PARIS, France—Systemic lupus erythematosus (SLE) patients treated with epratuzumab had outcomes good enough to justify re-starting phase III trials previously abandoned due to drug supply problems, according to data reported at the European League Against Rheumatism (EULAR) annual meeting. Daniel Wallace, MD, and colleagues found that patients treated with epratuzumab 360 mg/m² or epratuzumab 730 mg/m² achieved clinically meaningful corticosteroid sparing for the treatment of moderate and severe disease flares.¹

“This is an investigative biologic agent for use with moderate-to-severe lupus that appears to be safe. And it decreases steroid requirements, it improves quality of life and, we saw in another study, it decreases flares,” said Dr. Wallace, UCLA David Geffen School of Medicine in Los Angeles, in his EULAR presentation.

The epratuzumab odyssey

Dr. Wallace explained the circumstances surrounding the study. “These studies, SL0003 and SL0004, were meant to be phase III trials, but the manufacturer of the drug sold their company to UCB...and could not supply enough of the drug to finish the trials as planned. So UCB took all of the data from the subjects who had had enough treatment, and that data was analyzed for this presentation. Phase III research has been reinitiated.”

The goal of the analysis was to evaluate the corticosteroid-sparing effects and safety profile of epratuzumab treatment in SLE patients with severe (BILAG/ British Isles Lupus Assessment Group A) and/or moderate (BILAG B in ≥2 systems) SLE flares.

In the combined studies, the investigators analyzed data for 90 patients who had received placebo (n = 37), epratuzumab 360 mg/m² infusions (n = 42), or 720 mg/m² infusions (n = 11) for up to four treatment cycles over 48 weeks. First treatment cycle infusions occurred at weeks 0, 1, 2, 3, followed by treatment cycles of two infusions 1 week apart, every 12 weeks.

The investigators began systematic tapering of corticosteroids at week 4. By weeks 20-24, to be considered “responders,” subjects needed to have reduced corticosteroid use to ≤10 mg daily (in trial SL0003) or ≤7.5 mg daily prednisone equivalents (in trial SL0004). The main outcome measure was cumulative corticosteroid use of the treatment groups from weeks 0-24.

At baseline, >40% had high disease activity with BILAG A (mean BILAG score 13.2), >60% received immunosuppressives at baseline, and 43% received >25 mg corticosteroid dosing at baseline. All 720 mg/m² subjects had greater disease activity, higher baseline corticosteroid use, and more use of antimalarials. At weeks 20-24, the investigators reported that 24 (75%) of the epratuzumab 360 mg/m² subjects and all 6 (100%) epratuzumab 720 mg/m² subjects achieved corticosteroid tapering criteria, versus 13 (56.5%) of placebo subjects.

Adjusting for race and baseline medication use, epratuzumab-treated subjects used less corticosteroids than placebo subjects over 24 weeks, with epratuzumab 360 mg/m² subjects using 1051 mg less (P = .034) and epratuzumab 720 mg/m² using 1973 mg less.

The incidence of adverse events was similar in all treatment arms. All infusion site adverse events were grade 1 or 2 and most happened during the first three infusions. B-cell levels at week 24 were 65%, 28.5%, 81% of baseline B-cell levels for epratuzumab 360 mg/m², epratuzumab 720 mg/m², and placebo, respectively.

“Clinically meaningful steroid sparing was evident with both doses of epratuzumab, with a similar tolerability profile to placebo,” Dr. Wallace concluded. “The results support the conduct of additional studies assessing the efficacy, safety, and tolerability of epratuzumab in the treatment of patients with active moderate and severe SLE.”

Reference

1. Wallace D, Hobbs K, Houssiau F, et al. Randomized controlled trials of epratuzumab (anti-CD22 mab targeting B-cells) reveal clinically meaningful reductions in corticosteroid (CS) use with favorable safety profile in moderate and severe flaring SLE patients. Presented at: EULAR 2008; June 11-14, 2008; Paris, France. Presentation THU0238.