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Treatment strategies and outcome of induction-refractory Wegener's granulomatosis or microscopic polyangiitis: analysis of 32 patients with first-line induction-refractory disease in the WEGENT trial
  1. Raphaèle Seror1,
  2. Christian Pagnoux1,
  3. Marc Ruivard2,
  4. Isabelle Landru3,
  5. Denis Wahl4,
  6. Sophie Rivière5,
  7. Solveig Aussant6,
  8. Alfred Mahr1,
  9. Pascal Cohen1,
  10. Luc Mouthon1,
  11. Loïc Guillevin1,
  12. for the French Vasculitis Study Group
  1. 1Department of Internal Medicine, National Referral Center for Necrotizing Vasculitides and Systemic Sclerosis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, Paris, France
  2. 2Department of Internal Medicine A, Centre Hospitalier-Universitaire de Clermont-Ferrand, Hopital Hôtel-Dieu, Clermont-Ferrand, France
  3. 3Department of Nephrology, Centre Hospitalier Robert-Bisson, Lisieux, France
  4. 4Departement of Vascular Medicine, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-lès-Nancy, France
  5. 5Department of Internal Medicine, Hôpital Saint-Eloi, Montpellier, France
  6. 6Department of Internal Medicine, Centre Hospitalier Robert-Bisson, Lisieux, France
  1. Correspondence to Dr Raphaèle Seror, Department of Internal Medicine, Hôpital Cochin, 27, rue du faubourg Saint-Jacques, 75679 Paris Cedex 14, France; raphaele.seror{at}cch.aphp.fr

Abstract

Objectives To study the efficacy of rescue treatment strategies and outcomes in patients with Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) not achieving remission with first-line induction with corticosteroids (CS) and intravenous cyclophosphamide (CYC).

Methods 159 eligible patients in the Wegener's Granulomatosis-Entretien (WEGENT) trial newly diagnosed with systemic or renal WG or MPA with ≥1 poor prognosis factors were included in this prospective study. Rescue treatment strategies and outcomes in patients with induction-refractory disease were analysed and patient characteristics at diagnosis were compared with those of induction-responders.

Results Most patients (n=126, 79.2%) achieved remission; 1 stopped induction because of allergy and 32 were induction-refractory (24 WG and 8 MPA); 11 died rapidly within a median of 2.5 months, 6 of uncontrolled disease, 1 of an infectious complication and 4 of both. Treatment was discontinued in 1 patient with MPA with end-stage renal disease. Induction was switched to oral CYC in 20 patients, combined with infliximab in 1; 15 (75%) achieved remission or low disease activity state, 3 subsequently died of uncontrolled disease and 2 entered remission using several other agents including biological agents. Alveolar haemorrhage and a creatinine level >200 μmol/l were independently associated with induction-refractory disease. Among patients with induction-refractory disease, massive alveolar haemorrhage was associated with higher mortality.

Conclusion Switching to oral CYC can be an effective rescue treatment for patients with systemic forms of WG or MPA who fail to achieve remission with first-line CS and intravenous CYC. However, a more rapidly effective regimen remains to be identified for most severely affected patients whose outcomes can be rapidly fatal.

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Footnotes

  • Competing interests All the authors were employees of the Assistance Publique–Hôpitaux de Paris or their respective hospitals at the time the study was conducted and the article was written. No funding or grants from pharmaceutical or commercial companies were received in relation with this study.

  • Ethics approval This study was conducted with ethical committee approval for the WEGENT trial.

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

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