Benralizumab Treatment Produces Rapid Changes in Morning Peak Expiratory Flow in Patients With Severe, Uncontrolled Eosinophilic Asthma

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.