An interventional study of Prednisone 5mg/day extended of 12 additional months and Placebo 5mg/day extended of 12 additionnal months. in Granulomatosis With Polyangitis, sponsored by Hospices Civils de Lyon. Recruiting at 45 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-09-15.
Sponsored by Hospices Civils de Lyon · Not applicable, Interventional, and Prevention
Immunosuppressive therapy of granulomatosis with polyangiitis (GPA, Wegener's) and microscopic polyangiitis (MPA) has transformed the outcome from death to a strong likelihood of disease control and temporary remission. However, most patients have recurrent relapses that lead to damage and require repeated treatment associated with long-term morbidity and death.
Rituximab has been shown to be as effective as cyclophosphamide to induce remission and maintenance of remission in severe GPA and MPA patients, with an acceptable safety profile . Although rituximab is becoming the standard of care for maintenance therapy in these patients, relapse still occurs and the optimal duration of prednisone therapy remains debated.
On the one hand, most US studies use early withdrawal (6-12 months) because of feared side effects. On the other hand, most European trials propose late withdrawal (>18 months) given a lower observed relapse rate on long-term low dose glucocorticoids treatment.
In a systematic review and meta-analysis, glucocorticoids regimen was the most significant variable explaining the variability between the proportions of ANCA-associated vasculitis patients with relapses. Nevertheless, it was an indirect estimation of treatment effect because of the absence of dedicated randomized trial. This meta-analysis concluded that combined longer-term (i.e. >12 months) use of low dose prednisone or nonzero glucocorticoids target is associated with a 20% reduction of relapse compared to early withdrawal (i.e. ≤12 months).
The relapse rate in patients with early glucocorticoids (10-12 months) withdrawal was provided in two studies and was of 37 and 34%, respectively. By contrast, the relapse rate in patients with late prednisone withdrawal (18-24 months) and receiving rituximab as maintenance treatment was 14% at 24 months in the MAINRITSAN trial. Of note, the decision to withdraw glucocorticoids after 18 months was left to physician's discretion in this study and two thirds of the nonsevere relapses occurred when patients were off prednisone.
The trial detailed here is the first prospective trial evaluating the length of glucocorticoid administration as remission adjunctive treatment for patients with GPA or MPA.
Immunosuppressive therapy of granulomatosis with polyangiitis (GPA, Wegener's) and microscopic polyangiitis (MPA) has transformed the outcome from death to a strong likelihood of disease control and temporary remission. However, most patients have recurrent relapses that lead to damage and require repeated treatment associated with long-term morbidity and death.
Rituximab has been shown to be as effective as cyclophosphamide to induce remission and maintenance of remission in severe GPA and MPA patients, with an acceptable safety profile. Although rituximab is becoming the standard of care for maintenance therapy in these patients, relapse still occurs and the optimal duration of prednisone therapy remains debated.
On the one hand, most US studies use early withdrawal (6-12 months) because of feared side effects. On the other hand, most European trials propose late withdrawal (>18 months) given a lower observed relapse rate on long-term low dose glucocorticoids treatment.
In a systematic review and meta-analysis, glucocorticoids regimen was the most significant variable explaining the variability between the proportions of ANCA-associated vasculitis patients with relapses. Nevertheless, it was an indirect estimation of treatment effect because of the absence of dedicated randomized trial. This meta-analysis concluded that combined longer-term (i.e. >12 months) use of low dose prednisone or nonzero glucocorticoids target is associated with a 20% reduction of relapse compared to early withdrawal (i.e. ≤12 months).
The relapse rate in patients with early glucocorticoids (10-12 months) withdrawal was provided in two studies and was of 37 and 34%, respectively. By contrast, the relapse rate in patients with late prednisone withdrawal (18-24 months) and receiving rituximab as maintenance treatment was 14% at 24 months in the MAINRITSAN trial. Of note, the decision to withdraw glucocorticoids after 18 months was left to physician's discretion in this study and two thirds of the nonsevere relapses occurred when patients were off prednisone.
The trial detailed here is the first prospective trial evaluating the length of glucocorticoid administration as remission adjunctive treatment for patients with GPA or MPA.
