Belimumab Superior to Placebo in Yielding Systemic Lupus Erythematosus Responses

A new meta-analysis has found that belimumab was superior to placebo according to BICLA criteria in patients with systemic lupus erythematosus (SLE).1

“The results from this post hoc analysis of foundational phase III SLE belimumab trials have important implications for clinical practice, as they substantiate the clinical efficacy of belimumab through an additional widely used responder index of SLE.2 These findings may inform future trial design, while also supporting the use of belimumab in the management of SLE, in accordance with current recommendations,” lead investigator Ioannis Parodis, Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, and Center for Molecular Medicine (CMM), and Örebro University, Örebro, Sweden, and colleagues wrote.1

Parodis and colleagues conducted a post-hoc analysis of 5 randomized controlled trials evaluating intravenous (BLISS-52 [belimumab, 258; placebo, 259], BLISS-76 [belimumab, 251; placebo, 258], BLISS-NEA [belimumab, 372; placebo, 179], EMBRACE [belimumab, 258; placebo, 259]) or subcutaneous belimumab (BLISS-SC [belimumab, 526; placebo, 267]) in adults with active SLE over 52 weeks. Response was defined according to BICLA criteria, corresponding to BILAG improvement, no worsening of disease activity based on BILAG and Systemic Lupus Erythematosus Disease Activity Index-2K, no deterioration in Physician’s Global Assessment ≥0.3 (scale: 0–3), and no treatment failure.

The meta-analysis included 3086 patients that received belimumab (n = 1869) or placebo (n = 1217), with 2800 that had data available at 52 weeks. The investigators found that at 52 weeks, patients that received belimumab had a greater frequency of BICLA response compared with those who received placebo in BLISS-52 (OR, 1.49 [95% CI, 1.05–2.12]; P = .024), BLISS-NEA (OR, 1.62 [95% CI,1.12–2.33]; P = .010) and BLISS-SC (OR, 1.89 [95% CI, 1.39–2.57]; P <.001), for a highly significant difference in the overall pooled population (OR, 1.47 [95% CI, 1.25–1.72]; P <.001; adjusted for trial variance).1

Subgroup analyses confirmed belimumab’s efficacy, with the therapy yielding greater BICLA response frequencies than placebo irrespective of baseline glucocorticoid dose, patients with baseline SLEDAI-2K≥10 (OR, 1.67 [95% CI, 1.36-2.06]; P <.001), and in patients with positive anti-double-stranded (ds)DNA (OR, 1.59 [95% CI, 1.31-1.92]; P <.001)and/or low C3/C4 levels (OR, 1.54 [95% CI, 1.29-1.85]; P <.001) at baseline. Notably, belimumab combined with anti-malarials (AMA) yielded a greater frequency of achieving BICLA response.1

“In conclusion, using an additional key clinical responder index, BICLA, we validated the results from foundational trials originally assessing belimumab efficacy using SRI-4, thus corroborating the efficacy of belimumab in SLE. Important implications for clinical practice include the substantiation of the clinical efficacy of belimumab and support for its use as a treatment in the management of SLE, especially among patients with high disease activity or serologically active patients. Additionally, added benefits of belimumab were observed when used in combination with AMA,” Parodis and colleagues concluded.1

REFERENCES

1. Parodis I, Lindblom J, Palazzo L, et al. Outcomes of patients with systemic lupus erythematosus treated with belimumab: a post hoc efficacy analysis of five phase III clinical trials by British Isles Lupus Assessment Group-based Combined Lupus Assessment criteria. RMD Open. 2025;11(2):e005444. Published 2025 Apr 23. doi:10.1136/rmdopen-2025-005444

2. Parodis I, Lindblom J, Levy RA, et al. Attainment of remission and low disease activity after treatment with belimumab in patients with systemic lupus erythematosus: a post-hoc analysis of pooled data from five randomised clinical trials. Lancet Rheumatol. 2024;6:e751–61. doi: 10.1016/S2665-9913(24)00162-0