Deucravacitinib: Long-term safety and efficacy reaffirm its place in the psoriasis treatment landscape

IF 8.4 2区 医学 Q1 DERMATOLOGY
Ion Birkenmaier, Sezgi Sarikaya Solak, Julia-Tatjana Maul
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This selectivity enables targeted modulation of IL-12, IL-23 and type I interferon pathways, resulting in a distinct and potentially more favorable safety profile.<span><sup>1, 2</sup></span></p><p>Armstrong et al.<span><sup>1</sup></span> present 4-year results from the POETYK PSO-1, PSO-2 and their long-term extension trials, offering key insights into the durability of deucravacitinib's efficacy and safety. Given the chronic, immune-mediated nature of psoriasis, such findings are particularly relevant as they highlight the need for durable systemic treatment options.</p><p>The data are encouraging<span><sup>1</sup></span> – patients treated continuously with deucravacitinib maintained stable PASI 75 (72.0% at year one vs. 71.7% at year four) and PASI 90 response rates (45.6% at year one vs. 47.5% at year four) over 4 years. Nearly half of patients achieved DLQI 0/1, indicating minimal or no impact on their quality of life. 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引用次数: 0

Abstract

Deucravacitinib is an oral, highly selective TYK2 inhibitor approved for the treatment of moderate to severe plaque psoriasis.1, 2 A key aspect that differentiates this allosteric inhibitor from other oral immunomodulators is its selective binding to the regulatory domain of TYK2, avoiding inhibition of JAK1, JAK2 and JAK3. This selectivity enables targeted modulation of IL-12, IL-23 and type I interferon pathways, resulting in a distinct and potentially more favorable safety profile.1, 2

Armstrong et al.1 present 4-year results from the POETYK PSO-1, PSO-2 and their long-term extension trials, offering key insights into the durability of deucravacitinib's efficacy and safety. Given the chronic, immune-mediated nature of psoriasis, such findings are particularly relevant as they highlight the need for durable systemic treatment options.

The data are encouraging1 – patients treated continuously with deucravacitinib maintained stable PASI 75 (72.0% at year one vs. 71.7% at year four) and PASI 90 response rates (45.6% at year one vs. 47.5% at year four) over 4 years. Nearly half of patients achieved DLQI 0/1, indicating minimal or no impact on their quality of life. Importantly, the safety outcomes remained stable throughout the 4393 patient-years of exposure, with low and consistent rates of serious infections, malignancies, major cardiovascular events and venous thromboembolism. Notably, no new safety concerns emerged and discontinuations due to adverse events decreased over time.

Certain limitations, however, must be considered. As an open-label extension, the study inherently includes a responder bias, as participants who did not benefit or tolerate treatment in the initial phase likely discontinued. Moreover, the apremilast arm was discontinued after year 1, preventing direct long-term comparisons of efficacy and safety against other therapies, including newer biologics and oral agents.

Despite these limitations, Armstrong et al. provide robust evidence supporting deucravacitinib's role as a reliable long-term oral therapy for moderate to severe psoriasis. Importantly, in contrast to other JAK inhibitors, deucravacitinib has not been subject to a black box warning by the FDA. This is significant, particularly considering FDA concerns surrounding cardiovascular and malignancy risks with JAK1/2/3 inhibitors. The presented 4-year data thereby further reinforce the benefits of TYK2 selectivity.

The February 2025 update of the EuroGuiDerm guideline nevertheless recommends monitoring full blood count, liver enzymes, creatine phosphokinase and lipid profile where clinically indicated, every 3–6 months during treatment and advises treatment interruption if myopathy or liver injury is suspected.3 Reassuringly, the 4-year data did not show clinically meaningful changes from baseline in terms of laboratory tests, consistently supporting the safety profile.1

Recent literature also affirms that TYK2 inhibitors may combine the convenience of oral administration with an improved long-term benefit–risk profile compared to less selective JAK inhibitors (Shah et al. 2025 J Drugs Dermatol.).4 Patient surveys further emphasize that efficacy, safety and oral administration are key factors in treatment choice, particularly in chronic diseases like psoriasis (Armstrong et al. 2024 Dermatol Ther Heidel).5

Although the 4-year data attest to deucravacitinib's sustained efficacy and favourable safety profile, the mentioned limitations call for caution in interpreting these outcomes as definitive safety advantages. Its positioning among systemic psoriasis therapies will require further head-to-head comparisons with newer oral agents and biologics, as well as results from long-term real-world evidence studies. However, the current data suggest it is a well-tolerated oral option that provides long-lasting efficacy with potentially reduced safety risks associated with broader immunosuppression.

In summary, the long-term analysis from Armstrong et al. supports deucravacitinib's potential as a durable, safe and patient-friendly treatment for moderate to severe plaque psoriasis. From a clinician's perspective, such a well-tolerated oral therapy with sustained disease control is an encouraging addition to existing therapies—especially for patients who value the convenience of an oral treatment.

IB is an employee of the University Hospital of Zurich and PhD candidate at the University of Zurich and has declared no conflict of interest. SSS has received speaking fees and/or travel support from Abbvie, Janssen, Novartis and UCB, outside the submitted work. JTM has served as advisor and/or received speaking fees and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, BMS, Celgene, Eli Lilly, Incyte, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi and UCB.

