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Ann Rheum Dis doi:10.1136/annrheumdis-2013-205144
  • Clinical and epidemiological research
  • Extended report

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

  1. for the PEARL-SC Study
  1. 1North Shore–Long Island Jewish Health System, Great Neck, New York, USA
  2. 2Rheumatology Gynecology & Reproduction Institute, Lima, Peru
  3. 3Health and Research Centre, Trivandrum, Kerala, India
  4. 4Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  5. 5Anthera Pharmaceuticals, Hayward, California, USA
  6. 6Rheumatology Hospital Abreu Sodre Pesquisa Clínica, São Paulo, Brazil
  1. Correspondence to Dr Renee Martin, Anthera Pharmaceuticals, Inc. 25801 Industrial Blvd, Suite B., Hayward, CA 94545, USA; rmartin{at}anthera.com
  • Received 6 January 2014
  • Revised 18 March 2014
  • Accepted 23 March 2014
  • Published Online First 19 April 2014

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.

Trial registration number NCT01162681.

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