title: Efficacy and safety of epratuzumab in patients with moderate/severe flaring systemic lupus erythematosus: results from two randomized, double-blind, placebo-controlled, multicentre studies (ALLEVIATE) and follow-up.
abstract: OBJECTIVE
  To evaluate epratuzumab treatment in patients with moderately-to-severely active SLE in two international, randomized, controlled trials (ALLEVIATE-1 and -2) and an open-label extension study (SL0006).
  
  
  METHODS
  Ninety ALLEVIATE patients (43% BILAG A, median BILAG score 12.0) received standard of care plus 10 total doses of placebo (n = 37) or 360 mg/m(2) (n = 42) or 720 mg/m(2) (n = 11) epratuzumab, administered across 12-week cycles for up to 48 weeks, with BILAG assessments every 4 weeks. Patients were followed for ≥ 6 months and their data combined for analysis. The primary endpoint was BILAG response at week 12 (all BILAG A scores reduced to B/C/D and B scores to C/D, no new A and <2 new B scores). Twenty-nine patients continued in SL0006, receiving 12-week cycles of 360 mg/m(2) epratuzumab; this interim analysis was performed at median 120 weeks (range 13-184) of exposure.
  
  
  RESULTS
  Both ALLEVIATE trials were discontinued prematurely because of interruption in drug supply. Exploratory pooled analyses found that responses at week 12 were 15/34 (44.1%) and 2/10 (20.0%) for epratuzumab 360 and 720 mg/m(2), respectively, vs 9/30 (30.0%) for placebo. Total BILAG scores were lower in both epratuzumab arms vs placebo at week 48 and at all but two time points. The incidence of adverse events was similar between groups. In SL0006, median total BILAG score was 8.0 (n = 29) at study entry and 7.0 (n = 19) at week 100, with no additional safety signals.
  
  
  CONCLUSIONS
  This initial efficacy and safety profile of epratuzumab supports its continued development for SLE treatment.
authors.affiliation: Cedars-Sinai Medical Center, 8737 Beverly Blvd, Suite 302, West Hollywood, CA 90048, USA. dwallace@ucla.edu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wallace
authors.forename: Caroline
authors.initials: C
authors.lastname: Gordon
authors.forename: Vibeke
authors.initials: V
authors.lastname: Strand
authors.forename: Kathryn
authors.initials: K
authors.lastname: Hobbs
authors.forename: Michelle
authors.initials: M
authors.lastname: Petri
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kalunian
authors.forename: Frederic
authors.initials: F
authors.lastname: Houssiau
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: David A
authors.initials: DA
authors.lastname: Isenberg
authors.forename: Lexy
authors.initials: L
authors.lastname: Kelley
authors.forename: Brian
authors.initials: B
authors.lastname: Kilgallen
authors.forename: Anna N
authors.initials: AN
authors.lastname: Barry
authors.forename: William A
authors.initials: WA
authors.lastname: Wegener
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C448700:epratuzumab
keywords: ALLEVIATE; BILAG; CD22; SLE; clinical trial; epratuzumab; lupus; monoclonal antibody