Benralizumab effective when repurposed for asthma and COPD exacerbations, study finds

3rd December 2024

The monoclonal antibody benralizumab, which is currently used in the treatment of severe asthma, could help to treat exacerbations in asthma and COPD, according to a new UK trial.

Benralizumab was found to be more effective than a dose of steroids when patients had gone to urgent care clinics or emergency departments with acute symptoms and high eosinophil counts. This reduced the need for further treatment and hospitalisations.

Researchers at King’s College London said the findings could be ‘game-changing’ in an area of medicine that had not changed in 50 years.

In the trial, patients having an asthma or COPD attack were randomly assigned into three groups. The first was treated with a benralizumab injection and placebo tablets, the second received the standard of care of prednisolone 30mg daily for five days plus a placebo injection, and the third received both a benralizumab injection and the standard of care prednisolone.

After 28 days cough, wheeze, breathlessness and sputum were found to be better in patients who had received benralizumab and after 90 days, there were four times fewer people in the benralizumab group that failed treatment compared with those who only received prednisolone.

Writing in The Lancet Respiratory Medicine, the researchers also noted that treatment with benralizumab ‘took longer to fail’, meaning fewer visits to a GP or hospital. There was also an improvement in the quality of life for people with asthma and COPD.

Almost three quarters (74%) of patients who received standard of care prednisolone needed further treatment within 90 days, highlighting the poor outcomes currently seen with short-course steroids when treating eosinophilic exacerbations, they concluded.

The safety profile of benralizumab injections was similar to previous studies and the researchers said it could potentially be given in a GP practice or emergency department.

Eosinophilic exacerbations make up to 30% of COPD flare-ups and almost 50% of asthma attacks, with two million exacerbations of this type in the UK per year.

Study leader Professor Mona Bafadhel, director of the King’s Centre for Lung Health, said: ‘Benralizumab is a safe and effective drug already used to manage severe asthma.

‘We’ve used the drug in a different way – at the point of an exacerbation – to show that it’s more effective than steroid tablets, which is the only treatment currently available.’

She added that the big advancement in this study was discovering that targeted therapy works in asthma and COPD attacks.

‘Instead of giving everyone the same treatment, we found targeting the highest risk patients with very targeted treatment, with the right level of inflammation was much better than guessing what treatment they needed,’ she said.

Dr Samantha Walker, director of research and innovation, at the charity Asthma + Lung UK, said: ‘It’s great news for people with lung conditions that a potential alternative to giving steroid tablets has been found to treat asthma attacks and COPD exacerbations.

‘But it’s appalling that this is the first new treatment for those suffering from asthma and COPD attacks in 50 years, indicating how desperately underfunded lung health research is.’

The publication of this research comes as the long-awaited NICE/BTS/SIGN joint guidelines on management of asthma were launched.

In November, a report revealed that a digital asthma tool could reduce emergency appointments and save NHS £25m annually.

A version of this article was originally published by our sister publication Pulse.

Acute asthma admissions sharply declined during lockdowns as air quality improved, study reveals

9th February 2024

Reduced pollution levels and better air quality during the Covid-19 pandemic lockdowns strongly correlated with lower rates of acute asthma care provision, according to new research led by the University of Birmingham.

The retrospective time-series study, published in the BMJ Open, investigated the link between acute asthma hospital admissions and specific air pollutant levels in four Oxford postcodes during the national lockdowns of March to June and November to December 2020.

For adult residents, acute asthma admissions fell from 78 per 100,000 residents in 2015-19, to 46 per 100,000 residents in 2020 – a reduction of 41%.

This reduction in acute asthma care coincided with levels of air pollution falling significantly. Different pollutants dropped by 18-33% when compared to average values for the previous five-year period.

For example, nitrogen dioxide (NO₂) reduced by 26.7% from a 2015-19 average of 14.6 μg m-3 to 10.7 μg m-3 in 2020.

Fine particulate matter (PM_2.5) saw a reduction of 33.5% from 10.1 μg m-3 in 2015-19 to 6.7 μg m-3 in 2020, and PM₁₀ reduced by 18.6% from 13.2 μg m-3 in 2015-19 to 10.8 μg m-3 in 2020.

‘Large-scale measures to improve air quality have potential to protect vulnerable people living with chronic asthma in urban areas,’ the authors concluded.

