# Obinutuzumab in the treatment of idiopathic refractory membranous nephropathy: an observational case series

## TL;DR

Obinutuzumab, an anti-CD20 antibody, shows high remission rates and manageable side effects in treating a severe kidney disease called idiopathic refractory membranous nephropathy.

## Contribution

This observational case series demonstrates obinutuzumab's efficacy and safety in treating idiopathic refractory membranous nephropathy for the first time.

## Key findings

- 80% of patients achieved remission (complete or partial) within 12 months of obinutuzumab treatment.
- Anti-PLA2R antibody levels declined rapidly in 80% of patients within the first 3 months.
- All patients eventually achieved seroconversion to anti-PLA2R antibody negativity.

## Abstract

Idiopathic refractory membranous nephropathy (IRMN) is a subset of nephrotic syndrome with a high risk of progression to end-stage renal disease, yet treatment options remain limited. Obinutuzumab, a humanized type II anti-CD20 antibody, induces efficient CD20+ cell depletion, leading to favorable immunological and proteinuria responses in IRMN. This study sought to assess the effectiveness and safety of obinutuzumab for treating IRMN.

A total of 31 patients with IRMN were enrolled and received obinutuzumab therapy. They were followed for 12 months. The primary endpoint was the remission rate (complete or partial remission). Secondary outcomes included changes in proteinuria, serum albumin, serum creatinine, anti-PLA2R antibody levels, CD20/CD19 cell counts, and adverse events.

At 12 months, the overall remission rate was 80%, with 16% achieving complete remission and 64% achieving partial remission. The median time to remission was 4.5 months (IQR 2.0–7.0 months). The immunological remission rates at 3, 6, 9, and 12 months were 70, 83, 90, and 93%, respectively. Regarding anti-PLA2R antibodies, 80% of patients showed a rapid decline within the first 3 months (p < 0.001), with 64% achieving a > 50% reduction from baseline by month 3. At the last follow-up, all patients had achieved seroconversion to anti-PLA2R antibody negativity. Adverse events included infusion-related reactions such as fever, hypotension, tachycardia, and flushing. No deaths occurred.

Obinutuzumab effectively induces remission in patients with IRMN and demonstrates a tolerable safety profile.