title: Prolonged disease-free remission following rituximab and low-dose cyclophosphamide therapy for renal ANCA-associated vasculitis.
abstract: BACKGROUND
  Rituximab (RTX) has been shown to be effective as an induction agent in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), but studies have been limited by short-term follow-up. We decided to investigate the long-term efficacy and safety of an RTX-based cyclophosphamide (CYP)-sparing regimen (CycLowVas) for renal AAV.
  
  
  METHODS
  Consecutive patients with renal AAV presenting de novo or with a major relapse, except those with serum creatinine >500 μmol/L, previous treatment with RTX and pulmonary haemorrhage or cerebral vasculitis, were treated with two pulses of RTX 2 weeks apart and six fortnightly doses of CYP, as well as a reducing protocol of daily oral steroids. Maintenance was with low-dose steroids and azathioprine.
  
  
  RESULTS
  Twenty-three patients were treated. Median follow-up was 39 months, with 17 patients reaching >2 years of follow-up. All patients achieved clinical remission within 6 weeks. Three major and two minor relapses occurred in five patients at a median of 30 months, which were treated by re-dosing with RTX for major relapses and steroid increase alone for minor relapses. Adverse events included one severe drug reaction, four non-serious and one serious infective episodes in the first 3 months, one skin malignancy at 21 months and one death at 19 months not related to treatment or disease.
  
  
  CONCLUSIONS
  A RTX-based low-dose CYP regimen is effective at inducing long-term disease-free remission and may be the platform on which to develop a steroid-minimizing regimen to further decrease adverse events in the future.
authors.affiliation: Renal Section, Department of Medicine, Imperial College London, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Mansfield
authors.forename: Sally
authors.initials: S
authors.lastname: Hamour
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Habib
authors.forename: Ruth
authors.initials: R
authors.lastname: Tarzi
authors.forename: Jeremy
authors.initials: J
authors.lastname: Levy
authors.forename: Megan
authors.initials: M
authors.lastname: Griffith
authors.forename: Tom
authors.initials: T
authors.lastname: Cairns
authors.forename: H Terence
authors.initials: HT
authors.lastname: Cook
authors.forename: Charles D
authors.initials: CD
authors.lastname: Pusey
authors.forename: Alan D
authors.initials: AD
authors.lastname: Salama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide