SAN DIEGO, CA—At the 2013 ACR/ARHP Annual Meeting, study investigators presented that epratuzumab was associated with sustained improvements in disease activity in patients with moderate-to-severe systemic lupus erythematosus (SLE).
Megan Clowse, MD, MPH, from Duke University Medical Center, Durham, NC, and colleagues conducted an open-label extension of EMBLEM to examine the long-term data on the efficacy of epratuzumab.
EMBLEM was a dose-ranging Phase 2b study where epratuzumab demonstrated clinically relevant improvements in disease activity in patients with moderate-to-severe SLE. Patients from any of the EMBLEM treatment arms completing 12 weeks blinded treatment and those who discontinued due to lack of efficacy but completed >8 weeks were eligible.
In the open-label extension, patients received epratuzumab 1200mg at Weeks 0 and 2 of repeating 12-week cycles; evaluation was at Weeks 4 and 8 of each cycle. Efficacy endpoints included British Isles Lupus Assessment Group (BILAG) improvement, SLE Disease Activity Index (SLEDAI) score, Physician Global Assessment (PGA) and combined treatment response (defined as BILAG improvement without worsening, no SLEDAI worsening, no PGA worsening, relative to EMBLEM baseline). Observed data were recorded till Week 108 of the open-label extension (last time point when >50% of patients reported data for BILAG).
A total of 203 patients participated in the open-label extension and were assigned to placebo (n=35 [17%]) and various doses of epratuzumab (n=168 [83%]) for 12 weeks in EMBLEM.
BILAG improvements were observed between EMBLEM baseline and Week 108 of the open-label extension. Median BILAG total score decreased by 64% and the median BILAG total score was 25.0 (range 12–61) at EMBLEM baseline, 14.0 (range 0–57) at the open-label extension screening, and 9.0 (range 0–52) at Week 48, Week 96, and at Week 108.
At Week 108, 60.3% (70/116) of ongoing patients responded to treatment, according to combined treatment response criteria. Median SLEDAI total score was 12.0 (range 6–39) at EMBLEM baseline, 10.0 (range 0–34) at the open-label extension screening, 6.0 (range 0–30) at Week 48, 5.0 (range 0–22) at Week 96, and 4.0 (range 0–24) at Week 108. At Week 108, 94.0% (109/116) had no worsening in SLEDAI. Median PGA total score was 50.0 (range 9–90) at EMBLEM baseline, 31.0 (range 0–96) at the open-label extension screening, 18.0 (range 0–81) at Week 48, 19.0 (range 0–73) at Week 96, and 17.5 (range 0–69) at Week 108. At Week 108, 97.4% (113/116) had no worsening in PGA. Moreover, corticosteroid use decreased with long-term epratuzumab use. “The number of patients on [the] highest dose of steroids was almost halved during the OLE,” said Dr. Clowse.
“Responder rates were sustained beyond 2 years or increased during open-label treatment, particularly in patients previously treated with placebo,” noted Dr. Clowse.