Deucravacitinib:长期的安全性和有效性重申了其在牛皮癣治疗领域的地位
Deucravacitinib是一种口服高选择性TYK2抑制剂,被批准用于治疗中度至重度斑块性银屑病。1,2这种变构抑制剂与其他口服免疫调节剂的一个关键区别在于其选择性结合TYK2的调控结构域,避免了JAK1、JAK2和JAK3的抑制。这种选择性使得靶向调节IL-12、IL-23和I型干扰素通路成为可能,从而产生一种独特的、潜在的更有利的安全性。1,2 armstrong等人1介绍了POETYK PSO-1、PSO-2及其长期扩展试验的4年结果,为deucravacitinib疗效和安全性的持久性提供了关键见解。鉴于牛皮癣的慢性、免疫介导的性质,这些发现特别相关,因为它们强调了持久的全身治疗选择的必要性。数据令人鼓舞,持续接受deucravacitinib治疗的患者在4年内保持稳定的PASI 75(第一年72.0%对第四年71.7%)和PASI 90缓解率(第一年45.6%对第四年47.5%)。近一半的患者达到DLQI 0/1,表明对其生活质量的影响很小或没有影响。重要的是,在4393例患者年的暴露期间,安全性结果保持稳定,严重感染、恶性肿瘤、主要心血管事件和静脉血栓栓塞的发生率较低且一致。值得注意的是,没有出现新的安全性问题,并且由于不良事件引起的停药随着时间的推移而减少。但是,必须考虑到某些限制。作为一项开放标签扩展,该研究固有地包含应答者偏倚,因为在初始阶段没有受益或耐受治疗的参与者可能会停止治疗。此外,阿普雷米司特组在1年后就停止了,这阻止了与其他疗法(包括较新的生物制剂和口服药物)的疗效和安全性进行直接的长期比较。尽管存在这些局限性,Armstrong等人提供了强有力的证据,支持deucravacitinib作为中重度牛皮癣可靠的长期口服疗法。重要的是,与其他JAK抑制剂相比,deucravacitinib尚未受到FDA的黑盒警告。这很重要,特别是考虑到FDA对JAK1/2/3抑制剂的心血管和恶性风险的担忧。因此,提出的4年数据进一步强化了TYK2选择性的益处。然而,2025年2月更新的EuroGuiDerm指南建议在治疗期间每3-6个月监测一次全血细胞计数、肝酶、肌酸磷酸激酶和临床指征的脂质谱,如果怀疑有肌病或肝损伤,建议中断治疗令人放心的是,在实验室测试方面,4年的数据没有显示出与基线相比有临床意义的变化,始终支持安全性概况。最近的文献也证实,与选择性较低的JAK抑制剂相比,TYK2抑制剂可能结合了口服给药的便利性和改善的长期获益-风险特征(Shah等人,2025年J Drugs Dermatol.)患者调查进一步强调,疗效、安全性和口服给药是治疗选择的关键因素,特别是对于牛皮癣等慢性疾病(Armstrong et al. 2024 Dermatol Ther Heidel)。尽管4年的数据证明了deucravacitinib的持续有效性和良好的安全性,但上述局限性要求在将这些结果解释为确定的安全性优势时要谨慎。它在全身性银屑病治疗中的定位将需要与较新的口服药物和生物制剂进行进一步的正面比较,以及长期真实世界证据研究的结果。然而,目前的数据表明,它是一种耐受性良好的口服选择,提供持久的疗效,潜在地降低了与更广泛的免疫抑制相关的安全风险。总之,Armstrong等人的长期分析支持deucravacitinib作为一种持久、安全和患者友好的治疗中至重度斑块型银屑病的潜力。从临床医生的角度来看,这种耐受性良好且持续控制疾病的口服疗法是对现有疗法的一种令人鼓舞的补充,尤其是对那些重视口服治疗的便利性的患者。IB是苏黎世大学医院的员工,也是苏黎世大学的博士候选人,并声明没有利益冲突。在提交的工作之外,SSS已收到艾伯维、杨森、诺华和UCB的演讲费和/或旅行支持。JTM曾担任艾伯维(AbbVie)、Almirall、安进(Amgen)、BMS、Celgene、礼来(Eli Lilly)、Incyte、LEO Pharma、Janssen-Cilag、MSD、诺华(Novartis)、辉瑞(Pfizer)、Pierre Fabre、罗氏(Roche)、赛诺菲(Sanofi)和UCB赞助的临床试验的顾问和/或接受演讲费和/或参加临床试验。
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
CiteScore
10.70
自引率
8.70%
发文量
874
审稿时长
3-6 weeks
期刊介绍: The Journal of the European Academy of Dermatology and Venereology (JEADV) is a publication that focuses on dermatology and venereology. It covers various topics within these fields, including both clinical and basic science subjects. The journal publishes articles in different formats, such as editorials, review articles, practice articles, original papers, short reports, letters to the editor, features, and announcements from the European Academy of Dermatology and Venereology (EADV). The journal covers a wide range of keywords, including allergy, cancer, clinical medicine, cytokines, dermatology, drug reactions, hair disease, laser therapy, nail disease, oncology, skin cancer, skin disease, therapeutics, tumors, virus infections, and venereology. The JEADV is indexed and abstracted by various databases and resources, including Abstracts on Hygiene & Communicable Diseases, Academic Search, AgBiotech News & Information, Botanical Pesticides, CAB Abstracts®, Embase, Global Health, InfoTrac, Ingenta Select, MEDLINE/PubMed, Science Citation Index Expanded, and others.
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