Kirchhof Mark G, Prajapati Vimal H, Gooderham Melinda, Hong Chih-Ho, Lynde Charles W, Maari Catherine, Turchin Irina, Papp Kim A
Dermatology Division, Department of Medicine, University of Ottawa and The Ottawa Hospital, Ottawa, ON, Canada.
Probity Medical Research Inc., 135 Union St. E., Waterloo, ON, N2J 1C3, Canada.
Dermatol Ther (Heidelb). 2024 Sep;14(9):2653-2668. doi: 10.1007/s13555-024-01243-8. Epub 2024 Aug 8.
Oral Janus kinase inhibitors (JAKi), a class of advanced targeted systemic therapy, have demonstrated efficacy and safety in the treatment of moderate-to-severe atopic dermatitis (AD). Like other small molecules, oral JAKi have the potential for off-target effects including laboratory-related adverse events (AEs). Product labels for oral JAKi recommend an initial laboratory assessment and follow-up 4-12 weeks later to monitor for potential changes, based on evidence from clinical trials across therapeutic indications for oral JAKi, which may not reflect a population of moderate-to-severe AD patients typically seen in routine clinical practice. To address this gap, a panel of eight dermatologists with clinical and research experience with oral JAKi for the management of AD conducted a targeted review of the literature focused on key laboratory-related AEs associated with oral JAKi in the moderate-to-severe AD population. Based on the synthesis of evidence and informed opinion, a set of best practice statements related to fundamental standards of care and consensus recommendations on laboratory monitoring were suggested, and level of agreement was ascertained using a Likert scale from 0 to 100. There was a high level of agreement on three of the four suggested recommendations related to assessment and monitoring of key laboratory parameters and to dose reduction or switching in response to laboratory changes; there was a lower level of agreement related to the frequency of ongoing laboratory monitoring. Appropriate patient selection and laboratory assessment is an important strategy to mitigate the potential risks associated with oral JAKi when treating AD.
口服 Janus 激酶抑制剂(JAKi)是一类先进的靶向全身治疗药物,已在中重度特应性皮炎(AD)的治疗中显示出疗效和安全性。与其他小分子药物一样,口服 JAKi 存在脱靶效应的可能性,包括与实验室相关的不良事件(AE)。口服 JAKi 的产品标签建议进行初始实验室评估,并在 4 - 12 周后进行随访,以监测潜在变化,这一建议基于口服 JAKi across 治疗适应症的临床试验证据,但可能无法反映常规临床实践中常见的中重度 AD 患者群体。为了填补这一空白,由八位具有口服 JAKi 治疗 AD 临床和研究经验的皮肤科医生组成的小组对文献进行了有针对性的综述,重点关注中重度 AD 人群中与口服 JAKi 相关的关键实验室相关 AE。基于证据综合和专业意见,提出了一套与基本护理标准相关的最佳实践声明以及关于实验室监测的共识建议,并使用 0 至 100 的李克特量表确定了一致程度。在与关键实验室参数评估和监测以及根据实验室变化进行剂量减少或换药相关的四项建议中的三项上,达成了高度一致;与持续实验室监测频率相关的一致程度较低。在治疗 AD 时选择合适的患者并进行实验室评估是减轻与口服 JAKi 相关潜在风险的重要策略。