Gillard Louise, Pouchot Jacques, Cohen-Aubart Fleur, Koné-Paut Isabelle, Mouterde Gaël, Michaud Martin, Reumaux Héloïse, Savey Léa, Belot Alexandre, Fautrel Bruno, Mitrovic Stéphane
Service de Rhumatologie, Hôpital Pitié-Salpêtrière, Sorbonne Université.
Service de Médecine Interne, Hôpital Européen Georges Pompidou, Université Paris Cité.
Rheumatology (Oxford). 2023 Apr 3;62(4):1594-1604. doi: 10.1093/rheumatology/keac440.
Excessive and inappropriate production of pro-inflammatory cytokines plays a key role in Still's disease. Janus kinase inhibitor (JAKi) agents mainly block pro-inflammatory cytokine pathways, notably IL-6 and IFN. The objective was to assess the efficacy and safety of JAKi agents in difficult-to-treat systemic JIA or adult-onset Still's disease (AOSD).
This retrospective study was based on a national survey conducted in the departments of rheumatology, paediatric rheumatology and internal medicine of French hospitals regarding systemic JIA and AOSD patients who received JAKi agents. The data were collected with a standardized questionnaire and analysed at different times (treatment initiation, months 1, 3 and 6 and the end of follow-up).
Nine patients (seven adults) were included. All patients showed inadequate response to CS or conventional synthetic or biologic DMARDs. Baricitinib was used in five patients, ruxolitinib in two, tofacitinib in two and upadacitinib in one. A JAKi was used combined with CS in all but two patients. A JAKi was associated with anakinra and CS in one patient, and with MTX, anakinra and CS in another. The median (range) follow-up was 16 (1-33) months. Two cases out of nine showed complete remission, 3/9 partial response and 4/9 treatment failure. At the last visit, CS could be decreased but not stopped. Tolerance of the JAKi was acceptable (no severe adverse events).
JAKi agents may be a therapeutic option for some patients with difficult-to-treat Still's disease, especially those with partial response to medium- or high-dose CS or biologics.
促炎细胞因子的过度和不适当产生在斯蒂尔病中起关键作用。 Janus激酶抑制剂（JAKi）主要阻断促炎细胞因子途径，尤其是IL-6和IFN。目的是评估JAKi在难治性系统性幼年特发性关节炎或成人斯蒂尔病（AOSD）中的疗效和安全性。
这项回顾性研究基于法国医院风湿病科、儿科风湿病科和内科对接受JAKi治疗的系统性幼年特发性关节炎和AOSD患者进行的全国性调查。数据通过标准化问卷收集，并在不同时间（治疗开始时、第1、3和6个月以及随访结束时）进行分析。
纳入9例患者（7例成人）。所有患者对CS或传统合成或生物性改善病情抗风湿药反应不足。5例患者使用巴瑞替尼，2例使用鲁索替尼，2例使用托法替布，1例使用乌帕替尼。除2例患者外，所有患者均将JAKi与CS联合使用。1例患者将JAKi与阿那白滞素和CS联合使用，另1例患者将其与甲氨蝶呤、阿那白滞素和CS联合使用。中位（范围）随访时间为16（1-33）个月。9例中有2例完全缓解，3/9部分缓解，4/9治疗失败。在最后一次随访时，CS可以减量但不能停用。JAKi的耐受性可以接受（无严重不良事件）。
JAKi可能是一些难治性斯蒂尔病患者的治疗选择，尤其是那些对中高剂量CS或生物制剂有部分反应的患者。
