MANDARA
Trial question
Is benralizumab noninferior to mepolizumab in patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
60.0% female
40.0% male
N = 140
140 patients (84 female, 56 male).
Inclusion criteria: patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis who were receiving standard care.
Key exclusion criteria: diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis; organ or life-threatening eosinophilic granulomatosis with polyangiitis < 3 months prior to screening; current malignancy; unstable liver disease; severe or clinically significant uncontrolled CVD.
Interventions
N=70 benralizumab (at a dose of 30 mg SC every 4 weeks for 52 weeks).
N=70 mepolizumab (at a dose of 300 mg SC every 4 weeks for 52 weeks).
Primary outcome
Remission at weeks 36 and 48
59.2%
56.5%
59.2 %
44.4 %
29.6 %
14.8 %
0.0 %
Benralizumab
Mepolizumab
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in remission at weeks 36 and 48 (59.2% vs. 56.5%; AD 2.7%, 95% CI -12.5 to 18).
Secondary outcomes
No significant difference in the proportion of patients with remission within the first 24 weeks who remained in remission through week 52 (42% vs. 36%; AD 6%, 95% CI -9 to 20).
Significant increase in the rate of complete withdrawal of oral corticosteroids during weeks 48 through 52 (41.4% vs. 25.8%; AD 15.7%, 95% CI 0.7 to 30.7).
No significant difference in the rate of daily dose of corticosteroid ≤ 4 mg during weeks 48 through 52 (70.4% vs. 69.6%; AD 0.8%, 95% CI -14 to 16).
Safety outcomes
No significant difference in adverse events.
Conclusion
In patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis who were receiving standard care, benralizumab was noninferior to mepolizumab with respect to remission at weeks 36 and 48.
Reference
Michael E Wechsler, Parameswaran Nair, Benjamin Terrier et al. Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2024 Mar 7;390(10):911-921.
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