Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland.
Adv Ther. 2022 Nov;39(11):4910-4960. doi: 10.1007/s12325-022-02281-4. Epub 2022 Sep 5.
Baricitinib is an oral, selective inhibitor of Janus kinase (JAK)1/JAK2 that transiently and reversibly inhibits many proinflammatory cytokines. This mechanism is a key mediator in a number of chronic inflammatory diseases; accordingly, baricitinib has been studied and approved for the treatment of several rheumatological and dermatological disorders, as well as COVID-19. This narrative review summarises and discusses the safety profile of baricitinib across these diseases, with special focus on adverse events of special interest (AESI) for JAK inhibitors, using integrated safety data sets of clinical trial data, and puts findings into context with the underlying risk in the respective disease populations, using supporting literature. We show that rates of infection with baricitinib generally reflected the inherent risk of the disease populations being treated, with serious infections and herpes zoster being more frequent in rheumatic diseases than in dermatological disorders, and herpes simplex being reported particularly in atopic dermatitis. Similarly, rates of major adverse cardiovascular events (MACE), venous thromboembolism (VTE) and malignancies were generally within or below the ranges reported for the respective disease populations, thereby reflecting the underlying risk; these events were therefore more frequent in patients with rheumatic diseases than in those with dermatological disorders, the latter of whom generally had low absolute risk. AESI were usually more common in patients with risk factors specific for each event. When a population similar to that of ORAL Surveillance was considered, the incidence rate of MACE with baricitinib was numerically lower than that reported with tofacitinib and similar to that of tumour necrosis factor inhibitors. No safety concerns were observed in hospitalised patients with COVID-19 who received baricitinib for up to 14 days. Identifying the patterns and likelihoods of AEs that occur during treatment in large groups of patients with different diseases can help the physician and patient better contextualise the benefit-to-risk ratio for the individual patient.
巴利昔替尼是一种口服、选择性的 Janus 激酶（JAK）1/JAK2 抑制剂，可短暂和可逆地抑制许多促炎细胞因子。这一机制是许多慢性炎症性疾病的关键介质；因此，巴利昔替尼已被研究并批准用于治疗几种风湿性疾病和皮肤病，以及 COVID-19。本综述总结和讨论了巴利昔替尼在这些疾病中的安全性概况，特别关注 JAK 抑制剂的特殊关注不良事件（AESI），使用临床试验数据的综合安全性数据集，并结合各自疾病人群的潜在风险，使用支持文献对发现结果进行阐述。我们表明，巴利昔替尼的感染率通常反映了所治疗疾病人群的固有风险，风湿性疾病中的严重感染和带状疱疹比皮肤病更为常见，而单纯疱疹则在特应性皮炎中报告较多。同样，主要不良心血管事件（MACE）、静脉血栓栓塞（VTE）和恶性肿瘤的发生率通常在各自疾病人群报告的范围内或以下，从而反映了潜在风险；因此，风湿性疾病患者的这些事件比皮肤病患者更为常见，后者的绝对风险通常较低。AESI 通常在具有每种事件特定危险因素的患者中更为常见。当考虑与 ORAL Surveillance 相似的人群时，巴利昔替尼的 MACE 发生率在数值上低于托法替尼报告的发生率，与肿瘤坏死因子抑制剂相似。在接受巴利昔替尼治疗长达 14 天的 COVID-19 住院患者中，未观察到安全性问题。在不同疾病的大量患者中识别治疗期间发生 AEs 的模式和可能性，可以帮助医生和患者更好地将个体患者的获益-风险比进行背景化。
