Deoxyspergualin in relapsing and refractory Wegener's granulomatosis.
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 ref...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2009
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| _version_ | 1826270714525646848 |
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| author | Flossmann, O Baslund, B Bruchfeld, A Tervaert, J Hall, C Heinzel, P Hellmich, B Luqmani, R Nemoto, K Tesar, V Jayne, DR |
| author_facet | Flossmann, O Baslund, B Bruchfeld, A Tervaert, J Hall, C Heinzel, P Hellmich, B Luqmani, R Nemoto, K Tesar, V Jayne, DR |
| author_sort | Flossmann, O |
| collection | OXFORD |
| description | 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 Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status.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. |
| first_indexed | 2024-03-06T21:45:10Z |
| format | Journal article |
| id | oxford-uuid:4952e57b-43b2-4aa7-8960-b07a5892553e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:45:10Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:4952e57b-43b2-4aa7-8960-b07a5892553e2022-03-26T15:30:55ZDeoxyspergualin in relapsing and refractory Wegener's granulomatosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4952e57b-43b2-4aa7-8960-b07a5892553eEnglishSymplectic Elements at Oxford2009Flossmann, OBaslund, BBruchfeld, ATervaert, JHall, CHeinzel, PHellmich, BLuqmani, RNemoto, KTesar, VJayne, DR 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. |
| spellingShingle | Flossmann, O Baslund, B Bruchfeld, A Tervaert, J Hall, C Heinzel, P Hellmich, B Luqmani, R Nemoto, K Tesar, V Jayne, DR Deoxyspergualin in relapsing and refractory Wegener's granulomatosis. |
| title | Deoxyspergualin in relapsing and refractory Wegener's granulomatosis. |
| title_full | Deoxyspergualin in relapsing and refractory Wegener's granulomatosis. |
| title_fullStr | Deoxyspergualin in relapsing and refractory Wegener's granulomatosis. |
| title_full_unstemmed | Deoxyspergualin in relapsing and refractory Wegener's granulomatosis. |
| title_short | Deoxyspergualin in relapsing and refractory Wegener's granulomatosis. |
| title_sort | deoxyspergualin in relapsing and refractory wegener s granulomatosis |
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