RITUXIMAB-BASED treatment for systemic lupus erythematosus (SLE) with active lupus nephritis has not been shown to differ significantly in 52-week clinical effectiveness from mycophenolate mofetil-based or intravenous cyclophosphamide-based strategies, according to new real-world registry data, although immune cell changes have varied within each strategy.
Kidney involvement remains one of the most important organ manifestations determining prognosis in SLE, and current treatment aims to control renal inflammation, limit glucocorticoid-related toxicity, and prevent chronic kidney disease and flares. Induction options, including mycophenolate mofetil (MMF), intravenous cyclophosphamide (IVCY) and B-cell-targeted therapies such as rituximab (RTX), are used in clinical practice, but real-world data directly comparing their clinical efficacy and immune effects in lupus nephritis have remained limited.
This multicentre retrospective analysis used data from the LOOPS registry on patients with SLE and active lupus nephritis who received single-agent induction therapy with RTX, MMF, or IVCY in addition to glucocorticoids (GCs).
The co-primary endpoints were the achievement rates of complete renal response (CRR) and a urinary protein-to-creatinine ratio below 0.7 g/gCr at week 52.
At week 52, no significant differences were observed among the groups in CRR rates or improvement in proteinuria. Changes in estimated glomerular filtration rate, disease activity measures and concomitant GC dose also did not differ significantly.
Exploratory within-strategy analyses showed reduced B-cell subset proportions with RTX and broader reductions, including in activated T cells, with MMF and IVCY. However, the treatment strategy-by-time interaction was not significant, providing no evidence of between-strategy differences in longitudinal changes.
The 52-week clinical effectiveness of the three strategies for active lupus nephritis has not differed significantly, and the immunophenotypic patterns seen within each strategy have not been confirmed between strategies. These findings remain hypothesis generating and require further validation, although comprehensive immunophenotyping may help characterise immune dynamics and support future response stratification and precision medicine. RTX may be considered an induction option for selected patients for whom MMF or IVCY is difficult to use because of safety or tolerability concerns.
Reference
Ueno M et al. Clinical and immunological outcomes of rituximab-based, mycophenolate mofetil-based and cyclophosphamide-based treatment strategies for systemic lupus erythematosus with active kidney involvement from LOOPS registry. RMD Open. 2026;12:e007370.
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