ATS 2017. A4678 - Benralizumab Significantly Reduced Oral Corticosteroid Dosages and Asthma Exacerbation Rates for Patients with Severe, Uncontrolled Asthma: Results of the ZONDA Phase III Trial
P. Nair, MD, PhD, FRCP, FRCPC (Hamilton, ON, Canada) S. E. Wenzel, MD (Pittsburgh, PA, United States of America) K. Rabe, MD, PhD, FERS (Großhansdorf, Germany) A. Bourdin, MD (Montpellier, France) N. Lugogo, MD (Durham, NC, United States of America) P. Kuna, MD, PhD (Łódź, Poland) P. Barker, PhD (Gaithersburg, MD, United States of America) S. Sproule, PhD (Gaithersburg, MD, United States of America) S. Ponnarambil, MD (Cambridge, United Kingdom) M. Goldman, MD, PhD (Gaithersburg, MD, United States of America)
Results: Of 220 patients who were randomized and received treatment, 207 (94.1%) completed treatment. Benralizumab significantly reduced final OCS dosages by a median of 75% with the Q4W and Q8W regimens (p<0.001) compared with placebo (25%; table). The odds of a reduction in OCS dosage were 4.09-times greater (Q4W; p<0.001) and 4.12-times greater (Q8W; p<0.001) than with placebo. Benralizumab also significantly reduced annual asthma exacerbation rates by 55% (Q4W; p=0.003) and 70% (Q8W; p<0.001) vs. placebo, despite reduction in OCS dosages in the active treatment groups (table). Adverse events were numerically lower for the benralizumab Q4W and Q8W groups vs. placebo (68.1% and 75.3% vs. 82.7%, respectively).
Conclusion: Benralizumab was well-tolerated and demonstrated significant, clinically relevant OCS-sparing benefits and asthma exacerbation rate reduction compared with placebo.
CARE FACULTY PERSPECTIVE
In this largest study to date of prednisone-dependent patients, benralizumab administered in dose of 30 mg SC every 8 weeks allowed the dose of prednisone to be reduced by up to 75% while still reducing exacerbations by 70% and preserving FEV1. The odds of reducing prednisone was more than four-fold compared to placebo. The magnitude of treatment effect was more than previously reported with mepolizumab. It remains to be seen if the unique mechanism of action of antibody-dependent cytotoxic killing of eosinophils that express the IL-5 receptor leads to any long-term harmful consequences.
Provided by: Dr. Parameswaran Nair
CARE Respirology Faculty
Professor of Medicine, McMaster University
Staff Respirologist, St. Joseph’s Healthcare Hamilton