Patients who received 0.45mg doses of iberdomide saw a higher Systemic Lupus Erythematosus Responder Index response compared to placebo, according to a recent study published in The New England Journal of Medicine. 

“The regulation of multiple innate and adaptive immune pathways is remarkably disturbed in systemic lupus erythematosus (SLE). The zinc finger transcription factors Ikaros and Aiolos affect immune-cell development and homeostasis and are implicated in genetic predisposition to SLE,” Joan T. Merrill, MD, from the Oklahoma Medical Research Foundation in Oklahoma City, and colleagues wrote. “Ikaros induces development of B cells and plasmacytoid dendritic cells, which are major producers of type I interferon. Aiolos supports B-cell differentiation. Messenger RNAs for genes encoding Ikaros and Aiolos are overexpressed in patients with SLE.”

Merrill and colleagues evaluated iberdomide in patients with active moderate-to-severe SLE in a phase 2, randomized, placebo-controlled, double-blind trial at 117 sites in the US, Canada, Europe, South America, Mexico, and Russia between July 2017 and January 2020. 

A total of 288 patients were assigned 2:2:1:2 ratio to receive oral iberdomide (at a dose of 0.45, 0.30, or 0.15 mg) or placebo once daily for 24 weeks, in addition to standard medications. 

The primary end point at week 24 was a response on the SLE Responder Index (SRI-4), which was defined as a reduction of at least 4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 score (a 24-item weighted score of lupus activity that ranges from 0 to 105, with higher scores indicating greater disease activity), no new disease activity as measured on the British Isles Lupus Assessment Group 2004 index, and no increase of 0.3 points or more in the Physician’s Global Assessment score to 3.

Secondary endpoints included the percentage of patients with at least 4-point reduction in the Systemic Lupus Erythematosus Disease Activity Index 2000 score and the percentage of patients with at least a 50% decrease in the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity Score. Other secondary endpoints included the percentages of patients with no new BILAG-2004 organ involvement and no increase of 0.3 points or more in the Physician’s Global Assessment score, the mean change from baseline in the number of swollen joints and tender joints in patients who had at least 2 affected joints at trial enrollment, the mean change from baseline in the Physician’s Global Assessment score and the score on the Functional Assessment of Chronic Illness Therapy-Fatigue, and the percentages of patients receiving prednisone at a dose of 10 mg per day or more at baseline who had a reduction in the dose of glucocorticoid to less than 10 mg per day and to 7.5 mg per day or less by week 16 without flares.

Of the 288 patients included in the study, 81 received iberdomide at a dose of 0.45 mg, 82 received iberdomide at a dose of 0.30 mg, 42 received iberdomide at a dose of 0.15 mg, and 83 received placebo. 

According to the study, the percentages of patients with an SRI-4 at week 24 were 54% in the iberdomide 0.45-mg group, 40% in the iberdomide 0.30-mg group, 48% in the iberdomide 0.15-mg group, and 35% in the placebo group (adjusted difference between the iberdomide 0.45-mg group and the placebo group, 19.4 percentage points; 95% CI, 4.1-33.4; P = .01), with no significant differences between the groups that received the lower doses of iberdomide and the group that received placebo. 

Iberdomide-associated adverse events included urinary tract and upper respiratory tract infections and neutropenia, according to researchers. 

“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,” the researchers wrote. “Longer and larger trials are warranted to determine the effect and safety of iberdomide in patients with SLE.”

Disclosures: Authors declared financial ties to drugmakers. See full study for details.