Warren Richard B, See Kyoungah, Burge Russel, Zhang Ying, Brnabic Alan, Gallo Gaia, Garrelts Alyssa, Egeberg Alexander
Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester, UK.
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
Dermatol Ther (Heidelb). 2020 Feb;10(1):73-86. doi: 10.1007/s13555-019-00337-y. Epub 2019 Nov 4.
Rapid improvement of psoriasis is valued by patients and should be considered to be an important factor in treatment selection. We investigated Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) response rates within the first 12 weeks of treatment to compare the rapid response of 11 biologic therapies for moderate-to-severe psoriasis using Bayesian and Frequentist network meta-analyses (NMA).
A systematic literature review was conducted to identify phase 3, double-blind, randomized, controlled trials for adult patients with moderate-to-severe psoriasis treated with interleukin (IL)-17 (brodalumab, ixekizumab, secukinumab), IL-12/-23 (ustekinumab), IL-23 (guselkumab, risankizumab, tildrakizumab), or tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab). Outcome measures extracted from 32 publications were ≥ 75, ≥ 90, or 100% improvement in PASI score (PASI 75, PASI 90, or PASI 100, respectively) at weeks 2, 4, 8, and 12 and DLQI (0,1), where score (0,1) indicates no effect on patient's life, at week 12. Bayesian NMA (BNMA) used fixed-treatment effect and random-baseline effect, normal independent models. Frequentist NMA (fNMA) was conducted as sensitivity analyses to test the robustness of the findings.
Based on BNMA and fNMA, brodalumab and ixekizumab showed the most rapid treatment effects on PASI 75 at weeks 2, 4, and 8 and on PASI 90 and PASI 100 at weeks 2, 4, 8, and 12; ixekizumab overlapped with risankizumab on PASI 75 at week 12. Brodalumab, ixekizumab, and secukinumab yielded higher DLQI (0,1) gains at week 12 compared to all of the other biologics studied. Additional measures of quality of life were not assessed in this report.
Ixekizumab and brodalumab provide the most rapid response and earliest clinical benefit at week 2 among all of the biologics studied, including other biologic treatments such as secukinumab, ustekinumab, guselkumab, adalimumab, and etanercept. BNMA and fNMA results showed similar relative effect estimates and treatment rankings.
Eli Lilly and Company.
银屑病的快速改善受到患者重视，应被视为治疗选择的重要因素。我们调查了治疗前12周内银屑病面积和严重程度指数（PASI）以及皮肤病生活质量指数（DLQI）的缓解率，以使用贝叶斯和频率论网络荟萃分析（NMA）比较11种生物疗法对中度至重度银屑病的快速反应。
进行了一项系统文献综述，以确定针对中度至重度银屑病成年患者的3期双盲随机对照试验，这些患者接受白细胞介素（IL）-17（布罗达单抗、司库奇尤单抗、依奇珠单抗）、IL-12/-23（乌司奴单抗）、IL-23（古塞库单抗、瑞莎珠单抗、替拉珠单抗）或肿瘤坏死因子抑制剂（阿达木单抗、赛妥珠单抗、依那西普、英夫利昔单抗）治疗。从32篇出版物中提取的结局指标为第2、4、8和12周时PASI评分改善≥75%、≥90%或100%（分别为PASI 75、PASI 90或PASI 100）以及第12周时DLQI（0,1），其中评分（0,1）表示对患者生活无影响。贝叶斯NMA（BNMA）使用固定治疗效应和随机基线效应、正态独立模型。频率论NMA（fNMA）作为敏感性分析进行，以检验研究结果的稳健性。
基于BNMA和fNMA，布罗达单抗和依奇珠单抗在第2、4和8周时对PASI 75以及在第2、4、8和12周时对PASI 90和PASI 100显示出最快的治疗效果；依奇珠单抗在第12周时在PASI 75方面与瑞莎珠单抗重叠。与所有其他研究的生物制剂相比，布罗达单抗、依奇珠单抗和司库奇尤单抗在第12周时DLQI（0,1）改善更大。本报告未评估生活质量的其他指标。
在所有研究的生物制剂中，包括司库奇尤单抗、乌司奴单抗、古塞库单抗、阿达木单抗和依那西普等其他生物治疗，依奇珠单抗和布罗达单抗在第2周时提供了最快的反应和最早的临床益处。BNMA和fNMA结果显示出相似的相对效应估计和治疗排名。
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