Tacrolimus combined with methotrexate had comparable efficacy and safety to leflunomide combined with methotrexate for the treatment for rheumatoid arthritis, according to study data published in International Journal of Rheumatic Diseases.
Investigators conduced a 24-week, multicenter, double-blind, randomized, noninferiority study that included patients with moderate to severe rheumatoid arthritis (28-joint Disease Activity Score [DAS28] >3.2) who showed inadequate response to methotrexate. The study was conducted at 10 centers across South Korea. Patients were randomly assigned to receive either tacrolimus or leflunomide as add-on medications for methotrexate. Initial daily doses of tacrolimus and leflunomide were 1.5 and 10 mg, respectively, for 4 weeks. If tolerated, doses were doubled weekly until the conclusion of the study. Patient visits were conducted at 4, 8, 16, and 24 weeks, where joint examination, Health Assessment Questionnaire, DAS28, and laboratory tests were performed. As the primary end point, investigators compared DAS28 scores at 24 weeks with baseline DAS28 scores.
The final study cohort comprised 75 patients, among whom 37 were randomly assigned to tacrolimus and methotrexate and 38 were assigned to leflunomide and methotrexate. Baseline demographic data did not differ significantly between study groups. Compliance with study procedure was above 95% in each group. The proportion of patients who required dose reduction to 1 capsule per day during the study period was 11.8% in the tacrolimus and methotrexate group and 22.9% in the leflunomide and methotrexate group.
At 24 weeks, DAS28 was 3.06±1.45 in the tacrolimus and methotrexate group and 3.24±1.24 in the leflunomide and methotrexate group (P =.566). Compared with baseline values, these scores indicated significant clinical improvement over the study course for both groups. The mean difference in DAS28 at 24 weeks between groups was within the noninferior margin. DAS28 remission rate at 24 weeks was 48.7% in the tacrolimus and methotrexate group and 35.1% in the leflunomide and methotrexate group (P =.239). A greater number of adverse events were observed in the leflunomide and methotrexate group (66 events) compared with the tacrolimus and methotrexate group (49 events). Transaminitis was identified in 6 patients in the leflunomide and methotrexate group, compared with 2 patients in the tacrolimus and methotrexate group. Changes in other clinical values during the study course were comparable between groups.
These data underscore the efficacy and safety of tacrolimus as an add-on medication in patients with inadequate response to methotrexate. Further research to verify the long-term safety of both tacrolimus and leflunomide should be conducted prior to widespread clinical practice.
Shin K, Baek HJ, Kang YM, et al. Efficacy and safety of add‐on tacrolimus versus leflunomide in rheumatoid arthritis patients with inadequate response to methotrexate [published online March 12, 2019]. Int J Rheum Dis. doi:10.1111/1756-185X.13521