Background The belimumab BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) SLE trials utilized the SLE Responder Index (SRI) as the primary efficacy endpoint at wk 52. Increases in corticosteroid doses were allowed through wk 24.
Objectives The effect of belimumab on improvement in disease activity during the 52-wk period was studied to assess the time that clinical benefit would be expected to occur.
Methods Disease activity parameters were analyzed from pooled BLISS trial data to evaluate the effect of belimumab + standard therapy at wk 4, 8, and 12, and at or after wk 24 to determine the earliest time at which significant clinical improvement was observed. A ≥4-point SELENA-SLEDAI (SS) reduction was defined as clinically meaningful improvement. Clinical improvement was analyzed by determining odds ratios from logistic regression for comparisons between each belimumab dose and placebo (standard therapy alone) re SS reductions ≥4 thru 10, baseline (BL) scores ≤9 vs ≥10, and anti-double-stranded DNA (anti-dsDNA) positivity and hypocomplementemia at BL. Improvement in fatigue was assessed starting at wk 8 by FACIT-Fatigue using analysis of covariance for comparisons between each belimumab dose and placebo, adjusted for BL scores. Logistic regression was used for comparisons between each belimumab dose and placebo to assess steroid reduction.
Results As early as 8-12 wk, significant disease activity improvement with SS reductions ≥4 was observed in the overall population, in patients with BL SS ≥10, and in those with anti-dsDNA positivity and hypocomplementemia (table). Significant SS reductions ≥7 occurred as early as 16 wk.
Conclusions Belimumab treatment often resulted in clinically meaningful improvement with rapid reduction in disease activity in the first 3 mo.
Disclosure of Interest A. Doria Consultant for: GlaxoSmithKline/Human Genome Sciences, Speakers Bureau: GlaxoSmithKline/Human Genome Sciences, J. Sanchez-Guerrero Consultant for: GlaxoSmithKline, D. Tegzová: None Declared, E. Ginzler Grant/Research support from: GlaxoSmithKline/Human Genome Sciences, Consultant for: GlaxoSmithKline/Human Genome Sciences, Z. Zhong Shareholder of: Human Genome Sciences, Employee of: Human Genome Sciences, G. Dennis Shareholder of: Human Genome Sciences, Employee of: Human Genome Sciences, D. Wallace Consultant for: GlaxoSmithKline/Human Genome Sciences, Speakers Bureau: GlaxoSmithKline/Human Genome Sciences