Belimumab added to multi-target therapy in lupus nephritis: a retrospective cohort study of efficacy, divergent temporal response patterns, and safety

Background Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus. Belimumab, a B-cell-activating factor (BAFF) inhibitor, improves renal outcomes when added to standard therapy, but its efficacy and temporal effects when combined with multi-target therapy regimens containing tacrolimus remain poorly characterized. We compared multi-target therapy plus belimumab with multi-target therapy alone in active LN. Methods In this retrospective cohort study, 28 patients with active LN (14 per group) received multi-target therapy (glucocorticoid, mycophenolate mofetil, and tacrolimus, a calcineurin inhibitor) with (case group) or without (control group) belimumab. The patients were assessed at baseline and 3, 6, and 12 months after treatment initiation. Primary endpoints were 24-hour urinary protein (24hUP), estimated glomerular filtration rate (eGFR), and urine protein-to-creatinine ratio (UPCR). C3, C4, anti-dsDNA, SLEDAI-2K, and IgG/IgA/IgM were the secondary endpoints. Comparisons were conducted using Welch’s t or Mann-Whitney U tests (between-group), paired t or Wilcoxon tests (within-group), and Cohen’s d effect sizes. Results Compared to baseline, both groups exhibited significant improvement in proteinuria, SLEDAI-2K, anti-dsDNA, and complement. eGFR remained stable, with no significant between-group differences at any timepoint. Temporal patterns diverged: the belimumab group showed earlier reduction in proteinuria (from 3 months) and IgG/IgA/IgM levels, whereas multi-target therapy alone showed earlier recovery of complement levels, with weak C4 recovery after treatment with belimumab. During twelve months of treatment, adverse events were infrequent and comparable between groups (all p = 1.00). Conclusions Both regimens substantially improved renal and serological outcomes over 12 months with an acceptable safety profile. Although the addition of belimumab did not significantly outperform multi-target therapy alone, the two regimens exhibited distinct, mechanistically coherent temporal signatures: inhibition of the BAFF pathway versus broad immunosuppression. These findings warrant confirmation in larger prospective studies.