title: A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus.
abstract: OBJECTIVE
  To assess the safety, tolerability, biologic activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE).
  
  
  METHODS
  Patients with a Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score >/=4 (n = 449) were randomly assigned to belimumab (1, 4, or 10 mg/kg) or placebo in a 52-week study. Coprimary end points were the percent change in the SELENA-SLEDAI score at week 24 and the time to first SLE flare.
  
  
  RESULTS
  Significant differences between the treatment and placebo groups were not attained for either primary end point, and no dose response was observed. Reductions in SELENA-SLEDAI scores from baseline were 19.5% in the combined belimumab group versus 17.2% in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24-52 was significantly longer with belimumab treatment (154 versus 108 days; P = 0.0361). In the subgroup (71.5%) of serologically active patients (antinuclear antibody titer >/=1:80 and/or anti-double-stranded DNA [anti-dsDNA] >/=30 IU/ml), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA-SLEDAI score (-28.8% versus -14.2%; P = 0.0435), physician's global assessment (-32.7% versus -10.7%; P = 0.0011), and Short Form 36 physical component score (+3.0 versus +1.2 points; P = 0.0410). Treatment with belimumab resulted in a 63-71% reduction of naive, activated, and plasmacytoid CD20+ B cells, and a 29.4% reduction in anti-dsDNA titers (P = 0.0017) by week 52. The rates of adverse events and serious adverse events were similar in the belimumab and placebo groups.
  
  
  CONCLUSIONS
  Belimumab was biologically active and well tolerated. The effect of belimumab on the reduction of SLE disease activity or flares was not significant. However, serologically active SLE patients responded significantly better to belimumab therapy plus SOC than to SOC alone.
authors.affiliation: Cedars-Sinai Medical Center, University of California, Los Angeles, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wallace
authors.forename: William
authors.initials: W
authors.lastname: Stohl
authors.forename: Richard A
authors.initials: RA
authors.lastname: Furie
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Lisse
authors.forename: James D
authors.initials: JD
authors.lastname: McKay
authors.forename: Joan T
authors.initials: JT
authors.lastname: Merrill
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Petri
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Ginzler
authors.forename: W Winn
authors.initials: WW
authors.lastname: Chatham
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: McCune
authors.forename: Vivian
authors.initials: V
authors.lastname: Fernandez
authors.forename: Marc R
authors.initials: MR
authors.lastname: Chevrier
authors.forename: Z John
authors.initials: ZJ
authors.lastname: Zhong
authors.forename: William W
authors.initials: WW
authors.lastname: Freimuth
mesh_terms: D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004247:DNA / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C511911:belimumab; D004247:DNA