title: 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.
abstract: 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.
authors: David Geffen School of Medicine at UCLA, Cedars-Sinai Medical Center, UCLA, Los Angeles, California, USA.
authors: Daniel J
authors: DJ
authors: Wallace
authors: Kenneth
authors: K
authors: Kalunian
authors: Michelle A
authors: MA
authors: Petri
authors: Vibeke
authors: V
authors: Strand
authors: Frederic A
authors: FA
authors: Houssiau
authors: Marilyn
authors: M
authors: Pike
authors: Brian
authors: B
authors: Kilgallen
authors: Sabine
authors: S
authors: Bongardt
authors: Anna
authors: A
authors: Barry
authors: Lexy
authors: L
authors: Kelley
authors: Caroline
authors: C
authors: Gordon
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D010919:Placebos; C448700:epratuzumab
keywords: B cells; Systemic Lupus Erythematosus; Treatment