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Remission of ANCA-associated vasculitis can be obtained in approximately 80% of the patients with a combination of corticosteroids and cyclophosphamide. However, relapses are frequent. This point warrants the prescription of a maintenance treatment with a less toxic immunosuppressant for several months to years. The optimal drug in this indication is not determine. We decided therefore to compare the 2 most used drugs in this indication. Induction therapy consists in the combination of corticosteroids and intravenous cyclophosphamide pulses. Corticotherapy consisted first in one daily methylprednisolone pulse, for 1 to 3 days, followed by oral prednisolone at the dose of 1 mg/kg/d for 3 weeks, then progressively tapered and stopped at the 18th month from the diagnosis. Cyclophosphamide is administered every 2 weeks for the first 3 bolus (0.6 g/m2 - D1, 15 and 30), then every 3 weeks (0.7 g/m2). Once remission is achieved, patients receive 3 additional bolus (0.7 g/m2). At that time, patients are randomized for a maintenance treatment with azathioprine (2 mg/kg/d, orally) or oral methotrexate (starting at the dose of 0.3 mg/kg/wk, then progressively increased every weeks by 2.5mg, if necessary, to a maximum and optimal dose of 25 mg/wk) for 12 months.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azathioprine: 2 mg/kg/day | Drug | |||
| methotrexate 0.3 mg/kg/week, to a maximum and optimal dose of 25 mg/week | Drug |
| Measure | Description | Time Frame |
|---|---|---|
| Safety/Efficacy | ||
| Frequency of severe adverse events in each arm. Hypothesis based upon NIH data was a rate of 6% severe adverse event with methotrexate compared to 30% with azathioprine (24% in one study on RA and 46% in one study on Sjögren syndrome). | ||
| Evaluation was planned after the last included patient has completed the assigned trial regimen (after 12 months of maintenance regimen or because of drug withdrawal). |
| Measure | Description | Time Frame |
|---|---|---|
| Relapse-free survival rate. | ||
| Cumulative event-free survival rate (adverse event- and relapse-free survival rate). | ||
| Health quality assessment using HAQ and SF36. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jean-François CORDIER, MD | Hospices Civils de Lyon | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Christian PAGNOUX | Paris | 75 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19109574 | Derived | Pagnoux C, Mahr A, Hamidou MA, Boffa JJ, Ruivard M, Ducroix JP, Kyndt X, Lifermann F, Papo T, Lambert M, Le Noach J, Khellaf M, Merrien D, Puechal X, Vinzio S, Cohen P, Mouthon L, Cordier JF, Guillevin L; French Vasculitis Study Group. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008 Dec 25;359(26):2790-803. doi: 10.1056/NEJMoa0802311. |
| Label | URL |
|---|---|
| Related Info | View source |
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| Efficacy of induction therapy with pulsed cyclophosphamide. |
| Second evaluation of the same outcome parameters is planned 5 years after the last included patient has completed the assigned trial regimen. |
| ID | Term |
|---|---|
| D014890 | Granulomatosis with Polyangiitis |
| D055953 | Microscopic Polyangiitis |
| D056648 | Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis |
| ID | Term |
|---|---|
| D017563 | Lung Diseases, Interstitial |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D056647 | Systemic Vasculitis |
| D014657 | Vasculitis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D059345 | Cerebral Small Vessel Diseases |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D001379 | Azathioprine |
| D008727 | Methotrexate |
| ID | Term |
|---|---|
| D013872 | Thionucleosides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D015122 | Mercaptopurine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
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