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, multi-centre, 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 Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status.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, 0.5mg/kg/day, was self-administered by subcutaneous injection in six cycles of 21 days with a seven day washout between cycles. Cycles were stopped early for white blood count < 4,000/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 six 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 study (p<0.001). Prednisolone doses were reduced from 20 to 8mg/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 leukopaenias.
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 lead to treatment discontinuation.