Haag Carter, Alexis Andrew, Aoki Valeria, Bissonnette Robert, Blauvelt Andrew, Chovatiya Raj, Cork Michael J, Danby Simon G, Eichenfield Lawrence F, Eyerich Kilian, Gooderham Melinda, Guttman-Yassky Emma, Hijnen Dirk-Jan, Irvine Alan D, Katoh Norito, Murrell Dedee F, Leshem Yael A, Levin Adriane A, Vittrup Ida, Olydam Jill I, Orfali Raquel L, Paller Amy S, Renert-Yuval Yael, Rosmarin David, Silverberg Jonathan I, Thyssen Jacob P, Ständer Sonja, Stefanovic Nicholas, Todd Gail, Yu JiaDe, Simpson Eric L
Department of Dermatology, Oregon Health and Science University, Portland, OR, USA.
Br J Dermatol. 2024 Dec 23;192(1):135-143. doi: 10.1093/bjd/ljae342.
Janus kinase inhibitors (JAKi) have the potential to alter the landscape of atopic dermatitis (AD) management dramatically, owing to promising efficacy results from phase III trials and their rapid onset of action. However, JAKi are not without risk, and their use is not appropriate for all patients with AD, making this a medication class that dermatologists should understand and consider when treating patients with moderate-to-severe AD.
To provide a consensus expert opinion statement from the International Eczema Council (IEC) that provides a pragmatic approach to prescribing JAKi, including choosing appropriate patients and dosing, clinical and laboratory monitoring and advice about long-term use.
An international cohort of authors from the IEC with expertise in JAKi selected topics of interest were placed into authorship groups covering 10 subsections. The groups performed topic-specific literature reviews, consulted up-to-date adverse event (AE) data, referred to product labels and provided analysis and expert opinion. The manuscript guidance and recommendations were reviewed by all authors, as well as the IEC Research Committee.
We recommend that JAKi be considered for patients with moderate-to-severe AD seeking the benefits of a rapid reduction in disease burden and itch, oral administration and the potential for flexible dosing. Baseline risk factors should be assessed prior to prescribing JAKi, including increasing age, venous thromboembolisms, malignancy, cardiovascular health, kidney/liver function, pregnancy and lactation, and immunocompetence. Patients being considered for JAKi treatment should be current on vaccinations and we provide a generalized framework for laboratory monitoring, although clinicians should consult individual product labels for recommendations as there are variations among the different JAKi. Patients who achieve disease control should be maintained on the lowest possible dose, as many of the observed AEs occurred in a dose-dependent manner. Future studies are needed in patients with AD to assess the durability and safety of continuous long-term JAKi use, combination medication regimens and the effects of flexible, episodic treatment over time.
The decision to initiate JAKi treatment should be shared between the patient and provider, accounting for AD severity and personal risk-benefit assessment, including consideration of baseline health risk factors, monitoring requirements and treatment costs.
由于III期试验显示出有前景的疗效结果且起效迅速，Janus激酶抑制剂（JAKi）有可能极大地改变特应性皮炎（AD）的治疗格局。然而，JAKi并非没有风险，并非所有AD患者都适合使用，这使得皮肤科医生在治疗中重度AD患者时应了解并考虑这一类药物。
提供国际湿疹理事会（IEC）的共识专家意见声明，为JAKi的处方提供实用方法，包括选择合适的患者和剂量、临床及实验室监测以及长期使用建议。
IEC中具有JAKi专业知识的国际作者团队将选定的感兴趣主题分为涵盖10个小节的作者小组。各小组进行特定主题的文献综述，查阅最新的不良事件（AE）数据，参考产品标签并提供分析和专家意见。所有作者以及IEC研究委员会对稿件的指导和建议进行了审核。
我们建议，对于寻求快速减轻疾病负担和瘙痒、口服给药以及灵活给药可能性的中重度AD患者，可考虑使用JAKi。在开具JAKi处方之前，应评估基线风险因素，包括年龄增长、静脉血栓栓塞、恶性肿瘤、心血管健康、肾/肝功能、妊娠和哺乳期以及免疫功能。考虑接受JAKi治疗的患者应完成疫苗接种，我们提供了一个实验室监测的通用框架，不过由于不同JAKi之间存在差异，临床医生应参考个别产品标签获取建议。病情得到控制的患者应维持在尽可能低的剂量，因为许多观察到的不良事件呈剂量依赖性发生。AD患者未来需要开展研究，以评估持续长期使用JAKi、联合用药方案以及灵活的间歇性治疗随时间推移的耐久性和安全性。
启动JAKi治疗的决定应由患者和医疗服务提供者共同做出，要考虑AD的严重程度以及个人的风险效益评估，包括对基线健康风险因素、监测要求和治疗成本的考量。
