Efficacy, Safety, Pharmacokinetics, and Immunogenicity of ABBV-154 in Adults With Glucocorticoid-Dependent Polymyalgia Rheumatica: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial.

The antibody-drug conjugate ABBV-154 comprises adalimumab conjugated to a glucocorticoid receptor modulator.

抗体药物偶联物ABBV-154由阿达木单抗与糖皮质激素受体调节剂结合而成。

We evaluated ABBV-154 versus placebo in patients with glucocorticoid-dependent PMR.

我们在糖皮质激素依赖性多发性肌炎患者中评估了ABBV-154与安慰剂的效果。

Methods

In this phase 2, randomized, double-blind, placebo-controlled, dose-ranging study, eligible patients had confirmed PMR, glucocorticoid response and two or more unequivocal PMR flares while tapering glucocorticoids and still on ≥5 mg daily prednisone equivalent.

在这项2期、随机、双盲、安慰剂对照、剂量范围研究中，符合条件的患者被确诊为多发性肌炎，对糖皮质激素有反应，并在减量糖皮质激素时出现两次或更多明确的多发性肌炎发作，且仍在每天至少使用5毫克或等量的泼尼松。

Randomized patients received subcutaneous placebo or ABBV-154 40, 150, or 340 mg once every other week.

随机患者接受皮下注射安慰剂或ABBV-154 40、150或340毫克，每两周一次。

The primary efficacy endpoint was time to flare.

主要疗效终点是发作时间。

The sponsor voluntarily terminated the study early.

赞助商自愿提前终止了研究。

Results

Overall, 181 patients were randomized (placebo, n = 50; ABBV-154: 40 mg, n = 42; 150 mg, n = 45; 340 mg, n = 44), and 67.4% completed study drug at week 24.

总体而言，181名患者被随机分配（安慰剂组，n=50；ABBV-154：40毫克组，n=42；150毫克组，n=45；340毫克组，n=44），并且67.4%的患者在第24周完成了研究药物的使用。

Time to flare was longer for patients receiving ABBV-154 than those receiving placebo, with Kaplan-Meier estimate of 24-week flare-free rate being lower for placebo.

接受ABBV-154治疗的患者复发时间比接受安慰剂的患者更长，Kaplan-Meier估计的24周无复发率对安慰剂来说更低。

The hazard ratios of ABBV-154 versus placebo were 0.49 (95% confidence interval[CI], 0.27-0.88), P = 0.017 for 40 mg; 0.44 (95% CI, 0.25-0.79), P = 0.006 for 150 mg; 0.20 (95% CI, 0.09-0.42), P < 0.001 for 340 mg.

ABBV-154与安慰剂的危险比分别为40毫克0.49（95%置信区间[CI]，0.27-0.88），P = 0.017；150毫克0.44（95% CI，0.25-0.79），P = 0.006；340毫克0.20（95% CI，0.09-0.42），P < 0.001。

Incidences of treatment-emergent adverse events were similar between groups, and the most common across ABBV-154 cohorts was COVID-19 (16.0%).

两组间治疗后不良事件的发生率相似，其中ABBV-154队列中最常见的是COVID-19（占16.0%）

Conclusions

Treatment effects were observed for ABBV-154 cohorts compared with placebo for time to flare.

与安慰剂相比，观察到ABBV-154队列在发作时间上的治疗效果

ABBV-154 was generally well tolerated.

ABBV-154通常耐受性良好。

Due to early study termination, results should be interpreted with caution.

由于研究提前终止，结果应谨慎解释。