Year: 2026
Type: article
Study design: Clinical Trial
Abstract: Introduction: B cell depletion with rituximab leads to complete or partial remission (CR/PR) in only ∼60% of patients with primary membranous nephropathy (PMN). Adding belimumab to rituximab may result in greater depletion of memory B cells, limit the re-emergence 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 ≥ 4g/day and detectable serum anti-phospholipase A2 receptor (anti-PLA2R) antibodies. Participants received belimumab 200 mg subcutaneously weekly for 52 weeks and rituximab 1000 mg intravenously at weeks 4 and 6. Assessments included belimumab exposure at week 4 and CR/PR at week 104. Results: Seventeen participants started belimumab. Belimumab exposure was not significantly reduced in those with high (>8 g/day) proteinuria at week 4. Among all treated participants, 59% (10/17) achieved CR/PR at week 104, while in per protocol analyses, 91% (10/11) achieved CR/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 rituximab and were depleted by rituximab. B cell re-constitution occurred after week 52 with primarily naïve and transitional B cells. Belimumab with rituximab was well-tolerated, with one participant discontinuing belimumab due to infection. Conclusion: In this study, a high proportion of participants receiving belimumab with rituximab achieved CR/PR. Thus, a multi-targeted 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.
Source: Kidney International Reports
Authors: Sharon A. Chung, Lia Stelzig, Matthew A. Sherman, Wendy Gao, Patricia Tosta, Laura A. Cooney, Sharon Adler, Nabeel Aslam, Isabelle Ayoub, Andrew S. Bomback, Gaia Coppock, Vimal K. Derebail, Fahmeedah Kamal, Dana V. Rizk, Katherine R. Tuttle, Meryl Waldman, William T. Barry, Patrick H. Nachman
Institutions: Immune Tolerance Network, Rho (United States), National Institutes of Health, National Institute of Allergy and Infectious Diseases, University of California, Los Angeles, The Lundquist Institute, Mayo Clinic, Mayo Clinic in Florida, The Ohio State University, Columbia University Irving Medical Center, Columbia University, University of Pennsylvania, University of North Carolina at Chapel Hill, Stanford Medicine, Stanford University, University of Alabama at Birmingham, UAB Medicine, University of Washington, Inland Northwest Health Services, National Institute of Diabetes and Digestive and Kidney Diseases, University of Minnesota
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,800
Awards: G277117613, G4275790696, G554752038
OpenAlex ID: W7204782079