Department of Rheumatology, IDIVAL, Immunopathology Group, Hospital Universitario Marqués de Valdecilla, Avda. Valdecilla s/n, Santander, ES- 39008, Spain.
Neurology Department, Massachusetts General Hospital, Boston, MA, USA.
Arthritis Res Ther. 2024 Jun 5;26(1):116. doi: 10.1186/s13075-024-03314-9.
A substantial proportion of patients with giant cell arteritis (GCA) relapse despite standard therapy with glucocorticoids, methotrexate and tocilizumab. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is involved in the pathogenesis of GCA and JAK inhibitors (JAKi) could be a therapeutic alternative. We evaluated the effectiveness of JAKi in relapsing GCA patients in a real-world setting and reviewed available literature.
Retrospective analysis of GCA patients treated with JAKi for relapsing disease at thirteen centers in Spain and one center in United States (01/2017-12/2022). Outcomes assessed included clinical remission, complete remission and safety. Clinical remission was defined as the absence of GCA signs and symptoms regardless of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values. Complete remission was defined as the absence of GCA signs and symptoms along with normal ESR and CRP values. A systematic literature search for other JAKi-treated GCA cases was conducted.
Thirty-five patients (86% females, mean age 72.3) with relapsing GCA received JAKi therapy (baricitinib, n = 15; tofacitinib, n = 10; upadacitinib, n = 10). Before JAKi therapy, 22 (63%) patients had received conventional synthetic immunosuppressants (e.g., methotrexate), and 30 (86%) biologics (e.g., tocilizumab). After a median (IQR) follow-up of 11 (6-15.5) months, 20 (57%) patients achieved and maintained clinical remission, 16 (46%) patients achieved and maintained complete remission, and 15 (43%) patients discontinued the initial JAKi due to relapse (n = 11 [31%]) or serious adverse events (n = 4 [11%]). A literature search identified another 36 JAKi-treated GCA cases with clinical improvement reported for the majority of them.
This real-world analysis and literature review suggest that JAKi could be effective in GCA, including in patients failing established glucocorticoid-sparing therapies such as tocilizumab and methotrexate. A phase III randomized controlled trial of upadacitinib is currently ongoing (ClinicalTrials.gov ID NCT03725202).
尽管使用糖皮质激素、甲氨蝶呤和托珠单抗进行了标准治疗，仍有相当一部分巨细胞动脉炎（GCA）患者会复发。Janus 激酶/信号转导和转录激活因子（JAK/STAT）信号通路参与了 GCA 的发病机制，JAK 抑制剂（JAKi）可能是一种治疗选择。我们评估了 JAKi 在西班牙 13 个中心和美国 1 个中心的复发性 GCA 患者中的疗效，并回顾了现有文献。
对 13 个西班牙中心和 1 个美国中心接受 JAKi 治疗复发性疾病的 GCA 患者进行回顾性分析（2017 年 1 月至 2022 年 12 月）。评估的结局包括临床缓解、完全缓解和安全性。临床缓解定义为无论红细胞沉降率（ESR）和 C 反应蛋白（CRP）值如何，均不存在 GCA 体征和症状。完全缓解定义为不存在 GCA 体征和症状，同时 ESR 和 CRP 值正常。对其他接受 JAKi 治疗的 GCA 病例进行了系统的文献检索。
35 例（86%为女性，平均年龄 72.3 岁）复发性 GCA 患者接受了 JAKi 治疗（巴瑞替尼，n=15；托法替布，n=10；乌帕替尼，n=10）。在接受 JAKi 治疗之前，22 例（63%）患者接受了传统合成免疫抑制剂（如甲氨蝶呤）治疗，30 例（86%）患者接受了生物制剂（如托珠单抗）治疗。中位（IQR）随访 11（6-15.5）个月后，20 例（57%）患者达到并维持临床缓解，16 例（46%）患者达到并维持完全缓解，15 例（43%）患者因复发（n=11[31%]）或严重不良事件（n=4[11%]）而停用初始 JAKi。文献检索发现，另外 36 例接受 JAKi 治疗的 GCA 患者的临床改善情况也有报道。
这项真实世界分析和文献复习表明，JAKi 可能对 GCA 有效，包括对已接受糖皮质激素保留治疗（如托珠单抗和甲氨蝶呤）失败的患者。一项乌帕替尼的 III 期随机对照试验正在进行中（ClinicalTrials.gov ID NCT03725202）。
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