Division of Rheumatology, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu, Seoul, 136-705, South Korea.
Clin Rheumatol. 2018 Feb;37(2):323-330. doi: 10.1007/s10067-017-3857-5. Epub 2017 Oct 1.
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.
我们旨在评估在类风湿关节炎 (RA) 患者中推荐剂量下使用来氟米特或他克莫司单药治疗的相对疗效和耐受性。我们纳入了基于 RA 患者退出人数评估来氟米特 20mg、来氟米特 10mg、他克莫司 3mg、他克莫司 1.5-2mg 和安慰剂疗效和耐受性的随机对照试验 (RCT)。我们采用贝叶斯随机效应网络荟萃分析来合并 RCT 的直接和间接证据。纳入的 6 项 RCT 共纳入了 1510 例患者。与安慰剂组相比，来氟米特 20mg（OR 0.17，95%可信区间 [CrI] 0.08-0.34）；来氟米特 10mg（OR 0.16，95% CrI 0.02-0.75）；和他克莫司 3mg（OR 0.41，95% CrI 0.21-0.74）组患者因疗效不佳而退出的比例显著降低。基于累积排序曲线下面积（SUCRA）值的排名概率表明，来氟米特 20mg 因疗效不佳而退出的可能性最高（SUCRA=0.8530），其次是来氟米特 10mg（SUCRA=0.8321）、他克莫司 3mg（SUCRA=0.4965）、他克莫司 1.5-2mg（SUCRA=0.3035）和安慰剂（SUCRA=0.0150）。各组间因不良事件而退出的患者无显著差异；然而，安慰剂组的退出人数少于来氟米特 20mg 组（OR 0.22，95% CrI 0.07-0.74）。安慰剂具有成为最耐受治疗的最高可能性（SUCRA=0.8161），其次是他克莫司 3mg（SUCRA=0.6490）、他克莫司 1.5-2mg（SUCRA=0.4857）、来氟米特 10mg（SUCRA=0.4651）和来氟米特 20mg（SUCRA=0.0841）。来氟米特 20mg、来氟米特 10mg 和他克莫司 3mg 比安慰剂更有效，而来氟米特 20mg 比安慰剂更不耐受。来氟米特治疗 RA 的疗效可能优于他克莫司，但耐受性较差。
