Upper airway disease diagnosis as a predictive biomarker of therapeutic response to biologics in severe asthma

Abstract

Asthma is a heterogeneous disease sharing airway instability but with different biology, risk factors, and response-to-therapy patterns. Biologics have revolutionized the one-size-fits-to-all approach to personalized medicine in severe asthma (SA), which relies on the identification of biomarkers that define distinct endotypes. Thus, blood eosinophils and, to some extent, exhaled nitric oxide (FeNO) can predict the response to approved anti-type 2 (T2) biologics (anti-IgE, anti-IL-5, and anti-IL-4R alpha), whereas age at onset and comorbidities such as anxiety/depression, obesity, reflux, and upper airway disease (UAD) also influence therapeutic responses in SA. In this article, focusing on the predictive value of biomarkers for the therapeutic response to biologics in SA, we first summarize the level of prediction achieved by T2 biomarkers (blood eosinophils, FeNO) and then review whether data support the predictive value of upper airway diagnosis on such outcomes. Post hoc analysis of most studies with T2 biologics suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) and, to a lower extent, allergic rhinitis may help in predicting clinical response. Considering that T2 biologics are now also approved for the treatment of severe CRSwNP, diagnosis of upper airway disease is a key step in determining eligibility for such therapy.

Keywords: nasal polyposis; predictive biomarker; severe asthma; theragnostics; upper airway disease.

Figure 1

The “ABC” sets of biomarkers that influence the response to biologics in severe asthma, illustrated by their respective estimated impact on the response to anti–IL-5 therapies. For instance, the impact calculated (odds ratio, OR) for adult onset and CRSwNP on the probability to be defined as a responder to mepolizumab in a “real-life” series (88) were 1.20 and 1.36 (vs. the absence of CRSwNP), while it was not significant for eosinophils. Inset, illustrating the impact of UAD (in particular CRSwNP) on asthma outcomes upon biotherapy.