Mahil S K, Ezejimofor M C, Exton L S, Manounah L, Burden A D, Coates L C, de Brito M, McGuire A, Murphy R, Owen C M, Parslew R, Woolf R T, Yiu Z Z N, Uthman O A, Mohd Mustapa M F, Smith C H
St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, SE1 9RT, UK.
British Association of Dermatologists, London, W1T 5HQ, UK.
Br J Dermatol. 2020 Oct;183(4):638-649. doi: 10.1111/bjd.19325. Epub 2020 Aug 9.
The rapid expansion of psoriasis biologics has led to an urgent need to understand their relative efficacy and tolerability to inform treatment decisions better and, specifically, to inform guideline development.
To update a 2017 meta-analysis on the comparative efficacy and tolerability of biologic treatments for psoriasis.
We searched the MEDLINE, PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs), published up to 7 September 2018, of 11 licensed, NICE-approved biologics targeting tumour necrosis factor (adalimumab, etanercept, infliximab, certolizumab pegol), interleukin (IL)-12/IL-23p40 (ustekinumab), IL-17A (secukinumab, ixekizumab), IL-17RA (brodalumab) and IL-23p19 (guselkumab, tildrakizumab, risankizumab). A frequentist network meta-analysis ascertained direct or indirect evidence comparing biologics with one another, methotrexate or placebo. This was combined with hierarchical cluster analyses to consider efficacy (≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) or Physician's Global Assessment 0 or 1; PASI 75; Dermatology Life Quality Index improvement) and tolerability (drug withdrawal due to adverse events) outcomes at 10-16 weeks, followed by assessments of study quality, heterogeneity and inconsistency.
We identified 62 RCTs presenting data on direct comparisons (31 899 participants). All biologics were efficacious compared with placebo or methotrexate at 10-16 weeks. Hierarchical cluster analyses revealed that adalimumab, brodalumab, certolizumab pegol, guselkumab, risankizumab, secukinumab, tildrakizumab and ustekinumab were comparable with respect to high short-term efficacy and tolerability. Infliximab and ixekizumab clustered together, with high short-term efficacy but relatively lower tolerability than the other agents, although the number of drug withdrawal events across the network was low, so these findings should be treated with caution.
Using our methodology we found that most biologics cluster together with respect to short-term efficacy and tolerability, and we did not identify any single agent as 'best'. These data need to be interpreted in the context of longer-term efficacy, effectiveness data, safety, posology and drug acquisition costs when making treatment decisions.
银屑病生物制剂的迅速扩张导致迫切需要了解它们的相对疗效和耐受性,以便更好地为治疗决策提供依据,特别是为指南制定提供依据。
更新2017年关于银屑病生物治疗比较疗效和耐受性的荟萃分析。
我们检索了MEDLINE、PubMed、Embase和Cochrane数据库,以查找截至2018年9月7日发表的针对11种已获许可、经英国国家卫生与临床优化研究所(NICE)批准的靶向肿瘤坏死因子(阿达木单抗、依那西普、英夫利昔单抗、赛妥珠单抗)、白细胞介素(IL)-12/IL-23p40(乌司奴单抗)、IL-17A(司库奇尤单抗、伊克司单抗)、IL-17RA(布罗达单抗)和IL-23p19(古塞库单抗、替拉珠单抗、瑞莎珠单抗)的生物制剂的随机对照试验(RCT)。一项频率学派网状荟萃分析确定了比较生物制剂之间、与甲氨蝶呤或安慰剂之间的直接或间接证据。这与分层聚类分析相结合,以考虑在10 - 16周时的疗效(银屑病面积和严重程度指数(PASI)改善≥90%或医师整体评估为0或1;PASI 75;皮肤病生活质量指数改善)和耐受性(因不良事件停药)结果,随后评估研究质量、异质性和不一致性。
我们确定了62项提供直接比较数据的RCT(31899名参与者)。在10 - 16周时,与安慰剂或甲氨蝶呤相比,所有生物制剂均有效。分层聚类分析显示,阿达木单抗、布罗达单抗、赛妥珠单抗、古塞库单抗、瑞莎珠单抗、司库奇尤单抗、替拉珠单抗和乌司奴单抗在短期高疗效和耐受性方面具有可比性。英夫利昔单抗和伊克司单抗聚类在一起,具有较高的短期疗效,但耐受性相对低于其他药物,尽管整个网络中的停药事件数量较少,因此这些发现应谨慎对待。
使用我们的方法,我们发现大多数生物制剂在短期疗效和耐受性方面聚类在一起,并且我们没有确定任何单一药物为“最佳”。在做出治疗决策时,需要在长期疗效、有效性数据、安全性、用药剂量和药物获取成本的背景下解释这些数据。