Efficacy of Biologics in Patients with Allergic Severe Asthma, Overall and by Blood Eosinophil Count: A Literature Review

Abstract

Patients with uncontrolled, allergic severe asthma may be prescribed biologic therapies to reduce exacerbations and improve disease control. Randomized controlled trials (RCTs) of these therapies have differed in design, with varying results overall and by baseline blood eosinophil count (BEC). This study describes published annualized asthma exacerbation rate (AAER) reductions from RCTs in patients with allergic severe asthma, overall and by baseline BEC category. A literature search was performed to identify published phase 3 RCT data of US Food and Drug Administration-approved biologics for severe asthma in patients with severe, uncontrolled asthma and confirmed sensitization to perennial aeroallergens. Analyses focused on AAER reduction versus placebo in the overall population and/or in those with an elevated or low BEC at baseline or screening. Baseline serum total immunoglobulin E levels varied between RCT populations. In patients with allergic severe asthma across all BEC categories, data were available for tezepelumab, dupilumab, benralizumab and omalizumab only; the greatest AAER reduction was observed with tezepelumab. In patients with allergic severe asthma and BECs of ≥ 260 cells/µL or ≥ 300 cells/μL, AAER reductions were observed with all biologics (tezepelumab, dupilumab, mepolizumab, benralizumab and omalizumab); the greatest AAER reduction was observed with tezepelumab and the smallest AAER reduction was observed with omalizumab. In patients with allergic severe asthma and BECs of < 260 cells/µL or < 300 cells/μL (regardless of historical BEC), an AAER reduction was observed with tezepelumab but not with benralizumab or omalizumab. Differential mechanisms of action may explain the differences in results observed between biologics. Among patients with allergic severe asthma, the efficacy of biologics in RCTs varied considerably overall and by BEC. Tezepelumab was the only biologic to demonstrate AAER reductions consistently across all subgroups. These differences can inform provider treatment decisions when selecting biologic treatments for patients with allergic severe asthma.

Keywords: Allergic asthma; Biologic; Blood eosinophil; Efficacy; Exacerbations; Literature review; Perennial allergy; Randomized placebo-controlled trial; Severe asthma.

Fig. 1

Reduction in AAER by biologic therapy in patients with allergic severe asthma (all baseline BEC levels). ^aRegardless of serum total IgE level; ^brequired a serum total IgE level of ≥ 30 IU/mL; ^cpooled trials; ^drequired a serum total IgE level of 30–700 IU/mL. AAER annualized asthma exacerbation rate, BEC blood eosinophil count, CI confidence interval, IgE immunoglobulin E, Q2W every 2 weeks, Q4W every 4 weeks, Q8W every 8 weeks, SC subcutaneous

Fig. 2

Reduction in AAER by biologic therapy in patients with allergic severe asthma and BECs of ≥ 300 cells/μL. ^aRegardless of serum total IgE level; ^brequired a serum total IgE level of ≥ 30 IU/mL; ^cpooled doses; ^dpooled trials; ^epatient n numbers are reported for the overall population (breakdown by treatment group was not given); ^frequired a serum total IgE level of 30–700 IU/mL; ^gthe EXTRA trial of omalizumab reported patients with BECs of ≥ 260 cells/µL. AAER annualized asthma exacerbation rate, BEC blood eosinophil count, CI confidence interval, IgE immunoglobulin E, IV intravenous, NR not reported, Q2W every 2 weeks, Q4W every 4 weeks, Q8W every 8 weeks, SC subcutaneous

Fig. 3

Reduction in AAER by biologic therapy in patients with allergic severe asthma and BECs of < 300 cells/μL. Data that matched our inclusion criteria for this patient population were unavailable in the dupilumab or mepolizumab analyses. ^aRegardless of serum total IgE level; ^bpooled trials; ^cpatient n numbers are reported for the overall population (breakdown by treatment group was not given); ^drequired a serum total IgE level of 30–700 IU/mL; ^ethe EXTRA trial of omalizumab reported patients with BECs of < 260 cells/µL. AAER annualized asthma exacerbation rate, BEC blood eosinophil count, CI confidence interval, IgE immunoglobulin E, NR not reported, Q2W every 2 weeks, Q4W every 4 weeks, Q8W every 8 weeks, SC subcutaneous