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).

中文翻译：

---

Janus激酶抑制剂在现实临床实践中对复发性巨细胞动脉炎的有效性和文献综述


尽管采用糖皮质激素、甲氨蝶呤和托珠单抗的标准治疗，仍有相当大比例的巨细胞动脉炎 (GCA) 患者复发。 Janus 激酶/信号转导器和转录激活剂 (JAK/STAT) 信号通路参与 GCA 的发病机制，而 JAK 抑制剂 (JAKi) 可能是一种治疗替代方案。我们在现实环境中评估了 JAKi 对复发性 GCA 患者的有效性，并回顾了现有文献。对西班牙 13 个中心和美国 1 个中心接受 JAKi 治疗复发性疾病的 GCA 患者进行回顾性分析（01/2017-12/2022）。评估的结果包括临床缓解、完全缓解和安全性。临床缓解定义为不存在 GCA 体征和症状，无论红细胞沉降率 (ESR) 和 C 反应蛋白 (CRP) 值如何。完全缓解定义为没有 GCA 体征和症状，且 ESR 和 CRP 值正常。对其他 JAKi 治疗的 GCA 病例进行了系统的文献检索。 35 名复发性 GCA 患者（86% 为女性，平均年龄 72.3 岁）接受了 JAKi 治疗（巴瑞替尼，n = 15；托法替尼，n = 10；乌帕替尼，n = 10）。在 JAKi 治疗前，22 名 (63%) 患者接受了常规合成免疫抑制剂（例如甲氨蝶呤）和 30 名 (86%) 生物制剂（例如托珠单抗）。中位 (IQR) 随访 11 (6-15.5) 个月后，20 名 (57%) 患者实现并维持临床缓解，16 名 (46%) 患者实现并维持完全缓解，15 名 (43%) 患者停药由于复发 (n = 11 [31%]) 或严重不良事件 (n = 4 [11%]) 导致初始 JAKi。 文献检索发现了另外 36 例接受 JAKi 治疗的 GCA 病例，其中大多数病例报告临床有所改善。这项现实世界的分析和文献综述表明，JAKi 可能对 GCA 有效，包括对托珠单抗和甲氨蝶呤等既定糖皮质激素保留疗法失败的患者。 upadacitinib 的 III 期随机对照试验目前正在进行中（ClinicalTrials.gov ID NCT03725202）。