Leflunomide versus methotrexate: A comparison of the European and Americanexperience

This paper compares and contrasts the results of two major Phase III clinic al trials that compared the efficacy and safety of leflunomide, a new disea se-modifying antirheumatic drug (DMARD), and methotrexate. In both the Amer ican trial (US301) and the multinational trial (MN302), patients with activ e rheumatoid arthritis (RA) were given either leflunomide (20 mg/day after a loading dose of 100 mg/day for 3 days) or methotrexate (7.5-15 mg/week) f or 52 weeks. US301 was also placebo-controlled. Folate supplementation was mandatory in US301 but was given to < 10% of the patients in MN302. In US30 1, American College of Rheumatology (ACR) 20% response rates and improvemen t in tender and swollen joints were significantly better than placebo in bo th treatment groups, but were not significantly different from each other. Both treatments significantly retarded radiographically assessed progressio n of RA compared to placebo, but the degree of retardation was significantl y greater with leflunomide. In MN302, the ACR response rate and improvement in tender and swollen joints with leflunomide were similar to those seen i n US301. The ACR response rate and improvements in all efficacy variables w ith methotrexate were significantly greater than with leflunomide, however. Radiographically assessed disease progression was not statistically differ ent with the two treatments. Use of methotrexate without folate in MN302 wa s associated with a higher incidence of clinically significant elevations o f liver enzyme levels. These results indicate that both leflunomide and met hotrexate an effective DMARDs. The symptomatic relief provided by both drug s is similar when they are given with folate supplementation.