Exclusion Criteria:
Prednisone 5mg/day will be administered from Day 1 to Month 12
Drug: Prednisone 5mg/day extended of 12 additional months
Placebo 5mg/day will be administered from Day 1 to Month 12
Drug: Placebo 5mg/day extended of 12 additionnal months.
Prednisone 5mg/day orally during 12 Month + 1 mg/week tapering until 0mg.
1mg/week orally tapering Prednisone until Month 1 + Placebo orally 5mg/day until Month 13
Relapse-free survival, relapse being defined as BVAS > 0.
rate of relapse-free survival of patients continuing low-dose prednisone treatment until Month 10 VS those who will have prednisone treatment cessation at Month 1, on remission maintenance with Rituximab therapy, after achievement of remission of GPA or MPA, defined as a survival of patients maintaining a BVAS=0 at Month 30, in patient with newly-diagnosed or relapsing GPA or MPA and who will all have received glucocorticoids for 12 months after diagnosis or last flare before inclusion.
Time frame: from Screening to Month 30.
Compare the rate of serious adverse events between Inclusion and Month 30 after randomization
Proportion of patients with at least one adverse event between inclusion and Month 30. * Percentage of patients with at least one serious adverse event between inclusion and Month 30, corresponding to any adverse event that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity or congenital anomaly/birth defect or any other adverse event considered "medically significant". * Number of deaths, whatever the cause at Month 30.
Time frame: from Day 1 to Month 30
Compare the rate of predefined severe events related to glucocorticoids between inclusion and Month 30 including osteoporotic fracture and weight gain.
Percentage of patients with at least one predefined severe event corresponding to adverse events of grade 3 to 5 of the Common Terminology Criteria, including severe side effect related to glucocorticoids (infection requiring hospitalization or intravenous antibiotics, osteoporotic fracture, diabetes requiring medication, cardiovascular event, symptomatic osteonecrosis, psychiatric or mood disorder requiring drug administration, weight gain \>10 kg) between inclusion and Month 30 \- Weight gain between inclusion and Month 30
Time frame: From Screening to Month 30
To compare the rate of vasculitis relapse at Month 30
Proportion of patients with minor or major vasculitis relapse between inclusion and Month 30 (BVAS \>0) and time to first vasculitis relapse
Time frame: from Day 1 to Month 30
To compare the prednisone use between inclusion and Month 30
Prednisone area under the curve of administrated dose between inclusion and Month 30
Time frame: from screening to Month 30
To compare variation of the Bone mineral density and markers between inclusion and Month 30
Variation of the Bone mineral density between inclusion and Month 30 \- Variation of the Bone markers including C-terminal crosslinked telopeptide of type I collagen (CTX) and serum procollagen type 1 amino-terminal propeptide (P1NP) between inclusion and Month 30
Time frame: From Screening to Month 30
To compare sequelae assessed by BVAS (vasculitis activity) at 30 months
BVAS (vasculitis activity) at 30 months \- Variation of BVAS (Vasculitis activity)
Time frame: From Screening to Month 30.
To compare sequelae assessed by the Vasculitis Damage Index (VDI) at 30 months
* Vasculitis Damage Index at 30 months * Variation of VDI,
Time frame: From screening to Month 30.
- To compare sequelae assessed by Combined Damage Assessment Index (CDA) at 30 months
* Combined Damage Assessment Index at 30 months * Variation of CDA (damage),
Time frame: From Screening to Month 30.
- To compare functional disability at Month 30 after randomization (Day 1) in both arms
Variation of HAQ (disability) between inclusion and at Month 30
Time frame: From Day 1 to Month 30.
To compare quality of life at Month 30 after randomization (Day 1) in both arms
\- Variation of SF-36 (quality of life) between inclusion and at Month 30
Time frame: - From Day 1 to Month 30.
- To compare healthcare resource utilization at Month 30 after randomization (Day 1) in both arms
\- Healthcare resource utilization between inclusion and Month 30 being defined as the percentage of patients being hospitalized at least once except only for rituximab infusions
Time frame: From Day 1 to Month 30.
Plan to share: No
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Hospices Civils de Lyon