title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, National Referral Center for Necrotizing Vasculitides and Systemic Sclerosis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, Paris, France. raphaele.seror@cch.aphp.fr
authors.forename: Raphaèle
authors.initials: R
authors.lastname: Seror
authors.forename: Christian
authors.initials: C
authors.lastname: Pagnoux
authors.forename: Marc
authors.initials: M
authors.lastname: Ruivard
authors.forename: Isabelle
authors.initials: I
authors.lastname: Landru
authors.forename: Denis
authors.initials: D
authors.lastname: Wahl
authors.forename: Sophie
authors.initials: S
authors.lastname: Rivière
authors.forename: Solveig
authors.initials: S
authors.lastname: Aussant
authors.forename: Alfred
authors.initials: A
authors.lastname: Mahr
authors.forename: Pascal
authors.initials: P
authors.lastname: Cohen
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
authors.forename: Loïc
authors.initials: L
authors.lastname: Guillevin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D055953:Microscopic Polyangiitis / Q000188:drug therapy*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide