Rituximab as Rescue or Add-On Therapy for Relapsing or Refractory Lupus Nephritis: A Systematic Review and...

Relapsing and refractory lupus nephritis (LN) remains difficult to manage despite advances in immunosuppressive and targeted therapies. Rituximab (RTX) is often used as rescue or add-on therapy, but renal outcomes in this specific setting have not been quantitatively synthesized. PubMed, Embase, and Web of Science were searched from inception to March 30, 2026. Studies of RTX-based therapy in relapsing or refractory LN were included if renal outcomes were reported. Primary outcomes were complete renal response (CRR), partial renal response (PRR), and overall renal response (ORR) at 6, 12, and 24 months; secondary outcomes were changes in proteinuria and serum creatinine. Random-effects models were used. Nineteen studies involving 445 patients were included. Pooled CRR rates were 0.33 (95% CI 0.21-0.46), 0.41 (95% CI 0.28-0.54), and 0.42 (95% CI 0.26-0.60) at 6, 12, and 24 months, respectively. Corresponding PRR rates were 0.29 (95% CI 0.16-0.45), 0.23 (95% CI 0.07-0.46), and 0.19 (95% CI 0.07-0.34), and ORR rates were 0.67 (95% CI 0.52-0.80), 0.70 (95% CI 0.51-0.86), and 0.66 (95% CI 0.43-0.86). Proteinuria decreased by -2.69 g/day-equivalent (95% CI -3.23 to -2.16), and serum creatinine decreased by -11.79 μmol/L (95% CI -19.86 to -3.72). Sensitivity analyses were generally stable, and Egger's test detected no significant publication bias. In conclusion, RTX-based rescue or add-on therapy was associated with moderate renal response rates and reductions in proteinuria and serum creatinine in this difficult-to-treat population. Further prospective comparative studies are needed to define its role.