Dermatologikum Hamburg, Drehbahn 1-3, 20354 Hamburg, Germany.
Br J Dermatol. 2012 Jan;166(1):179-88. doi: 10.1111/j.1365-2133.2011.10583.x. Epub 2011 Nov 11.
Ustekinumab, a novel monoclonal antibody for the treatment of moderate to severe plaque-type psoriasis, has recently received regulatory approval in Europe, bringing the total number of biologic agents licensed in this indication to five. To assist treatment selection in daily practice it is essential to understand the benefit/risk profile of these agents and in the absence of a clinical trial comparing all available biologics a number of reviews have used statistical techniques to generate estimates of the comparative effectiveness of these therapies through the available network of randomized clinical trials. These estimates have previously been published for a limited range of psoriasis biologic treatments, although, to date no review has compared all the currently available agents in Europe.
To estimate the comparative effectiveness of all biologic agents indicated in the treatment of moderate to severe psoriasis currently available in Europe based on the primary trial endpoints.
A number of databases were searched for details of randomized controlled trials of available biologics in the treatment of plaque-type psoriasis in adults. Comparative effectiveness was estimated based on the reported Psoriasis Area and Severity Index (PASI) 50, 75 and 90 response rates. A network meta-analysis conducted on the ordered probit scale and implemented as a Bayesian hierarchical model provided estimates for the probability of response and relative risk vs. placebo, based on all observed comparisons.
Twenty trials were included in the meta-analysis including patients with a mean disease duration of 18-22years. Based on the indirect comparison and given a placebo PASI 50 response of 13%, infliximab had the highest predicted mean probability of response at PASI levels 50 (93%), 75 (80%) and 90 (54%), followed by ustekinumab 90 mg at 90%, 74% and 46%, respectively, and then ustekinumab 45mg, adalimumab, etanercept and efalizumab.
The ordered probit model allowed a quantitative comparison of all currently licensed biologics, providing estimates on comparative effectiveness and a suggested ranking of treatments that is of potential use to decision-makers. However, the analysis is based on indirect comparisons of the primary endpoint reported from short-term randomized trials.
乌司奴单抗是一种新型单克隆抗体,用于治疗中重度斑块型银屑病,最近已在欧洲获得监管批准,这使该适应证获批的生物制剂总数达到 5 种。为了协助日常实践中的治疗选择,了解这些药物的获益/风险概况至关重要,而且由于没有比较所有可用生物制剂的临床试验,因此许多综述使用统计技术通过现有的随机临床试验网络生成这些疗法的比较疗效估计。这些估计之前已针对有限范围的银屑病生物治疗药物发布,尽管迄今为止,还没有综述比较欧洲目前所有可用的药物。
根据主要临床试验终点,估计目前在欧洲治疗中重度银屑病的所有生物制剂的相对疗效。
检索了多个数据库,以获取有关成人斑块型银屑病治疗中可用生物制剂的随机对照试验的详细信息。根据报告的银屑病面积和严重程度指数(PASI)50、75 和 90 缓解率来评估相对疗效。在有序概率尺度上进行网络荟萃分析,并作为贝叶斯层次模型实施,基于所有观察到的比较,提供了缓解的概率和与安慰剂相比的相对风险的估计值。
共纳入 20 项荟萃分析,包括平均疾病持续时间为 18-22 年的患者。根据间接比较,在安慰剂 PASI 50 缓解率为 13%的情况下,英夫利昔单抗在 PASI 水平 50(93%)、75(80%)和 90(54%)的预测平均缓解概率最高,其次是乌司奴单抗 90mg 分别为 90%、74%和 46%,然后是乌司奴单抗 45mg、阿达木单抗、依那西普和依法利珠单抗。
有序概率模型允许对所有目前已获得许可的生物制剂进行定量比较,提供了相对疗效的估计值,并对治疗方案进行了排序,这对决策者具有潜在的用途。然而,该分析基于短期随机试验报告的主要终点的间接比较。