He Huan, Wu Wenwen, Zhang Yi, Zhang Meng, Sun Ning, Zhao Libo, Wang Xiaoling
Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, China.
Front Pharmacol. 2021 Jul 1;12:586827. doi: 10.3389/fphar.2021.586827. eCollection 2021.
The response time-course information of biologics and small targeted molecules for the treatment of moderate to severe plaque psoriasis which helps clinicians to understand the onset of action and maintenance of effect are unclear. Quantitative information about the efficacy comparation of different systemic agents are needed. Model-based meta-analysis was conducted and longitudinal models were developed by applying two clinical end points commonly reported in the clinical trials of psoriasis: the proportion of patients achieving ≥75% reduction from baseline Psoriasis Area and Severity Index score (PASI75) and the proportion of patients achieving ≥90% reduction from baseline Psoriasis Area and Severity Index score (PASI90). A total of 80 trials of thirteen biological agents and four small targeted molecules covering 235 treatment arms and 40323 patients with moderate to severe plaque psoriasis were included in this analysis. The drugs were divided into five classes of biologics and three classes of small molecules. Two longitudinal models of PASI75 and PASI90 were used to describe the time-varying drug effect and dose-effect relationship. The typical response-time courses for PASI75 and PASI90 increased over time and finally reached to the platform. For PASI75 end point at week 12, of all the therapeutic drugs, risankizumab administered as 150 mg at week 0, week 4, and q12w showed the most efficacious with PASI75 was 85.95% (95%CI, 75.71-92.60%), followed by ixekizumab administered as 160 mg at week 0, and q4w with PASI75 was 85.9% (95%CI, 76.12-92.79%). As for PASI90 end point at week 12, ixekizumab 160 mg at week 0, and q4w showed the greatest percentage of person achieved PASI90 (67.2%; 95%CI, 49.91-77.2%), followed by risankizumab 150 mg at week 0, week 4, and q12w (65.5%; 95%CI, 47.8-75.7%). What's more, the risankizumab provided the highest response of PASI90 at week 16 and week 24. This study provided a quantitative efficacy comparation of 17 systemic agents for psoriasis in term of efficacy only and that safety was not considered. Risankizumab and ixekizumab showed superiority for both the two end points.
用于治疗中度至重度斑块状银屑病的生物制剂和小分子靶向药物的反应时程信息尚不清楚，而这有助于临床医生了解起效时间和疗效维持情况。我们需要不同全身用药的疗效比较的定量信息。我们进行了基于模型的荟萃分析，并通过应用银屑病临床试验中常见报告的两个临床终点建立了纵向模型：达到银屑病面积和严重程度指数评分（PASI）较基线降低≥75%的患者比例（PASI75），以及达到PASI较基线降低≥90%的患者比例（PASI90）。本分析共纳入了13种生物制剂和4种小分子靶向药物的80项试验，涵盖235个治疗组和40323例中度至重度斑块状银屑病患者。这些药物被分为五类生物制剂和三类小分子药物。使用PASI75和PASI90的两个纵向模型来描述随时间变化的药物效果和剂量-效应关系。PASI75和PASI90的典型反应时程随时间增加，最终达到平台期。对于第12周的PASI75终点，在所有治疗药物中，在第0周、第4周和每12周一次给予150mg的司库奇尤单抗显示出最有效，PASI75为85.95%（95%CI，75.71-92.60%），其次是在第0周给予160mg且每4周一次的依奇珠单抗，PASI75为85.9%（95%CI，76.12-92.79%）。至于第12周的PASI90终点，在第0周给予160mg且每4周一次的依奇珠单抗达到PASI90的患者百分比最高（67.2%；95%CI，49.91-77.2%），其次是在第0周、第4周和每12周一次给予150mg的司库奇尤单抗（65.5%；95%CI, 47.8-75.7%）。此外，司库奇尤单抗在第16周和第24周时PASI90的反应最高。本研究仅在疗效方面提供了17种治疗银屑病的全身用药的定量疗效比较，未考虑安全性。司库奇尤单抗和依奇珠单抗在两个终点上均显示出优势。
