BMC Med. 2026 Jul 3. doi: 10.1186/s12916-026-05009-1. Online ahead of print.
ABSTRACT
BACKGROUND: Leflunomide (LEF) shows promising effect in Takayasu arteritis (TAK), but evidence from randomized controlled trials is lacking. This study aims to investigate the efficacy and safety of LEF versus placebo combined with prednisone for the treatment of TAK.
METHODS: This is a multicenter, randomized, double-blind, placebo-controlled trial at six sites across China, conducting from December 22, 2016, to November 4, 2022. A total of 116 eligible patients were recruited and randomized 1:1 to receive LEF (20 mg/d, p.o.) or matched placebo for 24 weeks, with all patients having initial prednisone of 0.6 mg/kg/d and following a taper starting at week 4. By week 24, patients in the LEF group who did not achieve clinical remission discontinued the study; all other patients (both LEF and placebo groups) received LEF (20 mg/d) from week 25 to week 52. The primary outcome was clinical remission at week 24. Secondary outcomes were time-to-clinical remission, mean prednisone dose at week 24, clinical remission in those who switched to LEF from week 25, disease recurrence and time-to-recurrence, imaging changes, and safety.
RESULTS: Fifty-four and 57, 45 and 48 patients were included in LEF and placebo group of modified intention-to-treat (mITT) and per-protocol set (PPS). In mITT set, clinical remission was achieved in 44/54 (81.5%) LEF- and 45/57 (78.9%) placebo-treated patients (risk difference: 2.6, 95%CI: -12.5, 17.2) at week 24. The same trend was observed in the sensitivity analyses. Post hoc analyses indicated greater risk differences (LEF minus placebo) in the female subgroup, ≤ 40 years subgroup, refractory subgroup, systemic symptoms subgroup, imaging type II subgroup and in those achieving the composite endpoint of both clinical remission and stable/improved imaging. At week 24, LEF group had a lower mean prednisone dose (mean difference: -2.1, [-4.3, 0.1] mg/d). Adverse events were observed in 13 (24.5%) LEF- and 22 (39.3%) placebo-treated patients. Serious adverse events were reported in six LEF- and four placebo-treated patients. One death was reported in placebo group.
CONCLUSIONS: Although the primary endpoint was not met, our results still provide evidence supporting LEF as a potential alternative treatment option for TAK.
TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02981979.
PMID:42399917 | DOI:10.1186/s12916-026-05009-1