Inclusion Criteria:

• - Patients with a diagnosis of EGPA independently of ANCA status, - Patients aged of 18 years or older, - Patients with newly-diagnosed disease or relapsing disease at the time of screening, with an active disease defined as a Birmingham Vasculitis Activity Score (BVAS) ≥3, - Patients within the first 21 days following initiation/increase of corticosteroids at a dose ≤ 1 mg/kg/day (pulses of methylprednisolone before oral corticosteroid therapy are authorized) - Patients having given their written informed consent prior to participation in the study.

• - Patients affiliated with social security or CMU (profit or being entitled)

  Exclusion Criteria:

  - Patients with GPA, MPA, or other vasculitis, defined by the ACR criteria and/or the Chapel Hill Consensus Conference, - Patients with vasculitis in remission of the disease defined as a BVAS <3.

• - Patients with severe cardiac failure defined as class IV in New York Heart Association.

• - Patients with acute infections or chronic active infections (including HIV, HBV or HCV and checked in the last 12 months), - Patients with active cancer or recent cancer (<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment, - Pregnant women and lactation.

Patients with childbearing potential should have reliable contraception for the 12 months duration of the study,

• - Patients with EGPA who have already been treated with mepolizumab within the previous 12 months, - Patients with hypersensitivity to a monoclonal antibody or biologic agent, - Patients with contraindication to use mepolizumab, cyclophosphamide, mesna, azathioprine or maintenance therapy used for vasculitis, - Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases, that could interfere with participation in the trial according to the protocol, - Patients included in other investigational therapeutic study within the previous 3 months, - Patients suspected not to be observant to the proposed treatments, - Patients who have white blood cell count ≤4,000/mm3, - Patients who have platelet count ≤100,000/mm3, - Patients who have ALT or AST level greater that 3 times the upper limit of normal that cannot be attributed to underlying EGPA disease, - Patients unable to give written informed consent prior to participation in the study.

• - Patients under tutorship or curatorship and protected adults.

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly called Churg-Strauss syndrome, is a rare systemic small-vessel vasculitis, associated with asthma and blood and tissue eosinophilia. EGPA belongs to the group of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), and commonly involves upper and lower respiratory tracts, the lungs, the peripheral nerve and the heart. Therapeutic management is based on glucocorticoids alone or in combination with conventional immunosuppressive agents, mainly azathioprine, methotrexate or cyclophosphamide, according to disease severity assessed by the Five Factor Score. Such treatments, in addition to their common side effects, are frequently insufficiently effective to control chronic asthma and/or rhinosinusitis, requiring long-term high-dose corticosteroids. Because EGPA shares common pathophysiological features with eosinophilic disorders and asthma, new therapeutic options used in these conditions could be of interest, in particular mepolizumab, a monoclonal anti-interleukin (IL)-5 antibody, which has shown promising results in two small preliminary studies to control disease activity and decrease glucocorticoids in cortico-dependant patients. In addition, mepolizumab has been recently evaluated in a prospective trial, the MIRRA trial, targeting a small niche of patients, i.e. those with corticodependent asthma unable to achieve disease control with low dose of glucocorticoids. Results published revealed that mepolizumab led to significantly more accrued weeks of remission than placebo (28% vs.#46; 3% of the participants had ≥24 weeks of accrued remission; odds ratio, 5.91; 95% confidence interval [CI], 2.68 to 13.03; P<0.001) and a higher percentage of participants in remission at both week 36 and week 48 (32% vs.#46; 3%; odds ratio, 16.74; 95% CI, 3.61 to 77.56; P<0.001). However, these studies did not evaluate the interest of mepolizumab during EGPA flare associating asthma, eosinophilic and vasculitis lesions, in order to induce remission of the disease and rapidly decrease and discontinue glucocorticoids. Also, recent pathophysiological date strongly support in addition to previous therapeutic studies the major interest to target IL-5 as soon as EGPA is diagnosed: 1) genetic association studies demonstrated that polymorphisms in the IL-5 pathway are associated with EGPA in comparison with controls, 2) increased expression of IL-5 in mice model are able to induce vasculitis lesions as observed in the human diseases. Patients will receive a standardized glucocorticoid tapering schedule. From day 28 post-baseline onwards, if the subject's BVAS=0 their oral prednisone dose should be tapered downwards. A standardized glucocorticoid tapering schedule provided in the protocol enables a reduction in oral prednisone dose every 2 weeks, with the intention of achieving a prednisone dose of 4 mg/day or less. Once a subject has achieved a dose of 4 mg/day prednisone, the investigator is encouraged to continue tapering downwards, if clinically warranted, at dose increments of 1.0 mg every week. Upwards dose adjustments within the 0-4.0 mg range are permitted without necessarily being considered a relapse.

Arms

Experimental: Patients with FFS=0 - Mepolizumab

Mepolizumab 300mg every 4 weeks until D336

Placebo Comparator: Patients with FFS=0 - Placebo

Placebo of Mepolizumab every 4 weeks until D336

Experimental: Patients with FFS≥1 - Mepolizumab

Mepolizumab 300mg every 4 weeks until D336 and placebo of Azathioprine 1mg/kg/day from D126 until D360 and placebo of cyclophosphamide/mesna at D1, D15, D28, D56, D84 and D112

Placebo Comparator: Patients with FFS≥1 - Placebo

Placebo of Mepolizumab every 4 weeks until D336, cyclophosphamide and mesna at D1, D15, D28, D56, D84 and D112 and Azathioprine 1mg/kg/day from D126 until D360

Interventions

Drug: - Mepolizumab

300 mg/month subcutaneous

Drug: - cyclophosphamide/azathioprine

Patients with FFS≥1 will receive cyclophosphamide then azathioprine

Drug: - Placebo

Patients with FFS=0 will receive placebo