Commenting on the ‘unique situation’ of temporary air quality improvement, Dr Suzanne Bartington, clinical associate professor of environmental health at the University of Birmingham and lead author of the study, said: ‘The results of air pollution levels falling may have had an impact on the number of severe asthma cases that need acute hospital care, with 41% fewer hospital stays compared to the previous five-year average.

‘Furthermore, we also identified a 4% increase in risk of asthma hospital admissions for every 1 μg m-3 increase in mean monthly NO₂, and an approximately 3% increase in risk for every 1 μg m-3 increase in mean monthly PM2.5 levels.

‘This is an important study to help us better understand how demand for NHS inpatient care may change when air quality is improved.’

The research team was supported by the University of Oxford, Oxfordshire County and City Councils and the then Oxfordshire Clinical Commissioning Group.

Commenting on the results, Councillor Nathan Ley, Oxfordshire County Council’s cabinet member for public health, inequalities and community safety, said: ‘We must now use what we have learned, thanks to this research with our partners, to improve our environment, in line with the Clean Air Strategy which we launched last year.

‘Elevated levels of NO₂, PM_2.5 and PM₁₀ contribute towards heart disease, chronic lung disease, cancers, preterm births, and many other avoidable events. The vision of Oxfordshire County Council to tackle this issue remains clear. We must continue to use all the tools at our disposal to lead the country, clean up our air and save lives.’

Earlier this week, the European Respiratory Society (ERS) warned of rising respiratory diseases, such as asthma, as well as premature death without urgent action on air quality.

This followed the ERS consensus statement on climate change and respiratory health, published in September 2023, which highlighted the damaging effects of air pollution on health and global warming.

Dupilumab treatment provides greatest benefit among mAbs in moderate to severe asthma

13th April 2023

Dupilumab treatment produced the lowest incidence of asthma exacerbations and greatest improvements in FEV1 among three currently used mAbs

Dupilumab treatment for 12 months leads to the lowest number of exacerbations and better improvements in FEV1 compared to two commonly used monoclonal antibodies (mAbs), omalizumab or mepolizumab, in adults with moderate to severe asthma, according to comparative analysis by US researchers.

The prevalence of severe asthma varies between 3.6 and 6.1% of all patients with the disease. Individuals with moderate to severe asthma have the opportunity of being treated with several monoclonal antibodies, which target key inflammatory cytokines involved in disease pathogenesis. All of these currently approved biologic therapies have been shown to improve asthma-related outcomes in individuals with asthma uncontrolled with conventional therapy. However, for patients with more than one phenotype such as allergic and eosinophilic asthma, trying to identify the most suitable agent is less clear. In the absence of direct head-to-head comparative trials, researchers can often utilise observational data to emulate a hypothetical pragmatic randomised trial, which is referred to as the target trial.

In the current analysis, the research team emulated a hypothetical randomised trial, making use electronic health records from a large US-based academic health care system. They included adult participants with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/μL with the objective of comparing the effectiveness of dupilumab treatment with omalizumab or mepolizumab in patients with moderate to severe asthma. The main outcomes of interest were the incidence of asthma-related exacerbations and the change in baseline FEV₁ value over 12 months of follow-up.

Dupilumab treatment and asthma outcomes over 12 months

In all, 68 individuals received dupilumab treatment 68 received omalizumab and 65 received mepolizumab.

Over the 12 month period of follow-up, asthma-related exacerbations occurred in 25.0% of those receiving dupilumab treatment compared to 43.1% for mepolizumab (adjusted hazard ratio, aHR = 0.35, 95% CI 0.18 – 0.71). Compared to omalizumab group, asthma exacerbations occurred in 39.7% of patients, giving a corresponding adjusted hazard ratio of 0.42 (95% CI 0.20 – 0.87).

The change in FEV₁ for the different agents were 0.11 L (95% CI -0.003 to 0.222 L) for dupilumab versus mepolizumab and 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab.

In patients with eosinophil counts of at least 300 cells/μL, the HR for dupilumab compared to mepolizumab was 0.26 (95% CI 0.10 – 0.67) and 0.24 (95% CI 0.09 – 0.63) for dupilumab vs omalizumab.

Based on these findings, the authors concluded that among patients with asthma and eosinophil counts of at least 150 cells/μL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV₁ value than either omalizumab or mepolizumab.

Citation
Akenroye AT et al. Comparative effectiveness of omalizumab, mepolizumab, and dupilumab in asthma: A target trial emulation. J Allergy Clin Immunol 2023