Seasonal variability of exacerbations of severe, uncontrolled eosinophilic asthma and clinical benefits of benralizumab.

DuBuske, Lawrence; Newbold, Paul; Yanping Wu; Trudo, Frank

Background: Benralizumab is a humanized, afucosylated, monoclonal antibody that targets interleukin-5 receptor alpha id induces direct, rapid, and nearly complete depletion of eosinophils via enhanced antibody-dependent v-me ted cytotoxicity. In the United States, benralizumab is indicated for add-on maintenance treatment of patients >12 years old with severe asthma and an eosinophilic phenotype. Objective: This study evaluated the effect of benralizumab treatment on seasonal ast a exaceri on ra. for patients with severe, uncontrolled asthma. Methods: This was a post hoc analysis of pooled data from the phase III SIROCCO (ClinicalTrials.gov identifier: NCT01928771) and CALIMA (NCT01914757) trials. The primary analysis population was patients ages 12-75 years treated with high-dosage inhaled corticosteroids and long-acting beta-2 agonist ho had baseline blood eosinophil counts of >300 cells/yL. Patients received benralizumab 30 mg subcutaneously every 4 weeks or every 8 weeks (the first three doses every 4 weeks) or placebo every 4 weeks. Crude exacerbation rates (asthma exacerbations per patient-year) were determined for each month and season. Marginal asthma exacerbation rates and exacerbation rate ratios were estimated by season or month by using a negative binomial model that included covariates for study code, treatment, region, use ofmaintenance oral corticosteroids, and number of exacerbations in the previous year. H,cisp, c seasons were accounted for by normalizing the study site locations. Results: Observed crude exacerbation rates were higher in the fall and winter than in the spring and summer for all the patients. For the patients who received placebo, benralizumab every 4 weeks, and benralizumab every 8 weeks, crude exacerbation rates were the following: fall, 1.52, 0.86, and 0.81, respectively; winter, 1.44, 0.91, and 0.82, respectively; spring, 1.11, 0.66, and 0.52, respectively; and summer, 1.02, 0.55, and 0.51, respectively. Rate reductions in seasonal marginal annual exacerbation rates were 37-50% versus 1acebo at each season (p < 0.001). Conclusion: Benralizumab significantly and consistently reduced asthma exacerbations across all seasons versus placebo for patients with severe, uncontrolled eosinophilic asthma.

DISEASE exacerbation; EOSINOPHILIA; ASTHMA treatment; THERAPEUTIC use of monoclonal antibodies; ADRENOCORTICAL hormones

Allergy & Asthma Proceedings, 2018, Vol 39, Issue 5, p345

1088-5412

Academic Journal

10.2500/aap.2018.39.4162