Real-World Safety and Effectiveness of Benralizumab in Japanese Patients with Severe Asthma: A Multicenter Prospective Observational Study

Abstract

Introduction

This study aimed to demonstrate whether benralizumab maintained the safety and effectiveness profiles established in randomized controlled trials among all patients with severe uncontrolled asthma initially prescribed benralizumab in the real-world setting in Japan.

Methods

This was a prospective, observational, multicenter post-marketing study (ClinicalTrial.gov, NCT03588546). The safety and tolerability of benralizumab over 1 year were assessed by the incidence of adverse events (AEs), serious AEs, adverse drug reactions (ADRs), and serious ADRs. Patient background characteristics indicating a more frequent onset of ADRs with benralizumab were explored. The main effectiveness assessment was the change in Asthma Control Questionnaire-5 (ACQ-5) score from baseline. Patients with baseline ACQ-5 scores ≥1.5 were defined as having severe uncontrolled asthma.

Results

In total, 632 patients were evaluated for safety and 274 for effectiveness; 139 patients were included in the severe uncontrolled asthma subgroup. ADRs were reported in 12.7% and serious AEs in 13.0% of patients. Serious infections occurred in 3.8%, serious hypersensitivity in 0.3%, and malignancy in 0.3% of patients. No helminthic infections occurred. In the effectiveness population, benralizumab improved the mean (standard deviation [95% confidence interval]) ACQ-5 score by −1.16 (1.40 [−1.36, −0.96]) from baseline; forced expiratory volume in 1 second by 0.151 (0.440 [0.09, 0.21]) L; and Mini-Asthma Quality of Life questionnaire score by 1.16 (1.29 [0.94, 1.38]) at the last observation. The annual asthma exacerbation rate was 0.42. A greater ACQ-5 score improvement was observed among patients with eosinophilic asthma characteristics.

Conclusion

No new safety concerns were raised, and patients experienced benefits consistent with previous studies of benralizumab, thus supporting the use of benralizumab for the add-on maintenance treatment of patients with eosinophilic severe uncontrolled asthma.

Keywords:

• benralizumab
• severe uncontrolled asthma
• anti-interleukin-5 receptor α monoclonal antibody
• eosinophils
• exacerbation
• asthma control
• quality of life

Abbreviations

ABPA, allergic bronchopulmonary aspergillosis; ACQ-5, Asthma Control Questionnaire-5; ADR, adverse drug reaction; AE, adverse event; AERD, aspirin-exacerbated respiratory disease; BMI, body mass index; CI, confidence interval; EOM, eosinophilic otitis media; FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroids; IgE, immunoglobulin E; IL, interleukin; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; LTRA, leukotriene receptor antagonist; MiniAQLQ, Mini-Asthma Quality of Life questionnaire; mOCS, maintenance oral corticosteroid; OCS, oral corticosteroid; RCT, randomized controlled trial; RMP, risk management plan; SABA, short-acting β₂-agonist; SD, standard deviation.

Data Sharing Statement

The data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/st/submission/disclosure.

Data for studies directly listed on Vivli can be requested through Vivli at www.vivli.org.

Data for studies not listed on Vivli could be requested through Vivli at https://vivli.org/members/enquiries-about-studies-not-listed-on-The-vivli-platform/.

The AstraZeneca Vivli member page is also available outlining further details: https://vivli.org/ourmember/astrazeneca/.

Acknowledgments

The authors wish to thank the investigators, research staff, health-care providers, and—in particular—the patients who participated in this study. The authors also wish to thank Toshimitsu Tokimoto, former employee of AstraZeneca K.K., for his contributions to the study and critically reviewing the manuscript, Tadataka Yabuta of Medical Department, AstraZeneca K.K. for critically reviewing the manuscript, and Keyra Martinez Dunn, MD, of Edanz, Japan for providing medical writing support, which was funded by AstraZeneca K.K., Japan, through EMC K.K., Japan, in accordance with Good Publication Practice 2022 guidelines (https://www.ismpp.org/gpp-2022).

Data from the manuscript were presented at the Japanese Society of Allergology meeting, Tokyo, Japan, 20–23 October 2023.

Author Contributions

All authors made a significant contribution to the work reported, whether that was in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Yamaguchi M: AstraZeneca K.K.: support for this study, consulting fees, and lecture fees.

Nishimura Y: AstraZeneca K.K.: support for this study and consulting fees.

Takumi Y, Hayashi N, and Sakamoto K: employees of AstraZeneca K.K. and stock ownership in the company.

Tohda Y: AstraZeneca K.K.: support for this study and consulting fees; Boehringer-Ingelheim Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Factory, Taiho, Teijin Pharma Co., Ltd., Astellas, GSK, Daiichi Sankyo Co., Ltd., Ono Pharmaceutical: grants or contracts; AstraZeneca K.K., Kyorin Pharmaceutical Co., Ltd., Teijin Pharma Co., Ltd., Boehringer Ingelheim Co., Ltd., Daiichi Sankyo Co., Ltd., Astellas, Pearl Therapeutics, Inc.: payment or honoraria.

Additional information

Funding

The study was funded by AstraZeneca K.K., Japan. The study sponsor provided funding for the study, publication, and medical writing and was involved in all stages of the study, such as the study design, data collection, analysis, and interpretation, as well as the review of the manuscript.