Methotrexate was more effective than leflunomide in the treatment of polyarticular juvenile rheumatoid arthritis, although both drugs resulted in high rates of clinical improvement in a multinational, randomized, controlled trial.
A total of 94 children, aged 3–17 years, with polyarticular juvenile rheumatoid arthritis (JRA) were randomized to either leflunomide (Arava) or methotrexate (MTX) for 16 weeks, followed by a 32-week blinded extension phase (N. Engl. J. Med. 2005;352:1655–66).
The dose of leflunomide was based on three weight categories: Patients weighing less than 20 kg received 100 mg of leflunomide for 1 day, followed by a maintenance dose of 10 mg every other day; 20 kg to 40 kg patients received 100 mg for 2 days, followed by 10 mg/day; and those weighing more than 40 kg received 100 mg for 3 days, followed by 20 mg/day. The MTX dose was 0.5 g/kg per week, with a maximum of 25 mg per week. Concomitant treatment with nonsteroidal anti-inflammatory drugs and prednisone was allowed.
At week 16, the rate of American College of Rheumatology Pediatric 30% (ACR Pedi 30) responses was significantly higher in the methotrexate group than in the leflunomide group (89% vs. 68%).
There was not a significant difference between the leflunomide and methotrexate groups in the other primary outcome variable, the Percent Improvement Index (−44.41% vs. −52.87%).
In both groups, the improvements achieved at week 16 were maintained at week 48. The results compare favorably with previously published ACR Pedi 30 response rates of 48% with methotrexate, 44% with sulfasalazine, and 74% after 3 months of open-label etanercept, according to the authors.
“The higher-than-expected rates of responses in both treatment groups may in part be attributed to the early stage of disease (median duration 4 months) in this population…,” wrote lead author Earl Silverman, M.D., of the University of Toronto, a paid consultant for Sanofi-Aventis, which supported the study.
The most common adverse events in both groups included gastrointestinal symptoms, headache, and nasopharyngeal symptoms. ALT elevations were more frequent with MTX than with leflunomide during both phases of the study.