Does adding concomitant immunosuppressive therapy to belimumab provide additional benefits in SLE? Results From the BEL-Spain Registry

Abstract Objectives Belimumab (BEL) is an approved biologic therapy for systemic lupus erythematosus (SLE) that, when added to standard care, reduces disease activity, flare rates, and glucocorticoid exposure. In clinical practice, BEL is frequently combined with conventional immunosuppressants (IS), but the added benefit of concomitant IS once disease control is achieved remains uncertain. Observational data suggest that BEL monotherapy may be effective in selected patients, but comparative real-world evidence is limited. Objectives were to evaluate the clinical effectiveness of BEL as monotherapy vs in combination with IS in patients with SLE included in the BEL-Spain Registry. Methods We performed a retrospective analysis of SLE patients treated with BEL with or without IS, with at least 12 months of follow-up. The primary outcome was remission according to the 2021 DORIS definition. Secondary outcomes included Lupus Low Disease Activity State (LLDAS), flare rates, and glucocorticoid use. Overlap propensity score weighting was applied to adjust for confounding by indication. Results Among 258 patients, 177 (68.6%) received BEL with IS and 81 (31.4%) BEL monotherapy. At 12 months, DORIS remission rates were 48.1% in the IS group and 51.4% in the monotherapy group (p=NS), with comparable LLDAS and flare rates. Propensity score–adjusted analyses confirmed no significant differences in remission rates (OR 0.89, 95% CI 0.37–2.14). Global treatment trajectories were stable, other than progressive glucocorticoid reduction in both groups. Conclusions In this real-world cohort, BEL monotherapy achieved similar outcomes to combination therapy with IS in selected SLE patients. Prospective studies are needed to confirm these findings and define optimal treatment strategies.