Spiera Robert F, Devauchelle-Pensec Valerie, Owen Claire E, Díaz-González Federico, Takeuchi Tsutomu, Drescher Edit, Anderson Jaclyn, Arikan Dilek, D'Cunha Ronilda, Parmentier Julie, Kruzikas Denise T, Zhao Weihan, Yang Yang, Stellpflug Karen, Buttgereit Frank
Hospital for Special Surgery and Weill Medical College of Cornell University, New York, New York.
INSERM U 1227, Brest University Hospital, Brest, France.
Arthritis Rheumatol. 2025 Aug;77(8):1041-1051. doi: 10.1002/art.43129. Epub 2025 Apr 2.
An unmet need exists for glucocorticoid-sparing treatments for patients with polymyalgia rheumatica (PMR). The antibody-drug conjugate ABBV-154 comprises adalimumab conjugated to a glucocorticoid receptor modulator. We evaluated ABBV-154 versus placebo in patients with glucocorticoid-dependent PMR.
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. Randomized patients received subcutaneous placebo or ABBV-154 40, 150, or 340 mg once every other week. The primary efficacy endpoint was time to flare. The sponsor voluntarily terminated the study early.
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. 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. 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. Incidences of treatment-emergent adverse events were similar between groups, and the most common across ABBV-154 cohorts was COVID-19 (16.0%).
Treatment effects were observed for ABBV-154 cohorts compared with placebo for time to flare. ABBV-154 was generally well tolerated. Due to early study termination, results should be interpreted with caution.
对于风湿性多肌痛（PMR）患者，存在对糖皮质激素节省疗法的未满足需求。抗体药物偶联物ABBV - 154由与糖皮质激素受体调节剂偶联的阿达木单抗组成。我们在糖皮质激素依赖的PMR患者中评估了ABBV - 154与安慰剂的疗效。
在这项2期、随机、双盲、安慰剂对照、剂量范围研究中，符合条件的患者确诊为PMR，有糖皮质激素反应，且在逐渐减少糖皮质激素用量且仍每日服用≥5 mg泼尼松等效剂量时出现两次或更多明确的PMR病情复发。随机分组的患者每隔一周皮下注射一次安慰剂或40、150或340 mg的ABBV - 154。主要疗效终点是病情复发时间。申办方自愿提前终止了该研究。
总体而言，181例患者被随机分组（安慰剂组，n = 50；ABBV - 154组：40 mg，n = 42；150 mg，n = 45；340 mg，n = 44），67.4%的患者在第24周完成了研究药物治疗。接受ABBV - 154治疗的患者病情复发时间比接受安慰剂治疗的患者更长，安慰剂组的24周无病情复发率的Kaplan - Meier估计值更低。ABBV - 154与安慰剂相比的风险比，40 mg组为0.49（95%置信区间[CI]，0.27 - 0.88），P = 0.017；150 mg组为0.44（95% CI，0.25 - 0.79），P = 0.006；340 mg组为0.20（95% CI，0.09 - 0.42），P < 0.001。各组治疗中出现的不良事件发生率相似，ABBV - 154各队列中最常见的是新冠病毒病（COVID - 19，16.0%）。
与安慰剂相比，ABBV - 154各队列在病情复发时间方面观察到了治疗效果。ABBV - 154总体耐受性良好。由于研究提前终止，结果应谨慎解读。
