Näslund-Koch Charlotte, Zachariae Claus, Skov Lone
Department of Dermatology and Allergy, Herlev and Gentofte Hospital, Copenhagen, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Ther Clin Risk Manag. 2020 Sep 24;16:903-916. doi: 10.2147/TCRM.S227880. eCollection 2020.
Psoriasis is a common immune-mediated chronic inflammatory disease, and observations have pointed toward the IL-23/Th17 cell axis as having a key role in the pathogenesis of psoriasis. This new immunological understanding of the pathogenesis has been translated into targeted and highly effective biologic therapies. Tildrakizumab is a humanized IgG1/k monoclonal antibody targeting the p19 unit of IL-23 and has been registered for the treatment of patients with moderate-to-severe chronic plaque psoriasis in adults since 2018. This review provides an overview of the efficacy and safety of tildrakizumab, focusing on the results from clinical trials. In both Phase II and III trials, tildrakizumab 100 and 200 mg was significantly more efficacious than both placebo and etanercept at week 12. The effect of tildrakizumab continued to increase until week 28. Long-term follow-up showed high levels of efficacy for up to 3 years. Despite no difference between 100 and 200 mg in Phase III studies, subgroup analyses showed better efficacy when treated with 200 mg in patients with bodyweight ≥90 kg. The overall drug safety was good, and besides discrete higher incidence of nasopharyngitis, the conducted clinical trials show that tildrakizumab was very well tolerated without any safety concerns. Compared to other IL-23p19 inhibitors, tildrakizumab seemed to have slightly lower efficacy. However, to determine its position in the treatment algorithm of psoriasis, head-to-head trials with other IL-17, IL-12/23, and IL-23 inhibitors and long-term real-world data are required.
银屑病是一种常见的免疫介导的慢性炎症性疾病,研究表明白细胞介素-23/辅助性T细胞17(IL-23/Th17)细胞轴在银屑病的发病机制中起关键作用。这种对发病机制的新免疫学认识已转化为有针对性的高效生物疗法。替拉珠单抗是一种靶向IL-23 p19亚基的人源化IgG1/κ单克隆抗体,自2018年以来已获批用于治疗成人中重度慢性斑块状银屑病患者。本综述概述了替拉珠单抗的疗效和安全性,重点关注临床试验结果。在II期和III期试验中,第12周时,100毫克和200毫克的替拉珠单抗均比安慰剂和依那西普显著更有效。替拉珠单抗的疗效持续增加直至第28周。长期随访显示,长达3年的疗效都很高。尽管III期研究中100毫克和200毫克剂量之间没有差异,但亚组分析显示,体重≥90千克的患者使用200毫克治疗时疗效更佳。总体药物安全性良好,除了鼻咽炎的发生率略有升高外,所进行的临床试验表明,替拉珠单抗耐受性良好,没有任何安全问题。与其他IL-23 p19抑制剂相比,替拉珠单抗的疗效似乎略低。然而,要确定其在银屑病治疗方案中的地位,需要与其他IL-17、IL-12/23和IL-23抑制剂进行头对头试验以及长期真实世界数据。