Boyadzhieva Zhivana, Ruffer Nikolas, Burmester Gerd, Pankow Anne, Krusche Martin
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Division of Rheumatology and Systemic Inflammatory Diseases, University Hospital Hamburg-Eppendorf (UKE), Hamburg, Germany.
Front Med (Lausanne). 2022 Jun 27;9:930071. doi: 10.3389/fmed.2022.930071. eCollection 2022.
Autoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage and serious long-term effects, like amyloidosis. Disease-specific anti-inflammatory therapeutic strategies are established for some AID. However, their clinical course frequently includes relapsing, uncontrolled conditions. Therefore, new therapeutic approaches are needed. Janus Kinase inhibitors (JAKi) block key cytokines of AID pathogenesis and can be a potential option.
A systematic review of the literature in accordance with the PRISMA guidelines was conducted. Three databases (MEDLINE, Embase and Cochrane Central Register of Controlled Trials) were searched for publications regarding the use of JAKi for AID. Data from the included publications was extracted and a narrative synthesis was performed. Criteria for defining treatment response were defined and applied.
We report data from 38 publications with a total of 101 patients describing the effects of JAKi in AID. Data on Type I Interferonopathies, Adult-Onset Still's Disease (AOSD), Systemic Juvenile Idiopathic Arthritis (sJIA), Familial Mediterranean Fever (FMF), and Behçet's Syndrome (BS) was identified. From a total of 52 patients with type I interferonopathies, in seven patients (7/52, 13.5%) a complete response was achieved, most (35/52, 67.3%) showed a partial response and a minority (10/52, 19.2%) showed no treatment response. For AOSD, a complete or a partial response was achieved by eleven (11/26, 42.3%) patients each. Two sJIA patients achieved complete response (2/4, 50%) and in two cases (2/4, 50%) a partial response was reported. Half of FMF patients showed a complete response and the other half had a partial one (3/6, 50.0%). Amongst BS patients most achieved a partial response (8/13, 61.5%). Five patients showed no response to therapy (5/13, 38.5%). Overall, the most frequent AEs were upper respiratory tract infections (17), pneumonia (10), BK virus viremia (10) and viruria (4), herpes zoster infection (5), viral gastroenteritis (2) and other infections (4).
The results from this systematic review show that JAKi can be beneficial in certain AID. The risk of AEs, especially viral infections, should be considered. To accurately assess the risk benefit ratio of JAKi for AID, clinical trials should be conducted.
自身炎症性疾病（AID）是一类罕见疾病，表现为无菌性炎症发作。这些疾病累及多个器官，可导致急性器官损伤和严重的长期影响，如淀粉样变性。针对某些AID已确立了疾病特异性抗炎治疗策略。然而，其临床病程常包括复发、控制不佳的情况。因此，需要新的治疗方法。Janus激酶抑制剂（JAKi）可阻断AID发病机制中的关键细胞因子，可能是一种潜在选择。
按照PRISMA指南对文献进行系统综述。检索了三个数据库（MEDLINE、Embase和Cochrane对照试验中央注册库），以查找有关使用JAKi治疗AID的出版物。提取纳入出版物的数据并进行叙述性综合分析。定义并应用了定义治疗反应的标准。
我们报告了38篇出版物中的数据，共101例患者描述了JAKi在AID中的作用。确定了关于I型干扰素病、成人斯蒂尔病（AOSD）、系统性幼年特发性关节炎（sJIA）、家族性地中海热（FMF）和白塞病（BS）的数据。在总共52例I型干扰素病患者中，7例（7/52，13.5%）实现了完全缓解，大多数（35/52，67.3%）表现为部分缓解，少数（10/52，19.2%）无治疗反应。对于AOSD，分别有11例（11/26，42.3%）患者实现了完全或部分缓解。2例sJIA患者实现了完全缓解（2/4，50%），2例（2/4，50%）报告为部分缓解。一半的FMF患者表现为完全缓解，另一半为部分缓解（3/6，50.0%）。在BS患者中，大多数实现了部分缓解（8/13，61.5%）。5例患者对治疗无反应（5/13，38.5%）。总体而言，最常见的不良事件是上呼吸道感染（17例）、肺炎（10例）、BK病毒血症（10例）和病毒尿（4例）、带状疱疹感染（5例）、病毒性肠胃炎（2例）和其他感染（4例）。
该系统综述的结果表明，JAKi在某些AID中可能有益。应考虑不良事件的风险，尤其是病毒感染。为准确评估JAKi治疗AID的风险效益比，应开展临床试验。
