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使用乌司奴单抗阻断IL12/23作为免疫相关皮肤不良事件的一种治疗方法。

IL12/23 Blockade with Ustekinumab as a Treatment for Immune-Related Cutaneous Adverse Events.

作者信息

Gu Stephanie L, Maier Tara, Moy Andrea P, Dusza Stephen, Faleck David M, Shah Neil J, Lacouture Mario E

机构信息

Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.

Department of Dermatology, Weill Cornell Medical College, New York, NY 10021, USA.

出版信息

Pharmaceuticals (Basel). 2023 Nov 2;16(11):1548. doi: 10.3390/ph16111548.

Abstract

: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is reminiscent of the psoriasiform/lichenoid ircAE phenotype. We report the use of ustekinumab as a therapeutic option. : Patients at Memorial Sloan Kettering Cancer Center, New York, who received immune checkpoint inhibitors and were treated with ustekinumab or had the keywords "ustekinumab" or "Stelara" in their clinical notes between 1 March 2017 and 1 December 2022 were retrospectively identified via a database query. Documentation from initial and follow-up visits was manually reviewed, and response to ustekinumab was categorized into complete cutaneous response (CcR, decrease to CTCAE grade 0), partial cutaneous response (PcR, any decrease in CTCAE grade exclusive of decrease to grade 0), and no cutaneous response (NcR, no change in CTCAE grade or worsening). Labs including complete blood count (CBC), cytokine panels, and IgE were obtained in a subset of patients as standard of care. Skin biopsies were reviewed by a dermatopathologist. : Fourteen patients with psoriasiform (85.7%), maculopapular (7.1%), and pyoderma gangrenosum (7.1%) ircAEs were identified. Ten (71.4%) receiving ustekinumab had a positive response to treatment. Among these 10 responders, 4 (40%) demonstrated partial cutaneous response and 6 (60%) demonstrated complete cutaneous resolution. Six patients (42.9%) experienced interruptions to their checkpoint inhibitor treatment as a result of intolerable ircAEs, and following ircAE management with ustekinumab, two (33.3%) were successfully rechallenged with their checkpoint inhibitors. On histopathology, patients primarily had findings of interface or psoriasiform dermatitis. No patients reported an adverse event related to ustekinumab. : Ustekinumab showed a benefit in a subset of patients with psoriasiform/lichenoid ircAEs. No safety signals were identified. However, further prospective randomized controlled trials are needed to confirm our findings.

摘要

免疫相关皮肤不良事件(ircAEs)很常见,可能会降低生活质量并影响持续给药。IL12/23与银屑病有关,这让人联想到银屑病样/苔藓样ircAE表型。我们报告了使用乌司奴单抗作为一种治疗选择。:通过数据库查询,回顾性识别了纽约纪念斯隆凯特琳癌症中心在2017年3月1日至2022年12月1日期间接受免疫检查点抑制剂治疗并接受乌司奴单抗治疗或临床记录中有“乌司奴单抗”或“喜达诺”关键词的患者。对初次和随访就诊的记录进行人工审核,并将对乌司奴单抗的反应分为完全皮肤反应(CcR,降至CTCAE 0级)、部分皮肤反应(PcR,CTCAE分级有任何降低但不包括降至0级)和无皮肤反应(NcR,CTCAE分级无变化或恶化)。作为标准治疗,在一部分患者中进行了包括全血细胞计数(CBC)、细胞因子检测和IgE在内的实验室检查。皮肤活检由皮肤病理学家进行评估。:确定了14例患有银屑病样(85.7%)、斑丘疹样(7.1%)和坏疽性脓皮病样(7.1%)ircAEs的患者。接受乌司奴单抗治疗的10例(71.4%)患者对治疗有阳性反应。在这10例有反应的患者中,4例(40%)表现为部分皮肤反应,6例(60%)表现为完全皮肤消退。6例患者(42.9%)因无法耐受的ircAEs而中断了检查点抑制剂治疗,在使用乌司奴单抗进行ircAE管理后,2例(33.3%)成功重新接受了检查点抑制剂治疗。在组织病理学上,患者主要表现为界面性皮炎或银屑病样皮炎。没有患者报告与乌司奴单抗相关的不良事件。:乌司奴单抗在一部分患有银屑病样/苔藓样ircAEs的患者中显示出益处。未发现安全信号。然而,需要进一步的前瞻性随机对照试验来证实我们的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0eb/10674871/54b938737ac3/pharmaceuticals-16-01548-g001.jpg

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