Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomised trial

Ann Rheum Dis. 2015 Jun;74(6):1178-82. doi: 10.1136/annrheumdis-2014-206404. Epub 2015 Mar 4.

Abstract

Objectives: The RITUXVAS trial reported similar remission induction rates and safety between rituximab and cyclophosphamide based regimens for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 12 months; however, immunosuppression maintenance requirements and longer-term outcomes after rituximab in ANCA-associated renal vasculitis are unknown.

Methods: Forty-four patients with newly diagnosed ANCA-associated vasculitis and renal involvement were randomised, 3:1, to glucocorticoids plus either rituximab (375 mg/m(2)/week×4) with two intravenous cyclophosphamide pulses (n=33, rituximab group), or intravenous cyclophosphamide for 3-6 months followed by azathioprine (n=11, control group).

Results: The primary end point at 24 months was a composite of death, end-stage renal disease and relapse, which occurred in 14/33 in the rituximab group (42%) and 4/11 in the control group (36%) (p=1.00). After remission induction treatment all patients in the rituximab group achieved complete B cell depletion and during subsequent follow-up, 23/33 (70%) had B cell return. Relapses occurred in seven in the rituximab group (21%) and two in the control group (18%) (p=1.00). All relapses in the rituximab group occurred after B cell return.

Conclusions: At 24 months, rates of the composite outcome of death, end-stage renal disease and relapse did not differ between groups. In the rituximab group, B cell return was associated with relapse.

Trial registration number: ISRCTN28528813.

Keywords: B cells; Cyclophosphamide; Granulomatosis with polyangiitis; Systemic vasculitis; Treatment.

Publication types

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

MeSH terms

  • Aged
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / complications
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / drug therapy
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / immunology
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Azathioprine / therapeutic use*
  • B-Lymphocytes / cytology
  • Cyclophosphamide / therapeutic use*
  • Disease Progression
  • Disease-Free Survival
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / therapeutic use*
  • Granulomatosis with Polyangiitis / complications
  • Granulomatosis with Polyangiitis / drug therapy*
  • Granulomatosis with Polyangiitis / immunology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Failure, Chronic / etiology
  • Lymphocyte Count
  • Male
  • Microscopic Polyangiitis / complications
  • Microscopic Polyangiitis / drug therapy*
  • Microscopic Polyangiitis / immunology
  • Middle Aged
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / etiology
  • Renal Insufficiency, Chronic / immunology
  • Rituximab

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Glucocorticoids
  • Immunosuppressive Agents
  • Rituximab
  • Cyclophosphamide
  • Azathioprine

Associated data

  • EudraCT/2005-003610-15
  • ISRCTN/ISRCTN28528813