Real-world data back benralizumab in severe eosinophilic asthma

Use of the interleukin (IL)-5-receptor monoclonal antibody benralizumab in a real-world setting appears to improve outcomes for patients with severe eosinophilic asthma (SEA), allowing some to fully come off their maintenance therapy while preserving disease control, as shown in a study.

“[I]n a large cohort of patients with SEA, we observed that benralizumab leads to clinically and statistically significant reductions in asthma exacerbations, with over 40 percent of patients remaining exacerbation-free at 1 year,” the investigators said. “This was achieved despite a median [drop] in maintenance oral corticosteroid (mOCS) dose of 100 percent, with 70 percent of patients able to stop taking mOCS for asthma.”

They also noted parallel improvements in patient-reported outcome measures (PROMs) and lung function.

“Our clinical experience with benralizumab reaffirms the central role of eosinophilic inflammation in the immunopathology and exacerbation pathogenesis of severe asthma,” the investigators pointed out. [Lancet 2016;388:2115-2127; N Engl J Med 2017;376:2448-2458]

“In particular, the observation that some patients previously reliant on mOCS were now exacerbation-free and off systemic steroids supports the notion that other aspects of T2 inflammation, including IL-13 and/or allergen-driven IL-4 pathways, may be of questionable relevance for a proportion of T2- high patients with severe asthma,” they added.

Effective but not a panacea

The analysis included 130 patients with SEA (average age, 52.8 years; 61.5 percent female; mean body mass index, 31.1 kg/m²) who were initiated on benralizumab. All of them had been taking the combination of inhaled corticosteroid plus a long-acting beta agonist at high dose at study entry, with 74 patients (56.9 percent) requiring mOCS. Despite treatment, patients had poor asthma control, demonstrated by recurrent exacerbations, airflow obstruction, persistent T2 airways inflammation, and impaired PROMs.

After 48 weeks of treatment with benralizumab, overall disease control was significantly improved. Annualized exacerbation rate (AER) decreased by 72.8 percent (from 4.92 to 1.34; p<0.001), with 57 patients (43.8 percent) being exacerbation-free with the drug. [Chest 2021;159:496-506]

Median daily prednisolone dose among patients receiving mOCS tumbled from 10 mg to 0 mg (p<0.001), with 38 patients (51.4 percent) able to wean off mOCS therapy. The positive changes in Asthma Control Questionnaire (ACQ6) and Mini-Asthma Quality of Life Questionnaire (mAQLQ) scores, as well as FEV 1, were also significant.

Overall, 51 patients (39 percent) met the super responder definition (zero exacerbations and mOCS discontinuation) whereas 112 (86 percent) met the responder definition (≥-50 percent reduction in AER or in mOCS dose). Super response with benralizumab was associated a strongly eosinophilic phenotype and less severe disease.

“Conversely, benralizumab is not a universal panacea, [and] 30 percent of patients reliant on mOCS at baseline continued to require at least 5-mg prednisolone [daily] to maintain asthma control, despite a year of treatment,” the investigators said.

“We hope our results may additionally facilitate shared decision making with the patient… What is apparent from our analysis is that the majority of patients achieve at least one of the outcome measures used to define a ‘super-responder’, but significant variability exists as to the degree of overlap between the outcome measures,” they added.

The investigators are hopeful that future research into asthma and other eosinophilic diseases will include the unique eosinophil-depleting opportunity that benralizumab presents to the scientific community.

“It is highly likely that such a course will promote a revised understanding of ‘T2-high’ vs ‘eosinophilic’ asthma’,” they said.