Epratuzumab effective, well tolerated by patients with moderate to severe lupus

Patients with moderately to severely active systemic lupus erythematosus experienced improvements in disease activity when assigned to a specific and well-tolerated dose of the CD22-targeted monoclonal antibody epratuzumab in a recent study.

In a phase 2b international, randomized controlled trial, researchers at 47 centers evaluated the effects of varying cumulative doses (cd) of epratuzumab used to treat 227 patients with systemic lupus erythematosus (SLE). Patients were assigned placebo or epratuzumab in the following cd: 200 mg (100 mg biweekly), 800 mg (400 mg biweekly), 2,400 mg (600 mg weekly), 2,400 mg (1,200 mg biweekly) or 3,600 mg (1,800 mg biweekly). Infusions occurred at baseline and weeks 1, 2 and 3, with the primary endpoint being response rates measured by the British Isles Lupus Assessment Group-based Combined Lupus Assessment at 12 weeks.

All epratuzumab patients responded better than placebo, with the greatest benefits coming for patients assigned to the 2,400-mg epratuzumab arms. Exploratory pairwise analysis of response was observed in patients receiving 600 mg weekly doses (OR=3.2; 95% CI, 1.1-8.8) compared with placebo, and OR was 2.6 (95% CI, 0.9-7.1) for 1,200-mg biweekly patients vs. placebo. Response among all combined 2,400-mg epratuzumab patients was greater than placebo (OR=2.9; 95% CI, 1.2-7.1). Patients who received 3,600 mg or less than 2,400 mg failed to show noticeable improvements.

Headache, nausea, upper respiratory tract infection and dizziness were the most common adverse events (AE) across the entire cohort, and incidence of serious adverse events (SAE) also was similar for epratuzumab patients and controls. There were no reported deaths. Median levels of immunoglobulins remained within normal range, and B-cell levels showed moderate reductions.

“The beneficial effects of 2,400 mg cd epratuzumab [in patients with moderately to severely active SLE] could be observed as early as week 8,” the researchers concluded. “The results … suggest that epratuzumab can improve SLE disease activity, and support continued development of this treatment. Phase 3 studies of epratuzumab have been initiated.”