Post-hoc analyses of pooled data from five phase III trials of belimumab

Belimumab is approved for treating active systemic lupus erythematosus (SLE) and lupus nephritis, alongside standard therapy.

During the American College of Rheumatology annual meeting (ACR Convergence) 2023, Parodis et al.¹ and Sheikh et al.² presented post-hoc analyses of pooled data from five phase III clinical trials on belimumab in patients with SLE. We summarize the key results below.

The Lupus hub has previously reported on a post-hoc analysis of renal and neuropsychiatric outcomes from these five phase III trials.

Methods

The post-hoc analyses was conducted on the below five randomized, placebo-controlled, phase III trials:

• BLISS-52 (NCT00424476; N = 577)
• BLISS-76 (NCT00410384; N = 548)
• Northeast Asia (NCT01345253; N = 677)
• BLISS-SC (NCT01484496; N = 836)
• EMBRACE (NCT01632241; N = 448)

Included patients were treated with belimumab (10 mg/kg/month intravenously or 200 mg/week subcutaneously) or placebo, alongside standard therapy for 52 weeks. Parodis et al.¹ analyzed the attainment of the definition of remission in SLE (DORIS) and Lupus Low Disease Activity State (LLDAS) with belimumab, while Sheikh et al.² evaluated the efficacy of belimumab by race and ethnicity.

Key findings

Among 1,869 patients treated with belimumab and 1,217 with placebo, 94.4% were female, with a mean age of 37 years. The racial subgroups at baseline comprised 36% Asian, 33% White, 21% Black African ancestry, 10% American Indian or Alaskan Native, <0.1% Native Hawaiian or Other Pacific Islander, while the ethnic distribution comprised 27% Hispanic/Latino and 73% non-Hispanic/Latino.

At Week 52, treatment with belimumab compared with placebo, resulted in:

• Greater attainment of DORIS and LLDAS (Figure 1A), noticeable as early as 20 and 24 weeks, respectively¹.
  • Early attainment of LLDAS in patients with baseline Systemic Lupus Erythematosus Disease Activity Index 2000 score ≥10 and anti-dsDNA positivity/low complement 3/complement 4 was observed with belimumab compared with the overall population¹.

• Higher proportions of patients to be SLE Responder Index-4 (SRI-4) responders in all subgroups by race and ethnicity, except for patients of Black African ancestry (Figure 1A)².
• Greater differences in time to first severe SFI (Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index Flare Index) flares and any SFI flares in all subgroups except for patients of Black African ancestry (Figure 1B)².
• Greater differences in time to first British Isles Lupus Assessment Group 1A/2B flares in all subgroups except for patients of White or Black African ancestry (Figure 1B)².

Figure 1. Attainment of A DORIS, LLDAS, and SRI-4 response and B time to first flares at Week 52*  

BILAG, British Isles Lupus Assessment Group; CI, confidence interval; DORIS, definition of remission in systemic lupus erythematosus; LLDAS, Lupus Low Disease Activity State; SFI, Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)–Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index; SRI-4, Systemic Lupus Erythematosus Responder Index-4.
*Adapted from Parodis, et al.¹ and Sheikh, et al.²