Since demonstrating efficacy in clinical trials, the monoclonal antibody benralizumab has been licensed for the treatment of severe eosinophilic asthma. However, the real-world effectiveness and baseline characteristics of benralizumab treatment are not yet know. Therefore, a new study aimed to assess the efficacy of the treatment in the real-world setting.
Severe eosinophilic asthma (SEA)
Severe uncontrolled asthma affects around 3% to 5% of all adult patients suffering from asthma. The condition is characterised by ongoing symptoms and recurrent exacerbations, despite patients adhering to high-dose inhaled therapies. SEA patients often show evidence of significant type 2 airway inflammation, which is identified by elevated blood and airway eosinophil counts and fractional exhaled nitric oxide, that is only partially responsive to inhaled corticosteroids (ICSs). This often leaves patients reliant on maintenance oral corticosteroids (mOCSs) to achieve a degree of disease control. However, there is an added mortality and morbidity risk associated with mOCSs, leading researchers to search for new treatment options.
The recent introduction of biologic therapies targeting key mediators of type 2 inflammation inducing IgE, IL-5/5 receptor, and IL-4/11 has provided the first opportunity for treatments that can help improve patients’ day-to-day symptoms and reduce exacerbation risk, without the excess morbidity and mortality associated with oral corticosteroids.
Benralizumab for treatment of asthma
The monoclonal antibody benralizumab binds to the receptor IL-5, which is expressed on eosinophils, eosinophilic precursors and basophils, resulting in the rapid apoptosis and near depletion of these cells through enhanced antibody-mediated cytotoxicity. There have been three phase III randomised controlled trials that have assessed the efficacy of benralizumab for treatment of SEA. The CALIMA and SIROCCO trials both demonstrated significant reductions in exacerbations as well as improvements in lung function, asthma control and quality-of-life measures. Whereas the ZONDA trial recruited patients with SEA requiring mOCS therapy and demonstrated a median reduction in daily mOCS dose of 50% vs placebo, as well as a 70% reduction in the annualised exacerbation rate.
Despite the promising results from clinical trials, it is recognised that the patients recruited for these trials are not fully representative of severe asthma clinic populations. More specifically, recruited patients often have moderate to severe asthma, rather than genuinely severe forms of the disease. This is evidenced by the large improvements in symptoms, lung function and exacerbation frequency in the patients receiving the placebo in these studies. Similarly, trial recruitment criteria often exclude patients with fixed airflow obstruction, a history of smoking and medical comorbidities. Moreover, there is a lack of real-world data to support these clinical trial results for benralizumab treatment in SEA patients. Therefore, these researchers conducted a real-world study to assess the effectiveness of benralizumab in a large cohort of SEA patients.
Real-world study of benralizumab for treatment of asthma
The researchers performed a retrospective analysis of all patients with SEA who commenced treatment with benralizumab between May 2018 and April 2019, at a tertiary referral asthma centre in the UK. All patients included in the study were identified as fulfilling the ERS/ATS definition of severe asthma, and had confirmed adherence to background therapy. Patients began benralizumab therapy if they had an eosinophil count of ≥ 0.4 × 109/L in the preceding 12 months and experienced a minimum of three exacerbations in the prior year. Exacerbations were defined as a worsening of asthma control resulting in ≥ 3 days of oral prednisolone treatment.
The administered benralizumab dose was 30 mg sc every 4 weeks for the first three doses. This was followed by administration of 30 mg sc every 8 weeks. Baseline exacerbation frequency was determined by a combination of patient report and confirmation by medical review of the prescription records. Patients who did not complete ≥ 24 weeks of benralizumab treatment were not included in the analysis.
Clinical assessment was performed at each clinic visit where a benralizumab dose was administered. The data collected at these time points included: clinic spirometry, Feno, blood eosinophil count, Asthma Control Questionnaire 6 (ACQ6) score, Mini-Asthma Quality of Life Questionnaire (mAQLQ) score, mOCS dose, and number of exacerbations since the last clinic visit. Patient demographic data was obtained from the electronic patient record. Patients were classified as responders or nonresponders after 48 weeks of treatment. Responders were defined as patients presenting a ≥ 50% reduction in the annualized exacerbation rate or, for patients requiring mOCS therapy, a ≥ 50% reduction in daily dose of mOCS. Any patients that did not complete a full year of treatment because of lack of responses were classified as nonresponders.
Results
Overall, 130 patients were included in the study. At 48 weeks, a 72.8% reduction in AER was noted, from 4.92 ± 3.35 per year in the year preceding biologic treatment to 1.34 ± 1.71 per year. In addition to that 57 of the patients (43.8%) were exacerbation-free following benralizumab treatment. Out of the 130 patients, 74 were receiving mOCSs (56.9%) and in those patients the median daily prednisolone dose fell from 10 mg to 0 mg. Even more promisingly, 38 of the 74 patients (51.4%) were able to discontinue mOCS therapy completely.
The researchers identified significant clinical and statistical improvements in ACQ6 scores, mAQLQ scores, and FEV1. Overall, 51 patients (39%) met the researchers super responder definition, and 112 patients (86%) met the responder definition. The optimal regression model of super responders compared with other responders included baseline characteristics associated with a strongly eosinophilic phenotype and less severe disease. Eighteen patients (13.8%) were identified as nonresponders. The researchers found evidence of chronic airway infection in 6 of 18 nonresponder patients, and an increase in the blood eosinophil count, which is consistent with the development of anti-drug antibodies, was observed in 5 of those 18 patients.
Summary
This study presented the first real-world data to support benralizumab treatment in a large cohort of patients with severe asthma. Overall, benralizumab led to significant improvement in all clinical outcome measures, and a lack of response was seen in a minority of patients, which should be a focus for future investigation into the real-world effectiveness of benralizumab for the treatment of SEA.
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