Safety and Efficacy of Epratuzumab in Patients with Lupus Confirmed in a Long-Term Open-Label Extension Study

Epratuzumab is an anti-CD22 monoclonal antibody that modulates B-cell activation and has demonstrated clinically relevant improvements in disease activity in patients with moderate-to-severe systemic lupus erythematosus (SLE) in the phase 2b EMBLEM study (Wallace DJ, et al. Ann Rheum Dis. 2013 Jan 12. Epub ahead of print). At the American College of Rheumatology annual meeting held in San Diego, California from October 25-30, 2013, 2 related presentations provided long-term efficacy and safety data on epratuzumab in the treatment of patients with SLE from an open-label extension study of EMBLEM.

Clowse and colleagues (Abstract 1738) presented 2-year efficacy data from 203 patients with SLE who had completed 12 weeks of blinded treatment in EMBLEM and who then received epratuzumab 1200 mg at weeks 0 and 2 of repeating 12-week cycles in the open-label extension (OLE) study. Of the 203 patients who entered this OLE study, 90 patients droppted out prematurely, because of adverse events, lack or loss of efficacy, or other non­-disease-related reasons, resulting in  a total of113 patients who completed the OLE phase of this study.

Between the end of the EMBLEM study and week 108 of the OLE study, a further decrease of 64% in British Isles Lupus Assessment Group (BILAG) scores was observed; this was especially apparent in patients who had received placebo during the blinded phase of the EMBLEM Study. The median BILAG score was 14 at the OLE screening and 10 at the last visit ofthe OLE phase. The SLE Disease Activity Index (SLEDAI) total score was10 at the OLE screening, 6 at week 48 of the OLE study, and 4 at week 108. The median SLEDAI score at the last visit of the OLE trial was 8.

At week 108 of the OLE study, 47%of the patients had responded to epratuzumab, with more than an 8-point improvement in the SLEDAI score, and corticosteroid use had decreased from a median dose of 10 mg daily at OLE screening to 5 mg daily at week 115 of epratuzumab use, suggesting that epratuzumab is associated with sustained improvements in disease activity beyond 2 years in patients with moderate-to-severe SLE. Moreover, the Physician Global Assessment (PGA) and Patient-Reported Assessment (PtGA) scores remained stable over the 1-yearlong OLE trial. The long-term safety of epratuzumab in the OLE study was acceptable, with no new signs of adverse events reported. One weakness of the presentation by Clowse and colleagues was that it was unclear what percentage of patients with SLE had responded to epratuzumab, because the vast majority of the data presented were median improvements in disease activity scores.

In a related presentation by Wallace and colleagues (Abstract 1606), pooled safety data with epratuzumab in patients with moderate-to-severe SLE were evaluated from 2 completed OLE pilot studies (015 and SL0002) and 4 completed and ongoing long-term OLE studies (ALLEVIATE-OLE, EMBLEM-OLE, EMBODY-OLE, and SL0027). Data were presented for 488 patients who had received a total monthly dose of epratuzumab 2400 mg; these data represent a total of 726 patient-years of exposure to the drug. The overall rates of adverse events (AEs), serious AEs, and infusion reactions were 458/100 patient-years, 21/100 patient-years, and 23/100 patient-years, respectively.

The most common AEs with epratuzumab were upper respiratory tract infections (17% of patients), urinary tract infection (14%), and headache (12%). The most common serious AEs were worsening of SLE (2%), and cholelithiasis, pneumonia, sepsis, depression, and dyspnea (each affecting 0.6% of patients). These data suggest that epratuzumab 2400 mg monthly was reasonably well-tolerated over more than 700 patient-years of exposure, and support the further development of this agent for patients with moderate-to-severe SLE.