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.