Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial.
BACKGROUND: Current therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are limited by toxicity. OBJECTIVE: To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission. DESIGN: Randomized, controlled trial. Random assignments were computer...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2009
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| _version_ | 1797069836947292160 |
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| author | de Groot, K Harper, L Jayne, DR Flores Suarez, L Gregorini, G Gross, W Luqmani, R Pusey, C Rasmussen, N Sinico, R Tesar, V Vanhille, P Westman, K Savage, C |
| author_facet | de Groot, K Harper, L Jayne, DR Flores Suarez, L Gregorini, G Gross, W Luqmani, R Pusey, C Rasmussen, N Sinico, R Tesar, V Vanhille, P Westman, K Savage, C |
| author_sort | de Groot, K |
| collection | OXFORD |
| description | BACKGROUND: Current therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are limited by toxicity. OBJECTIVE: To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission. DESIGN: Randomized, controlled trial. Random assignments were computer-generated; allocation was concealed by faxing centralized treatment assignment to providers at the time of enrollment. Patients, investigators, and assessors of outcomes were not blinded to assignment. SETTING: 42 centers in 12 European countries. PATIENTS: 149 patients who had newly diagnosed generalized ANCA-associated vasculitis with renal involvement but not immediately life-threatening disease. INTERVENTION: Pulse cyclophosphamide, 15 mg/kg every 2 to 3 weeks (76 patients), or daily oral cyclophosphamide, 2 mg/kg per day (73 patients), plus prednisolone. MEASUREMENT: Time to remission (primary outcome); change in renal function, adverse events, and cumulative dose of cyclophosphamide (secondary outcomes). RESULTS: Groups did not differ in time to remission (hazard ratio, 1.098 [95% CI, 0.78 to 1.55]; P = 0.59) or proportion of patients who achieved remission at 9 months (88.1% vs. 87.7%). Thirteen patients in the pulse group and 6 in the daily oral group achieved remission by 9 months and subsequently had relapse. Absolute cumulative cyclophosphamide dose in the daily oral group was greater than that in the pulse group (15.9 g [interquartile range, 11 to 22.5 g] vs. 8.2 g [interquartile range, 5.95 to 10.55 g]; P < 0.001). The pulse group had a lower rate of leukopenia (hazard ratio, 0.41 [CI, 0.23 to 0.71]). LIMITATIONS: The study was not powered to detect a difference in relapse rates between the 2 groups. Duration of follow-up was limited. CONCLUSION: The pulse cyclophosphamide regimen induced remission of ANCA-associated vasculitis as well as the daily oral regimen at a reduced cumulative cyclophosphamide dose and caused fewer cases of leukopenia. PRIMARY FUNDING SOURCE: The European Union. |
| first_indexed | 2024-03-06T22:30:21Z |
| format | Journal article |
| id | oxford-uuid:58117359-4172-45fb-ae0f-42c5d210da29 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:30:21Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:58117359-4172-45fb-ae0f-42c5d210da292022-03-26T17:00:51ZPulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:58117359-4172-45fb-ae0f-42c5d210da29EnglishSymplectic Elements at Oxford2009de Groot, KHarper, LJayne, DRFlores Suarez, LGregorini, GGross, WLuqmani, RPusey, CRasmussen, NSinico, RTesar, VVanhille, PWestman, KSavage, CBACKGROUND: Current therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are limited by toxicity. OBJECTIVE: To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission. DESIGN: Randomized, controlled trial. Random assignments were computer-generated; allocation was concealed by faxing centralized treatment assignment to providers at the time of enrollment. Patients, investigators, and assessors of outcomes were not blinded to assignment. SETTING: 42 centers in 12 European countries. PATIENTS: 149 patients who had newly diagnosed generalized ANCA-associated vasculitis with renal involvement but not immediately life-threatening disease. INTERVENTION: Pulse cyclophosphamide, 15 mg/kg every 2 to 3 weeks (76 patients), or daily oral cyclophosphamide, 2 mg/kg per day (73 patients), plus prednisolone. MEASUREMENT: Time to remission (primary outcome); change in renal function, adverse events, and cumulative dose of cyclophosphamide (secondary outcomes). RESULTS: Groups did not differ in time to remission (hazard ratio, 1.098 [95% CI, 0.78 to 1.55]; P = 0.59) or proportion of patients who achieved remission at 9 months (88.1% vs. 87.7%). Thirteen patients in the pulse group and 6 in the daily oral group achieved remission by 9 months and subsequently had relapse. Absolute cumulative cyclophosphamide dose in the daily oral group was greater than that in the pulse group (15.9 g [interquartile range, 11 to 22.5 g] vs. 8.2 g [interquartile range, 5.95 to 10.55 g]; P < 0.001). The pulse group had a lower rate of leukopenia (hazard ratio, 0.41 [CI, 0.23 to 0.71]). LIMITATIONS: The study was not powered to detect a difference in relapse rates between the 2 groups. Duration of follow-up was limited. CONCLUSION: The pulse cyclophosphamide regimen induced remission of ANCA-associated vasculitis as well as the daily oral regimen at a reduced cumulative cyclophosphamide dose and caused fewer cases of leukopenia. PRIMARY FUNDING SOURCE: The European Union. |
| spellingShingle | de Groot, K Harper, L Jayne, DR Flores Suarez, L Gregorini, G Gross, W Luqmani, R Pusey, C Rasmussen, N Sinico, R Tesar, V Vanhille, P Westman, K Savage, C Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. |
| title | Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. |
| title_full | Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. |
| title_fullStr | Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. |
| title_full_unstemmed | Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. |
| title_short | Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. |
| title_sort | pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody associated vasculitis a randomized trial |
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