Assessments of fatigue and disease activity in patients with systemic lupus erythematosus enrolled in the Phase 2 clinical trial with blisibimod

Lupus. 2017 Jan;26(1):27-37. doi: 10.1177/0961203316654767. Epub 2016 Jun 26.


This report evaluates the effects of blisibimod (A-623, AMG 623), a potent and selective inhibitor of B-cell activating factor (BAFF), on patient-reported fatigue and disease activity in the Phase 2b PEARL-SC clinical trial in patients with systemic lupus erythematosus (SLE). A total of 547 individuals who met the American College of Rheumatology (ACR) classification criteria for SLE, were positive for anti-double-stranded DNA or antinuclear antibodies, and had a Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥6 at baseline, were randomized to receive placebo or blisibimod for at least 24 weeks. Patient self-reported fatigue was evaluated using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale, and disease activity was evaluated using Physician's Global Assessment, SELENA-SLEDAI, and British Isles Lupus Assessment Group Score. Statistically significant improvements in FACIT-Fatigue score were observed among individuals randomized to blisibimod, especially in the 200 mg QW group where favorable effects on disease activity with blisibimod compared to placebo were observed as early as Week 8. The mean improvement from baseline of 6.9 points at Week 24, compared with 4.4 points with placebo, met the criteria for minimal clinically important improvement difference defined for patients with SLE. Despite concomitant improvements in FACIT-Fatigue, SLE Responder Index (SRI) and SLE biomarkers (reported previously), FACIT-Fatigue score correlated only weakly with disease activity. While poor correlation between fatigue and disease activity is not new, the observation that correlation remains poor despite concurrent population improvements in disease and fatigue brings a new facet to our understanding of SLE.

Keywords: B-lymphocyte; Systemic lupus erythematosus (SLE); fatigue.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Fatigue / drug therapy*
  • Fatigue / etiology
  • Female
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / therapeutic use*
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / physiopathology
  • Male
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / therapeutic use*
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome


  • AMG623 peptibody
  • Biomarkers
  • Immunologic Factors
  • Recombinant Fusion Proteins