Deoxyspergualin in relapsing and refractory Wegener's granulomatosis.

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 Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status.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
• 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
• Granulomatosis with Polyangiitis (drug therapy)
• Guanidines (therapeutic use)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Male
• Middle Aged
• Prospective Studies
• Recurrence
• Remission Induction
• Treatment Outcome
• Young Adult