Most patients with eosinophilic asthma who are dependent upon oral corticosteroid (OCS) undergoing benralizumab therapy are able to discontinue or substantially reduce their use of OCS, despite a high prevalence of adrenal insufficiency among these patients. These were among study findings published in The Lancet Respiratory Medicine.
The investigators sought to evaluate the efficacy and safety of a rapid, individualized steroid-reduction algorithm, including monitoring for adrenal insufficiency, following the initiation of benralizumab, an anti-interleukin-5 receptor-α monoclonal antibody. The investigators aimed to assess whether the use of benralizumab in patients with severe asthma will ultimately decrease eosinophilic inflammation in these individuals. The multicenter, open-label, single-arm PONENTE trial (ClinicalTrials.gov identifier: NCT03557307) was conducted at 138 clinical asthma centers across 17 countries.
Eligible patients were at least 18 years of age with severe eosinophilic asthma (defined as having a blood eosinophilic count of ≥150 cells/µL at enrollment or ≥300 cells/µL in the prior year) and required maintenance OCS for at least 3 months before study enrollment. Patients received a 30-mg subcutaneous injection of benralizumab every 4 weeks for 3 doses, followed by every 8 weeks thereafter. The OCS reduction phase began at week 4 with daily OCS dosages decreased by 1 to 5 mg every 1 to 4 weeks, based on the starting dose, an individual’s degree of asthma control, and adrenal function status. Asthma control was evaluated via use of the Asthma Control Questionnaire.
Primary study endpoints were the percentage of patients who eliminated daily OCS, sustained for 4 weeks or more, and the percentage achieving elimination or a daily prednisone or prednisolone dosage of 5 mg or less, for at least 4 weeks, if the reason for no further reduction was adrenal insufficiency. Efficacy and safety analyses included all participants who received at least 1 dose of benralizumab. The recently published trial findings are based on analyses following the OCS reduction phase of the PONENTE trial; a maintenance phase of the trial is ongoing.
From April 1, 2018, to September 5, 2020, total of 705 patients were evaluated for eligibility, with 598 of them recruited to receive at least 1 dose of benralizumab. Overall, 62.88% (376 of 598) of the patients (95% CI, 58.86-66.76) eliminated OCS use and 81.94% (490 of 598) of the patients (95% CI, 78.62-84.94) eliminated OCS use or attained a dosage of 5 mg of less if the reason for halting the reduction was adrenal insufficiency.
Dosage reductions were attained regardless of baseline eosinophil count, baseline OCS dosage, or duration of OCS therapy. Adrenal insufficiency was observed in 60% (321 of 533) of patients at initial evaluation and in 38% (205 of 533) of patients 2 to 3 months later. The safety profile was consistent with that of previous benralizumab experience. Overall, 75% (448 of 598) of the patients reported no asthma exacerbations during the OCS reduction phase, with an annualized exacerbation rate of 0.63. Only 6% (38 of 598) of the patients experienced a total of 46 exacerbations that necessitated emergency department/urgent care visits or hospitalizations.
The investigators concluded that the PONENTE trial algorithm for OCS dosage reductions and adrenal function monitoring could aid in the elimination of daily OCS use in patients with severe asthma — a necessary and valuable addition to the current knowledge regarding the treatment of asthma — and help inform clinical practice and guideline development.
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Menzies-Gow A, Gurnell M, Heaney LG, et al. Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, single-arm study. Lancet Respir Med. 2022;10(1):47-58. doi:10.1016/S2213-2600(21)00352-0