Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials

Abstract

Objective: To evaluate the effects of belimumab versus placebo, plus standard systemic lupus erythematosus (SLE) therapy, on organ domain-specific SLE disease activity.

Methods: Data obtained after 52 weeks of treatment from two phase III trials (BLISS-52 and BLISS-76) comparing belimumab 1 and 10 mg/kg versus placebo, plus standard therapy, in 1684 autoantibody-positive patients were analysed post hoc for changes in British Isles Lupus Assessment Group (BILAG) and Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ domain scores.

Results: At baseline, the domains involved in the majority of patients were musculoskeletal and mucocutaneous by both BILAG and SELENA-SLEDAI, and immunological by SELENA-SLEDAI. At 52 weeks, significantly more patients treated with belimumab versus placebo had improvement in BILAG musculoskeletal and mucocutaneous domains (1 and 10 mg/kg), and in SELENA-SLEDAI mucocutaneous (10 mg/kg), musculoskeletal (1 mg/kg) and immunological (1 and 10 mg/kg) domains. Improvement was also observed in other organ systems with a low prevalence (≤16%) at baseline, including the SELENA-SLEDAI vasculitis and central nervous system domains. Significantly fewer patients treated with belimumab versus placebo had worsening in the BILAG haematological domain (1 mg/kg) and in the SELENA-SLEDAI immunological (10 mg/kg), haematological (10 mg/kg) and renal (1 mg/kg) domains.

Conclusions: Belimumab treatment improved overall SLE disease activity in the most common musculoskeletal and mucocutaneous organ domains. Less worsening occurred in the haematological, immunological and renal domains.

Figure 1

Baseline (A) British Isles Lupus Assessment Group (BILAG) and (B) Safety of Oestrogens in Lupus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA–SLEDAI) organ involvement in the BLISS-52 and BLISS-76 studies. BILAG involvement is depicted as A, B, C or D score at baseline. CNS, central nervous system.

Figure 2

(A) Proportions of patients with improvements from baseline in British Isles Lupus Assessment Group (BILAG) organ domain scores at week 52 (pooled BLISS-52 and BLISS-76 data) among those with an A or B score at baseline. Improvement was defined as a step down from an A or B score to a B, C or D score. (B) Improvement from baseline by one, two, or three-score shift at week 52 in patients with an A or B score at baseline. A one-score shift is a shift from an A score at baseline to a B score at week 52, or a B score at baseline to a C score at week 52; a two-score shift is from A to C or B to D; a three-score shift is from A to D. *p<0.01; †p<0.05.

Figure 3

Proportions of patients with improvements from baseline in Safety of Oestrogens in Lupus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA–SLEDAI) organ domain scores at week 52 in (A) total pooled population and (B) total pooled population according to the number of organ domains improved; (C) proportions in total pooled population with improvements in most common SELENA–SLEDAI individual organ domain item scores; and proportions with improvements in SELENA–SLEDAI organ domain scores at week 52 in (D) subgroup with high serological activity at baseline and (E) subgroup with high serological activity according to the number of organ domains improved. Improvement was defined as negative score shift. *p<0.01; †p<0.001; ‡p<0.05. CNS, central nervous system