艾伯多米德对系统性红斑狼疮皮肤表现的影响：一项随机2期临床试验。

Effect of iberdomide on cutaneous manifestations in systemic lupus erythematosus: A randomized phase 2 clinical trial.

作者信息

Werth Victoria P, Merrill Joan T, Furie Richard, Dörner Thomas, van Vollenhoven Ronald, Lipsky Peter, Weiswasser Michael, Korish Shimon, Schafer Peter H, Stern Mark, Li Stan, Delev Nikolay

机构信息

University of Pennsylvania and the Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania.

Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.

出版信息

J Am Acad Dermatol. 2025 Mar;92(3):435-443. doi: 10.1016/j.jaad.2024.09.074. Epub 2024 Oct 25.

DOI:10.1016/j.jaad.2024.09.074

PMID:39461504

Abstract

BACKGROUND

Iberdomide, a cereblon modulator, promotes degradation of transcription factors Ikaros and Aiolos.

OBJECTIVE

Evaluate iberdomide efficacy and safety in cutaneous lupus erythematosus (CLE) in a phase 2 study.

METHODS

Patients were randomized (2:2:1:2) to iberdomide 0.45 (n = 81), 0.30 (n = 82), or 0.15 mg (n = 42) or placebo (n = 83) daily while continuing background lupus medications.

RESULTS

The mean (SD) baseline Cutaneous Lupus Area and Severity Index Activity (CLASI-A) score was 6.9 (7.0); 28% of patients had a score ≥8; 56% had acute CLE, 29% chronic CLE, and 16% subacute CLE. Mean CLASI-A improvement in patients with baseline score ≥8 was 39.7% for iberdomide 0.45 mg versus 20.1% for placebo at week 4 (P = .032), with continued improvement through week 24 (66.7% vs 54.2%; P = .295). Proportions of patients achieving ≥50% CLASI-A reduction from baseline at week 24 were significantly greater for iberdomide 0.45 mg versus placebo for patients with subacute (91.7% vs 52.9%, P = .035) and chronic (62.1% vs 27.8%; P = .029) CLE but not for the overall population (55.6% vs 44.6%) or patients with baseline CLASI-A ≥8 (66.7% vs 50.0%).

LIMITATIONS

Small patient subgroups of CLE subtypes.

CONCLUSIONS

Iberdomide showed beneficial effects when added to background lupus medications in patients with subacute and chronic CLE.

摘要

背景

艾伯多米德是一种大脑神经酰胺调节剂，可促进转录因子伊卡洛斯和爱奥洛斯的降解。

目的

在一项2期研究中评估艾伯多米德治疗皮肤性红斑狼疮（CLE）的疗效和安全性。

方法

患者被随机分组（2:2:1:2），分别每日服用0.45毫克（n = 81）、0.30毫克（n = 82）或0.15毫克（n = 42）的艾伯多米德或安慰剂（n = 83），同时继续使用狼疮背景药物。

结果

皮肤狼疮面积和严重程度指数活动度（CLASI-A）的平均（标准差）基线评分为6.9（7.0）；28%的患者评分≥8；56%为急性CLE，29%为慢性CLE，16%为亚急性CLE。基线评分≥8的患者在第4周时，0.45毫克艾伯多米德组的CLASI-A平均改善率为39.7%，而安慰剂组为20.1%（P = 0.032），至第24周时持续改善（66.7%对54.2%；P = 0.295）。对于亚急性（91.7%对52.9%，P = 0.035）和慢性（62.1%对27.8%；P = 0.029）CLE患者，在第24周时，0.45毫克艾伯多米德组相比安慰剂组，CLASI-A从基线降低≥50%的患者比例显著更高，但总体人群（55.6%对44.6%）或基线CLASI-A≥8的患者（66.7%对50.0%）并非如此。