| Abstract | OBJECTIVES: 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 Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status.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 | O Flossmann, B Baslund, A Bruchfeld, J W Cohen Tervaert, C Hall, P Heinzel, B Hellmich, R A Luqmani, K Nemoto, V Tesar, D R W Jayne
(Affiliation: Vasculitis Unit, Addenbrooke's Hospital, Cambridge, UK. oflossmann at doctors.org.uk)
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| Journal | Annals of the rheumatic diseases
(Ann Rheum Dis)
Vol. 68
Issue 7
Pg. 1125-30
(Jul 2009)
ISSN: 1468-2060 [Electronic] England |
| PMID | 18713783
(Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Guanidines
- Immunosuppressive Agents
- gusperimus
|
| Topics |
- Adult
- Aged
- Female
- Guanidines
(therapeutic use)
- Humans
- Immunosuppressive Agents
(therapeutic use)
- Male
- Middle Aged
- Prospective Studies
- Recurrence
- Remission Induction
- Treatment Outcome
- Wegener Granulomatosis
(drug therapy)
- Young Adult
|
