Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Arthritis Care Res (Hoboken). 2021 Jun;73(6):893-897. doi: 10.1002/acr.24200.
To evaluate the efficacy and safety of ustekinumab (UST) in giant cell arteritis (GCA).
We conducted a prospective, open-label trial of UST in patients with active new-onset or relapsing GCA. Active disease was defined as the presence of GCA symptoms and elevation of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level within 6 weeks of baseline. All patients received a 24-week prednisone taper and subcutaneous UST 90 mg at baseline and at weeks 4, 12, 20, 28, 36, and 44. The primary endpoint, prednisone-free remission, was defined as the absence of relapse through week 52 and normalization of the ESR and CRP level. Relapse was defined as the recurrence of GCA symptoms requiring treatment intensification. A sensitivity analysis excluding ESR/CRP level normalization from the prednisone-free remission definition was performed.
The study enrolled 13 patients (target sample size 20). Enrollment was closed prematurely after 7 of the initial 10 patients relapsed. Five patients (39%) had new-onset disease. The initial prednisone doses were 20 mg (1 patient), 40 mg (9 patients), and 60 mg (3 patients). All patients entered disease remission within 4 weeks of baseline. Only 3 (23%) achieved the primary endpoint. Of the 10 patients (77%) who failed to achieve the primary endpoint, 7 relapsed after a mean period of 23 weeks. The remaining 3 patients met the alternative definition of prednisone-free remission that did not require ESR/CRP level normalization. One serious adverse event occurred.
UST combined with 24 weeks of prednisone was associated with a high rate of treatment failure in this prospective GCA trial.
评估乌司奴单抗（UST）治疗巨细胞动脉炎（GCA）的疗效和安全性。
我们开展了一项 UST 治疗新发或复发 GCA 患者的前瞻性、开放性试验。活动性疾病定义为基线 6 周内出现 GCA 症状和红细胞沉降率（ESR）或 C 反应蛋白（CRP）水平升高。所有患者接受 24 周的泼尼松减量治疗和基线及第 4、12、20、28、36 和 44 周时皮下注射 UST 90mg。主要终点为无复发泼尼松停药缓解，定义为至 52 周时无复发且 ESR 和 CRP 水平正常。复发定义为 GCA 症状复发需要强化治疗。对排除泼尼松停药缓解定义中 ESR/CRP 水平正常的情况进行敏感性分析。
该研究纳入了 13 名患者（目标样本量 20 名）。最初 10 名患者中有 7 名复发后提前终止入组。5 名患者（39%）患有新发疾病。初始泼尼松剂量为 20mg（1 名患者）、40mg（9 名患者）和 60mg（3 名患者）。所有患者在基线 4 周内进入疾病缓解期。仅有 3 名患者（23%）达到主要终点。在 10 名未达到主要终点的患者中，7 名在平均 23 周后复发。其余 3 名患者符合不要求 ESR/CRP 水平正常的替代泼尼松停药缓解定义。发生 1 例严重不良事件。
在这项前瞻性 GCA 试验中，UST 联合 24 周泼尼松治疗的失败率较高。
