Biologics’ Efficacy in Severe, Uncontrolled Asthma Associated With Higher Blood Eosinophil Count

Biologics’ efficacy in patients with severe, uncontrolled asthma may be linked to their having higher baseline blood eosinophil count (BEC), according to a recent review. Although all biologics in this study showed some efficacy in reducing asthma exacerbations, the researchers identified tezepelumab as the only biologic to consistently show efficacy in groups of patients with a lower BEC.

“This systematic review of [randomized controlled trials] demonstrates that the efficacy of biologics in patients with severe, uncontrolled asthma in reducing exacerbations and improving lung function, asthma control, and health-related quality of life varies with baseline BEC,” the researchers wrote. “This differential efficacy was most pronounced for biologics targeting T2 inflammatory pathways (eosinophilic and/or allergic inflammation).”

This systemic review was published in Advances in Therapy.

The studies included in this review were peer-reviewed articles focused on placebo-controlled randomized controlled trials of biologic therapies in patients with severe, uncontrolled asthma, and the outcome of interest was annualized asthma exacerbation rate (AAER) reduction. All studies included in this review were sourced from MEDLINE/PubMed on May 27, 2021, using searches pertaining to severe, uncontrolled asthma, as well as biologic therapies, eosinophils, and clinical outcomes.

A total of 298 articles were initially identified from the database, of which 278 were excluded for not meeting eligibility criteria, leaving 33 full studies that were screened for review. Finally, after excluding for ineligible data and duplicates, 20 publications were included in the review. These studies included efficacy data on biologics tezepelumab, dupilumab, benralizumab, reslizumab, mepolizumab, and omalizumab.

The investigators compared AAER ratios and change from baseline in other outcomes vs placebo across BEC subgroups.

Additionally, commonly reported outcomes other than AAER were exacerbations requiring hospitalization or an emergency department visit, change from baseline in prebronchodilator forced expiratory volume per 1 second (FEV₁), Asthma Control Questionnaire score, and Asthma Quality of Life Questionnaire score.

After review, the researchers found that patients with baseline BEC of at least 300 cells/µL experienced a reduction in AAER with the use of all biologics, with other outcomes generally improved. Patients with a BEC of 0 to less than 300 cells/µL showed consistent AAER reduction only with the use of tezepelumab, with improvements in other outcomes being inconsistent across all biologics. In patients with BEC of 150 to less than 300 cells/µL, consistent AAER reduction was observed with tezepelumab and 300-mg dosage of dupilumab. Lastly, in patients with BEC of 0 to less 150 cells/µL, AAER reduction was observed only with tezepelumab.

The researchers acknowledge that there were some limitations to their study, including having data from different studies with different patient populations, overlapping of subgroups, and the fact that many of the articles used in this study were not prepared for eosinophil subgroup analyses.

Despite these limitations, the researchers believe their data suggest that the efficacy of biologics in reducing asthma exacerbations and improving patient outcomes may be linked to higher BEC at baseline, demonstrating the importance of choosing the biologic treatment that will produce the best results for an individual patient.

“The biologics studied all have different mechanisms of action,” wrote the researchers. “This fact underscores the importance of comparing results across their randomized, placebo-controlled studies, as providers must choose between biologics with different mechanisms to identify the biologic best suited for their patients.”

Reference

Korn S, Cook B, Simpson LJ, Llanos JP, Ambrose CS. Efficacy of biologics in severe, uncontrolled asthma stratified by blood eosinophil count: a systematic review. Adv Ther. 2023;40(7):2944-2964. doi:10.1007/s12325-023-02514-0