Iberdomide shows Better Outcomes in Cutaneous Manifestations in Systemic Lupus Erythematosus in Multinational Trial

A phase 2 multinational clinical trial was carried out by randomization (2:2:1:2) to receive Iberdomide (0.45 mg, 0.30 mg, or 0.15 mg) or placebo for 24 weeks along with continuing their standard SLE medications. Treatment stratification was done based on baseline steroid use and the SLE disease activity index 2000 to balance disease severity. After 24 weeks individuals were rerandomized to Iberdomide (0.45 mg or 0.30 mg) who continued on their initial dose through week 52 and could enroll in a long-term extension for up to 2 years. The primary endpoint was the assessment of Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score, assessing erythema, scale/hypertrophy, mucous membrane lesions, and nonscarring alopecia. The exploratory endpoint included CLASI-50 achieving a 50% reduction from baseline in CLASI-A score. Post-hoc assessments were done for CLASI-A based on CLE subtypes and gene expression levels.

Findings:

• The mean (SD) baseline CLASI-A score was 6.9 (7.0).
• About 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=0.032), with continued improvement through week 24 (66.7% vs 54.2%; P=0.295).
• 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 and chronic CLE but not for the overall population or patients with baseline CLASI-A ≥8.