Efficacy and safety of add‐on tacrolimus versus leflunomide in rheumatoid arthritis patients with inadequate response to methotrexate

Abstract

To investigate the efficacy and safety of tacrolimus (TAC) versus leflunomide (LEF) when combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients. This was a 24-week multi-center, double-blind, randomized, non-inferiority study targeting RA patients with moderate to severe Disease Activity Score of 28 joints (DAS28>3.2) who showed inadequate response to MTX. Patients were randomized into TAC or LEF (add-on to MTX) groups. Initial daily doses of TAC and LEF were 1.5 and 10mg, respectively, for 4weeks and then doubled until the end of the study. The primary endpoint was DAS28 comparison at 24weeks. Eighty-seven patients were screened in 10 centers and 75 patients were randomized into two groups. Baseline demographics were comparable between TAC+MTX and LEF+MTX groups. The TAC+MTX group was non-inferior to the LEF+MTX group in terms of DAS28 at 24weeks (mean difference of DAS28: -0.1812, 95% confidence interval: -0.8073, 0.4450). There was a greater number of adverse events in the LEF+MTX group (66 in LEF+MTX and 49 in TAC+MTX). Six patients presented with transaminitis in the LEF+MTX group compared with two patients in the TAC+MTX group. The efficacy of TAC combined with MTX was non-inferior to LEF+MTX. It had a reasonable safety profile in RA patients with moderate to severe disease activity (http://cris.nih.go.kr; KCT0000781).