Farahnik Benjamin, Beroukhim Kourosh, Nakamura Mio, Abrouk Michael, Zhu Tian Hao, Singh Rasnik, Lee Kristina, Bhutani Tina, Koo John
J Drugs Dermatol. 2016 Mar;15(3):311-6.
Studies investigating the molecular basis of psoriasis have established the central roles of TNFa, interleukin (IL)-12, IL-22 and IL-23, and now there is increasing evidence that IL-17 plays a vital role in the complex pathophysiology of this disease. Preclinical and phase II studies of medications targeting IL-17 and its receptor have thus far proved to be promising.
We reviewed the results of the phase III clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent.
By week 12, the proportion of patients reaching a 75% improvement from baseline Psoriasis Area and Severity Index (PASI 75) was comparable between the different agents (secukinumab 83%, ixekizumab 89%, and brodalumab 85%). The safety profiles of the agents were similar with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction.
The anti-IL-17 agents demonstrated a rapid and robust clinical improvement accompanied by a favorable short-term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis treatment.
研究银屑病分子基础的各项研究已证实肿瘤坏死因子α(TNFα)、白细胞介素(IL)-12、IL-22和IL-23起核心作用,现在越来越多的证据表明IL-17在该疾病复杂的病理生理学中起关键作用。迄今为止,针对IL-17及其受体的药物的临床前研究和II期研究已证明颇具前景。
我们回顾了抗IL-17药物司库奇尤单抗、依奇珠单抗和布罗达单抗的III期临床试验结果,以评估每种药物的疗效和安全性。
到第12周时,不同药物之间达到银屑病面积和严重程度指数较基线改善75%(PASI 75)的患者比例相当(司库奇尤单抗83%,依奇珠单抗89%,布罗达单抗85%)。这些药物的安全性相似,最常报告的不良事件为鼻咽炎、上呼吸道感染、头痛和注射部位反应。
抗IL-17药物显示出快速且显著的临床改善,同时具有良好的短期安全性。III期试验结果继续强化了IL-17通路是银屑病治疗重要靶点这一理论。