Rituximab protocol based on PLA2R1 epitope spreading outperforms the standard GEMRITUX protocol in membranous nephropathy

A personalised treatment regimen based on PLA2R1 epitope spreading analysis can offer improved remission rates in participants with membranous nephropathy, according to a recent phase 2 trial.

The discovery of the M-type phospholipase A2 receptor (PLA2R) as the primary target in membranous nephropathy greatly advanced basic and clinical research [1]. The current multicentre, randomised, clinical trial (NCT03804359) analysed the clinical remission effect of a personalised treatment scheme based on the presence or absence of baseline PLA2R1 epitope spreading in participants with membranous nephropathy compared to the standard GEMRITUX protocol. Prof. Barbara Seitz-Polski (Université Côte d'Azur, Nice, France) presented the results [2].

The personalised treatment regimens (n=33) under investigation were: participants without PLA2R1 epitope spreading at baseline received the GEMRITUX protocol and participants with epitope spreading at baseline or who had persistent nephrotic syndrome at month 6 were treated immediately with 2 high-dose rituximab infusions. The control GEMRITUX protocol (n=31) entailed symptomatic treatment for 6 months, with 2 additional rituximab infusions after 6 months if persistent nephrotic syndrome was present. Outcome measures were clinical remission, defined as a urine protein-creatinine ratio <0.3 g/g, with a normal serum albumin and eGFR >60 mL/min/1.73 m², or partial clinical remission (urine protein-creatinine ratio <3.5 g/g with ≥50% improvement from baseline, improvement or normalisation of serum albumin and stable serum creatinine).

A significantly higher proportion of participants receiving the personalised regimen achieved partial clinical remission (69% vs 34%; P=0.0105) at month 12 compared with the GEMRITUX regimen. “It is important to note that we have the same level of spontaneous remission for participants who were never treated in the personalised arm compared to the GEMRITUX arm, showing that we did not overtreat participants”, added Prof. Seitz-Polski. The personalised versus GEMRITUX regimen led to significantly improved kidney function assessed by variation between baseline and month 12 in creatinaemia (P=0.0323) and eGFR (P=0.0303). The adverse event rates between both study groups did not differ (P=0.6071).

“Personalised rituximab treatment based on PLA2R1 epitope spreading recognition was superior to the standard protocol in achieving remission and gain in eGFR at 12 months. Participants with multiple domain recognition should be treated immediately with high doses of rituximab to increase their chances of remission”, concluded Prof. Seitz-Polski.

1. Beck Jr LH, et al. N Engl J Med. 2009;361(1):11–21.
2. Seitz-Polski B, et al. Protocol based on PLA2R1 epitope recognition is superior to standard protocol in achieving remission in PLA2R1-associated membranous nephropathy. Abstract #992, ERA 2024, 23–26 May, Stockholm, Sweden.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 20 June 202424 June 2024