Rituximab in Eosinophilic Granulomatosis With Polyangiitis
Rituximab in Eosinophilic Granulomatosis With Polyangiitis
Phase III, comparative, multicenter, randomized, controlled, double-blind and superiority
 research, comparing rituximab-based regimen with conventional therapeutic strategy for the
 induction of remission in patients with eosinophilic granulomatosis with polyangiitis (EGPA).

 Patients with newly diagnosed or relapsing EGPA will be randomized in a 1:1 ratio to receive:

 -  Experimental therapeutic strategy based on the use of rituximab (experimental group)

 -  Conventional therapeutic strategy based on Five-Factor Score (FFS)-assessed disease
 severity (comparative group)
Systemic vasculitides are inflammatory diseases of blood vessels, among which anti-neutrophil
 cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are often severe with
 life-threatening manifestations or complications. AAV include granulomatosis with
 polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with
 polyangiitis (EGPA, formerly Churg-Strauss syndrome).

 Cytotoxic drugs and glucocorticoids have been the standard of care for remission induction
 for nearly five decades. This regimen improved the outcome of severe AAV from death to a
 strong likelihood of disease control and temporary remission. However, a remission is not
 obtained in all patients with this combination of drugs, and most patients experience disease
 flares requiring repeated treatment with associated significant morbidity and mortality.

 In 2 prospective controlled trials, rituximab, an anti-CD20 monoclonal antibody, was shown to
 be non inferior to cyclophosphamide to induce remission with an acceptable safety profile in
 patients with systemic GPA and MPA. However, patients with EGPA were not included in these
 trials and rituximab has not been evaluated prospectively to induce remission in this disease
 which pathogenesis is complex and not only restricted to ANCA responsibility.

 In patients with EGPA, overall survival is good when treatment is stratified according to
 prognostic factors (Five Factor Score) but long-term outcome is not so good since relapses
 occur in more than 40% of patients, leading to high cumulative morbidity and damage. In small
 retrospective studies, rituximab seems promising as a remission-induction agent in patients
 with EGPA, independently from the ANCA status.

 The trial detailed here is the first prospective trial evaluating rituximab as
 induction-remission treatment for EGPA.
Inclusion Criteria:

 -  Patients with a diagnosis of EGPA independently of ANCA status,

 -  Patient 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) ,

 -  Patient able to give written informed consent prior to participation in the study.

 Exclusion Criteria:

 -  Patients with GPA, MPA, or other vasculitides, 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 Assocation

 -  Patients with acute infections or chronic active infections (including HIV, HBV or
 HCV),

 -  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 rituximab within the previous 12
 months,

 -  Patients with hypersensitivity to a monoclonal antibody or biologic agent,

 -  Patients with contraindication to use rituximab, cyclophosphamide, mesna or
 azathioprine,

 -  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.