Iberdomide Proven Effective in Treating Patients With SLE


Iberdomide, a high-affinity cereblon modulator, works by affecting leukocyte development and autoimmunity.

Phase 2 trial results indicate that patients with systemic lupus erythematosus (SLE) receiving 0.45 mg of iberdomide reported a higher percentage of patients with an SLE Responder Index (SRI-4) response when compared with placebo, according to a study published in The New England Journal of Medicine.1

In this randomized, placebo-controlled, double-blind study, patients with moderate-to-severe SLE were assigned in a 2:2:1:2 ratio to receive either oral iberdomide (0.45 mg, 0.30 mg, or 15 mg) or placebo once daily for 24 weeks. Iberdomide, a high-affinity cereblon modulator, works by affecting leukocyte development and autoimmunity.

Results were collected from July 2017 through January 2020. Baseline prednisone dose and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores were obtained. All patients received at least 1 form of thromboprophylaxis.

Eligible patients were aged 18 years or older, met the American College of Rheumatology classification criteria for SLE, had a score of 6 or more on the SLEDAI-2K, a clinical SLEDAI-2K score of 4 or more, and antinuclear antibody titers of 1:40 or more.

The primary endpoint was the SRI-4 at week 24. SRI-4 was defined as a reduction of 4 or more points in the Systemic Lupus Erythematosus Disease Activity Index 2000 score, no new disease activity, and no increase of 0.3 points or more in the Physician’s Global Assessment (PGA) score.

Secondary endpoints included the percentage of patients with a 50% or more decrease in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)–Activity Score (CLASI-A).

Out of 288 patients who met the classification criteria, 86% completed the 24-week period. Age, race, and disease activity were comparable across all treatment arms, with sex being generally representative of all patients with SLE (97% female). A total of 81 patients received iberdomide 0.45 mg daily, 82 received iberdomide 0.30 mg daily, 42 received iberdomide 0.15 mg daily, and 83 were given the placebo.

By week 24, SRI-4 responses were seen in 54% of the iberdomide 0.45 mg cohort, 40% in the iberdomide 0.30 mg cohort, 48% in the iberdomide 0.15 mg cohort, and 35% in those receiving the placebo. No significant differences were seen between lower doses of the drug compared with those who received placebo.

SLEDAI-2K scores decreasing 4 or more points from baseline were reported in 56% of patients receiving iberdomide 0.45 (n = 45) and 36% (n = 30) receiving placebo.

Adverse events occurred in 78% (n = 63) of patients receiving iberdomide 0.45 mg, 78% (n = 64) receiving iberdomide 0.30 mg, 74% (n = 31) receiving iberdomide 0.15 mg, and 65% (n = 54) receiving placebo. The most common adverse events, which were classified as mostly mild or moderate, were urinary tract infections, upper respiratory tract infections, neutropenia, and influenza.

Serious adverse events occurred in 6% of the iberdomide group and 8% of those in the placebo cohort. There were no deaths in the iberdomide groups.

Excluding patients with an increased thrombotic risk, active lupus nephritis, or neuropsychiatric manifestations of SLE limited the study. Generalizability was restricted by the lack of diversity within the patient population, including the low percentage of Black patients.

“In patients with SLE, iberdomide at the highest dose, but not at lower doses, was superior to placebo with respect to the primary end point of an SRI-4 response at 24 weeks,” investigators concluded. “Longer and larger trials are warranted to determine the effect and safety of iberdomide in patients with SLE.”


Merrill JT, Werth VP, Furie R, et al. Phase 2 Trial of Iberdomide in Systemic Lupus Erythematosus. N Engl J Med. 2022;386(11):1034-1045. doi:10.1056/NEJMoa2106535

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