title: Outcomes of nonsevere relapses in antineutrophil cytoplasmic antibody-associated vasculitis treated with glucocorticoids.
abstract: OBJECTIVE
  Nonsevere relapses are more common than severe relapses in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but their clinical course and treatment outcomes remain largely unexamined. We undertook this study to analyze the outcomes of patients with nonsevere relapses in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial who were treated with prednisone according to a prespecified protocol.
  
  
  METHODS
  RAVE was a randomized, double-blind, placebo-controlled trial comparing rituximab (RTX) to cyclophosphamide (CYC) followed by azathioprine (AZA) for induction of remission. Patients who experienced nonsevere relapses between months 1 and 18 were treated with a prednisone increase without a concomitant change in their nonglucocorticoid immunosuppressants, followed by a taper.
  
  
  RESULTS
  Forty-four patients with a first nonsevere relapse were analyzed. In comparison to the 71 patients who maintained relapse-free remission over 18 months, these patients were more likely to have proteinase 3-ANCAs, diagnoses of granulomatosis with polyangiitis (Wegener's), and a history of relapsing disease at baseline. A prednisone increase led to remission in 35 patients (80%). However, only 13 patients (30%) were able to maintain second remissions through the followup period (mean 12.5 months); 31 patients (70%) had a second disease relapse, 14 of them with severe disease. The mean time to second relapse was 9.4 months (4.7 months in the group treated with RTX versus 13.7 months in the group treated with CYC/AZA; P < 0.01). Patients who experienced nonsevere relapses received more glucocorticoids than those who maintained remission (6.7 grams versus 3.8 grams; P < 0.01).
  
  
  CONCLUSIONS
  Treatment of nonsevere relapses in AAV with an increase in glucocorticoids is effective in restoring temporary remission in the majority of patients, but recurrent relapses within a relatively short interval remain common. Alternative treatment approaches are needed for this important subset of patients.
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: E M
authors.initials: EM
authors.lastname: Miloslavsky
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: U
authors.initials: U
authors.lastname: Specks
authors.affiliation: University of Pennsylvania, Philadelphia.
authors.forename: P A
authors.initials: PA
authors.lastname: Merkel
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: P
authors.initials: P
authors.lastname: Seo
authors.affiliation: Hospital for Special Surgery, New York, New York.
authors.forename: R
authors.initials: R
authors.lastname: Spiera
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: C A
authors.initials: CA
authors.lastname: Langford
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: G S
authors.initials: GS
authors.lastname: Hoffman
authors.affiliation: University of Groningen and University Medical Center, Groningen, The Netherlands.
authors.forename: C G M
authors.initials: CG
authors.lastname: Kallenberg
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: E W
authors.initials: EW
authors.lastname: St Clair
authors.affiliation: Immune Tolerance Network, South San Francisco, California.
authors.forename: N K
authors.initials: NK
authors.lastname: Tchao
authors.affiliation: National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland.
authors.forename: L
authors.initials: L
authors.lastname: Ding
authors.affiliation: Rho, Chapel Hill, North Carolina.
authors.forename: D
authors.initials: D
authors.lastname: Iklé
authors.affiliation: Rho, Chapel Hill, North Carolina.
authors.forename: M
authors.initials: M
authors.lastname: Villareal
authors.affiliation: Immune Tolerance Network, Bethesda, Maryland.
authors.forename: N
authors.initials: N
authors.lastname: Lim
authors.affiliation: Genentech, South San Francisco, California.
authors.forename: P
authors.initials: P
authors.lastname: Brunetta
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: F C
authors.initials: FC
authors.lastname: Fervenza
authors.affiliation: Boston University and Boston Medical Center, Boston, Massachusetts.
authors.forename: P A
authors.initials: PA
authors.lastname: Monach
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: J H
authors.initials: JH
authors.lastname: Stone
mesh_terms: D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy / Q000276:immunology; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology; D001379:Azathioprine / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D060046:Maintenance Chemotherapy; D008297:Male; D055953:Microscopic Polyangiitis / Q000188:drug therapy* / Q000276:immunology; D053146:Myeloblastin / Q000276:immunology; D009195:Peroxidase / Q000276:immunology; D011241:Prednisone / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D009195:Peroxidase; D053146:Myeloblastin; D001379:Azathioprine; D011241:Prednisone