Benralizumab Treatment Produces Rapid Changes in Morning Peak Expiratory Flow in Patients With Severe, Uncontrolled Eosinophilic Asthma
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Geoffrey Chupp, MD, Gary T. Ferguson, Ian Hirsch, Mitchell Goldman, James Zangrilli, Frank Trudo
RATIONALE: We evaluated benralizumab’s onset of action by assessing changes in morning PEF following initiation of treatment.

METHODS: We used data for patients aged ≥12 years receiving high-dosage ICS/LABA with baseline blood eosinophils ≥300 cells/µL from the Phase III SIROCCO (48 weeks; Lancet. 2016;388:2115–27) and CALIMA (56 weeks; Lancet. 2016;388:2128–41) trials. Patients received benralizumab 30 mg every 8 weeks (Q8W; first three doses Q4W; SIROCCO, n=267; CALIMA, n=239), or placebo (SIROCCO, n=267; CALIMA, n=248). In this post-hoc analysis, patients’ average weekly changes from baseline in morning PEF were modeled over time by an exponential relationship using a Bayesian nonlinear mixed-effects approach.

RESULTS: Benralizumab Q8W increased mean morning PEF changes from baseline to end of treatment by 22.74 L/min (SIROCCO; 95% CI, 21.25‒24.20) and 23.73 L/min (CALIMA; 95% CI, 22.52‒24.99) vs. placebo. Differences in mean PEF changes from baseline between benralizumab Q8W vs. placebo were observed during the first week (SIROCCO: 14.05 L/min [95% CI, 13.16‒14.96] vs. 7.16 L/min [95% CI, 6.28‒7.99]; and CALIMA: 14.58 L/min [95% CI, 13.71‒15.83] vs. 8.75 L/min [95% CI, 7.91‒9.65]). These differences had increased by subsequent time points. The mean time to achieve a 25-L/min increase in morning PEF with benralizumab Q8W was 20.7 days in SIROCCO (95% CI, 19.3‒22.1) and 20.0 days in CALIMA (95% CI, 18.6‒21.7). A 25-L/min increase was not reached for placebo in both trials.

CONCLUSIONS: Benralizumab Q8W produced rapid and sustained increases in morning PEF in patients with severe, uncontrolled eosinophilic asthma.