宾夕法尼亚大学Peter A. Merkel小组的最新研究提出了Upadacitinib治疗巨细胞动脉炎的3期临床试验。这一研究成果发表在2025年4月2日出版的国际学术期刊《新英格兰医学杂志》上。

背景：巨细胞动脉炎是一种治疗方案有限的全身性血管炎。Upadacitinib是一种选择性Janus激酶（JAK）抑制剂，可阻断几种细胞因子（包括白细胞介素-6和干扰素-γ）的信号传导，其在巨细胞动脉炎患者中的疗效和安全性尚不清楚。

方法：该课题组人员随机分配新发或复发巨细胞动脉炎患者，以2:1:1的比例，接受Upadacitinib治疗，剂量为15mg或7.5 mg，口服一次，每日一次，加26周糖皮质激素减量治疗，或安慰剂加52周糖皮质激素减量治疗。主要终点是第52周的持续缓解，即从第12周到第52周没有巨细胞动脉炎的体征或症状，并遵守方案指定的糖皮质激素减量。

结果：共有209名患者接受了15mg剂量的Upadacitinib， 107名患者接受了7.5 mg剂量的Upadacitinib， 112名患者接受了安慰剂；70%的患者为新发巨细胞动脉炎。在主要终点方面，15mg剂量的Upadacitinib优于安慰剂(46.4% vs 29.0%；P = 0.002)。在分级预先指定和多重控制的关键次要终点持续完全缓解、疾病爆发时间、累积糖皮质激素暴露和患者报告的结果的分析中，15mg剂量的Upadacitinib优于安慰剂。在主要终点方面，7.5 mg剂量的Upadacitinib并不优于安慰剂（41.1%）。在52周的治疗期间，Upadacitinib组和安慰剂组的安全性结果相似。虽然心血管风险是JAK抑制剂的潜在问题，但在Upadacitinib组中没有发生主要的不良心血管事件。

研究结果表明，在巨细胞动脉炎患者中，Upadacitinib剂量为15mg（而不是7.5 mg）， 26周糖皮质激素逐渐减少，其疗效优于安慰剂，52周糖皮质激素逐渐减少。

附：英文原文

Title: A Phase 3 Trial of Upadacitinib for Giant-Cell Arteritis

Author: Daniel Blockmans, Sara K. Penn, Arathi R. Setty, Wolfgang A. Schmidt, Andrea Rubbert-Roth, Ellen M. Hauge, Helen I. Keen, Tomonori Ishii, Nader Khalidi, Christian Dejaco, Maria C. Cid, Bernhard Hellmich, Meng Liu, Weihan Zhao, Ivan Lagunes, Ana B. Romero, Peter K. Wung, Peter A. Merkel

Issue&Volume: 2025-04-02

Abstract: BACKGROUND

Giant-cell arteritis is a systemic vasculitis with limited treatment options. The efficacy and safety of upadacitinib — a selective Janus kinase (JAK) inhibitor that blocks the signaling of several cytokines, including interleukin-6 and interferon-γ — are unknown in patients with giant-cell arteritis.

METHODS

We randomly assigned patients with new-onset or relapsing giant-cell arteritis, in a 2:1:1 ratio, to receive upadacitinib at a dose of 15 mg or 7.5 mg orally once daily plus a 26-week glucocorticoid taper or placebo plus a 52-week glucocorticoid taper. The primary end point was sustained remission at week 52, defined by the absence of signs or symptoms of giant-cell arteritis from week 12 through week 52 and adherence to the protocol-specified glucocorticoid taper.

RESULTS

A total of 209 patients received upadacitinib at a dose of 15 mg, 107 received upadacitinib at a dose of 7.5 mg, and 112 received placebo; 70% of the patients had new-onset giant-cell arteritis. Upadacitinib at a dose of 15 mg showed superiority over placebo with respect to the primary end point (46.4% [95% confidence interval {CI}, 39.6 to 53.2] vs. 29.0% [95% CI, 20.6 to 37.5]; P=0.002). Upadacitinib at a dose of 15 mg was superior to placebo in the analysis of the hierarchically prespecified and multiplicity-controlled key secondary end points of sustained complete remission, time to a disease flare, cumulative glucocorticoid exposure, and patient-reported outcomes. Upadacitinib at a dose of 7.5 mg was not superior to placebo with respect to the primary end point (41.1% [95% CI, 31.8 to 50.4]). Safety outcomes during the treatment period of 52 weeks were similar in the upadacitinib and placebo groups. Although cardiovascular risk is a potential concern with a JAK inhibitor, no major adverse cardiovascular events occurred in the upadacitinib groups.

CONCLUSIONS

In patients with giant-cell arteritis, upadacitinib at a dose of 15 mg — but not 7.5 mg — with a 26-week glucocorticoid taper showed efficacy superior to that of placebo with a 52-week glucocorticoid taper.

DOI: NJ202504020000001

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2413449