title: Clinical outcomes of remission induction therapy for severe antineutrophil cytoplasmic antibody-associated vasculitis.
abstract: OBJECTIVE
  To evaluate the reasons that complete remission is not achieved or maintained with original treatment in some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with rituximab (RTX) or with cyclophosphamide/azathioprine (CYC/AZA).
  
  
  METHODS
  The Rituximab in AAV trial was a randomized, double-blind, placebo-controlled trial comparing the rate of remission induction among patients treated with RTX (n = 99) and patients treated with CYC followed by AZA (n = 98). Glucocorticoids were tapered over a period of 5 months. The primary outcome measure was lack of disease activity without glucocorticoid treatment at 6 months. To determine the most important reason for failure to achieve the primary outcome, 7 hierarchical categories of reasons were defined retrospectively (uncontrolled disease, adverse event leading to therapy discontinuation, severe flare, limited flare, Birmingham Vasculitis Activity Score for Wegener's Granulomatosis >0, prednisone treatment at any dosage, and other).
  
  
  RESULTS
  Although remission (lack of disease activity) was achieved in 170 of the 197 patients (86%) in the first 6 months, the primary outcome measure was not achieved in 42%. There were 3 deaths. Twenty-four percent of the patients failed to achieve the primary end point due to active disease: 10 (5%) experienced uncontrolled disease in the first month and 37 (19%) experienced flares after initial improvement. In the majority of such patients, treatment with blinded crossover or according to best medical judgment led to disease control. Ninety-one percent of patients who had uncontrolled disease or experienced a severe flare had proteinase 3 (PR3)-ANCA. When patients with uncontrolled disease were excluded from analysis, those who were PR3-ANCA positive were found to experience fewer flares when treated with RTX compared to CYC/AZA (8 of 59 [14%] versus 20 of 62 [32%]; P = 0.02). Neither ANCA titers nor B cell counts predicted disease flare.
  
  
  CONCLUSIONS
  Current treatment regimens are largely successful in controlling AAV, but in approximately one-fourth of patients, active disease persists or recurs in the first 6 months despite treatment. PR3-ANCA positivity is a risk factor for recurrence or persistence of severe disease. ANCA titers and B cell detectability are poor predictors of both disease relapse and disease quiescence in the first 6 months.
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: E M
authors.initials: EM
authors.lastname: Miloslavsky
authors.forename: U
authors.initials: U
authors.lastname: Specks
authors.forename: P A
authors.initials: PA
authors.lastname: Merkel
authors.forename: P
authors.initials: P
authors.lastname: Seo
authors.forename: R
authors.initials: R
authors.lastname: Spiera
authors.forename: C A
authors.initials: CA
authors.lastname: Langford
authors.forename: G S
authors.initials: GS
authors.lastname: Hoffman
authors.forename: C G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: E W
authors.initials: EW
authors.lastname: St Clair
authors.forename: N K
authors.initials: NK
authors.lastname: Tchao
authors.forename: L
authors.initials: L
authors.lastname: Viviano
authors.forename: L
authors.initials: L
authors.lastname: Ding
authors.forename: L P
authors.initials: LP
authors.lastname: Sejismundo
authors.forename: K
authors.initials: K
authors.lastname: Mieras
authors.forename: D
authors.initials: D
authors.lastname: Iklé
authors.forename: B
authors.initials: B
authors.lastname: Jepson
authors.forename: M
authors.initials: M
authors.lastname: Mueller
authors.forename: P
authors.initials: P
authors.lastname: Brunetta
authors.forename: N B
authors.initials: NB
authors.lastname: Allen
authors.forename: F C
authors.initials: FC
authors.lastname: Fervenza
authors.forename: D
authors.initials: D
authors.lastname: Geetha
authors.forename: K
authors.initials: K
authors.lastname: Keogh
authors.forename: E Y
authors.initials: EY
authors.lastname: Kissin
authors.forename: P A
authors.initials: PA
authors.lastname: Monach
authors.forename: T
authors.initials: T
authors.lastname: Peikert
authors.forename: C
authors.initials: C
authors.lastname: Stegeman
authors.forename: S R
authors.initials: SR
authors.lastname: Ytterberg
authors.forename: J H
authors.initials: JH
authors.lastname: Stone
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use*; D001379:Azathioprine / Q000008:administration & dosage / Q000627:therapeutic use; D018592:Cross-Over Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D055953:Microscopic Polyangiitis / Q000188:drug therapy*; D012074:Remission Induction / Q000379:methods*; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D001379:Azathioprine