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

Abstract

BackgroundTreatment 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).MethodsA 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.ResultsOf 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).ConclusionsThe 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.

Circulating B Cells, Plasma Cells, and Treg Associate with ANCA Levels in ANCA-associated Vasculitis

“…Of note, conventional therapy such as cyclophosphamide, not only targets B cells but also plasma cells. Despite a recent retrospective, single-center study demonstrating equal efficacy for rituximab and cyclophosphamide as induction therapy, 7 patients presenting with more severe AAV tended to receive cyclophosphamide to reach rapid suppression of disease activities. Our data on plasma cells may in part explain the importance of plasma-cell depletion in the induction phase.…”

A Patient of Crescentic Glomerulonephritis with Positive Anti Myeloperoxidase Antibodies and Immunoglobulin a Deposits on Immunofluorescence: The Conundrum Continues

“…This was the best option available to us for treatment of crescentic GN at that time based on the international guidelines [9]. However, recent evidence has shown that rituximab is an equally effective option in patients with severe renal dysfunction [10].…”

ANCA-Associated Vasculitis: An Update

“…RTX and CYC were also compared in a retrospective study of 225 patients with severe renal involvement (defined as eGFR < 30 mL/min/1.73 m 2 ) [ 103 ]. The RTX and CYC regimens were similar to what was used in RAVE and both treatment groups were treated with glucocorticoids.…”

“…However, a meta-analysis of 10 PLEX randomized controlled studies in AAV that included MEPEX and PEVIAS demonstrated no difference in the rates of the composite of death or ESRD at 3 or 12 months, but showed a decreased overall incidence of ESRD [ 111 ]. This meta-analysis did not include the observational study of Casal Moura et al [ 103 ] which did not demonstrate any benefit of PLEX on remission-induction at 6 months, the rate of ESRD and/or death at 18 months, progression to ESRD, and survival at 24 months.…”