Abstract: TH-OR023

Immunological Remission in PLA2R-Antibody Associated Membranous Nephropathy (MN): Cyclophosphamide versus Rituximab

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • van de Logt, Anne-Els, Radboud University Medical Center, Nijmegen, Netherlands
  • Dahan, Karine, Hospital Tenon, Paris, France
  • Rousseau, Alexandra, AP-HP, Paris, France
  • Debiec, Hanna, INSERM UMR S702, Paris, France
  • Ronco, Pierre M., Hospital Tenon, Paris, France
  • Wetzels, Jack F., Radboud University Medical Center, Nijmegen, Netherlands
Background

Rituximab (cumulative dose 750 mg/m2) induces remissions in patients with MN (Kahan JASN2017). However, efficacy is limited in patients with high anti-PLA2R (aPLA2R) levels. Cyclophosphamide therapy is effective independent of aPLA2R levels (van de Logt SA-PO 631, kidneyweek 2016). Incidence of partial remissions was higher with Cyclophosphamide vs Rituximab (van de Brand JASN2017). We questioned if differences in the immunological (aPLA2R) response could explain these observations. We therefore evaluated the change in aPLA2R levels during treatment with Cyclophosphamide (1.5mg/kg/day, duration 8-24 weeks; Nijmegen cohort) and Rituximab (the GEMRITUX cohort (rituximab 375 mg/m2 at day 1 and 8).

Methods

We included 30 anti-PLA2R positive patients treated with Cyclophosphamide and 27 patients treated with Rituximab. In stored samples (baseline, and at the end of therapy or after 6 months ) aPLA2R were measured with ELISA (Euroimmun®).

Results

In the Cyclophosphamide cohort 19 patients were male, mean age was 56 ± 13 years, median serum creatinine level was 1.3 g/dl (IQR 1.1-1.6) and median protein creatinine ratio 7.7 g/g (IQR 5.5-11.3) . In the Rituximab cohort, 21 patients were male, mean age was 51 ± 14 years, median serum creatinine level was 1.1 g/dl (IQR 0.93-1.3) and median protein creatinine ratio 8.4 g/g (IQR 4.4-11.0) . aPLA2R disappeared in all but one patient treated with Cyclophosphamide, and in 13 of 27 patients treated with Rituximab. The reponse was associated with baseline titers (table 1). Rituximab did not induce immunological remission in patients in the highest tertile of aPLA2R levels.

Conclusion

Rituximab in a dose of 750mg/m2 is less effective than Cyclophosphamide in inducing an immunological remission in patients with MN and high antibody levels. Our study highlights the potential role of PLA2R antibody measurements in predicting outcome to therapy. Higher doses of Rituximab must be evaluated.

Disappearance of aPLA2R during treatment with Cyclophosphamide and Rituximab
aPLA2R titer in Cyc groupLowest Tertile n=10Middle Tertile n=10Highest Tertile n=10
ElISA titer RU/ml (range)15-6786-134136-776
Cumulative percentage samples negative after 24 wk100 %100 %90 %
aPLA2R titer in RTX groupLowest Tertile n=9Middle Tertile n=9Highest Tertile n=9
ElISA titer RU/ml (range)17-4162-276314-2900
Cumulative percentage samples negative after 24 wk89 %56 %0 %

Funding

  • Government Support - Non-U.S.