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Abstract: TH-PO484

Analysis of Serum Belimumab Pharmacokinetics in Primary Membranous Nephropathy: Data From the REBOOT Study

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

  • Nachman, Patrick H., University of Minnesota Health, Minneapolis, Minnesota, United States
  • Weiner, Lia, Rho, Inc., Durham, North Carolina, United States
  • Chung, Sharon, Immune Tolerance Network, San Francisco, California, United States
  • Ding, Linna, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States
  • Barry, William T., Rho, Inc., Durham, North Carolina, United States

Group or Team Name

  • ITN080AI REBOOT Study Investigators
Background

Patients with primary membranous nephropathy (PMN) are known to lose immunoglobulin in the urine at rates affected by the severity of proteinuria. This loss could impact the dosing of monoclonal antibodies used for treatment. Belimumab (BEL), an IgG1 monoclonal antibody, has been detected in the urine of patients with PMN receiving this therapy. We conducted this study to examine the relationship between serum BEL exposure and baseline proteinuria to inform dosing in PMN.

Methods

REBOOT is a two-part clinical trial examining the efficacy of BEL and rituximab therapy in PMN (NCT03949855). Part A is an open-label study examining how baseline proteinuria affects BEL exposure. Participants received subcutaneous BEL at a dose of 200 mg weekly. Serum BEL trough levels were drawn after each of the first 4 doses. The relationship between BEL exposure and baseline proteinuria was assessed using longitudinal mixed models, which included the defined low (>4 to ≤ 8 g/day) and high (≥ 8 g/day) proteinuria subgroups.

Results

The baseline proteinuria of the 12 evaluated participants ranged from 4.1-21.3 g/day, with 4 participants in the low and 8 participants in the high proteinuria groups. The ratio of the mean serum BEL trough levels at week 4 between the high and low proteinuria groups was 0.78 (95% CI 0.52-1.2). Regression models predicted that a 1 g/day increase in proteinuria results in a 1.9% decrease in trough levels (p=0.262). Figure 1 shows the serum trough levels after the fourth BEL dose by baseline proteinuria level, and the predicted BEL levels from regression modeling.

Conclusion

This data suggests that serum BEL exposure is not significantly associated with baseline proteinuria levels in PMN, and does not support increasing the dose of BEL in individuals with higher levels of proteinuria.

Figure 1: Week 4 serum belimumab trough levels by baseline proteinuria. The line presents the predicted belimumab level values from a mixed model.

Funding

  • Other NIH Support