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Extended report
Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis
  1. Alexandre Karras1,2,
  2. Christian Pagnoux3,
  3. Marion Haubitz4,
  4. Kirsten de Groot5,
  5. Xavier Puechal6,
  6. Jan Willem Cohen Tervaert7,
  7. Mårten Segelmark8,
  8. Loic Guillevin2,6,
  9. David Jayne9
  10. On behalf of the European Vasculitis Society
  1. 1Department of Nephrology, AP-HP, Hôpital Européen Georges Pompidou, Paris, France
  2. 2Université Paris Descartes, Paris, France
  3. 3Vasculitis Clinic, Division of Rheumatology, Mount Sinai Hospital, Toronto, Ontario, Canada
  4. 4Department of Nephrology and Hypertension, Center for Internal Medicine and Medical Clinic III, Klinikum Fulda, Fulda, Germany
  5. 5IIIrd Medical Department, Klinikum Offenbach, Offenbach, Germany
  6. 6Department of Internal Medicine, National Referral Center for Rare Autoimmune and Systemic Diseases, AP-HP, Hôpital Cochin, Paris, France
  7. 7Department of Immunology, Maastricht University, Maastricht, The Netherlands
  8. 8Department of Medical and Health Sciences and Department of Nephrology, Linköping University, Linköping, Sweden
  9. 9Department of Medicine, University of Cambridge, Cambridge, UK
  1. Correspondence to Pr Alexandre Karras, Department of Nephrology, AP-HP, Hôpital Européen Georges Pompidou, Paris 75015, France; alexandre.karras{at}egp.aphp.fr

Abstract

Objectives A prospective randomised trial to compare two different durations of maintenance immunosuppressive therapy for the prevention of relapse in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV).

Methods Patients with AAV were recruited 18–24 months after diagnosis if they were in stable remission after cyclophosphamide/prednisolone-based induction followed by azathioprine/prednisolone maintenance therapy. They were randomised (1:1) to receive continued azathioprine/prednisolone to 48 months from diagnosis (continuation group) or to withdraw azathioprine/prednisolone by 24 months (withdrawal group). The primary endpoint was the relapse risk, from randomisation to 48 months from diagnosis.

Results One hundred and seventeen patients were randomised and 110 remained to the trial end. At entry, median serum creatinine was 116 μmol/L (range 58–372), 53% were ANCA positive. The percentage of patients presenting with relapse was higher in the withdrawal than in the continuation treatment group (63% vs 22%, p<0.0001, OR 5.96, 95% CI 2.58 to 13.77). ANCA positivity at randomisation was associated with relapse risk (51% vs 29%, p=0.017, OR 2.57, 95% CI 1.16 to 5.68). Renal function, ANCA specificity, vasculitis type and age were not predictive of relapse. Severe adverse events were more frequent in the continuation than withdrawal groups (nine vs three events), but the continuation group had better renal outcome (0 vs 4 cases of end-stage renal disease), with no difference in patient survival.

Conclusions Prolonged remission maintenance therapy with azathioprine/prednisolone, beyond 24 months after diagnosis reduces relapse risk out to 48 months and improves renal survival in AAV.

Trial registration number ISRCTN13739474

  • ANCA
  • maintenance therapy
  • relapse
  • azathioprine
  • vasculitis

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Footnotes

  • Contributors AK contributed to data collection, data analysis and interpretation, manuscript preparation and review. CP contributed to data generation, collection, analysis and interpretation, manuscript preparation and review. MH contributed to study design and set-up, data generation, analysis and interpretation, manuscript preparation and review. KdG contributed to data generation, analysis and interpretation, manuscript preparation and review. XP contributed to data generation, analysis and interpretation, manuscript preparation and review. JWCT contributed to data generation, analysis and interpretation, manuscript preparation and review. MS contributed to study design and set-up, data generation, analysis and interpretation, manuscript preparation and review. LG contributed to data generation, analysis and interpretation, manuscript preparation and review. DJ contributed to study design and set-up, data generation and collection, analysis and interpretation, manuscript preparation and review.

  • Competing interests AK has received lecture fees from Roche/Genentech. DJ has received research grants and lecture fees from Roche/Genentech. CP has received research grants and lecture fees from Roche/Genentech and advisory board fees from ChemoCentryx and Sanofi.

  • Patient consent Patient.

  • Ethics approval NHS Executive North West MREC, Gateway House, Piccadilly South, Manchester M60 7LP, Reference Number: MREC/00/8/74.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All study data are included in this manuscript.

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