Real-World Long-term Comparisons of Rituximab versus Calcineurin Inhibitors for Membranous Nephropathy in the Cure Glomerulonephropathy Study
Jul 2026·
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Meghan K. Gerety
Vivek Charu
Madison Simmons
Nicholas J. Seewald
Dorey A. Glenn
Douglas E. Schaubel
Abigail R. Smith
Dhruti Chen
Louis-Philippe Laurin
Michelle Denburg
Lawrence B. Holzman
Laurence H. Beck
Laura H. Mariani
Jarcy Zee
Abstract
Background
Clinical trials in rare glomerular disease may establish short-term treatment efficacy but are limited by small sample sizes and short study duration. Observational data are needed to assess longer-term outcomes and can provide insights into real-world prescribing practices. This study applied modern statistical methods to real-world data from the Cure Glomerulonephropathy (CureGN) network to compare the effectiveness of rituximab and calcineurin inhibitors on long-term primary membranous nephropathy outcomes.
Methods
CureGN participants with biopsy-confirmed primary membranous nephropathy who initiated either of the two treatments at least 6 months after any previous immunosuppressant exposure were eligible. Inverse-probability-of-treatment weighting balanced covariates at treatment initiation. Inverse-probability-of-censoring weights accounted for censoring individuals if another immunosuppressant was started during follow-up. Outcomes included time from treatment initiation to composite kidney disease progression (40% decline in eGFR, kidney replacement therapy, or eGFR <15), proteinuria remission, and relapse following remission. Hazard ratios and differences in restricted mean survival times were estimated.
Results
325 treatment initiations across 250 unique participants were eligible, with median follow-up 53 months (25th-75th percentile: 24-79). Participants on calcineurin inhibitors had significantly higher risks of disease progression (HR=2.81; 95% CI: 1.16, 6.80). Hazard ratios for proteinuria remission (HR=0.77; 95% CI: 0.50, 1.17) and relapse (HR=1.42, 95% CI: 0.69, 2.92) had wide confidence intervals.
Conclusions
Rituximab was associated with better kidney function preservation than calcineurin inhibitors over long follow-up. Proteinuria remission and relapse results favored rituximab but did not reach statistical significance. Long-term treatment comparative effectiveness in rare diseases can be evaluated with real-world data.
Clinical trials in rare glomerular disease may establish short-term treatment efficacy but are limited by small sample sizes and short study duration. Observational data are needed to assess longer-term outcomes and can provide insights into real-world prescribing practices. This study applied modern statistical methods to real-world data from the Cure Glomerulonephropathy (CureGN) network to compare the effectiveness of rituximab and calcineurin inhibitors on long-term primary membranous nephropathy outcomes.
Methods
CureGN participants with biopsy-confirmed primary membranous nephropathy who initiated either of the two treatments at least 6 months after any previous immunosuppressant exposure were eligible. Inverse-probability-of-treatment weighting balanced covariates at treatment initiation. Inverse-probability-of-censoring weights accounted for censoring individuals if another immunosuppressant was started during follow-up. Outcomes included time from treatment initiation to composite kidney disease progression (40% decline in eGFR, kidney replacement therapy, or eGFR <15), proteinuria remission, and relapse following remission. Hazard ratios and differences in restricted mean survival times were estimated.
Results
325 treatment initiations across 250 unique participants were eligible, with median follow-up 53 months (25th-75th percentile: 24-79). Participants on calcineurin inhibitors had significantly higher risks of disease progression (HR=2.81; 95% CI: 1.16, 6.80). Hazard ratios for proteinuria remission (HR=0.77; 95% CI: 0.50, 1.17) and relapse (HR=1.42, 95% CI: 0.69, 2.92) had wide confidence intervals.
Conclusions
Rituximab was associated with better kidney function preservation than calcineurin inhibitors over long follow-up. Proteinuria remission and relapse results favored rituximab but did not reach statistical significance. Long-term treatment comparative effectiveness in rare diseases can be evaluated with real-world data.
Type
Publication
Kidney360