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Kidney Week

Abstract: SA-PO911

Combined Rituximab and Cyclophosphamide Therapy in PLA2Rab-Associated Membranous Nephropathy (MN)

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • van de Logt, Anne-Els, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Vink-van Setten, Coralien, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Wetzels, Jack F., Radboudumc, Nijmegen, Gelderland, Netherlands
Background

Optimal treatment of MN is debated: oral high-dose cyclophosphamide (CP) is effective (>90% immunological remission (IR)), but associated with toxicity. Rituximab (RTX) is less toxic, but also less effective (IR 65%). We evaluated the “McAdoo” treatment regimen (RTX 2*1000mg; CP 1.5mg/kg/day * 8weeks and prednisone (iv 2* 1gr + 3 weeks oral starting at 1mg/kg) in high risk MN. In this preliminary analysis, we evaluated PLA2Rab kinetics and immunological remission, a surrogate biomarker for later onset clinical remission.

Methods

We analysed data of incident patients with MN, at high risk for progression, treated according the prescribed protocol. aPLA2Rab levels were measured by ELISA in available samples collected at baseline (n=26), and 2 (n=18), 4 (n=20) , 8 (n=20) and 12 (n=23) weeks after start of therapy.

Results

We included 26 patients (M/F 15/11, age 60 [47-68] years, Screatinine 128 µmol/l [102-136], Salbumin 18 g/l [14-21] and UPCR 7.1 gram/10 mmol [5.7-10.0]). Baseline PLA2Rab levels were 176 RU/ml [115-460]. Overall, there was a very fast decrease of PLA2Rab levels, with a decrease > 50% within 2 weeks in all but two patients. Within 8 weeks complete IR (ELISA < 2RU/ml) was 83 %. IR was associated with baseline PLA2Rab tertile (Table). The lower IR rate at 8weeks in patients in the highest tertile was not merely explained by the high baseline PLA2Rab levels, but more likely the consequence of a prolonged PLA2Rab half-life (Table). Most patients with high baseline PLA2Rab levels have received additional therapy (mostly RTX 2 gr).

Conclusion

Our study showed early and high immunological response rate in patients with PLA2Rab associated MN. The longer T1/2 in patients with very high PLA2Rab levels suggest immunological differences (increased B cell proliferation, presence of long-lived plasmacells). Assessment of PLA2Rab levels within 2-4 weeks after start of therapy may enable to identify patients who need more intensive therapy.

Tertiles of baseline PLA2Rab and outcome
PLA2Rab tertileLow MiddleHigh
PLA2Rab (RU/ml)16-131151-273280-1500
IR after 8 weeks100 %100 %43 %
PLA2Rab T1/2 > 7 days0 %0 %71 %
Additional therapy0 %11 %75 %