Secukinumab responses vary across the spectrum of congenital ichthyosis in adults.
Secukinumab responses vary across the spectrum of congenital ichthyosis in adults.
复制标题
苏金单抗的反应因成人先天性鱼鳞病的不同而有所不同。
DOI：
10.1007/s00403-022-02325-3
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发表时间：
2023
影响因子：
3
通讯作者：
Paller,AmyS
中科院分区：
文献类型：
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作者：
Lefferdink,Rachel;Rangel,StephanieM;Chima,Margot;Ibler,Erin;Pavel,AnaB;Kim,HeeJin;Wu,Benedict;Abu-Zayed,Hajar;Wu,Jianni;Jackson,Kathryn;Singer,Giselle;Choate,KeithA;Guttman-Yassky,Emma;Paller,AmyS
先天性鱼鳞病的治疗主要集中在逆转皮肤鳞屑，而不是基于发病机制。目的确定IL-17A抑制剂Suckinumab是否可以改善几种先天性鱼鳞病亚型中的鱼鳞病。设计为期16周的双盲、随机、安慰剂对照试验，比较Suckinumab每4周300 mg与安慰剂(1：1随机)在成人和四种主要先天性鱼鳞病亚型(NCT03041038)中的疗效，随后进行16周的开放标记期以评估安慰剂组和延长20周的安全性。两个三级转诊中心：芝加哥西北大学范伯格医学院和纽约西奈山伊坎医学院。20名 ≥ 18岁的受试者患有经基因确认的表皮松解性鱼鳞病、Netherton综合征、板层性鱼鳞病或先天性鱼鳞状红皮病，且至少有中度红斑。在WK32有29-50%临床改善的5名患者要求继续用药。与基线或安慰剂治疗水平相比，Th17相关生物标志物没有显著降低。限制样本量小；异质性鱼鳞病亚群。结论Suckinumab抑制IL-17是安全的，但在成人鱼鳞病的光谱中并不有效。临床试验。政府注册编号NCT03041038；首次发布于2017年2月2日。
ImportanceTreatment of congenital ichthyoses primarily focuses on reversing skin scaling and is not pathogenesis based. Recent studies showed Th17 immune skewing, as in psoriasis, across the spectrum of ichthyosis, suggesting that targeting this pathway might broadly reduce disease severity.ObjectiveTo determine whether secukinumab, an IL-17A inhibitor, can improve ichthyosis across several congenital ichthyosis subtypes.DesignExploratory 16-week double-blind, randomized, placebo-controlled trial comparing secukinumab 300 mg every 4wks to placebo (1:1 randomization) in adults with the four major congenital ichthyosis subtypes (NCT03041038), followed by a 16-week open-label phase to evaluate response of the placebo-first group and a 20-week extension for safety. Significant differences in secukinumab- vs. placebo-treated subjects at Wk16 in the Ichthyosis Area Severity Index (IASI) score and lack of increased mucocutaneous bacterial and/or fungal infections were the co-primary efficacy and safety endpoints, respectively.SettingTwo tertiary referral centers: Northwestern University Feinberg School of Medicine, Chicago, and Mount Sinai Icahn School of Medicine, New York.ParticipantsTwenty subjects ≥ 18 yo with genotype-confirmed epidermolytic ichthyosis, Netherton syndrome, lamellar ichthyosis, or congenital ichthyosiform erythroderma with at least moderate erythroderma.ResultsIL-17A inhibition did not significantly reduce severity or increase mucocutaneous infections among the 18 who completed the 16-week double-blind phase. Five patients with 29–50% clinical improvement at Wk32 requested drug continuation. Th17-related biomarkers were not significantly reduced vs. baseline or placebo-treated levels.LimitationsSmall sample size; heterogeneous ichthyosis subsets.ConclusionIL-17 inhibition with secukinumab is safe, but not efficacious across the spectrum of adult ichthyoses.ClinicalTrials.gov registration numberNCT03041038; first posted on 02/02/2017.