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)

Research output: Contribution to journalArticle

Authors

  • David Isenberg
  • Daiana Licu
  • Samuel Copt
  • Claudia Pena Rossi
  • David Wofsy

Colleges, School and Institutes

External organisations

  • University College London
  • Merck Serono S.A., Geneva, Switzerland.
  • Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, California, USA.

Abstract

Objectives 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.

Trial registration number EudraCT: 2007-003698-13; NCT00624338.

Details

Original languageEnglish
Pages (from-to)2006-2015
Number of pages10
JournalAnnals of the Rheumatic Diseases
Volume74
Issue number11
Early online date20 Jun 2014
Publication statusPublished - Nov 2015

Keywords

  • Autoantibodies, Autoimmunity, B cells, Infections, Systemic Lupus Erythematosus