Omalizumab in Asthma with Fixed Airway Obstruction: Post Hoc Analysis of EXTRA.

Abstract

BACKGROUND:

Although asthma is typically characterized by bronchodilator responsiveness (BDR), fixed airflow obstruction (FAO) occurs in ∼50% of patients with severe asthma.

OBJECTIVE:

Do FAO/BDR associate with efficacy of omalizumab, a monoclonal antibody that targets IgE?

METHODS:

In EXTRA, patients aged 12-75 years with inadequately controlled severe allergic asthma despite high-dose inhaled corticosteroids plus long-acting β2-agonists were randomized to omalizumab (n = 427) or placebo (n = 423) for 48 weeks of treatment. In this post hoc analysis, high/low BDR were defined as ≥12%/<12% increases in baseline forced expiratory volume in 1 second (FEV1) after bronchodilator administration, respectively. FAO presence (+)/absence (-) were defined as baseline postbronchodilator FEV1/forced vital capacity <70%/≥70%, respectively. Poisson regression/analysis of covariance models were used to estimate exacerbation relative rate reductions (RRRs)/least-squares mean changes in FEV1, respectively.

RESULTS:

In patients with high BDR, omalizumab reduced exacerbations more than placebo over the 48-week treatment period regardless of FAO status (RRR [95% confidence interval (CI)]: FAO+, 59.8% [17.7-80.4%]; FAO-, 44.3% [16.6-62.8%]). Omalizumab improved FEV1 compared with placebo in the FAO-, high BDR subgroup (FEV1 change from baseline [95% CI] for omalizumab vs placebo, 0.065 L [-0.071 to 0.201 L] to 0.236 L [0.112-0.359 L]) across 48 weeks. This was not observed in patients with low BDR, irrespective of FAO.

CONCLUSION:

Omalizumab was more efficacious than placebo at reducing exacerbations in patients with high, but not low, BDR, regardless of the presence of FAO. Lung function improvement primarily occurred in FAO-, high BDR patients, suggesting that asthma with low BDR may represent a difficult-to-treat phenotype.

• Authors: Nicola A Hanania, Spyridon Fortis, Tmirah Haselkorn, Sachin Gupta, Nayla Mumneh, Bongin Yoo, Cecile T J Holweg, Bradley E Chipps
• Journal: The journal of allergy and clinical immunology. In practice (J Allergy Clin Immunol Pract) Vol. 10 Issue 1 Pg. 222-228 (01 2022) ISSN: 2213-2201 [Electronic] United States
• PMID: 34419680 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Asthmatic Agents
• Omalizumab

Topics

• Adolescent
• Adult
• Aged
• Airway Obstruction (drug therapy)
• Anti-Asthmatic Agents (therapeutic use)
• Asthma (drug therapy)
• Child
• Forced Expiratory Volume
• Humans
• Middle Aged
• Omalizumab (therapeutic use)
• Treatment Outcome
• Young Adult