title: A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of subcutaneous blisibimod, an inhibitor of B cell activating factor, in patients with systemic lupus erythematosus (SLE) in a dose-ranging Phase 2b clinical trial.
  
  
  METHODS
  547 patients with SLE with anti-double stranded DNA or antinuclear antibodies and Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥6 at baseline were randomised to receive placebo or blisibimod at one of 3 dose levels. The primary end point, measured at Week 24, was the SLE Responder Index-5 (SRI-5, meeting established SRI criteria but with ≥5 point improvement in SELENA-SLEDAI).
  
  
  RESULTS
  Although SRI-5 response rates were not significantly improved in the pooled blisibimod groups compared with placebo, they were higher in subjects randomised to the highest dose of blisibimod (200 mg once-weekly (QW)) compared with pooled placebo, from Week 16 to Week 24, reaching statistical significance at Week 20 (p=0.02). SRI response rates compared with placebo were higher still in subjects who attained SELENA-SLEDAI improvements of ≥8, and in a subgroup of patients with severe disease (SELENA-SLEDAI ≥10 and receiving corticosteroids at baseline). In subjects with protein:creatine ratios of 1-6 at baseline, significant reductions in proteinuria were observed with blisibimod. Significant (p<0.01) changes in anti-double stranded DNA antibodies, complement C3 and C4, and reductions in B cells were observed with blisibimod.No imbalances in serious adverse events or infections (4/280 and 3/266), deaths (4/280 and 3/266) and malignancies (2/280 and 2/266) were reported for blisibimod compared with placebo.
  
  
  CONCLUSIONS
  This study successfully identified a safe, effective and convenient dose, study population and end point for evaluation of blisibimod effect in Phase 3.
  
  
  BACKGROUND
  NCT01162681.
authors.affiliation: North Shore-Long Island Jewish Health System, Great Neck, New York, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Furie
authors.affiliation: Rheumatology Gynecology & Reproduction Institute, Lima, Peru.
authors.forename: G
authors.initials: G
authors.lastname: Leon
authors.affiliation: Health and Research Centre, Trivandrum, Kerala, India.
authors.forename: M
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Petri
authors.affiliation: Anthera Pharmaceuticals, Hayward, California, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Chu
authors.affiliation: Anthera Pharmaceuticals, Hayward, California, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hislop
authors.affiliation: Anthera Pharmaceuticals, Hayward, California, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Martin
authors.affiliation: Rheumatology Hospital Abreu Sodre Pesquisa Clínica, São Paulo, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Scheinberg
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000974:Antibodies, Antinuclear / Q000276:immunology; D000962:Antimalarials / Q000627:therapeutic use; D003176:Complement C3 / Q000276:immunology; D003181:Complement C4 / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: C573858:AMG623 peptibody; D000305:Adrenal Cortex Hormones; D000974:Antibodies, Antinuclear; D000962:Antimalarials; D003176:Complement C3; D003181:Complement C4; D007155:Immunologic Factors; D011993:Recombinant Fusion Proteins
keywords: Autoimmunity; B cells; Systemic Lupus Erythematosus