Efficacy of Rituximab and Plasma Exchange in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Severe Kidney Disease

J Am Soc Nephrol. 2020 Nov;31(11):2688-2704. doi: 10.1681/ASN.2019111197. Epub 2020 Aug 21.

Abstract

Background: Treatment of patients with ANCA-associated vasculitis (AAV) and severe renal involvement is not established. We describe outcomes in response to rituximab (RTX) versus cyclophosphamide (CYC) and plasma exchange (PLEX).

Methods: A retrospective cohort study of MPO- or PR3-ANCA-positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR <30 ml/min per 1.73 m2). Remission, relapse, ESKD and death after remission-induction with CYC or RTX, with or without the use of PLEX, were compared.

Results: Of 467 patients with active renal involvement, 251 had severe kidney disease. Patients received CYC (n=161) or RTX (n=64) for remission-induction, and 51 were also treated with PLEX. Predictors for ESKD and/or death at 18 months were eGFR <15 ml/min per 1.73 m2 at diagnosis (IRR 3.09 [95% CI 1.49 to 6.40], P=0.002), renal recovery (IRR 0.27 [95% CI 0.12 to 0.64], P=0.003) and renal remission at 6 months (IRR 0.40 [95% CI 0.18 to 0.90], P=0.027). RTX was comparable to CYC in remission-induction (BVAS/WG=0) at 6 months (IRR 1.37 [95% CI 0.91 to 2.08], P=0.132). Addition of PLEX showed no benefit on remission-induction at 6 months (IRR 0.73 [95% CI 0.44 to 1.22], P=0.230), the rate of ESKD and/or death at 18 months (IRR 1.05 [95% CI 0.51 to 2.18], P=0.891), progression to ESKD (IRR 1.06 [95% CI 0.50 to 2.25], P=0.887), and survival at 24 months (IRR 0.54 [95% CI 0.16 to 1.85], P=0.330).

Conclusions: The apparent benefits and risks of using CYC or RTX for the treatment of patients with AAV and severe kidney disease are balanced. The addition of PLEX to standard remission-induction therapy showed no benefit in our cohort. A randomized controlled trial is the only satisfactory means to evaluate efficacy of remission-induction treatments in AAV with severe renal involvement.

Keywords: ANCA; Plasmapheresis; cyclophosphamide; glomerulonephritis; rituximab.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / complications
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / therapy*
  • Antibodies, Antineutrophil Cytoplasmic
  • Combined Modality Therapy
  • Cyclophosphamide / therapeutic use
  • Disease Progression
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Immunologic Factors / therapeutic use*
  • Immunosuppressive Agents / therapeutic use
  • Kaplan-Meier Estimate
  • Kidney Failure, Chronic / physiopathology
  • Male
  • Middle Aged
  • Plasma Exchange*
  • Recurrence
  • Remission Induction
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / physiopathology*
  • Renal Insufficiency, Chronic / therapy*
  • Retrospective Studies
  • Rituximab / therapeutic use*
  • Survival Rate

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Immunologic Factors
  • Immunosuppressive Agents
  • Rituximab
  • Cyclophosphamide