A new way of treating serious asthma and chronic obstructive pulmonary disease (COPD) attacks could be a “game-changer” and is the first leap in treatment for 50 years, researchers say.
Offering patients an injection is more effective than the current care of steroid tablets and cuts the need for further treatment by 30%, according to a study, The Independent reports.
Benralizumab is a monoclonal antibody that targets specific white blood cells, called eosinophils, to reduce lung inflammation.
It is currently used as a repeat treatment for severe asthma at a low dose, but a new clinical trial has found that a higher single dose can be very effective if injected at the time of a flare-up.
The findings, published in the Lancet Respiratory Medicine, included 158 people who needed medical attention in A&E for their asthma or COPD attack.
Patients were given a quick blood test to see what type of attack they were having, with those suffering an “eosinophilic exacerbation” involving eosinophils (a type of white blood cell) being suitable for treatment.
Around 50% of asthma attacks are eosinophilic exacerbations, as are 30% of COPD ones, according to the scientists.
The clinical trial, led by King’s College London and carried out at Oxford University Hospitals NHS Foundation Trust and Guy’s and St Thomas’ NHS Foundation Trust, saw patients randomly split into three groups.
One group received the benralizumab injection and dummy tablets, another received standard care (prednisolone steroids 30mg daily for five days) and a dummy injection, and the third group received both the benralizumab injection and steroids.
After 28 days, respiratory symptoms of cough, wheeze, breathlessness and sputum were found to be better in people on benralizumab.
And after 90 days, there were four times fewer people in the benralizumab group who failed treatment compared with those receiving steroids.
Treatment with the benralizumab injection also took longer to fail, meaning fewer visits to a GP or hospital for patients, researchers said.
Furthermore, people also reported a better quality of life on the new regime.
Scientists at King’s said steroids can have severe side-effects such as increasing the risk of diabetes and osteoporosis, meaning switching to benralizumab could provide huge benefits.
Lead investigator Professor Mona Bafadhel, from King’s, said: “This could be a game-changer for people with asthma and COPD.
“Treatment for asthma and COPD exacerbations have not changed in 50 years, despite causing 3.8 million deaths worldwide a year combined.
“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.”
The Lancet – Treating eosinophilic exacerbations of asthma and COPD with benralizumab (ABRA): a double-blind, double-dummy, active placebo-controlled randomised trial
Study details
Treating eosinophilic exacerbations of asthma and COPD with benralizumab (ABRA): a double-blind, double-dummy, active placebo-controlled randomised trial
Sanjay Ramakrishnan, MBBSa,b ∙ Richard E K Russell, PhDb,d ∙ Hafiz R Mahmood, MBBSa ∙ Karolina Krassowska, MScb ∙ James Melhorn, MBBSb ∙ Christine Mwasuku, MScb∙ et al.
Summary
Background
Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are important events and are associated with critical illness. Eosinophilic inflammation is a treatable trait commonly found during acute exacerbations of asthma and COPD. We hypothesised that for patients with eosinophilic exacerbations, a single injection of benralizumab, a humanised monoclonal antibody against interleukin-5 receptor-α, alone or in combination with prednisolone, will improve clinical outcomes compared with prednisolone, the standard of care.
Methods
The Acute exacerbations treated with BenRAlizumab trial (ABRA) was a multicentre, phase 2, double-blind, double-dummy, active placebo-controlled randomised trial completed in the UK at Oxford University Hospitals NHS Foundation Trust and Guy's and St Thomas' NHS Foundation Trust. Patients were recruited from urgent care clinics and emergency departments of these two hospitals. At the time of an acute exacerbation of asthma or COPD, adults with blood eosinophil counts of equal to or more than 300 cells per μL were randomly assigned in a 1:1:1 ratio to receive acute treatment with: prednisolone 30 mg once daily for 5 days and 100 mg benralizumab subcutaneous injection once (BENRA plus PRED group); placebo tablets once daily for 5 days and 100 mg benralizumab subcutaneous injection once (BENRA group); or prednisolone 30 mg once daily for 5 days and placebo subcutaneous injection once (PRED group). Randomisation was performed with a centralised interactive computer randomisation service. All patients and study research staff involved in data collection were masked to study blood results and treatment allocation. The co-primary outcomes were proportion of treatment failures over 90 days and total visual analogue scale (VAS) symptoms at day 28 in the pooled benralizumab groups compared with the prednisolone alone group and analysed in the intention-to-treat population. The trial was registered on Clinicaltrials.govNCT04098718.
Findings
Between May 13, 2021, and Feb 5, 2024, 287 patients were screened for study inclusion. 129 were excluded due to not having an exacerbation captured or not meeting the eosinophil exclusion criteria. 158 patients were randomly assigned at acute eosinophilic exacerbation of asthma or COPD where 86 (54%) patients were female and 72 (46%) were male with a mean age of 57 years (range, 18–84). 53 patients were randomly assigned to the PRED group, 53 were randomly assigned to the BENRA group, and 52 were assigned to the BENRA plus PRED treatment group. At 90 days, treatment failures occurred in 39 (74%) of 53 in the PRED group, and 47 (45%) of 105 in the pooled-BENRA group (OR 0·26 [95% CI 0·13–0·56]; p=0·0005). The 28-day total VAS mean difference was 49 mm (95% CI 14–84; p=0·0065), favouring the pooled-BENRA group. There were no fatal adverse events and benralizumab was well tolerated. Notably, hyperglycaemia and sinusitis or sinus infection adverse events were related to the prednisolone study drug only.
Interpretation
Benralizumab can be used as a treatment of acute eosinophilic exacerbations and achieves better outcomes than the current standard of care with prednisolone alone. These results offer a new way of treating eosinophilic endotypes of asthma and COPD exacerbations.
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