CLINICAL AND EPIDEMIOLOGICAL RESEARCH

Deoxyspergualin in relapsing and refractory Wegener’s granulomatosis

O Flossmann¹, B Baslund², A Bruchfeld³, J W Cohen Tervaert⁴, C Hall⁷, P Heinzel⁵, B Hellmich⁶, R A Luqmani⁷, K Nemoto⁵, V Tesar⁸, D R W Jayne¹

¹ Vasculitis Unit, Addenbrooke’s Hospital, Cambridge, UK
² Rheumatology Clinic, Rigshospitalet, Copenhagen, Denmark
³ Department of Nephrology, Karolinska University Hospital at Huddinge, Stockholm, Sweden
⁴ Department of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands
⁵ Euro Nippon Kayaku GmbH, Frankfurt/Main, Germany
⁶ Department of Rheumatology, University Hospital Schleswig-Holstein, Lübeck, Germany
⁷ Rheumatic Diseases Unit, Western General Hospital, Edinburgh, UK
⁸ Department of Nephrology, General Faculty Hospital, Prague, Czech Republic

Dr O Flossmann, Box 118, Vasculitis Unit, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK; oflossmann{at}doctors.org.uk

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) 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 Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status.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/mm³. 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 ( 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.

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