Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study
- Daniel J Wallace1,
- Kenneth Kalunian2,
- Michelle A Petri3,
- Vibeke Strand4,
- Frederic A Houssiau5,
- Marilyn Pike6,
- Brian Kilgallen7,
- Sabine Bongardt8,
- Anna Barry7,
- Lexy Kelley7,
- Caroline Gordon9,10
- 1David Geffen School of Medicine at UCLA, Cedars-Sinai Medical Center, UCLA, Los Angeles, California, USA
- 2UCSD School of Medicine, La Jolla, California, USA
- 3Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA
- 4Division of Immunology and Rheumatology, Stanford University, Palo Alto, California, USA
- 5Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
- 6Massachussetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- 7UCB Pharma, Raleigh, North Carolina, USA
- 8UCB Pharma, Monheim, Germany
- 9Rheumatology Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- 10Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Correspondence to Dr Daniel J Wallace, Cedars-Sinai Medical Center, 8737 Beverly Blvd, Suite 302, West Hollywood, CA 90048, USA;
- Received 1 October 2012
- Revised 19 December 2012
- Accepted 21 December 2012
- Published Online First 12 January 2013
Objective To identify a suitable dosing regimen of the CD22-targeted monoclonal antibody epratuzumab in adults with moderately to severely active systemic lupus erythematosus (SLE).
Methods A phase IIb, multicentre, randomised controlled study (NCT00624351) was conducted with 227 patients (37–39 per arm) receiving either: placebo, epratuzumab 200 mg cumulative dose (cd) (100 mg every other week (EOW)), 800 mg cd (400 mg EOW), 2400 mg cd (600 mg weekly), 2400 mg cd (1200 mg EOW), or 3600 mg cd (1800 mg EOW). The primary endpoint (not powered for significance) was the week 12 responder rate measured using a novel composite endpoint, the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA).
Results Proportion of responders was higher in all epratuzumab groups than with placebo (overall treatment effect test p=0.148). Exploratory pairwise analysis demonstrated clinical improvement in patients receiving a cd of 2400 mg epratuzumab (OR for 600 mg weekly vs placebo: 3.2 (95% CI 1.1 to 8.8), nominal p=0.03; OR for 1200 mg EOW vs placebo: 2.6 (0.9 to 7.1), nominal p=0.07). Post-hoc comparison of all 2400 mg cd patients versus placebo found an overall treatment effect (OR=2.9 (1.2 to 7.1), nominal p=0.02). Incidence of adverse events (AEs), serious AEs and infusion reactions was similar between epratuzumab and placebo groups, without decreases in immunoglobulin levels and only partial reduction in B-cell levels.
Conclusions Treatment with epratuzumab 2400 mg cd was well tolerated in patients with moderately to severely active SLE, and associated with improvements in disease activity. Phase III studies are ongoing.
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