Benralizumab offers relief during eosinophilic asthma, COPD flare-ups

A single subcutaneous injection of benralizumab, administered alone or in combination with glucocorticoids, helps minimize treatment failure and improve symptoms in patients with an eosinophilic exacerbation of asthma or chronic obstructive pulmonary disorder (COPD), as shown in the phase II ABRA trial.

At 90 days, significantly fewer patients who received benralizumab (alone or in combination with prednisolone) showed no response to treatment compared with those who were treated with prednisolone alone (45 percent vs 74 percent), with benralizumab being associated with 74-percent lower odds of treatment failure (odds ratio [OR], 0.26, 95 percent confidence interval [CI], 0.13–0.56; p=0.0005). [Lancet Respir Med 2024;doi:10.1016/S2213-2600(24)00299-6]

Furthermore, the 28-day total visual analogue scale (VAS) score (0–100) for respiratory symptoms was significantly lower in the pooled benralizumab arm than in the prednisolone arm (least-square mean difference, 49 mm, 95 percent CI, 14–84; p=0.0065).

The number needed to treat with benralizumab was four patients to prevent a treatment failure.

Results for other outcomes were consistently better in the pooled benralizumab arm than in the prednisolone arm. These included the time to first treatment failure event within 90 days (hazard ratio, 0.39, 95 percent CI, 0.25–0.61; p=0.0003), the number of treatment failures within 30 days (OR, 0.30, 95 percent CI, 0.14–0.63; p=0.0015), and the scores on the Medical Research Council dyspnoea scale (mean difference, 0.39, 95 percent CI, 0.08–0.69; p=0.013) and asthma-specific symptom questionnaire (ACQ₇: mean difference 0.5; p=0.029; AQLQ_total: mean difference 0.53; p=0.035) at day 28, among others.

As for safety, benralizumab was well tolerated, with no fatal adverse events reported. Adverse events occurred in 75 percent of patients who received benralizumab plus prednisolone, 77 percent of those who received benralizumab alone, and 91 percent of those who received prednisolone alone. Notably, hyperglycaemia and sinusitis or sinus infection were documented in the prednisolone arm only.

According to the investigators, ABRA provides evidence of a new way of treating eosinophilic endotypes of asthma and COPD exacerbations, given that current treatment strategies are limited to systemic glucocorticoids, antibiotic therapy, or both. This has important implications, given that even short courses of systemic corticosteroids in this population are associated with harm, they added. [BMJ 2017;357:j1415; J Asthma Allergy 2018;11:193-204; Int J Chron Obstruct Pulmon Dis 2023;18:2565-2580; Respir Res 2017;18:129]

“Our study findings suggest that benralizumab treatment acutely reduces subsequent systemic glucocorticoid cumulative dosing. Using benralizumab in acute eosinophilic exacerbations can support the vision of eradication of systemic glucocorticoid use in asthma and COPD treatment,” they said. [Lancet 2022;400:921-972; Lancet 2018;391:350-400]

ABRA included 158 patients (mean age 57 years, 54 percent female) with blood eosinophil counts of ≥300 cells per μL during an acute exacerbation of asthma or COPD. These patients were randomly assigned to receive acute treatment with prednisolone 30 mg once daily for 5 days plus benralizumab 100 mg subcutaneous injection once (n=52), placebo tablets once daily for 5 days and 100 mg benralizumab subcutaneous injection once (n=53), or prednisolone 30 mg once daily for 5 days and placebo subcutaneous injection once (n=53).

“ABRA is the first trial to target the eosinophilic treatable trait during exacerbations,” the investigators said.