Belimumab With Rituximab for the Treatment of Primary Membranous Nephropathy.
17 affiliations
- 1Immune Tolerance Network, San Francisco, California, USA.
- 2Rho, Durham, North Carolina, USA.
- 3Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
- 4Immune Tolerance Network, Ann Arbor, Michigan, USA.
- 5Division of Nephrology, Hypertension, and Transplantation, Department of Internal Medicine, University of California, Los Angeles, Los Angeles, California, USA.
- 6Lundquist Research Institute, Torrance, California, USA.
- 7Division of Nephrology and Hypertension, Mayo Clinic, Jacksonvill, Florida, USA.
- 8Division of Nephrology, Department of Medicine, Ohio State University, Columbus, Ohio, USA.
- 9Division of Nephrology, Department of Medicine, David Koch Jr. Glomerular Kidney Center, Columbia University, New York City, New York, USA.
- 10Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
- 11Division of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
- 12Division of Nephrology, Department of Medicine, Stanford University, Palo Alto, California, USA.
- 13Nephrology Division, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
- 14Providence Medical Research Center, Providence Inland Northwest Health, Spokane, Washington, USA.
- 15Division of Nephrology and Kidney Research Institute, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
- 16Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
- 17Division of Nephrology and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Abstract
Introduction
B cell depletion with rituximab (RTX) leads to complete or partial remission (CR or PR) in approximately 60% of patients with primary membranous nephropathy (PMN). Adding belimumab (BEL) to RTX may result in greater depletion of memory B cells, limit the reemergence of autoreactive B cells, and improve clinical responses.Methods
REBOOT Part A (NCT03949855) is a single arm, open-label, pharmacokinetic study where all participants had proteinuria (≥ 4 g/d) and detectable serum anti-phospholipase A2 receptor (anti-PLA2R) antibodies. Participants received BEL 200 mg subcutaneously weekly for 52 weeks and RTX 1000 mg intravenously at weeks 4 and 6. Assessments included BEL exposure at week 4 and CR or PR at week 104.Results
A total of 17 participants started BEL. BEL exposure was not significantly reduced in those with high proteinuria (≥8 g/day) at week 4. Among all treated participants, 10/17 (59%) achieved CR or PR at week 104, whereas in per protocol analyses, 10/11 (91%) achieved CR or PR at week 104. All participants in per protocol analyses had normal serum albumin and undetectable serum anti-PLA2R by week 104. Circulating memory B cells increased before RTX and were depleted by RTX. B cell reconstitution occurred after week 52 with primarily naive and transitional B cells. BEL with RTX was well-tolerated, with 1 participant discontinuing BEL due to infection.Conclusion
In this study, a high proportion of participants receiving BEL with RTX achieved CR or PR. Therefore, a multitargeted approach to B cell depletion may improve immunologic and clinical outcomes in PMN and is being studied in a larger, randomized, placebo-controlled clinical trial.
Versions
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BibTeX
@article{chung2026belimumab,
title = {{Belimumab With Rituximab for the Treatment of Primary Membranous Nephropathy.}},
author = {Sharon A Chung and Lia Stelzig and Matthew A Sherman and Wendy Gao and Patricia Tosta and Laura A Cooney and Sharon Adler and Nabeel Aslam and Isabelle Ayoub and Andrew S Bomback and Gaia Coppock and Vimal K Derebail and Fahmeedah Kamal and Dana V Rizk and Katherine R Tuttle and Meryl Waldman and William T Barry and Patrick H Nachman},
journal = {Kidney international reports},
year = {2026},
month = sep,
doi = {10.1016/j.ekir.2026.107075},
url = {https://europepmc.org/article/MED/42926931},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Belimumab With Rituximab for the Treatment of Primary Membranous Nephropathy.
AU - Sharon A Chung
AU - Lia Stelzig
AU - Matthew A Sherman
AU - Wendy Gao
AU - Patricia Tosta
AU - Laura A Cooney
AU - Sharon Adler
AU - Nabeel Aslam
AU - Isabelle Ayoub
AU - Andrew S Bomback
AU - Gaia Coppock
AU - Vimal K Derebail
AU - Fahmeedah Kamal
AU - Dana V Rizk
AU - Katherine R Tuttle
AU - Meryl Waldman
AU - William T Barry
AU - Patrick H Nachman
PY - 2026
DA - 2026/09/07
JO - Kidney international reports
DO - 10.1016/j.ekir.2026.107075
UR - https://europepmc.org/article/MED/42926931
AB - Introduction B cell depletion with rituximab (RTX) leads to complete or partial remission (CR or PR) in approximately 60% of patients with primary membranous nephropathy (PMN). Adding belimumab (BEL) to RTX may result in greater depletion of memory B cells, limit the reemergence of autoreactive B cells, and improve clinical responses.Methods REBOOT Part A (NCT03949855) is a single arm, open-label, pharmacokinetic study where all participants had proteinuria (≥ 4 g/d) and detectable serum anti-phospholipase A2 receptor (anti-PLA2R) antibodies. Participants received BEL 200 mg subcutaneously weekly for 52 weeks and RTX 1000 mg intravenously at weeks 4 and 6. Assessments included BEL exposure at week 4 and CR or PR at week 104.Results A total of 17 participants started BEL. BEL exposure was not significantly reduced in those with high proteinuria (≥8 g/day) at week 4. Among all treated participants, 10/17 (59%) achieved CR or PR at week 104, whereas in per protocol analyses, 10/11 (91%) achieved CR or PR at week 104. All participants in per protocol analyses had normal serum albumin and undetectable serum anti-PLA2R by week 104. Circulating memory B cells increased before RTX and were depleted by RTX. B cell reconstitution occurred after week 52 with primarily naive and transitional B cells. BEL with RTX was well-tolerated, with 1 participant discontinuing BEL due to infection.Conclusion In this study, a high proportion of participants receiving BEL with RTX achieved CR or PR. Therefore, a multitargeted approach to B cell depletion may improve immunologic and clinical outcomes in PMN and is being studied in a larger, randomized, placebo-controlled clinical trial.
SN - 2468-0249
ER -