Liu Yixiao, Xu Ling, Wang Xinrui, Wu Lijuan, Cai Ruifen, Li Lujin, Zheng Qingshan
Center for Drug Clinical Research, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Expert Rev Clin Pharmacol. 2023 Jul-Dec;16(10):999-1008. doi: 10.1080/17512433.2023.2259300. Epub 2023 Sep 14.
Further dose optimization is required for patients with moderate-to-severe plaque psoriasis who do not benefit from the approved secukinumab dose regimen. This study aimed to develop an exposure-response model for secukinumab to recommend dose regimens for patients of different body weights.
We searched the PubMed and Cochrane Library databases for randomized controlled trials using PASI 75 and PASI 90 response rates as primary outcomes. A model-based meta-analysis was developed to quantitatively analyze the distribution of six secukinumab dose regimens in patients weighing 50-120 kg.
Sixteen trials involving 6,197 subjects were included in the analysis. The established model accurately described the time-course characteristics of PASI 75 and PASI 90 response rates over 52 weeks. Simulations indicated that maintenance doses could be reduced to 150 mg every 4 weeks and to 150 mg every 3 weeks for patients weighing 50 and 60 kg, respectively. In contrast, maintenance doses of 300 mg every 3 weeks should be selected for patients weighing 120 kg. Patients weighing 70-110 kg remained on approved maintenance doses of 300 mg every 4 weeks.
Based on patient body weights, the exposure-response model recommends efficacious and economical dose regimens for patients with moderate-to-severe plaque psoriasis.
对于中度至重度斑块状银屑病患者，若未从已获批的司库奇尤单抗剂量方案中获益，则需要进一步优化剂量。本研究旨在建立司库奇尤单抗的暴露-反应模型，为不同体重的患者推荐剂量方案。
我们在PubMed和Cochrane图书馆数据库中检索了以银屑病面积和严重程度指数（PASI）改善75%和90%的缓解率作为主要结局的随机对照试验。开展了基于模型的荟萃分析，以定量分析六种司库奇尤单抗剂量方案在体重50 - 120千克患者中的分布情况。
分析纳入了16项试验，共6197名受试者。所建立的模型准确描述了52周内PASI改善75%和90%缓解率的时间进程特征。模拟结果表明，对于体重分别为50千克和60千克的患者，维持剂量可分别减至每4周150毫克和每3周150毫克。相比之下，对于体重120千克的患者，应选择每3周300毫克的维持剂量。体重70 - 110千克的患者维持使用已获批的每4周300毫克的维持剂量。
基于患者体重，暴露-反应模型为中度至重度斑块状银屑病患者推荐了有效且经济的剂量方案。
