Original Contribution A randomized trial of benralizumab, an antiinterleukin 5 receptor α monoclonal antibody, after acute asthma☆ , ☆☆ ,★,★★, ☆☆☆ Richard M. Nowak, MD a , Joseph M. Parker, MD b, ⁎, Robert A. Silverman, MD c , Brian H. Rowe, MD, MSc d , Howard Smithline, MD e , Faiz Khan, MD f, 1 , Jon P. Fiening, MS g , Keunpyo Kim, PhD h , Nestor A. Molfino, MD, MSc i, 2 a Clinical Trial Center, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, USA b Clinical Development, MedImmune, One MedImmune Way, Gaithersburg, MD, USA c Department of Emergency Medicine, North Shore–Long Island Jewish Medical Center, 270-05 76th Ave New Hyde Park, NY, USA d Department of Emergency Medicine and School of Public Health, University of Alberta, 1G1.42 Walter Mackenzie Centre, Edmonton, Alberta, Canada e Department of Emergency Medicine, Baystate Emergency Medicine, 759 Chestnut St, Springfield, MA, USA f Department of Emergency Medicine, Nassau University Medical Center, 2201 Hempstead Turnpike, Box 14, East Meadow, NY, USA g Clinical Operations, MedImmune, One MedImmune Way, Gaithersburg, MD, USA h Clinical Biostatistics, MedImmune, One MedImmune Way, Gaithersburg, MD, USA i Clinical Research, MedImmune, One MedImmune Way, Gaithersburg, MD, USA abstract article info Article history: Received 30 May 2014 Received in revised form 25 September 2014 Accepted 26 September 2014 Background: Patients with frequent asthma exacerbations resulting in emergency department (ED) visits are at increased risk for future exacerbations. We examined the ability of 1 dose of benralizumab, an investigational antiinterleukin 5 receptor α monoclonal antibody, to reduce recurrence after acute asthma exacerbations. Methods: In this randomized, double-blind, placebo-controlled study, eligible subjects presented to the ED with an asthma exacerbation, had partial response to treatment, and greater than or equal to 1 additional exacerbation within the previous year. Subjects received 1 intravenous infusion of placebo (n = 38) or benralizumab (0.3 mg/kg, n = 36 or 1.0 mg/kg, n = 36) added to outpatient management. The primary outcome was the proportion of subjects with greater than or equal to 1 exacerbation at 12 weeks in placebo vs the combined benralizumab groups. Other outcomes included the time-weighted rate of exacerbations at week 12, adverse events, blood eosinophil counts, asthma symptom changes, and health care resource utilization. Results: The proportion of subjects with greater than or equal to 1 asthma exacerbation at 12 weeks was not dif- ferent between placebo and the combined benralizumab groups (38.9% vs 33.3%; P = .67). However, compared with placebo, benralizumab reduced asthma exacerbation rates by 49% (3.59 vs 1.82; P = .01) and exacerbations resulting in hospitalization by 60% (1.62 vs 0.65; P = .02) in the combined groups. Benralizumab reduced blood eosinophil counts but did not affect other outcomes, while demonstrating an acceptable safety profile. Conclusions: When added to usual care, 1 dose of benralizumab reduced the rate and severity of exacerbations experienced over 12 weeks by subjects who presented to the ED with acute asthma. © 2014 Elsevier Inc. All rights reserved. American Journal of Emergency Medicine 33 (2015) 14–20 ☆ Role of the funding source: This study was funded by MedImmune (Gaithersburg, MD). The sponsor contributed to the study design, monitoring the conduct of the study, data analysis, data interpretation, and writing of the manuscript. The corresponding author had full access to all of the study data and had final responsibility for the decision to submit for publication. ☆☆ Support: This study was sponsored by MedImmune. ClinicalTrials.gov number: NCT00768079. ★ Prior presentations: Data from this study have been presented as an abstract and oral presentation at the American Thoracic Society 108th International Conference, May 18, 2012, San Francisco, California; International Conference on Emergency Medicine, June 27, 2012; the American College of Chest Physicians: CHEST 2012, October 20, 2012, Atlanta, Georgia; and the International Eosinophil Society Eighth Biennial Symposium, July 13, 2013, Oxford, England. ★★ Author contributions: N Molfino proposed the concept. R Nowak, R Silverman, J Parker, and N Molfino designed the study. N Molfino, J Parker, and K Kim contributed to protocol development, interpreted results, and drafted and approved the final manuscript. JP Fiening contributed to protocol development, monitored the study, and drafted and approved the final manuscript. R Nowak and R Silverman contributed to the study design and protocol development. R Nowak, F Khan, RA Silverman, BH Rowe, and H Smithline recruited 80% of subjects and critically revised and approved the manuscript for important intellectual content. ☆☆☆ Author conflict of interest: None of the site investigators were employees of MedImmune, nor were they paid for their participation; none owns stock in MedImmune. N Molfino, J Parker, JP Fiening, and K Kim are full-time employees of MedImmune. Dr Rowe is supported by the Canadian Institutes of Health Research as a Tier I Canada Research Chair in Evidence- Based Emergency Medicine from the Government of Canada (Ottawa, ON). ⁎ Corresponding author at: MedImmune, One MedImmune Way, Gaithersburg, MD, USA, 20878. Tel.: +1 301 398 4095; fax: +1 301 398 9095. E-mail addresses: rnowak1@hfhs.org (R.M. Nowak), parkerj@medimmune.com (J.M. Parker), aresilv@aol.com (R.A. Silverman), brian.rowe@ualberta.ca (B.H. Rowe), howard.smithline@bhs.org (H. Smithline), faizkhan3@aol.com (F. Khan), fieningj@medimmune.com (J.P. Fiening), kimk@medimmune.com (K. Kim), nmolfino@kalobios.com (N.A. Molfino). 1 Currently employed at City MD Urgent Care, New York, NY, USA. 2 Currently employed at KaloBios, 260 East Grand Ave, South San Francisco, CA, USA. http://dx.doi.org/10.1016/j.ajem.2014.09.036 0735-6757/© 2014 Elsevier Inc. All rights reserved. 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