Evaluate the Remission MAINtenance Using Extended Administration of Prednisone in Systemic Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis.

Condition(s) studied

Investigational drug(s) / intervention(s)

Prednisone 5mg/day extended of 12 additional months: Prednisone 5mg/day orally during 12 Month + 1 mg/week tapering until 0mg.

Placebo 5mg/day extended of 12 additionnal months.: 1mg/week orally tapering Prednisone until Month 1 + Placebo orally 5mg/day until Month 13

Study summary

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.

Eligibility

Primary outcome measure(s)

• Relapse-free survival, relapse being defined as BVAS > 0. — from Screening to Month 30.
  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.

Trial sites (45)

+ 5 more sites — see the full list on the official registry below.

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