Granulomatosis With Polyangitis Clinical Trial
Official title:
A Prospective, Multicentric, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Remission MAINtenance Using Extended Administration of Prednisone in Systemic Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis.
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.
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