P103 The relationship between FeNO and response to anti-IL5/5R biologic therapies in severe eosinophilic asthma

Introduction

Mepolizumab and benralizumab target the IL-5/eosinophil pathway and are highly effective therapies for severe eosinophilic asthma (SEA). Fractional exhaled nitric oxide (FeNO) is a marker of IL-13 and elevated baseline levels are associated with an improved response to the anti-IL4R mAb dupilumab. However, FeNO was not measured in the phase 3 program for either mepolizumab or benralizumab and so it is unclear whether this same relationship exists for these therapies as well.

Methods

We performed a retrospective analysis of adult patients with SEA who had received Mepolizumab and Benralizumab at our tertiary severe asthma centre. Clinical characteristics including asthma control (ACQ6), annualised exacerbation rate (AER), maintenance OCS (mOCS) requirements and T2 biomarkers were recorded at baseline and at regular intervals throughout the first year of treatment. Patients were stratified into quartiles according to their baseline FeNO and the clinical effectiveness of mepolizumab and benralizumab compared between FeNO groups.

Results

229 patients (99 mepolizumab, 130 benralizumab) were included in the analysis. Stratifying the cohort according to baseline FeNO produced quartile ranges of <26, 26–43, 44–74 and >74. With the exception of FeNO there was no difference in baseline characteristics between the FeNO groups. Both mepolizumab and benralizumab significantly improved all clinical outcome measures of interest, however, the degree of clinical response did not appear to differ between the FeNO groups (figure 1). Following initiation of anti-IL5/5R treatment, numerically large and statistically significant reductions in FeNO level was seen in only the highest FeNO quartile (Q4): baseline median FeNO 96ppb (IQR 85-136ppb), 1 year median 64.5ppb (IQR 37-107), p <0.001.

Conclusion

Although FeNO is a biomarker of IL-13 biology, we highlight that high FeNO is associated with an excellent response to anti-IL5/5R therapies in a real-world setting. This calls into question the unproven notion that severe eosinophilic patients with high baseline FeNO may derive superior outcomes with dupilumab as compared to mepolizumab or benralizumab.