title: Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response.
abstract: OBJECTIVE
  To identify factors that predict response to belimumab treatment in the phase 3 BLISS trials of autoantibody-positive systemic lupus erythematosus (SLE) and further analyse clinical efficacy in various patient subsets.
  
  
  METHODS
  The BLISS trials compared belimumab 1 and 10 mg/kg versus placebo, all plus standard SLE therapy, over 52 or 76 weeks. Pooled subgroup analyses of week 52 SLE responder index rates (the primary endpoint in both trials) were performed based on demographic characteristics and baseline disease activity indicators. Pooled multivariate analysis was performed to determine predictors of response and treatment effect.
  
  
  RESULTS
  Pooled univariate and multivariate analyses (N=1684) identified baseline factors associated with an increased benefit of belimumab versus placebo. These factors included the Safety Of Estrogens In Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) ≥10, low complement, anti-dsDNA positivity and corticosteroid use. Efficacy outcomes were assessed in the low complement/anti-dsDNA-positive and SELENA-SLEDAI ≥10 subgroups. Week 52 SLE Responder Index rates in the low complement/anti-dsDNA-positive subgroup were 31.7%, 41.5% (p=0.002) and 51.5% (p<0.001) with placebo and belimumab 1 mg/kg and 10 mg/kg, respectively; corresponding rates in the SELENA-SLEDAI ≥10 subgroup were 44.3%, 58.0% (p<0.001) and 63.2% (p<0.001). Further analysis of secondary endpoints in the low complement/anti-dsDNA-positive subgroup showed that compared with placebo, belimumab produced greater benefits regarding severe flares, corticosteroid use and health-related quality of life.
  
  
  CONCLUSIONS
  These findings suggest that belimumab has greater therapeutic benefit than standard therapy alone in patients with higher disease activity, anti-dsDNA positivity, low complement or corticosteroid treatment at baseline.   CLINICALTRIALS.GOV:  identifiers NCT00424476 and NCT00410384.
authors.affiliation: Unit for Clinical Therapy Research, Inflammatory Diseases, The Karolinska Institute, Stockholm, Sweden. ronald.van.vollenhoven@ki.se
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Petri
authors.forename: Ricard
authors.initials: R
authors.lastname: Cervera
authors.forename: David A
authors.initials: DA
authors.lastname: Roth
authors.forename: Beulah N
authors.initials: BN
authors.lastname: Ji
authors.forename: Christi S
authors.initials: CS
authors.lastname: Kleoudis
authors.forename: Z John
authors.initials: ZJ
authors.lastname: Zhong
authors.forename: William
authors.initials: W
authors.lastname: Freimuth
mesh_terms: D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006304:Health Status; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D017063:Outcome Assessment, Health Care / Q000379:methods*; D011379:Prognosis; D011788:Quality of Life; D012008:Recurrence; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; D007155:Immunologic Factors; C511911:belimumab