Identification of distinct phenotypes related to benralizumab responsiveness in patients with severe eosinophilic asthma

Nakajima, Masayuki; Matsuyama, Masashi; Morishima, Yuko; Arai, Naoki; Hida, Norihito; Nakaizumi, Taisuke; Masuko, Hironori; Yatagai, Yohei; Saito, Takefumi; Hizawa, Nobuyuki

doi:10.1371/journal.pone.0248305

Cited by 13 publications

(5 citation statements)

References 7 publications

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“…Five clusters were identified with different responsiveness. The most responsive cluster was characterized by a relatively low level of FeNO and IgE compared with blood eosinophils [34]. Similar analyses have been recently performed with omalizumab [35].…”

Section: Cluster Analysissupporting

confidence: 72%

Severe asthma and personalized approach in the choice of biologic

Bona

Spataro

Carlucci

et al. 2022

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewSevere asthma requires intensive pharmacological treatment to achieve disease control. Oral corticosteroids are effective, but their use is burdened with important side effects. Biologics targeting the specific inflammatory pathways underpinning the disease have been shown to be effective but not all patients respond equally well. As we treat more patients than those who can respond, our inability to predict responders has important healthcare costs considering that biologics are expensive drugs. Thus, a more precise choice of the 'right patients' to be prescribed with the 'right biologics' would be desirable. Recent findingsMachine learning techniques showed that it is possible to increase our ability to predict outcomes in patients treated with biologics. Recently, we identified by cluster analysis four different clusters within the T2 high phenotype with differential benralizumab response. Two of these clusters, characterized by higher levels of inflammatory markers, showed the highest response rate (80--90%).

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Section: Cluster Analysissupporting

confidence: 72%

Severe asthma and personalized approach in the choice of biologic

Bona

Spataro

Carlucci

et al. 2022

Current Opinion in Allergy &Amp; Clinical Immunology

View full text Add to dashboard Cite

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“…Previous studies showed that the biomarker for benralizumab is type-2 inflammation, with, for example, peripheral eosinophil levels over 300/µl. The presence of non-type-2 inflammation with smoking or obesity might hinder the effect of benralizumab [ 26 ]. Some patients with a smoking history, asthma COPD overlap syndrome (ACO), and obesity were included in the present study.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of benralizumab in elderly patients with severe eosinophilic asthma

Somekawa,

Watanabe,

Seki

et al. 2024

European Clinical Respiratory Journal

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Background Biologics are the important drugs for severe asthma, but clinical trials included few elderly patients. Data on the safety and efficacy of benralizumab in elderly asthma patients are limited. Methods This clinical study was a multicentre, retrospective, observational study at two hospitals. Patients aged ≥18 years diagnosed with severe asthma treated with benralizumab were included. Elderly patients were defined as those aged 70 years or older. Efficacy and safety were then analyzed in elderly and non-elderly patients. The primary endpoints were the annual number of asthma exacerbations for efficacy and the discontinuation rate due to adverse events for safety. Results Between August 2016 and October 2022, 61 patients were enrolled; 10 patients were excluded, and 51 (22 elderly, 29 non-elderly) patients were analyzed. In elderly patients, the annual number of asthma exacerbations before treatment with benralizumab (pre-benralizumab) was 3.78, and the number during treatment with benralizumab was 1.26, a decrease of 2.52 (95% confidence interval [CI], 1.3 to 3.74, p < 0.001). In non-elderly patients, the annual number of asthma exacerbation in the pre-benralizumab period was 3.24, and during treatment with benralizumab it was 0.68, a decrease of 2.56 (95% CI, 1.3 to 3.82, p < 0.001). There was no significant difference in discontinuation due to treatment-related adverse events (elderly vs non-elderly, 2 (9%) vs 0 (0%), p = 0.18). Conclusion Benralizumab reduced the annual number of asthma exacerbations and was well tolerated in elderly patients.

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“…On another side, the dose-related insufficient response may be explained the modest response of benralizumab in obese asthmatic patients, however, future real-world studies should be focus on the possibility of this hypothesis. Nevertheless, the acceptable elucidation for the poor response of benralizumab in patients with higher BMI could be related to the emergence of non-type two inflammations [66].…”

Section: Discussionmentioning

confidence: 99%

“…Research suggests that patients with high BMI levels may experience reduced efficacy of benralizumab due to systemic inflammation caused by elevated levels of obesity-related cytokines like TNF-α, IL-6, and leptin [66]. Factors like smoking or non-type two inflammations can also hinder the drug's effectiveness, primarily targeting amplified type 2 immunity.…”

Section: Discussionmentioning

confidence: 99%

Factors influencing poor response to type 2 targeted therapies in severe asthma: a retrospective cohort study

Al-Ahmad,

Ali,

Maher

2023

BMC Pulm Med

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Background A significant breakthrough has been made in treating severe asthma, with the recognition of various asthma phenotypes and an updated management guideline. Type 2 targeted therapies, such as benralizumab and omalizumab; have been identified as an effective treatment for severe asthma, improving patient response, lung function tests and asthma symptom control. This study aimed to evaluate factors contributing to poor response to therapy. Methods A retrospective single-center cohort study of 162 patients with severe asthma who started biologic therapy; their data were retrieved from medical records for further analysis. Poor responders were patients remained clinically and functionally uncontrolled despite even after augmenting all treatment options. Results Childhood-onset asthma, bronchiectasis, poor symptom control (ACT below 19), severe airway obstruction (< 60% predicted), and maintenance oral corticosteroid (mOCS) use were significantly associated with poor response to omalizumab and benralizumab; p = 0.0.4 and 0.01; 0.003 and 0.01; 0.01 and 0.001, 0.05 and 0.04; 0.006 and 0.02, respectively. However, chronic rhinosinusitis and IgE < 220kIU/L were associated with higher poor response rates to omalizumab (p = 0.01 and 0.04, respectively). At the same time, female patients and those with blood eosinophils level < 500 cells/mm3 had a higher poor response rate to benralizumab (p = 0.02 and 0.01, respectively). Ischemic heart disease (IHD), bronchiectasis, and continued use of OCS increased the likelihood of poor response to omalizumab by 21, 7, and 24 times (p = 0.004, 0.008, and 0.004, respectively). In contrast, the female gender, childhood-onset asthma and higher BMI increased the likelihood of poor response to benralizumab by 7, 7 and 2 times more, p = 0.03, 0.02 and 0.05, respectively. Conclusion Poor response to omalizumab treatment was independently associated with ischemic heart disease (IHD), bronchiectasis, and a history of maintenance oral corticosteroid (mOCS) use. Conversely, poor response to benralizumab therapy was independently linked to female gender, childhood-onset asthma and higher body mass index (BMI).

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Identification of distinct phenotypes related to benralizumab responsiveness in patients with severe eosinophilic asthma

Cited by 13 publications

References 7 publications

Severe asthma and personalized approach in the choice of biologic

Severe asthma and personalized approach in the choice of biologic

Efficacy and safety of benralizumab in elderly patients with severe eosinophilic asthma

Factors influencing poor response to type 2 targeted therapies in severe asthma: a retrospective cohort study

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