Treatment with leflunomide slows radiographic progression of rheumatoid arthritis - Results from three randomized controlled trials of leflunomide inpatients with active rheumatoid arthritis

Objective. To determine whether treatment with leflunomide (LEF), methotrex ate (MTX), or sulfasalazine (SSZ) for 6-12 months retards progression of ra diographic damage and to identify clinical variables that correlate with ra diographic progression. Methods. Radiographs of the hands and feet were performed at baseline and a t the end of study or early exit in 3 randomized controlled trials. Protoco l US301 was a 12-month controlled trial of LEF or MTX treatment compared wi th placebo in 482 patients randomized in a 3:3:2 ratio. Protocol MN301 comp ared 6 months of LEF or SSZ treatment with placebo in 358 patients, randomi zed in a 3:3:2 ratio, with continued blinded treatment in the active contro l arms for 12 months. Protocol MN302 compared 12 months of LEF treatment wi th MTX in 999 patients. Radiographs were blinded for sequence and treatment and were scored for erosions and joint space narrowing. All analyses were by intent-to-treat. Sensitivity analyses were performed to account for miss ing data. Results. LEF, MTX, and SSZ treatment resulted in statistically significantl y less radiographic progression compared with placebo at 6 and 12 months: f or protocol US301, LEF versus placebo P = 0.0007 and MTX versus placebo P = 0.0196; for protocol MN301, LEF versus placebo P = 0.0004 and SSZ versus p lacebo P = 0.0484, The effect of LEF treatment was similar to that of MTX a nd SSZ, Conclusion. These are the first 6- and 12-month randomized placebo- and act ive drug-controlled trials to demonstrate retardation of radiographic progr ession by a new disease-modifying antirheumatic drug (DMARD), LEF, as well as 2 commonly used DMARDs, MTX and SSZ.