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Ann Rheum Dis doi:10.1136/annrheumdis-2013-205067
  • Clinical and epidemiological research
  • Extended report

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)

Open Access
  1. 1Division of Medicine, Centre for Rheumatology, University College London, London, UK
  2. 2Rheumatology Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
  3. 3Merck Serono S.A., Geneva, Switzerland
  4. 4Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, California, USA
  1. Correspondence to Professor David Isenberg, Division of Medicine, Centre for Rheumatology, University College London, The Rayne Building, 4th Floor, Room 424, 5 University Street, London WC1E 6JF, UK; d.isenberg{at}ucl.ac.uk
  • Received 13 December 2013
  • Revised 28 May 2014
  • Accepted 31 May 2014
  • Published Online First 20 June 2014

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.

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