Efficacy and Safety of Rituximab in the Treatment of Good Prognosis Microscopic Polyangiitis
Overview
- Phase
- Phase 3
- Intervention
- Rituximab
- Conditions
- Microscopic Polyangiitis (MPA)
- Sponsor
- Assistance Publique - Hôpitaux de Paris
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Disease free survival rate
- Status
- Active, not recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of the study is to determine wether a rituximab-based treatment compared to standard therapy (glucocorticoid alone) in patients with microscopic polyangiitis without any bad prognosis marker increases the remission and reduces the relapse free survival rate.
Detailed Description
Microscopic polyangiitis (MPA), is a small-sized vessel necrotizing vasculitis associated with anti-neutrophils cytoplasmic antibody (ANCA). Treatment of ANCA associated vasculitis (AAV) was previously based on glucocorticoids (GC) and cyclophosphamide. It has been demonstrated in two prospective randomized trials that rituximab is as effective as cyclophosphamide in the induction treatment of GPA and severe MPA. In addition, it was shown in GPA and MPA that rituximab is superior to azathioprine as maintenance therapy. Patients with MPA without poor prognosis factor (Five factor score (FFS)=0) have not been included in the previous studies and GC alone is considered as the reference treatment in these patients. However, as much as 50% of these patients experience relapses after a 24 months follow-up and only 40% of patients have a long lasting remission. In the group of patients with MPA without any poor prognosis factor (FFS=0), an additional treatment with rituximab might decrease the relapse rate from 40% to 15% after an 18 months' follow-up. The efficacy and safety of this proposal must be tested.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient (male or female) over 18 year old
- •Patient agree to participate in the study and signed written informed consent
- •Patient with MPA according to the CHCC established in 2012
- •Absence of any poor prognosis factor (modified five factor score (FFS) 1996 = 0)
- •Patient with recent onset or relapse of the disease (\<1 month) defined by BVAS \> 0, who did not received any other treatment than glucocorticoids during last month. For patients with a BVAS\<3, activity of vasculitis (either relapse or new onset) has to be confirmed by the coordinating investigator. One to 3 initial glucocorticoids pulse(s) are allowed.
- •Patient with anti-MPO antibody measured by enzyme - linked immunosorbent assay (ELISA).
- •Negative pregnancy test (serum β-hCG) for women of child-bearing potential and a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study and 12 months after stopping therapy
Exclusion Criteria
- •Small-sized vessels vasculitis not associated to anti-MPO antibody or associated with anti-PR3 positivity.
- •Patients with either GPA or EGPA vasculitis according to ACR criteria
- •Patient with a modified FFS 1996 ≥ 1
- •Patient with alveolar hemorrhage requiring mechanical ventilation
- •Patient with previous glucocorticoids treatment \>1 month and \> 10mg/day either for vasculitis or for any other reason.
- •Patient already receiving immunosuppressant or biological agent.
- •Prior treatment with any of the following:
- •azathioprine, methotrexate, mycophenolate mophetil, mycophenolic acid within 4 weeks before inclusion
- •alkylant agent such as cyclophosphamide within 6 months before inclusion
- •anti-TNF inhibitors : infliximab within 8 weeks, adalimumab and etanercept within 2 weeks before inclusion
Arms & Interventions
Rituximab
Experimental regimen: One year Glucocorticoid treatment and Rituximab IV 1 gram on Day 1 and 15
Intervention: Rituximab
Rituximab-Placebo
Standard regimen: One-year Glucocorticoid treatment and Placebo-Rituximab IV on Day 1 and 15
Intervention: placebo
Outcomes
Primary Outcomes
Disease free survival rate
Time Frame: 18 months
Failure free survival in patients with microscopic polyangiitis treated with rituximab and glucocorticoids compared to glucocorticoids alone. * Primary failure: Vasculitis requiring a modification of immunosuppressive treatment or prednisone tapering protocol before M3 * Remission is defined by the absence of sign attributable to vasculitis and a Birmingham Vasculitis Activity Score (BVAS)=0 at M3 * Relapse is defined after visit M3 by a BVAS\>0 or the impossibility to decrease glucocorticoids according to the predefined protocol. Therefore, patients who experience a primary failure or fail to enter remission or relapse will be considered as treatment failure. Death will also be considered as a treatment failure
Secondary Outcomes
- Among patients who relapse, proportion of minor relapses(18 months)
- Quality of life:Short Form Health Survey Questionnaire (SF-36)(18 months)
- Cumulative dose of GC in each group(18 months)
- Among patients who relapse, proportion of major relapses(18 months)
- Proportion of patients who still receive GC at the end of follow-up(18 months)
- Proportion of patients who achieve a complete remission defined by the absence of sign attributable to vasculitis and a BVAS=0(1 month)
- Mortality rate(18 months)
- Severity of sequels linked to vasculitis as(18 months)
- Compare proportion of patients who relapse and time to first relapse(18 months)
- Disability(18 months)
- Number and severity of side effect.(18 months)