Obesity alters asthma biologic efficacy, with tezepelumab showing benefit and GLP-1RAs emerging as promising

The obese asthma phenotype is a growing concern, characterized by increased disease severity, poorer symptom control, and altered treatment response compared to non-obese asthmatics. This distinct presentation stems from complex interactions involving mechanical factors, chronic low-grade systemic inflammation, and metabolic dysfunction. While biologics target specific inflammatory pathways in severe asthma, obesity-related metabolic and inflammatory changes can significantly diminish their effectiveness. Understanding this interplay is crucial for optimizing management strategies.

This narrative review systematically assessed current evidence regarding the intricate link between obesity, airway inflammation, lung function, and the efficacy of biologic treatments in asthma. The authors synthesized findings from existing literature to characterize the obese asthma phenotype, evaluate the performance of current biologics in this population, and identify emerging therapeutic strategies. The review aimed to provide a comprehensive overview of proposed mechanisms for altered biologic responses and highlight critical areas for future research.

Obese asthma patients frequently exhibit a shift towards a T2-low endotype, characterized by increased airway neutrophils and altered cytokine profiles, although both T2-high and T2-low endotypes can be present. Current biologics, which target specific cytokines, demonstrate varying results in treatment efficacy within this population. > Tezepelumab consistently shows the most benefit among existing biologics for obese asthma patients, suggesting its broader mechanism of action may be advantageous. Reduced efficacy of other biologics is proposed to involve altered pharmacokinetics/dynamics and modifications to inflammatory and immunologic pathways. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are identified as promising emerging therapies, with mechanisms of action extending beyond simple weight reduction, suggesting a direct impact on obesity-related inflammatory pathways relevant to asthma.