title: Factors Determining the Clinical Utility of Serial Measurements of Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3.
abstract: Relapse following remission is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly with ANCAs directed at proteinase 3 (PR3). This study was undertaken to evaluate the association of an increase in PR3-ANCA level with subsequent relapse.
  
  
  
  Data from the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial were used. Starting from the time of achieving complete remission, serial measurements by direct and capture enzyme-linked immunosorbent assays (ELISAs) were analyzed in 93 patients with PR3-ANCA, using Cox proportional hazards regression.
  
  
  
  An increase in PR3-ANCA level was identified in 58 of 93 subjects (62.4%) by direct ELISA and in 59 of 93 (63.4%) by capture ELISA. Relapses occurred in 55 of 93 subjects (59.1%), with 25 and 21 occurring within 1 year after an increase by direct ELISA and capture ELISA, respectively. An increase by direct ELISA was associated with subsequent severe relapses (hazard ratio [HR] 4.57; P < 0.001), particularly in patients presenting with renal involvement (HR 7.94; P < 0.001) and alveolar hemorrhage (HR 24.19; P < 0.001). Both assays identified increased risk for severe relapse in the rituximab group (HR 5.80; P = 0.002 for direct ELISA and HR 4.54; P = 0.007 for capture ELISA) but not the cyclophosphamide/azathioprine group (P = 0.103 and P = 0.197, respectively).
  
  
  
  The association of an increase in PR3-ANCA level with the risk of subsequent relapse is partially affected by the PR3-ANCA detection methodology, disease phenotype, and remission induction treatment. An increase in PR3-ANCA level during complete remission conveys an increased risk of relapse, particularly severe relapse, among patients with renal involvement or alveolar hemorrhage and those treated with rituximab. Serial measurements of PR3-ANCA may be informative in this subset of patients, but the risk of relapse must be weighed carefully against the risks associated with therapy.
authors.affiliation: Mayo Clinic and Mayo Foundation for Medical Education and Research, Rochester, Minnesota.
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Fussner
authors.affiliation: Mayo Clinic and Mayo Foundation for Medical Education and Research, Rochester, Minnesota.
authors.forename: Amber M
authors.initials: AM
authors.lastname: Hummel
authors.affiliation: Mayo Clinic and Mayo Foundation for Medical Education and Research, Rochester, Minnesota.
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Schroeder
authors.affiliation: Universidad del Desarrollo, Santiago, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Silva
authors.affiliation: Mayo Clinic and Mayo Foundation for Medical Education and Research, Rochester, Minnesota.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Cartin-Ceba
authors.affiliation: Mayo Clinic and Mayo Foundation for Medical Education and Research, Rochester, Minnesota.
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Snyder
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hoffman
authors.affiliation: University of Groningen, Groningen, The Netherlands.
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Langford
authors.affiliation: University of Pennsylvania, Philadelphia.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.affiliation: Boston University, Boston University Medical Center, and VA Boston Healthcare System, Boston, Massachusetts.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Monach
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Philip
authors.initials: P
authors.lastname: Seo
authors.affiliation: Hospital for Special Surgery, New York, New York.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Spiera
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: E
authors.initials: E
authors.lastname: William St Clair
authors.affiliation: Immune Tolerance Network, San Francisco, California.
authors.forename: Nadia K
authors.initials: NK
authors.lastname: Tchao
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
authors.affiliation: Mayo Clinic and Mayo Foundation for Medical Education and Research, Rochester, Minnesota.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Specks
mesh_terms: D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology*; D011446:Prospective Studies; D012074:Remission Induction; D018570:Risk Assessment; D000069283:Rituximab / Q000627:therapeutic use
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D053146:Myeloblastin