Effectiveness of guselkumab for avelumab-induced psoriasis in urothelial carcinoma: A case report

IF 2.9 3区 医学 Q2 DERMATOLOGY
Kazuki Yatsuzuka, Satoshi Yoshida, Noriyoshi Miura, Nobushige Kohri, Jun Muto, Ken Shiraishi, Yasuhiro Fujisawa
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In severe cases, ICIs may need to be withheld.<span><sup>1</sup></span> ICI-mediated psoriasis (ICMP), characterized by new-onset or worsening psoriasis, is a recognized adverse effect of ICI.<span><sup>2</sup></span> Recent studies have demonstrated the successful management of ICMP using biologics without ICI discontinuation.<span><sup>3</sup></span> We present a case of ICMP effectively treated with biologics while continuing ICI therapy.</p><p>A 59-year-old man presented with widespread erythematous plaques. Despite achieving near-complete remission of psoriasis vulgaris with topical steroids for the past 6 months, he developed erythematous plaques with infiltration and scaling on his face, extremities, and trunk within a month of initiating avelumab for advanced urothelial carcinoma (Figure 1a,b). A skin biopsy revealed hyperkeratosis, parakeratosis, elongation of the rete ridges, and neutrophil infiltration into the epidermis (Figure 1c,d). 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引用次数: 0

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, their use is often accompanied by immune-related adverse events, including skin manifestations. Although topical corticosteroids are typically effective, systemic therapies are sometimes required. In severe cases, ICIs may need to be withheld.1 ICI-mediated psoriasis (ICMP), characterized by new-onset or worsening psoriasis, is a recognized adverse effect of ICI.2 Recent studies have demonstrated the successful management of ICMP using biologics without ICI discontinuation.3 We present a case of ICMP effectively treated with biologics while continuing ICI therapy.

A 59-year-old man presented with widespread erythematous plaques. Despite achieving near-complete remission of psoriasis vulgaris with topical steroids for the past 6 months, he developed erythematous plaques with infiltration and scaling on his face, extremities, and trunk within a month of initiating avelumab for advanced urothelial carcinoma (Figure 1a,b). A skin biopsy revealed hyperkeratosis, parakeratosis, elongation of the rete ridges, and neutrophil infiltration into the epidermis (Figure 1c,d). We diagnosed a flare-up of psoriasis vulgaris induced by avelumab and temporarily suspended avelumab despite its oncological efficacy. Psoriasis area and severity index (PASI) score at flare-up was 13.2. Since the eruptions were resistant to very strong topical steroids, we added narrowband UV-B therapy and the PASI score improved to 2.1 after 3 weeks. Although avelumab was reintroduced, the PASI score worsened to 8.4 within a month. After the addition of apremilast, the PASI score decreased to 1.4. However, 10 months after apremilast initiation, a third flare-up occurred, with the PASI score escalating to 9.6 (Figure 1e,f). Considering the sustained partial response of urothelial carcinoma to avelumab, we decided to switch psoriasis treatment to guselkumab while continuing avelumab. Consequently, a 50% PASI improvement was observed at 12 weeks (Figure 1g,h), with further improvement to a PASI score of 1.2 at 28 weeks without AEs. His urothelial cancer remains under control with continued avelumab.

Topical agents are the mainstay of treatment for ICMP. Switching to a different class of ICI should also be considered. Nikolaou et al.2 proposed algorithm-based management strategies. Although their algorithm prioritizes ICI continuation, a significant proportion of their cohort (18%) required permanent ICI discontinuation because of psoriasis.2 Recent studies have emphasized the efficacy and safety of biologics, particularly interleukin (IL) 23 and IL-17 inhibitors, in the management of psoriasis concurrently with cancer treatment.4 Studies have shown that reduced tumor expression of psoriasis pathway mediators such as IL-17A and IL-23A do not affect overall survival for most tumor types.2 Recent case reports have demonstrated successful psoriasis management with biologics in patients receiving ICIs without compromising antitumor efficacy.3, 5 To our knowledge, this is the first successful use of guselkumab for avelumab-induced psoriasis in a patient with urothelial carcinoma without discontinuing ICI. Considering the pivotal role of ICIs in oncology, the judicious use of biologics should be considered as a primary therapeutic strategy for psoriasis in this patient population rather than premature ICI discontinuation. However, the combination of ICIs and biologics might complicate the immune system, increase the risk of immune-related adverse events and opportunistic infections, and require careful follow-up.

Kazuki Yatsuzuka has received speaker's fees from Abbvie, Eli Lilly, Janssen, Maruho, Novartis, Sun pharma, Taiho, and UCB; and has received research grants from Sun pharma outside the submitted work. Jun Muto has received speaker's fees from Abbvie, Eli Lilly, and Maruho; and has received research grants from Rohto outside the submitted work. Satoshi Yoshida, Noriyoshi Miura, Nobushige Kohri, Ken Shiraishi, and Yasuhiro Fujisawa have declared no conflict of interest. Yasuhiro Fujisawa is an editorial board member of the Journal of Dermatology and a co-author of this article. To minimize bias, he was excluded from all editorial decision-making related to the acceptance of this article for publication.

