Department of Dermatology, Centro Hospitalar Universitário do Porto, Porto, Portugal.
Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.
Am J Clin Dermatol. 2022 Nov;23(6):891-904. doi: 10.1007/s40257-022-00722-y. Epub 2022 Aug 17.
Drug survival, defined as the length of time from initiation to discontinuation of a given therapy, allows comparisons between drugs, helps to predict patient's likelihood of remaining on a specific treatment, and achieving the best decision for each patient in daily clinical practice.
The aim of this study was to provide data on drug survival of secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab in a large international cohort, and to identify clinical predictors that might have an impact on the drug survival of these drugs.
This was a retrospective, multicentric, multi-country study that provides data of adult patients with moderate to severe psoriasis who started treatment with an interleukin (IL)-17 or IL-23 inhibitor between 1 February 2015 and 31 October 2021. Data were collected from 19 distinct hospital and non-hospital-based dermatology centers from Canada, Czech Republic, Italy, Greece, Portugal, Spain, and Switzerland. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis.
A total of 4866 treatment courses (4178 patients)-overall time of exposure of 9500 patient-years-were included in this study, with 3164 corresponding to an IL-17 inhibitor (secukinumab, ixekizumab, brodalumab) and 1702 corresponding to an IL-23 inhibitor (guselkumab, risankizumab, tildrakizumab). IL-23 inhibitors had the highest drug survival rates during the entire study period. After 24 months of treatment, the cumulative probabilities of drug survival were 0.92 (95% confidence interval [CI] 0.89-0.95) for risankizumab, 0.90 (95% CI 0.88-0.92) for guselkumab, 0.80 (95% CI 0.76-0.84) for brodalumab, 0.79 (95% CI 0.76-0.82) for ixekizumab, and 0.75 (95% CI 0.73-0.77) for secukinumab. At 36 months, only guselkumab [0.88 (95% CI 0.85-0.91)], ixekizumab [0.73 (95% CI 0.70-0.76)], and secukinumab [0.67 (95% CI 0.65-0.70)] had more than 40 patients at risk of drug discontinuation. Only two drugs had more than 40 patients at risk of drug discontinuation at 48 months, with ixekizumab demonstrating to have a higher cumulative probability of drug survival [0.71 (95% CI 0.68-0.75)] when compared with secukinumab [0.63 (95% CI 0.60-0.66)]. Secondary failure was the main cause for drug discontinuation. According to the final multivariable model, patients receiving risankizumab, guselkumab, and ixekizumab were significantly less likely to discontinue treatment than those receiving secukinumab. Previous exposure to biologic agents, absent family history of psoriasis, higher baseline body mass index (BMI), and higher baseline Psoriasis Area and Severity Index (PASI) were identified as predictors of drug discontinuation.
The cumulative probability of drug survival of both IL-17 and IL-23 inhibitors was higher than 75% at 24 months, with risankizumab and guselkumab demonstrating to have overall cumulative probabilities ≥ 90%. Biological agent chosen, prior exposure to biologic agents, higher baseline BMI and PASI values, and absence of family history of psoriasis were identified as predictors for drug discontinuation. Risankizumab, guselkumab, and ixekizumab were less likely to be discontinued than secukinumab.
药物生存时间是指从开始治疗到停止治疗的时间长度，它可以用来比较不同药物，有助于预测患者继续接受特定治疗的可能性，并为每个患者在日常临床实践中做出最佳决策。
本研究旨在提供在一个大型国际队列中司库奇尤单抗、依奇珠单抗、布罗达单抗、古塞库单抗、替西珠单抗和瑞莎珠单抗的药物生存数据，并确定可能影响这些药物药物生存的临床预测因素。
这是一项回顾性、多中心、多国研究，提供了 2015 年 2 月 1 日至 2021 年 10 月 31 日期间接受白细胞介素（IL）-17 或 IL-23 抑制剂治疗的中重度银屑病成年患者的数据。数据来自加拿大、捷克共和国、意大利、希腊、葡萄牙、西班牙和瑞士的 19 个不同的医院和非医院皮肤科中心。使用 Kaplan-Meier 估计器和比例风险 Cox 回归模型进行药物生存分析。
本研究共纳入 4866 个治疗疗程（4178 例患者）-总暴露时间为 9500 患者年-其中 3164 个疗程对应于 IL-17 抑制剂（司库奇尤单抗、依奇珠单抗、布罗达单抗），1702 个疗程对应于 IL-23 抑制剂（古塞库单抗、瑞莎珠单抗、替西珠单抗）。在整个研究期间，IL-23 抑制剂的药物生存时间最高。治疗 24 个月后，药物生存的累积概率分别为瑞莎珠单抗 0.92（95%置信区间 0.89-0.95）、古塞库单抗 0.90（95%置信区间 0.88-0.92）、布罗达单抗 0.80（95%置信区间 0.76-0.84）、依奇珠单抗 0.79（95%置信区间 0.76-0.82）和司库奇尤单抗 0.75（95%置信区间 0.73-0.77）。在 36 个月时，只有古塞库单抗（0.88，95%置信区间 0.85-0.91）、依奇珠单抗（0.73，95%置信区间 0.70-0.76）和司库奇尤单抗（0.67，95%置信区间 0.65-0.70）有超过 40 名患者面临停药风险。只有两种药物在 48 个月时有超过 40 名患者面临停药风险，依奇珠单抗的药物生存时间累积概率更高[0.71（95%置信区间 0.68-0.75）]，而司库奇尤单抗[0.63（95%置信区间 0.60-0.66）]。次要失效是停药的主要原因。根据最终的多变量模型，接受瑞莎珠单抗、古塞库单抗和依奇珠单抗治疗的患者停药的可能性明显低于接受司库奇尤单抗治疗的患者。先前暴露于生物制剂、无银屑病家族史、较高的基线体重指数（BMI）和较高的基线银屑病面积和严重程度指数（PASI）被确定为停药的预测因素。
在 24 个月时，两种 IL-17 和 IL-23 抑制剂的药物生存时间累积概率均高于 75%，瑞莎珠单抗和古塞库单抗的总体累积概率均≥90%。选择的生物制剂、先前暴露于生物制剂、较高的基线 BMI 和 PASI 值以及无银屑病家族史被确定为停药的预测因素。与司库奇尤单抗相比，瑞莎珠单抗、古塞库单抗和依奇珠单抗更不容易被停药。
