Symmetron Limited, London, UK.
Institute of Health and Medicine, University of Linköping, Linköping, Sweden.
J Eur Acad Dermatol Venereol. 2019 Feb;33(2):355-366. doi: 10.1111/jdv.15277. Epub 2018 Oct 31.
BACKGROUND: Patients with moderate-to-severe psoriasis require long-term treatment, yet few trials compare outcomes beyond a short-term induction period. Quantitative comparisons of long-term outcomes in patients with psoriasis are limited. To our knowledge, no network meta-analysis (NMA) of such data has been performed. OBJECTIVE: To compare novel systemic therapies, both biologic and non-biologic, approved for moderate-to-severe psoriasis by conducting a systematic review (SR) and NMA of Psoriasis Area and Severity Index (PASI) outcomes measured at or around 1 year. METHODS: An SR was conducted to identify studies reporting PASI 75, PASI 90 and PASI 100 responses. Feasibility of an NMA on maintenance phase endpoints was assessed and sources of heterogeneity considered. Data appropriate for analysis were modelled using a Bayesian multinomial likelihood model with probit link. Wherever possible, data corresponding to an intention-to-treat approach with non-responder imputation were used. RESULTS: Twenty-four studies reporting outcomes at 40-64 weeks were identified, but heterogeneity in study design allowed synthesis of only 17. Four 52-week randomized controlled trials (RCTs) comprised the primary analysis, which found brodalumab was significantly more efficacious than secukinumab, ustekinumab and etanercept. Secukinumab was also more efficacious than ustekinumab and both outperformed etanercept. In a secondary analysis, evidence from 13 additional studies and 4 further therapies (adalimumab, apremilast, infliximab and ixekizumab) was included by comparing long-term outcomes from active interventions to placebo outcomes extrapolated from induction. Results were consistent with the primary analysis: brodalumab was most effective, followed by ixekizumab and secukinumab, then ustekinumab, infliximab and adalimumab. Etanercept and apremilast had the lowest expected long-term efficacy. Results were similar when studies with low prior exposure to biological therapies were excluded. CONCLUSION: Results suggest that brodalumab is associated with a higher likelihood of sustained PASI response, including complete clearance, at week 52 than comparators. Further long-term active-comparator RCT data are required to better assess relative efficacy across therapies.
背景:中重度银屑病患者需要长期治疗,但很少有试验能比较短期诱导期以外的结果。对银屑病患者长期结局的定量比较是有限的。据我们所知,尚未进行过此类数据的网络荟萃分析(NMA)。
目的:通过系统评价(SR)和对银屑病面积和严重程度指数(PASI)在 1 年左右的疗效进行 NMA,比较中重度银屑病的新型系统治疗方法,包括生物制剂和非生物制剂。
方法:进行了一项 SR,以确定报告 PASI75、PASI90 和 PASI100 应答的研究。评估了在维持期终点进行 NMA 的可行性,并考虑了异质性的来源。使用带有概率单位链接的贝叶斯多项似然模型对适合分析的数据进行建模。只要可能,使用对应于非应答者推断的意向治疗方法的数据进行分析。
结果:确定了 24 项在 40-64 周时报告结局的研究,但由于研究设计的异质性,仅可综合分析 17 项研究。主要分析包括 4 项 52 周随机对照试验(RCT),结果发现布罗达卢单抗的疗效明显优于司库奇尤单抗、乌司奴单抗和依那西普。司库奇尤单抗也优于乌司奴单抗,且均优于依那西普。在二次分析中,通过比较活性干预与从诱导期推断的安慰剂结局,纳入了来自 13 项额外研究和 4 种其他疗法(阿达木单抗、阿普米司特、英夫利昔单抗和依奇珠单抗)的长期结局证据。结果与主要分析一致:布罗达卢单抗最有效,其次是依奇珠单抗和司库奇尤单抗,然后是乌司奴单抗、英夫利昔单抗和阿达木单抗。依那西普和阿普米司特的长期疗效预期最低。当排除了先前暴露于生物疗法的研究时,结果相似。
结论:结果表明,与对照相比,在第 52 周时,布罗达卢单抗更有可能维持 PASI 应答,包括完全清除。需要进一步进行长期的活性对照 RCT 数据,以更好地评估各疗法之间的相对疗效。
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