Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse

Research output: Contribution to journalArticle

Authors

  • Matthew Morgan
  • Matthew Szeto
  • Michael Walsh
  • David Jayne
  • Kerstin Westman
  • Niels Rasmussen
  • Thomas F Hiemstra
  • Oliver Flossmann
  • Annelies Berden
  • Peter Höglund
  • Lorraine Harper
  • European Vasculitis Society (EUVAS)

Colleges, School and Institutes

External organisations

  • Renal Immunobiology, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. m.d.morgan@bham.ac.uk.
  • Queen Elizabeth Hospital Birmingham, Area 5, Level 7, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB, UK. m.d.morgan@bham.ac.uk.
  • Renal Immunobiology, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
  • Population Health Research Institute, Hamilton Health Sciences/McMaster University, Hamilton, Canada.
  • Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge Cambridge Experimental Cancer Medicine Centre and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
  • Department of Nephrology, Skane University Hospital Malmö, Lund University, Lund, Sweden.
  • Department of Autoimmune Serology, Statens Seruminstitut, Copenhagen, Denmark.
  • University of Cambridge
  • Renal Department, Royal Berkshire Hospital, Reading, UK.
  • Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
  • Competence Centre for Clinical Research, Skane University Hospital, Lund, Sweden.

Abstract

BACKGROUND: Relapse of disease is frequent in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). It is unclear whether persistent ANCA when starting maintenance therapy increases the risk of relapse. We examined the association between ANCA status and relapse in two randomised controlled trials.

METHODS: ANCA-positive patients in two trials, CYCLOPS and IMPROVE, were switched from cyclophosphamide to maintenance therapy after achieving clinical remission. We classified patients as being either ANCA-positive or ANCA-negative at the time they started maintenance therapy. We compared the risk of relapse in ANCA-positive and ANCA-negative patients.

RESULTS: Of 252 patients included, 102 (40%) experienced at least one relapse during the follow-up period. At the time of the switch from induction to maintenance therapy, 111 were ANCA-positive, of whom 55 (50%) relapsed, compared to 141 patients who were ANCA-negative, of whom 47 (33%) relapsed. In multivariable time-to-event analysis, a reduced risk of relapse was associated with having become ANCA-negative at the time of switching to maintenance therapy (hazard ratio 0.63, 95% confidence interval 0.42-0.95; p = 0.026). In addition, initial proteinase 3 (PR3)-ANCA, younger age, lower serum creatinine, pulsed cyclophosphamide for remission induction, and mycophenolate mofetil for remission maintenance were all associated with an increased risk of relapse.

CONCLUSIONS: Becoming ANCA-negative before the switch to maintenance is associated with a reduced risk of relapse.

TRIAL REGISTRATION: CYCLOPS: ClinicalTrials.gov, NCT00430105 . Registered retrospectively on 31 January 2007.

IMPROVE: ClinicalTrials.gov, NCT00307645 . Registered retrospectively on 27 March 2006.

Details

Original languageEnglish
Pages (from-to)129
JournalArthritis Research & Therapy
Volume19
Issue number1
Publication statusPublished - 7 Jun 2017

Keywords

  • Journal Article