Belimumab With Rituximab for the Treatment of Primary Membranous Nephropathy

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.

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.

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.

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.