title: Efficacy and safety of atacicept for prevention of flares in patients with moderate-to-severe systemic lupus erythematosus (SLE): 52-week data (APRIL-SLE randomised trial).
abstract: OBJECTIVE
  Despite advances in systemic lupus erythematosus (SLE) treatment, many patients suffer from the disease and side effects. Atacicept is a fusion protein that blocks B-lymphocyte stimulator and a proliferation-inducing ligand, which are increased in patients with SLE.
  
  
  METHODS
  In this double-blind, placebo-controlled study, patients with moderate-to-severe SLE were randomised to atacicept 75 mg or atacicept 150 mg administered subcutaneously, or placebo twice-weekly for 4 weeks, then weekly for 48 weeks. Primary and secondary efficacy measures were the proportion of patients experiencing at least one flare of British Isles Lupus Assessment Group A or B, and time to first flare, respectively.
  
  
  RESULTS
  Enrolment in the atacicept 150 mg arm was discontinued prematurely due to two deaths. In the intention-to-treat population (n=461), there was no difference in flare rates or time to first flare between atacicept 75 mg and placebo. Analysis of patients treated with atacicept 150 mg suggested beneficial effect versus placebo in flare rates (OR: 0.48, p=0.002) and time to first flare (HR: 0.56, p=0.009). Both atacicept doses were associated with reductions in total Ig levels and anti-dsDNA antibodies, and increases in C3 and C4 levels. Most treatment-emergent adverse events were mild or moderate.
  
  
  CONCLUSIONS
  There was no difference between atacicept 75 mg and placebo for flare rate or time to first flare. Analysis of atacicept 150 mg suggested benefit.
  
  
  BACKGROUND
  EudraCT: 2007-003698-13; NCT00624338.
authors.affiliation: Division of Medicine, Centre for Rheumatology, University College London, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Isenberg
authors.affiliation: Rheumatology Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gordon
authors.affiliation: Merck Serono S.A., Geneva, Switzerland.
authors.forename: Daiana
authors.initials: D
authors.lastname: Licu
authors.affiliation: Merck Serono S.A., Geneva, Switzerland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Copt
authors.affiliation: Merck Serono S.A., Geneva, Switzerland.
authors.forename: Claudia Pena
authors.initials: CP
authors.lastname: Rossi
authors.affiliation: Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, California, USA.
authors.forename: David
authors.initials: D
authors.lastname: Wofsy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000276:immunology; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D003176:Complement C3 / Q000276:immunology; D003181:Complement C4 / Q000276:immunology; D018450:Disease Progression; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D018501:Antirheumatic Agents; D003176:Complement C3; D003181:Complement C4; D007136:Immunoglobulins; D011993:Recombinant Fusion Proteins; C524618:TACI receptor-IgG Fc fragment fusion protein
keywords: Autoantibodies; Autoimmunity; B cells; Infections; Systemic Lupus Erythematosus