Papp Kim A, Vender Ron, Purdy Kerri, Lovegrove Fiona, Oroz Irina, Grewal Parbeer, Lansang Perla, Park-Wyllie Laura, Abbarin Nastaran, Yang Ya-Wen, Hooper Becky, Vigelis Sandra, Disher Tim, Langley Richard G
Probity Medical Research Inc., Waterloo, ON, Canada.
Alliance Clinical Trials, Waterloo, ON, Canada.
Dermatol Ther (Heidelb). 2025 Jul 17. doi: 10.1007/s13555-025-01463-6.
For some patients with plaque psoriasis (PsO), a rapid response (i.e. short interval to time to onset of action [TOA]) is desired. The primary objective was to determine average time to achieve a Psoriasis Area and Severity Index (PASI) 90 response (50% of patients) for individual biologics or targeted therapies. Secondary outcomes included the average time to achieve a PASI 75 response (50% of patients), as well as PASI 90 and PASI 75 responses over the first 16 weeks of therapy.
A systematic targeted literature review was conducted to identify phase III and IV randomised, double-blinded trials according to pre-specified eligibility criteria that investigated interleukin (IL)-12/23 inhibitors, IL-17 inhibitors, IL-23 inhibitors, Janus kinase (JAK) inhibitors, and phosphodiesterase (PDE) inhibitors. Using proportions of patients achieving PASI 90 or 75 responses over 16 weeks, network meta-analyses were conducted to estimate response over time. This was presented as curves, and TOA was summarized as median time to reach the 50th percentile.
Forty-five trials were included in the main analyses. The IL-17 inhibitors bimekizumab, ixekizumab, brodalumab, and secukinumab 300 mg were estimated to provide the earliest onset of PASI 90 response at approximately 6 to 8 weeks. This was followed by the IL-23 inhibitors risankizumab and guselkumab at approximately 9-10 weeks, and the IL-12/23 inhibitor at 11-12 weeks. Although wide and overlapping credible intervals and similar point estimates were observed, these results suggest onset of action does not vary greatly across biologics in these classes. Onset of PASI 90 response could not be estimated by the model for tildrakizumab, and JAK and PDE4 inhibitors. Onset of PASI 75 response showed similar trends to PASI 90 response.
IL-17 inhibitors, followed by IL-23 inhibitors, have the most rapid TOA among PsO biologics evaluated; any differences in onset of action between specific agents within the same drug class are not statistically or clinically significant. These analyses will allow clinicians to make more informed treatment decisions for their patients.
对于一些斑块状银屑病（PsO）患者而言，期望有快速反应（即达到起效时间[TOA]的间隔时间短）。主要目标是确定个体生物制剂或靶向疗法达到银屑病面积和严重程度指数（PASI）90反应（50%的患者）的平均时间。次要结局包括达到PASI 75反应（50%的患者）的平均时间，以及治疗前16周内的PASI 90和PASI 75反应。
根据预先指定的纳入标准进行系统的靶向文献综述，以识别研究白细胞介素（IL）-12/23抑制剂、IL-17抑制剂、IL-23抑制剂、Janus激酶（JAK）抑制剂和磷酸二酯酶（PDE）抑制剂的III期和IV期随机双盲试验。利用16周内达到PASI 90或75反应的患者比例，进行网状荟萃分析以估计随时间的反应。结果以曲线呈现，TOA总结为达到第50百分位数的中位时间。
45项试验纳入主要分析。估计IL-‑17抑制剂比美吉珠单抗、司库奇尤单抗、布罗达单抗和300 mg司库奇尤单抗在约6至8周时最早出现PASI 90反应。其次是IL-23抑制剂瑞莎珠单抗和古塞库单抗，约在9至10周出现反应，IL-12/23抑制剂在11至12周出现反应。尽管观察到较宽且重叠的可信区间以及相似的点估计值，但这些结果表明这些类别中的生物制剂在起效时间上差异不大。替拉珠单抗、JAK和PDE4抑制剂的模型无法估计PASI 90反应的起效时间。PASI 75反应的起效时间显示出与PASI 90反应相似的趋势。
在评估的PsO生物制剂中，IL-17抑制剂其次是IL-23抑制剂，具有最快的TOA；同一药物类别中特定药物之间起效时间的任何差异在统计学或临床上均无显著意义。这些分析将使临床医生能够为其患者做出更明智的治疗决策。
