Reply to Yilmaz: Selection of Biologics for Type 2-High Asthma.

From the Authors:

We thank Dr. Yilmaz for the thoughtful comments in his letter to the editor regarding our review, “Role of Biologics in Asthma” (1).

Dr. Yilmaz makes an important point when discussing atopic asthma as a type 2 (T2)-high condition. The PROSPERO (Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab) study we referenced demonstrates similar benefits of omalizumab in patients with both high and low absolute blood eosinophil counts and fractional exhaled nitric oxide levels (2). Although these are important biomarkers of T2 inflammation, allergic (atopic) asthma is also driven by T2 inflammation, and thus it is better to describe these subgroups of allergic asthma as high- and lower-biomarker groups rather than T2-high and -low groups. The important takeaway point from the PROSPERO trial was that patients who were deemed candidates for omalizumab in a real-world setting responded irrespective of their biomarker profile, and thus omalizumab should be considered in patients with allergic asthma regardless of the biomarker levels. However, if the patients have asthma that is severe enough to require high-dose maintenance corticosteroids, anti-IgE therapy is unlikely to be effective even if the patients are atopic (3), implying that IgE may not be the main driver of symptoms in those patients.

The recently updated 2019 GINA (Global Initiative for Asthma) guidelines (4) do suggest that blood eosinophils ≥ 260/μl, fractional exhaled nitric oxide ≥ 20 ppb, allergen-driven symptoms, and childhood-onset asthma may be predictors of response to anti-IgE therapy. As noted in our review, although retrospective analyses have suggested that patients with high biomarker profiles treated with omalizumab may have a greater reduction in exacerbation rates (5), this difference may be a result of the higher rate of exacerbation in the high biomarker group. Future studies that prospectively evaluate factors that predict response to omalizumab and other biologics are paramount in the era of precision medicine.