Benralizumab trumps steroids in treatment of asthma, COPD eosinophilic exacerbations

The time of steroids as the treatment of choice for asthma and chronic obstructive pulmonary disease (COPD) exacerbations appears to be nearing its end with the arrival of a new monoclonal antibody therapy, according to the results of the ABRA study.

Researchers in the UK have shown the superiority of benralizumab to prednisolone in managing eosinophilic exacerbations of asthma or COPD.

“[N]ot all exacerbations are the same,” said lead researcher Dr Mona Bafadhel from King’s College London, UK, who presented their findings at the recent ERS 2024. “When we look at the inflammatory endotypes … there are subgroups of exacerbations. Importantly, the eosinophilic exacerbation happens in about a third of patients with COPD and at least 50 percent of patients with asthma.”

However, despite the considerable number of such cases, “there have been no new treatments for exacerbations of asthma and COPD for well over 50 years,” according to Bafadhel.

Bafadhel also stressed the high burden of oral corticosteroids, which is associated with morbidity in patients with asthma and with mortality in those with COPD. “The treatment effect, as we all know, is short, and treatment failure rates are high,” she said.

“[T]he ABRA study shows for the first time the first new treatment for exacerbations of asthma and COPD,” Bafadhel claimed. “Benralizumab as a single injection at the time of an acute eosinophilic exacerbation was superior to standard of care with prednisolone.”

ABRA is a double-blind, double-dummy, active-placebo, multicentre, randomized controlled trial. Bafadhel and her team included patients aged ≥18 years diagnosed with asthma or COPD, who have one exacerbation in the previous 12 months, a historic blood eosinophil >250 cells/μL, and blood eosinophils ≥300 cells/μL at exacerbation.

Eligible patients were randomized 1:1:1 to receive oral prednisolone 30 mg for 5 days plus 100-mg benralizumab subcutaneously (SC) once, or placebo tablets for 5 days plus 100-mg benralizumab SC once, or prednisolone 30 mg for 5 days plus placebo SC once.

The proportion of treatment failures at 90 days and total visual analogue scale (VAS) symptoms at day 28 were the coprimary endpoints, while secondary ones included time to treatment failure (TTF) and lung function.

Fewer treatment failure

Overall, 158 patients were included in the trial. Of these, 88 (55.7 percent) had asthma, 51 (32.2 percent) had COPD, and 19 (12.0 percent) had both asthma and COPD.

At 90 days, 39 out of 53 patients (73.6 percent) who received prednisolone only and 47 out of 105 patients (44.8 percent) who received benralizumab alone or in combination with prednisolone experienced treatment failure (odds ratio [OR], 0.264, 95 percent confidence interval [CI], 0.125‒0.556; p<0.001). [Bafadhel, et al, ERS 2024]

The mean difference in total VAS symptoms at day 28 was 49 mm (95 percent CI, 14‒84; p=0.006), in favour of benralizumab.

For the secondary outcomes, TTF was longer with benralizumab than with prednisolone (hazard ratio, 0.393, 95 percent CI, 0.252‒0.612; p<0.001), and lung function was similar between treatment groups.

In a subgroup analysis, benralizumab alone was as good as benralizumab plus prednisolone in terms of TTF (monotherapy: OR, 0.298, 95 percent CI, 0.129‒0.688; p=0.005; combination therapy: OR, 0.232, 95 percent CI, 0.0.099‒0.544; p<0.001) and mean total VAS change (monotherapy: 46, 95 percent CI, 5‒87; combination therapy: 52, 95 percent CI, 11‒93; p=0.013).

There was “[n]o difference between benralizumab [alone] and benralizumab plus prednisolone for the coprimary outcome and any of the secondary outcomes,” Bafadhel said.

“Benralizumab is a monoclonal antibody licensed for the treatment of eosinophilic asthma,” Bafadhel noted. “It rapidly depletes eosinophils and was tested for the treatment of acute asthma as an add-on therapy to prednisolone.”