Mycophenolate mofetil in the treatment of adults with advanced rheumatoid arthritis: three 24-week, randomized, double-blind, placebo- or ciclosporin-controlled trials

Abstract

Background: Mycophenolate mofetil is an immunosuppressive agent approved for the prophylaxis of renal, cardiac and hepatic transplant rejection. With its proven immunosuppressive effects and favourable toxicity profile, mycophenolate mofetil was postulated as a potential candidate for treating rheumatoid arthritis.

Objectives: To evaluate the efficacy and safety profile of mycophenolate mofetil in the treatment of adults with advanced refractory rheumatoid arthritis.

Methods: The effectiveness of mycophenolate mofetil (1 g twice daily) in the treatment of advanced refractory rheumatoid arthritis was assessed in three 24-week, randomized, double-blind, parallel-group trials (two placebo-controlled [n = 229 and n = 214] and one with ciclosporin 2.5-4 mg/kg/day as a comparator [n = 842]). Patients had American Rheumatism Association functional class II or III disease, a mean disease duration of 9.8-13 years, and had failed treatment with a median of three to four disease-modifying antirheumatic drugs. Overall, 959/1262 (76%) of patients in the main analysis group were female and 1189/1262 (94%) were Caucasian.

Results: In the placebo-controlled trials, the American College of Rheumatology 20% responder index rate did not differ significantly between mycophenolate mofetil and placebo (19.7% [29/147] vs 13.0% [9/69] and 15.8% [22/139] vs 10.1% [7/69]; p > 0.05 for both studies). Consequently, the active-comparator trial was stopped prematurely before completion and efficacy analyses were not performed. Treatment-emergent adverse events were experienced by 51.6% (371/719), 73.1% (304/416) and 36.1% (53/147) of patients receiving mycophenolate mofetil, ciclosporin and placebo, respectively. Hypertension, increased serum creatinine, muscle cramps, hirsutism and hypertrichosis were more than twice as common with ciclosporin as with mycophenolate mofetil. In all three trials, the incidence of serious adverse events with mycophenolate mofetil was 12.1% (compared with 11.3% and 7.5% for ciclosporin and placebo, respectively).

Conclusion: Mycophenolate mofetil did not achieve a significant difference from placebo in terms of disease improvement in patients with refractory rheumatoid arthritis. A descriptive analysis of adverse events suggests mycophenolate mofetil was generally as well tolerated as ciclosporin in this patient population.