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. 2024 Oct 9:17:977-982.
doi: 10.2147/JAA.S476774. eCollection 2024.

Reduced Effectiveness of Anti-IgE Treatment Among Adults with Severe Asthma with Older Age of Asthma Onset: Results from the CHRONICLE Study

Dennis K Ledford  1 , Warner W Carr  2 , Wendy C Moore  3 , Njira L Lugogo  4 , Arjun Mohan  4 , Bradley Chipps  5 , Alexander R Mackie  6 , Andrew W Lindsley  7 , Joseph Spahn  6 , Christopher S Ambrose  8
Affiliations

Reduced Effectiveness of Anti-IgE Treatment Among Adults with Severe Asthma with Older Age of Asthma Onset: Results from the CHRONICLE Study

Dennis K Ledford et al. J Asthma Allergy. .

Abstract

Purpose: Younger age of asthma onset (AAO) has been associated with an allergic phenotype, whereas eosinophilic phenotypes have been associated with older AAO. In randomized trials, biologic efficacy among adults with severe asthma (SA) has varied by age at asthma onset. To determine whether these associations observed in trials apply to real-world outcomes, this study examined biologic effectiveness by AAO and biologic class in a large, real-world cohort.

Patients and methods: CHRONICLE is an ongoing, real-world study of US adults with subspecialist-treated SA receiving biologics, maintenance corticosteroids, or who are uncontrolled on high-dosage inhaled corticosteroids with additional controllers. Patients enrolled between February 2018 and February 2022 who initiated a biologic for SA and had complete data for analysis were included. A locally estimated scatterplot smoothing (LOESS) analysis was used to plot the relationship between percentage exacerbation rate reduction and AAO by biologic class.

Results: Of 578 patients with complete data, 198, 149, and 231 were diagnosed with asthma at age <18, 18-39, and ≥40 years, respectively. Across subgroups, patients were predominantly White (72-78%), female (67-73%), and commercially insured (54-71%). In the LOESS analysis, exacerbation rate reductions were similar for anti-IgE and anti-IL-5/5R and anti-IL-4R subgroups with younger AAO, but the exacerbation rate reduction diminished for patients with older AAO receiving anti-IgE therapy, particularly with asthma onset age ≥40 years.

Conclusion: Clinicians should consider age of onset in biologic treatment decisions, given reduced effectiveness of omalizumab in patients with asthma onset at age ≥40 years.

Clinicaltrialsgov identifier: NCT03373045.

Keywords: Biologics; age of asthma onset; anti-immunoglobulin E therapy; anti-interleukin therapy; effectiveness; severe asthma.

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Conflict of interest statement

DKL: Consultant and speaker – AstraZeneca, Genentech/Roche, GlaxoSmithKline, Novartis, and Sanofi/Regeneron; Grant support – AstraZeneca. Royalties – Taylor and Francis and Wolters Kluwer Health; Contributing editor to Ask the Expert - American Academy of Allergy, Asthma & Immunology. WWC: Speaker – AstraZeneca, Boehringer Ingelheim, Regeneron, Sanofi, and Teva; Consultant – Aerocrine, Alcon Laboratories, AstraZeneca, Baxalta, Boehringer Ingelheim, Circassia, CSL Behring, Genentech, GlaxoSmithKline, Greer Laboratories, Grifols, Horizon Pharma, Kaleo, Meda, Mylan, Novartis, Optinose, Pfizer, Regeneron, Sanofi, Shire, Teva, and Valeant Pharmaceuticals. WCM: Advisory boards and grant support – Areteia Therapeutics; AstraZeneca; Genentech; GlaxoSmithKline; National Heart, Lung, and Blood Institute; Sanofi Regeneron; and Teva, and GlaxoSmithKline. NLL: Advisory board and consultant – Amgen, AstraZeneca, Genentech, GlaxoSmithKline, Novartis, Regeneron, Sanofi, and Teva; Grant support – Amgen, AstraZeneca, Avillion Life Sciences, Gossamer Bio, Genentech, GlaxoSmithKline, Janssen, Regeneron, Sanofi, and Teva. AM: Personal fees from Verona Pharma, outside the submitted work. BC: Personal fees from AstraZeneca, Regeneron, and Sanofi Genzyme, outside the submitted work. ARM: Employee and shareholder – AstraZeneca. AWL: Employee and shareholder – Amgen. JS and CSA: Employees and shareholders – AstraZeneca. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Exacerbation rate reductions 6 months pre- and post-initiation of anti-IgE and anti–IL-5/5R/4R biologics by age of asthma onset The percentages of rate reduction were calculated only among patients with ≥1 exacerbation 6 months pre-biologic initiation (anti-IgE: n = 64; anti–IL-5/5R/4R: n = 198).
See this image and copyright information in PMC

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