A Phase 3 Trial of Brepocitinib in Dermatomyositis.

Methods

In this phase 3, double-blind, randomized, placebo-controlledtrial, adults with dermatomyositis were assigned in a 1:1:1 ratio to receive once-daily oral brepocitinib at a dose of 30 mg, brepocitinib at a dose of 15 mg, or placebo for 52 weeks.

在这项 III 期、双盲、随机、安慰剂对照试验中，患有皮肌炎的成年人按 1:1:1 的比例被分配，每天一次口服 30 mg 的 brepocitinib、15 mg 的 brepocitinib 或安慰剂，持续 52 周。

Standard therapies were continued, and glucocorticoids were tapered.

继续使用标准治疗方案，并逐渐减少糖皮质激素的剂量。

The primary end point was the Total Improvement Score, a validated composite myositis index (with scores ranging from 0 to 100 and higher scores indicating greater improvement) at week 52.

主要终点是第52周的总改善评分，这是一个经过验证的复合性肌炎指数（评分范围从0到100，分数越高表示改善越大）。

Key secondary end points, including skin disease activity, glucocorticoid tapering, and physical function, were tested in a multiplicity-controlled sequence.

关键次要终点，包括皮肤疾病活动性、糖皮质激素减量和身体功能，在多重控制序列中进行了测试。

Results

A total of 241 patients underwent randomization: 81 to receive brepocitinib 30 mg, 81 to receive brepocitinib 15 mg, and 79 to receive placebo.

共有241名患者进行了随机分组：81名接受30毫克的brepocitinib治疗，81名接受15毫克的brepocitinib治疗，79名接受安慰剂治疗。

At week 52, the mean Total Improvement Score was 46.5, 37.5, and 31.2, respectively (difference with brepocitinib 30 mg vs. placebo, 15.3; 95% confidence interval[CI], 6.7 to 24.0; P<0.001; difference with brepocitinib 15 mg vs. placebo, 6.3; 95% CI, -2.4 to 14.9).

在第52周，平均总改善评分分别为46.5、37.5和31.2（与安慰剂相比，brepocitinib 30 mg的差异为15.3；95%置信区间[CI]，6.7至24.0；P<0.001；与brepocitinib 15 mg相比的差异为6.3；95% CI，-2.4至14.9）。

Brepocitinib 30 mg was superior to placebo across all nine key secondary end points, including skin disease activity, systemic glucocorticoid tapering, and functional disability, with improvements observed as early as week 4.

在所有九个关键次要终点方面，brepocitinib 30 mg均优于安慰剂，包括皮肤疾病活动性、全身糖皮质激素减量和功能障碍，早在第4周就观察到改善。

Serious infections were more frequent in the brepocitinib 30-mg group than in the placebo group (10% vs. 1%).

在30毫克布雷普西替尼组中，严重感染的发生率高于安慰剂组（10%对比1%）。

No deaths occurred during the trial.

试验期间没有发生死亡事件。

Conclusions

In adults with dermatomyositis that was resistant to previous therapy, the use of brepocitinib at a dose of 30 mg (but not at a dose of 15 mg) resulted in significant benefits with respect to a composite myositis index, skin disease severity, glucocorticoid tapering, and functional disability.

在对先前治疗有抗药性的成人皮肌炎患者中，使用30毫克的brepocitinib（而非15毫克剂量）在复合肌炎指数、皮肤疾病严重程度、糖皮质激素减量和功能障碍方面带来了显著益处。

(Funded by Priovant Therapeutics; ClinicalTrials.gov number, NCT05437263.).

(由Priovant Therapeutics资助；ClinicalTrials.gov编号，NCT05437263。)