Geoffrey Chupp1, Njira L Lugogo2, Joel N Kline3, Gary T Ferguson4, Ian Hirsch5, Mitchell Goldman5, James G Zangrilli5, Frank Trudo6. 1. Yale Center for Asthma and Airway Disease, New Haven, Connecticut. Electronic address: geoffrey.chupp@yale.edu. 2. University of Michigan Medical Center, Ann Arbor, Michigan. 3. University of Iowa Carver College of Medicine, Iowa City, Iowa. 4. Pulmonary Research Institute of Southeast Michigan, Farmington Hills, Michigan. 5. AstraZeneca, Gaithersburg, Maryland. 6. AstraZeneca, Wilmington, Delaware.
Abstract
BACKGROUND: Benralizumab is a unique eosinophil-depleting monoclonal antibody that significantly reduces asthma exacerbations, improves lung function and asthma symptoms, and permits the reduction of maintenance oral corticosteroid dosage for patients with severe, uncontrolled eosinophilic asthma. OBJECTIVE: To assess benralizumab's onset of action and efficacy by examining change in morning peak expiratory flow (PEF) after initiation of treatment in the phase 3 clinical trials SIROCCO, CALIMA, and ZONDA. METHODS: Mixed-model repeated-measures analysis was used to calculate PEF using daily least squares mean changes from baseline in morning PEF as well as differences between the benralizumab every 8 weeks (first 3 doses every 4 weeks) and placebo groups. A Bayesian nonlinear mixed-effects approach with an exponential relationship was used to model trial data to determine time to clinically meaningful improvement in morning PEF (defined as ≥25 L/min). RESULTS: Least squares mean morning PEF improvement from baseline was numerically greater by Day 2 after initiation of benralizumab therapy in all 3 trials. The Bayesian nonlinear mixed-effects model indicated that PEF improvement reached the clinically meaningful threshold within 3 weeks in SIROCCO and CALIMA and 2 weeks in ZONDA. CONCLUSION: In 3 phase 3 randomized clinical trials, benralizumab provided notable improvement in morning PEF 2 days after initiation and clinically meaningful improvements within 3 weeks for patients with severe, uncontrolled eosinophilic asthma. The rapid improvement in PEF demonstrated in these trials suggests that benralizumab's unique mechanism of action rapidly improves lung function for patients with severe, eosinophilic asthma. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT01928771 (SIROCCO), NCT01914757 (CALIMA), and NCT02075255 (ZONDA).
BACKGROUND:Benralizumab is a unique eosinophil-depleting monoclonal antibody that significantly reduces asthma exacerbations, improves lung function and asthma symptoms, and permits the reduction of maintenance oral corticosteroid dosage for patients with severe, uncontrolled eosinophilic asthma. OBJECTIVE: To assess benralizumab's onset of action and efficacy by examining change in morning peak expiratory flow (PEF) after initiation of treatment in the phase 3 clinical trials SIROCCO, CALIMA, and ZONDA. METHODS: Mixed-model repeated-measures analysis was used to calculate PEF using daily least squares mean changes from baseline in morning PEF as well as differences between the benralizumab every 8 weeks (first 3 doses every 4 weeks) and placebo groups. A Bayesian nonlinear mixed-effects approach with an exponential relationship was used to model trial data to determine time to clinically meaningful improvement in morning PEF (defined as ≥25 L/min). RESULTS: Least squares mean morning PEF improvement from baseline was numerically greater by Day 2 after initiation of benralizumab therapy in all 3 trials. The Bayesian nonlinear mixed-effects model indicated that PEF improvement reached the clinically meaningful threshold within 3 weeks in SIROCCO and CALIMA and 2 weeks in ZONDA. CONCLUSION: In 3 phase 3 randomized clinical trials, benralizumab provided notable improvement in morning PEF 2 days after initiation and clinically meaningful improvements within 3 weeks for patients with severe, uncontrolled eosinophilic asthma. The rapid improvement in PEF demonstrated in these trials suggests that benralizumab's unique mechanism of action rapidly improves lung function for patients with severe, eosinophilic asthma. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT01928771 (SIROCCO), NCT01914757 (CALIMA), and NCT02075255 (ZONDA).
Authors: Carlos Martínez-Rivera; Ignasi Garcia-Olivé; Blanca Urrutia-Royo; Maria Basagaña-Torrento; Antoni Rosell; Jorge Abad Journal: BMC Pulm Med Date: 2021-01-21 Impact factor: 3.317
Authors: Corrado Pelaia; Maria Teresa Busceti; Alessandro Vatrella; Marco Ciriolo; Eugenio Garofalo; Claudia Crimi; Rosa Terracciano; Nicola Lombardo; Girolamo Pelaia Journal: SAGE Open Med Case Rep Date: 2020-02-16