Low-dose belimumab reduced risk of flares in patients with systemic lupus erythematosus: a multicentre, randomised, double-blind, placebo-controlled trial.

Abstract

The efficacy of low-dose belimumab for disease flare prevention in patients with lupus with low disease activity was evaluated (NCT04515719). In this 52-week, randomised, placebo-controlled trial, patients who had a Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score of ≤6, with no A and ≤ 1 B on British Isles Lupus Assessment Group, and who had prednisone ≤20 mg/d at screening were enrolled and randomly assigned 1:1 to intravenous 120 mg belimumab or placebo (saline). The primary outcome was disease flares within 52 weeks. The trial was terminated prematurely on 10 April 2022 when Renji Hospital was designated as a COVID-19 referral centre during the Shanghai lockdown. Overall, 90.5% and 86.1% of patients in the belimumab (n = 116) and placebo (n = 115) arms completed the study within a follow-up of 31 ± 16.1 weeks. The primary endpoint was met. In total, 7.8% of patients receiving low-dose belimumab had disease flares, significantly lower than that in the placebo group (19.1%) (P = .012; difference 11.3%; 95% CI 1.8%-20.9%). Kaplan-Meier curves also demonstrated lower cumulative flare rates in the belimumab arm (P = .011, Hazard Ratio (HR), 0.38; 95% CI 0.17-0.83). Glucocorticoid-sparing effects were comparable (Δprednisone from baseline, -1.55 ± 10.11 mg/d vs -0.91 ± 7.43 mg/d, P = .075). SELENA-SLEDAI was reduced by 0.62 ± 2.14 in the belimumab group; however, it increased by 0.12 ± 2.80 in the placebo group (P = .009). Any adverse events were comparable (61.2% vs 64.3%). Only 4 (3.4%) and 6 (5.2%) severe adverse events occurred in 2 groups, respectively. Treatment with low-dose belimumab helped reduce the risks of disease flares in Chinese patients with systemic lupus erythematosus at low disease activity. Belimumab was generally well-tolerated.