Phase III trial results with blisibimod, a selective inhibitor of B-cell activating factor, in subjects with systemic lupus erythematosus (SLE): results from a randomised, double-blind, placebo-controlled trial

Ann Rheum Dis. 2018 Jun;77(6):883-889. doi: 10.1136/annrheumdis-2018-213032. Epub 2018 Mar 21.


Background: Targeted inhibitors of B-cell activating factor (BAFF) have been evaluated in phase III trials in over 4000 patients with systemic lupus erythematosus (SLE). Post hoc analyses of these studies identify greater treatment effect in patients entering with higher disease activity, greater corticosteroid doses, anti double-stranded DNA (dsDNA) and low complement C3 or C4.

Objectives: To evaluate the efficacy and safety of blisibimod, a BAFF inhibitor, in a population of patients with SLE enriched for high disease activity.

Methods: 442 patients with SLE with antinuclear antibodies or anti-dsDNA and Safety of Estrogen in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥10 on standard-of-care medications were randomised to receive weekly subcutaneous blisibimod (200 mg) or placebo. Corticosteroid taper was encouraged from week 8. The primary end point was the week 52 SLE Responder Index-6 (SRI-6).

Results: The SRI-6 primary end point was not met. There was a statistically significant steroid-sparing effect, and significantly more blisibimod-treated subjects achieved corticosteroid taper. Increased blisibimod treatment effect on SRI-6 was observed in subjects who achieved a concomitant decrease in corticosteroid dose from baseline. In subjects with baseline urinary protein:creatinine ratio (UPCR) ≥56.5 mg/mmol, significantly higher proportions of blisibimod subjects achieved >50% reduction in UPCR and/or UPCR <56.5 mg/mmol. Reductions in SLE autoantibodies and B cells, and increases in complement C3 and C4 were observed with blisibimod.Blisibimod was well-tolerated. The most common adverse events were upper respiratory tract infection, urinary tract infection, injection site erythema/reaction and diarrhoea.

Conclusions: Although the SRI-6 end point was not met, blisibimod was associated with successful steroid reduction, decreased proteinuria and biomarker responses.

Trial registration number: NCT01395745.

Keywords: B cells; corticosteroids; systemic lupus erythematosus.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Antinuclear / blood
  • B-Cell Activating Factor / antagonists & inhibitors*
  • B-Lymphocytes / immunology
  • Biomarkers / blood
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Injections, Subcutaneous
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Prednisone / administration & dosage
  • Prednisone / therapeutic use
  • Quality of Life
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / therapeutic use*
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult


  • AMG623 peptibody
  • Antibodies, Antinuclear
  • B-Cell Activating Factor
  • Biomarkers
  • Glucocorticoids
  • Immunologic Factors
  • Recombinant Fusion Proteins
  • Prednisone

Associated data