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

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.

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.

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).

In this observational cohort, belimumab was associated with similar rates of low disease activity as rituximab. Drug survival differed and warrants further study.