Systemic Wegener's Granulomatosis
Conditions
Keywords
Wegener's granulomatosis,, microscopic polyangiitis,, ANCA-associated vasculitis,, methotrexate,, azathioprine
Brief summary
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.
Interventions
DRUGAzathioprine: 2 mg/kg/day
DRUGmethotrexate 0.3 mg/kg/week, to a maximum and optimal dose of 25 mg/week
Sponsors
Hospices Civils de Lyon
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged over 18 years-old with newly diagnosed systemic Wegener's granulomatosis, * microscopic polyangitis with at least one factor of poor prognosis according to the five factors score (proteinuria \> 1 g/day, renal insufficiency defined as a serum creatininemia \> 140 µmol/L, specific cardiomyopathy, gastrointestinal tract and/or CNS involvement).
Exclusion criteria
* MPA patients with no poor prognosis factor; * localized WG; * relapse of previously known WG or MPA; * treatment with corticosteroids for more than 1 month prior to diagnosis and start of immunosuppressant; * co-existence of another multi-system autoimmune disease; * malignancy (unless considered in complete remission and with no therapy for at least 3 years); * contra-indication to corticosteroids or study immunosuppressants; pregnancy or no use of contraception in non-menopaused women; * infection with human immunodeficiency virus; mental or physical disturbances not permitting to give consent.
Design outcomes
Primary
| Measure | 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). | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy of induction therapy with pulsed cyclophosphamide. | — |
| Relapse-free survival rate. | — |
| Second evaluation of the same outcome parameters is planned 5 years after the last included patient has completed the assigned trial regimen. | — |
| Cumulative event-free survival rate (adverse event- and relapse-free survival rate). | — |
| Health quality assessment using HAQ and SF36. | — |
Countries
France
Outcome results
None listed