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聚焦布罗达单抗治疗中度至重度斑块状银屑病:设计、研发及在治疗中的潜在地位

Spotlight on brodalumab in the treatment of moderate-to-severe plaque psoriasis: design, development, and potential place in therapy.

作者信息

Roman Michael, Chiu Melvin W

机构信息

David Geffen School of Medicine at UCLA.

Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

出版信息

Drug Des Devel Ther. 2017 Jul 7;11:2065-2075. doi: 10.2147/DDDT.S113683. eCollection 2017.

Abstract

Brodalumab is a novel fully human immunoglobulin G2 monoclonal antibody that antagonizes the interleukin (IL)-17 pathway by binding with high affinity to human IL-17RA. The role of IL-17A in the pathogenesis of psoriasis, as well as the remarkable effectiveness of IL-17 inhibitors in the treatment of moderate-to-severe plaque psoriasis, is well established. The mechanism of action of brodalumab is unique in that it inhibits the IL-17 receptor compared to the two other currently FDA-approved IL-17 inhibitors, secukinumab and ixekizumab, which inhibit the IL-17A molecule itself. The efficacy of brodalumab in the treatment of moderate-to-severe plaque psoriasis has been demonstrated in phase 2 and 3 trials, and subsequently the FDA approved this medication in February 2017. Brodalumab was approved in Japan in July 2016 and approval is pending in Europe. The safety and adverse effects of brodalumab were reviewed across several clinical trials, which, similar to other IL-17 inhibitors, demonstrated increased rates of neutropenia and infections. Brodalumab treatment, similar to ixekizumab and secukinumab, showed no improvement in inflammatory bowel disease patients, and on the contrary, more exacerbations were encountered. Suicidal ideation and behavior events have been reported with brodalumab treatment and are of significant concern. Brodalumab provides another highly effective treatment option for moderate-to-severe plaque psoriasis.

摘要

布罗达单抗是一种新型的全人源免疫球蛋白G2单克隆抗体,它通过与人类白细胞介素(IL)-17受体A高亲和力结合来拮抗IL-17信号通路。IL-17A在银屑病发病机制中的作用,以及IL-17抑制剂在治疗中度至重度斑块状银屑病方面的显著疗效,已得到充分证实。与目前另外两种获美国食品药品监督管理局(FDA)批准的IL-17抑制剂司库奇尤单抗和依奇珠单抗不同,布罗达单抗的作用机制独特,它抑制的是IL-17受体,而司库奇尤单抗和依奇珠单抗抑制的是IL-17A分子本身。布罗达单抗治疗中度至重度斑块状银屑病的疗效已在2期和3期试验中得到证实,随后FDA于2017年2月批准了这种药物。布罗达单抗于2016年7月在日本获批,在欧洲的获批正在等待中。多项临床试验对布罗达单抗的安全性和不良反应进行了评估,结果显示,与其他IL-17抑制剂类似,布罗达单抗会使中性粒细胞减少和感染的发生率增加。与依奇珠单抗和司库奇尤单抗一样,布罗达单抗治疗并未使炎症性肠病患者病情改善,相反,还出现了更多病情加重的情况。有报道称布罗达单抗治疗会出现自杀意念和行为事件,这令人高度关注。布罗达单抗为中度至重度斑块状银屑病提供了另一种高效的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6d8/5511025/97802c85e086/dddt-11-2065Fig1.jpg

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