Comparative efficacy and tolerability of monotherapy with leflunomide or tacrolimus for the treatment of rheumatoid arthritis: a Bayesian network meta-analysis of randomized controlled trials

Abstract

We aimed to assess the relative efficacy and tolerability of monotherapy with leflunomide or tacrolimus at recommended dosages in rheumatoid arthritis (RA) patients. Randomized controlled trials (RCTs) examining the efficacy and tolerability of leflunomide 20 mg, leflunomide 10 mg, tacrolimus 3 mg, tacrolimus 1.5-2 mg, and placebo, based on the number of withdrawals of RA patients, were included. We performed a Bayesian random-effects network meta-analysis to combine direct and indirect evidence from the RCTs. Six RCTs including 1510 patients met the inclusion criteria. The proportion of patient withdrawals owing to lack of efficacy was significantly lower in the leflunomide 20 mg (OR 0.17, 95% credible interval (CrI) 0.08-0.34); leflunomide 10 mg (OR 0.16, 95% CrI 0.02-0.75); and tacrolimus 3 mg (OR 0.41, 95% CrI 0.21-0.74) groups than in the placebo group. Rank probability based on the surface under the cumulative ranking curve (SUCRA) values indicated that leflunomide 20 mg had the highest probability of being the best treatment based on the number of withdrawals owing to lack of efficacy (SUCRA = 0.8530), followed by leflunomide 10 mg (SUCRA = 0.8321), tacrolimus 3 mg (SUCRA = 0.4965), tacrolimus 1.5-2 mg (SUCRA = 0.3035), and placebo (SUCRA = 0.0150). Patient withdrawals owing to adverse events did not differ significantly among the groups; however, withdrawals in the placebo group were fewer than those in the leflunomide 20 mg group (OR 0.22, 95% CrI 0.07-0.74). Placebo had the highest probability of being the most tolerable treatment (SUCRA = 0.8161) followed by tacrolimus 3 mg (SUCRA = 0.6490), tacrolimus 1.5-2 mg (SUCRA = 0.4857), leflunomide 10 mg (SUCRA = 0.4651), and leflunomide 20 mg (SUCRA = 0.0841). Leflunomide 20 mg, leflunomide 10 mg, and tacrolimus 3 mg were more efficacious than placebo, while leflunomide 20 mg was less tolerable than placebo. Leflunomide is likely to be more efficacious but less tolerable than tacrolimus for RA treatment.

Keywords: Leflunomide; Meta-analysis; Rheumatoid arthritis; Tacrolimus.