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

• Published in: International journal of rheumatic diseases 2019-06, Vol.22 (6), p.1115-1122
• Main Authors: Shin, Kichul, Baek, Han Joo, Kang, Young Mo, Cha, Hoon‐Suk, Kang, Seong Wook, Park, Sung‐Hwan, Jun, Jae‐Bum, Lee, Yun Jong, Choi, In Ah, Song, Yeong Wook
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Demography; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Joint diseases; Leflunomide; Leflunomide - administration & dosage; Leflunomide - adverse effects; Male; Methotrexate; Methotrexate - administration & dosage; Methotrexate - adverse effects; Middle Aged; non‐inferiority; Republic of Korea; Rheumatoid arthritis; Safety; Severity of Illness Index; Tacrolimus; Tacrolimus - administration & dosage; Tacrolimus - adverse effects; Time Factors; Treatment Outcome; Young Adult
• ISSN: 1756-1841; 1756-185X
• DOI: 10.1111/1756-185X.13521

Aim To investigate the efficacy and safety of tacrolimus (TAC) versus leflunomide (LEF) when combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients. Method 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 10 mg, respectively, for 4 weeks and then doubled until the end of the study. The primary endpoint was DAS28 comparison at 24 weeks. Results 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 24 weeks (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. Conclusion 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).