title: Deoxyspergualin in relapsing and refractory Wegener's granulomatosis.
abstract: OBJECTIVE
  Conventional therapy of Wegener's granulomatosis with cyclophosphamide and corticosteroids is limited by incomplete remissions and a high relapse rate. The efficacy and safety of an alternative immunosuppressive drug, deoxyspergualin, was evaluated in patients with relapsing or refractory disease.
  
  
  METHODS
  A prospective, international, multicentre, single-limb, open-label study. Entry required active Wegener's granulomatosis with a Birmingham vasculitis activity score (BVAS) > or =4 and previous therapy with cyclophosphamide or methotrexate. Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status. Deoxyspergualin, 0.5 mg/kg per day, was self-administered by subcutaneous injection in six cycles of 21 days with a 7-day washout between cycles. Cycles were stopped early for white blood count less than 4000 cells/mm(3). The primary endpoint was complete remission (BVAS 0 for at least 2 months) or partial remission (BVAS <50% of entry score). After the sixth cycle azathioprine was commenced and follow-up continued for 6 months.
  
  
  RESULTS
  42/44 patients (95%) achieved at least partial remission and 20/44 (45%) achieved complete remission. BVAS fell from 12 (4-25), median (range) at baseline to 2 (0-14) at the end of the study (p<0.001). Prednisolone doses were reduced from 20 to 8 mg/day (p<0.001). Relapses occurred in 18 (43%) patients after a median of 170 (44-316) days after achieving remission. Severe or life-threatening (> or = grade 3) treatment-related adverse events occurred in 24 (53%) patients mostly due to leucopaenias.
  
  
  CONCLUSIONS
  Deoxyspergualin achieved a high rate of disease remission and permitted prednisolone reduction in refractory or relapsing Wegener's granulomatosis. Adverse events were common but rarely led to treatment discontinuation.
authors: Vasculitis Unit, Addenbrooke's Hospital, Cambridge, UK. oflossmann@doctors.org.uk
authors: O
authors: O
authors: Flossmann
authors: B
authors: B
authors: Baslund
authors: A
authors: A
authors: Bruchfeld
authors: J W Cohen
authors: JW
authors: Tervaert
authors: C
authors: C
authors: Hall
authors: P
authors: P
authors: Heinzel
authors: B
authors: B
authors: Hellmich
authors: R A
authors: RA
authors: Luqmani
authors: K
authors: K
authors: Nemoto
authors: V
authors: V
authors: Tesar
authors: D R W
authors: DR
authors: Jayne
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy*; D006146:Guanidines / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006146:Guanidines; D007166:Immunosuppressive Agents; C037258:gusperimus