Background Tacrolimus (TAC) is used as a disease modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA). Combination of TAC with methotrexate (MTX) has been shown to be effective and safe in RA, yet comparative clinical studies are insufficient to date.
Objectives To investigate the efficacy and safety of TAC versus leflunomide (LEF) when combined with MTX in RA patients
Methods The PLATINUM-X study is a 24-week multi-center, double-blinded randomized non-inferior (phase 4) study targeting RA patients with moderate to active disease activity (DAS28(ESR) >3.2) that had a inadequate clinical response to MTX. Patients were randomized into the TAC or LEF (add-on) group. The initial daily dose of TAC and LEF were 1.5 mg and 10 mg, respectively for 4 weeks, then increased to 3 mg, 20 mg until the end of the study. Clinical (DAS28, Korean (K-) HAQ) and laboratory data were obtained at 4, 8, 16, and 24 weeks. The primary endpoint was to compare DAS28 in both groups at 24 weeks. Non-Inferiorly was established if the upper limit of the 95% confidence interval (CI) for DAS28 difference was less than 0.7. Secondary endpoint variables included DAS28, K-HAQ as well as swollen/tender joint counts at each visit. Safety profiles were assessed at each patient's visit. The per protocol set was used for statistical analysis.
Results Eighty seven patients were screened in 9 centers, and 75 patents were randomized into 2 groups. Baseline demographics of patients were comparable with baseline DAS28 being 4.54 ± 0.61 and 4.91 ± 1.01 in the TAC and LEF group, respectively. TAC was non-inferior to LEF in terms of reduction of DAS28 at 24 weeks (mean difference -0.0565, CI -0.6513, 0.5384). Improvement of DAS28, K-HAQ throughout each visit was not statistically different between the 2 groups. Yet, reduction in tender joint count was significant in the TAC group compared with LEF (-5.97 ± 4.89 versus -3.08 ± 5.55 at 24 weeks, p=0.0145). There was more numbers of adverse events (AE) or adverse drug reactions in the LEF group (89 in LEF and 64 in TAC); 6 patients presented transaminitis in the LEF group compared with 2 in TAC.
Conclusions The efficacy of TAC plus MTX is non-inferior to LEF combined the MTX, with reasonable safety profile in RA patients with moderate to active disease activity (cris.nih.go.kr KCT0000781).
Tacrolimus in RA patients receiving concomitant MTX. Kremer et al. Arthritis Rheum 2003
Efficacy and safety of tacrolimus in patients with RA. Youcum et al. Arthritis Rheum 2003
Disclosure of Interest None declared