We obtained written informed consent from the patient to publish his clinical details.

Abstract Image

古塞库单抗治疗尿路上皮癌阿维鲁单抗诱导银屑病的疗效:1例报告。
免疫检查点抑制剂(ICIs)已经彻底改变了癌症治疗;然而,它们的使用往往伴随着免疫相关的不良事件,包括皮肤表现。虽然局部皮质类固醇通常有效,但有时需要全身治疗。在严重的情况下,可能需要停止使用iciICI介导的牛皮癣(ICMP)以新发或恶化的牛皮癣为特征,是公认的ICI的不良反应。最近的研究表明,使用生物制剂治疗ICMP是成功的,而无需停止使用ICI我们报告一例在继续ICI治疗的同时用生物制剂有效治疗ICMP的病例。59岁男性,表现为大面积红斑斑块。尽管在过去的6个月里,局部类固醇治疗的寻常型银屑病几乎完全缓解,但在开始使用avelumab治疗晚期尿路上皮癌的一个月内,他的面部、四肢和躯干出现了红斑斑块,伴有浸润和鳞屑(图1a,b)。皮肤活检显示角化过度、角化不全、网状嵴伸长和中性粒细胞浸润到表皮(图1c,d)。我们诊断了由avelumab引起的寻常型牛皮癣的突然发作,并暂时停用avelumab,尽管它具有肿瘤功效。发作时银屑病面积及严重程度指数(PASI)评分为13.2。由于皮疹对非常强的局部类固醇具有耐药性,我们添加了窄带UV-B治疗,3周后PASI评分提高到2.1。尽管再次使用avelumab, PASI评分在一个月内恶化至8.4。加用阿普雷司特后,PASI评分降至1.4。然而,在阿普利司特开始使用10个月后,第三次发作发生,PASI评分上升至9.6(图1e,f)。考虑到尿路上皮癌对avelumab的持续部分反应,我们决定在继续使用avelumab的同时将牛皮癣治疗转为guselkumab。因此,在12周时观察到50%的PASI改善(图1g,h),在28周时PASI评分进一步改善至1.2,无ae。他的尿路上皮癌仍在持续使用avelumab的控制之下。局部药物是治疗ICMP的主要方法。还应考虑切换到不同类别的ICI。Nikolaou等人2提出了基于算法的管理策略。尽管他们的算法优先考虑持续ICI,但由于牛皮癣,他们的队列中有很大一部分(18%)需要永久停止ICI最近的研究强调了生物制剂的有效性和安全性,特别是白细胞介素(IL) 23和IL-17抑制剂,在银屑病和癌症治疗的同时管理研究表明,在大多数肿瘤类型中,IL-17A和IL-23A等银屑病通路介质的肿瘤表达降低并不影响总体生存最近的病例报告表明,在接受ICIs的患者中,生物制剂治疗牛皮癣成功,且不影响抗肿瘤疗效。3,5据我们所知,这是首次成功使用guselkumab治疗尿路上皮癌患者阿维鲁单抗诱导的牛皮癣,而没有停止ICI。考虑到ICI在肿瘤学中的关键作用,明智地使用生物制剂应被视为银屑病患者群体的主要治疗策略,而不是过早停用ICI。然而,ICIs和生物制剂联合使用可能会使免疫系统复杂化,增加免疫相关不良事件和机会性感染的风险,需要仔细随访。Kazuki Yatsuzuka获得了来自艾伯维、礼来、杨森、Maruho、诺华、太阳制药、Taiho和UCB的演讲费;并在提交的工作之外获得了太阳制药的研究资助。武藤俊从艾伯维(Abbvie)、礼来(Eli Lilly)和丸浩(Maruho)获得了演讲费;并在提交的工作之外获得了Rohto的研究资助。吉田聪、三浦则吉、高利信重、白石健和藤泽康弘都宣布没有利益冲突。Yasuhiro Fujisawa是《皮肤病学杂志》的编辑委员会成员,也是本文的合著者。为了尽量减少偏倚,他被排除在所有与接受这篇文章发表相关的编辑决策之外。我们获得了患者的书面知情同意以发表其临床细节。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Dermatology
Journal of Dermatology 医学-皮肤病学
CiteScore
4.60
自引率
9.70%
发文量
368
审稿时长
4-8 weeks
期刊介绍: The Journal of Dermatology is the official peer-reviewed publication of the Japanese Dermatological Association and the Asian Dermatological Association. The journal aims to provide a forum for the exchange of information about new and significant research in dermatology and to promote the discipline of dermatology in Japan and throughout the world. Research articles are supplemented by reviews, theoretical articles, special features, commentaries, book reviews and proceedings of workshops and conferences. Preliminary or short reports and letters to the editor of two printed pages or less will be published as soon as possible. Papers in all fields of dermatology will be considered.
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