Exploratory Analysis of the Roles of Multiple Biomarkers in Predicting Response to Omalizumab in Allergic Asthma

Rationale: Biomarkers of Type-2 (Th2-high) inflammation, such as fractional exhaled nitric oxide (FeNO) and peripheral blood eosinophils (EOS), appear to predict response to biologic treatments in patients with severe asthma.  However, the relative value of assessing multiple biomarkers simultaneously in predicting response to biologics in allergic asthma has not been established.

Methods: Predictive properties of FeNO, within high and low EOS subgroups, were evaluated in patients with severe allergic asthma in this post-hoc analysis of the 48-week EXTRA study of omalizumab (Hanania et al, 2011). Patients were divided into predefined subgroups based on cohort median levels of FeNO (low [<19.5 ppb] or high [≥19.5 ppb]) and EOS (low [<260/μL] or high [≥260/μL]). Treatment effect was evaluated as the number of observed protocol-defined exacerbations, controlling for pre-specified protocol-defined covariates.

Results: Patients with higher FeNO and treated with omalizumab demonstrated clinically relevant mean reductions in exacerbation frequency vs placebo whether or not their EOS were high (53.1% [95%CI: 18.7%, 72.9%]; n=120; p=0.007) or low (51.0% [95%CI: −2.8%, 76.7%]; n=68; p=0.059).  Among patients with lower FeNO, exacerbation reduction response to omalizumab appeared less pronounced (7.1% [95%CI: −102%, 57.4%]; n=70; p=0.85) among EOS high and (18.0% [95%CI: −44.9%, 53.6%]; n=108; p=0.50) among EOS low.

Conclusions: These findings suggest that multiple biomarkers of T2 may be important in optimally stratifying patients according to possible biologic treatment responses. Caution must be used in interpretation of results, given their post-hoc nature and the availability of both FeNO and EOS data in only a single omalizumab clinical trial.