Long-term comparative outcomes of rituximab and belimumab in lupus patients

Objectives Although rituximab and belimumab are recommended for systemic lupus erythematosus (SLE) and lupus nephritis, direct long-term comparative evidence is limited. We aimed to compare the effectiveness of rituximab versus belimumab in a real-world setting for treating SLE. Methods This prospective, single-centre, observational cohort study analysed SLE patients who initiated biologics in the BILAG-BR registry at Addenbrooke’s Hospital (2011–2025). We compared treatment periods with rituximab and belimumab among patients stable on therapy, without switching or entering clinical trials. The primary outcome was achieving low disease activity (SLEDAI-2K ≤4 and prednisolone ≤ 5 mg/day). Drug survival (time to drug switch or loss to follow-up) was also analysed. Results Overall, 176 patients were included, contributing 175 rituximab treatment courses in 148 patients and 58 belimumab treatment courses in 58 patients. Median follow-up was 3.4 (2.0-5.0) years for rituximab and 2.0 (1.0-3.4) years for belimumab (p < 0.001). At baseline, belimumab users had higher SLEDAI-2K scores (12.4 ± 4.9 vs 9.5 ± 5.4, p < 0.001).In multivariate analyses, belimumab and rituximab did not differ in achieving low disease activity in either the multivariable Cox model (HR 0.92, 95% CI 0.57–1.48) or the propensity score overlap-weighted analysis (HR 0.86, 95% CI 0.54–1.37). Drug survival was similar when used as first-line biologic therapy. In contrast, among second-line biologic users, belimumab showed higher drug survival than rituximab(HR 1.34, 95% CI 1.03-1.77). Conclusion In this observational cohort, belimumab was associated with similar rates of low disease activity as rituximab. Drug survival differed and warrants further study.