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

J Am Acad Dermatol. 2024 Oct 25:S0190-9622(24)03044-5. doi: 10.1016/j.jaad.2024.09.074. Online ahead of print.

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.

Keywords: Aiolos; Cutaneous Lupus Area and Severity Index Activity score; Ikaros; cereblon modulator; cutaneous lupus erythematosus; systemic lupus erythematosus.