Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Manchester, M13 9PT, U.K.
St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, SE1 9RT, U.K.
Br J Dermatol. 2019 Dec;181(6):1265-1271. doi: 10.1111/bjd.17849. Epub 2019 Jul 2.
Patients recruited in randomized controlled trials (RCTs) for biologic therapies in psoriasis are not fully representative of the real-world psoriasis population.
Firstly, to investigate whether patient characteristics are associated with being included in a psoriasis RCT. Secondly, to estimate the differences in the incidence of severe adverse events (SAEs) and the response rate between RCT and real-world populations of patients on biologic therapies for psoriasis using a standardization method.
Data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) were appended to individual participant-level data from two RCTs assessing ustekinumab in patients with psoriasis. Baseline variables were assessed for association of being in an RCT using a multivariable logistic regression model. Propensity score weights were derived to reweigh the registry population so that variables had the distribution of the trial population. We measured the C-statistic of the model with trial status as the dependent variable, and the risk differences in the incidence rate of SAEs in the first year and Psoriasis Area and Severity Index (PASI) after 6 months in the BADBIR cohort before and after weighting.
In total 6790 registry and 2021 RCT participants were included. The multivariable logistic regression model had a C-statistic of 0.82 [95% confidence interval (CI) 0.81-0.83]. The risk differences for the incidence rate of SAEs and the proportion of patients with PASI < 1.5 were 9.27 (95% CI -3.91-22.5) per 1000 person-years and 0.95 (95% CI -1.98-4.15), respectively.
Our results suggest that RCTs of biologic therapies in patients with psoriasis are not fully representative of the real-world population, but this lack of external validity does not account for the efficacy-effectiveness gap. What's already known about this topic? Patients with psoriasis who would not be eligible for randomized controlled trials (RCTs) investigating biologic therapies have a greater risk of serious adverse events and lower treatment effectiveness than patients who would have been eligible. What does this study add? Baseline patient characteristics were shown to be predictive of whether a patient would have been eligible for enrolment in an RCT for psoriasis biologic therapy. We did not find any efficacy-effectiveness gap between the sample representative of the real-world population of patients with psoriasis and the sample representative of the RCT population. Factors outside of baseline patient characteristics, such as observer effect and higher adherence in RCTs, may be more influential in any efficacy-effectiveness gap between trial and real-world populations of patients with psoriasis.
在银屑病的生物疗法随机对照试验（RCT）中招募的患者不能完全代表真实世界的银屑病人群。
首先，研究患者特征是否与参与银屑病 RCT 有关。其次，使用标准化方法估计生物治疗银屑病患者 RCT 和真实世界人群中严重不良事件（SAE）发生率和反应率的差异。
将英国皮肤病学家协会生物制剂和免疫调节剂登记处（BADBIR）的数据附加到两项评估乌司奴单抗治疗银屑病患者的 RCT 的个体参与者水平数据中。使用多变量逻辑回归模型评估 RCT 中基线变量的相关性。为了使变量具有试验人群的分布，得出倾向评分权重以重新加权登记人群。我们以试验状态为因变量，衡量模型的 C 统计量，并在加权前后测量 BADBIR 队列中第一年 SAE 发生率和 6 个月时银屑病面积和严重程度指数（PASI）的风险差异。
共纳入 6790 名登记患者和 2021 名 RCT 参与者。多变量逻辑回归模型的 C 统计量为 0.82 [95%置信区间（CI）0.81-0.83]。SAE 发生率和 PASI <1.5 的患者比例的风险差异分别为每 1000 人年 9.27（95%CI-3.91-22.5）和 0.95（95%CI-1.98-4.15）。
我们的结果表明，银屑病生物治疗的 RCT 不能完全代表真实世界人群，但这种外部有效性的缺乏并不能说明疗效-有效性差距。
关于这个主题已经知道了什么？不符合生物治疗随机对照试验（RCT）条件的银屑病患者发生严重不良事件的风险较高，治疗效果较低，与符合条件的患者相比。
这项研究增加了什么？研究表明，患者的基线特征可预测其是否有资格参加银屑病生物治疗的 RCT。我们没有发现 RCT 代表性样本和真实世界银屑病患者样本之间存在疗效-有效性差距。在 RCT 和真实世界银屑病患者人群之间的任何疗效-有效性差距中，可能有更多因素超出了基线患者特征，例如观察者效应和更高的 RCT 依从性。
