cs) and methotrexate (MTX) in patients with rheumatoid arthritis. This Sandoz-sponsored, multicenter, randomized, double-blind study compared the effects of Cs (2.5-5 mg/kg of body weight/day) plus MTX versus MTX plus placebo in a six-month trial in 148 RA patients who had achieved "partial but substantial" responses to MTX alone but who still had active disease and disability. Cs doses could be altered depending upon changes in serum creatinine. MTX was administered at the maximum tolerated dose which did not exceed 15 mg/week. Outcome measures included tender and swollen joint counts, pain, patient and physician overall assessment, degree of disability, and ESR.

The two study groups were comparable at entry with the majority of patients having advanced disease. The number of early withdrawals was similar in both groups, and was usually secondary to an adverse reaction to treatment. Statistically signif1cant differences were noted between the two groups for all clinical measures. Patients in the Cs + MTX group versus the MTX + placebo group had a statistically more significant improvement in tender joint count, swollen joint count, physician and patient assessment, joint pain, and degree of disability. The ESR increased by 4.2 mm/hr in the CS group compared to a decrease of 4.8 mm/hr in the placebo group. Additionally, 48 percent of the Cs-treated rheumatoids and I6 percent of the placebo group (p<0.001) satisfied the ACR criteria for improvement in RA.

Side effect profiles were generally similar between the two groups, although some significant differences were noted. In Cs-treated patients (mean dose approximately 3 mg/kg/day), the serum creatinine rose by 0.14 mg/dl by six months compared to an increase of 0.05 mg/dl in the placebo group. (p=0.02).

The authors correctly point out some concerns which will temper enthusiasm for this combination. Continued studies are obviously needed to determine if these results can be sustained with more prolonged treatment, and if the toxicity profiles change with chronic therapy. Furthermore, the effects of Cs + MTX versus SITX alone on mortality and disability will require long-term monitoring. As is the case for all combination therapy in RA, usage should be reserved for patients failing to respond to monotherapy with a clear understanding of the potential toxicities and increased cost of these medications.

Prepared by Paul Katz, MD, and Robert Thoburn, MD

Co-Editors, ACR Hotline

July 19, 1995

This Hotline is provided by the American College of Rheumatology Communications and Marketing Group as an informational service to members. This Hotline does not represent a position statement of the College.