Benralizumab eliminates oral corticosteroid use in certain patients with severe asthma

Patients with oral corticosteroid-dependent asthma treated with benralizumab achieved OCS elimination or reduction in those in whom adrenal insufficiency was detected, regardless of baseline eosinophil count, in the PONENTE trial.

The multicenter, open-label, single-arm phase 3b trial evaluated the safety and efficacy of daily OCS dose reduction following initiation of benralizumab (Fasenra, AstraZeneca). The trial enrolled 598 patients with asthma (mean age, 53.3 years; 64% women) requiring high-dose inhaled corticosteroids and long-acting beta-agonists for 6 months or more plus OCS ( 5 mg prednisone) for at least 3 months. Those enrolled had a baseline blood eosinophil count of150 cells/L or higher, or 300 cells/L or higher in the previous 12 months.

Benralizumab was administered by subcutaneous injection throughout the induction and OCS-reduction phases at 30 mg every 4 weeks for the first three doses and then every 8 weeks; following the 4-week induction phase, the researchers began to withdraw OCS to 20 mg/day, 10 mg/day, 7.5 mg/day or 5 mg/day.

Patients were categorized as having normal adrenal function (40%), complete adrenal insufficiency (27%) or partial adrenal insufficiency (33%) following a hypothalamic-pituitary-adrenal axis assessment.

The primary outcome was the percentage of patients that achieved full daily OCS reduction and the percentage of patients that achieved full dose reduction or a reduction to daily OCS dose of 5 mg or less if the patient had adrenal insufficiency. Secondary outcomes included asthma symptom assessment during the OCS-reduction phase and safety outcomes.

Median baseline daily OCS dose was 10 mg. About 25% of patients were on a daily OCS dose of more than 10 mg.

Sixty-two percent of patients achieved complete OCS elimination. Eighty percent of patients eliminated or reduced OCS use to 5 mg or less if adrenal insufficiency prevented further reduction, according to the results. Ninety-one percent of patients achieved a daily OCS dose of 5 mg or less, regardless of reason for stopping the reduction, the researchers reported.

More than 74% of patients did not experience an asthma exacerbation during the OCS-reduction phase. Thirty-nine patients (6.5%) required a visit to the ED or urgent care or were hospitalized due to asthma exacerbation during the study.

At the start of the study, 60% of patients tested had partial or complete adrenal insufficiency; this decreased to 37.5% 2 to 3 months following benralizumab treatment.

Blood eosinophil counts did not impact the ability for researchers to reduce or eliminate OCS use, according to the results.

The researchers concluded that the safety profile “was consistent with what is known from clinical trials and previous experience” with benralizumab.

“Moving forward, we are very hopeful that the findings from PONENTE can inform physician decisions in clinical practice and support the use of a personalized oral corticosteroid reduction algorithm,” Andrew Menzies-Gow, MD, consultant in respiratory medicine and director of the lung division at Royal Brompton & Harefield NHS Foundation Trust, London, said during a presentation of the poster at the virtual American Academy of Allergy, Asthma and Immunology Annual Meeting.