B32-47 The Relationship Between Fractional Exhaled Nitric Oxide and Change in Quality of Life in Patients With COPD Treated With Dupilumab

Rationale

Blood eosinophil count (BEC) is a well-established biomarker of type 2 inflammation in chronic obstructive pulmonary disease (COPD). Fractional exhaled nitric oxide (FeNO) may represent an alternative marker of type 2 inflammation with the potential to identify additional treatment responders, but the extent to which it provides independent theragnostic information is uncertain. This post hoc analysis of pooled data from BOREAS and NOTUS assessed the relationship between baseline FeNO levels and change in quality of life (QoL) in patients with COPD treated with dupilumab or placebo.

Methods

BOREAS (NCT03930732) and NOTUS (NCT04456673) enrolled patients aged 40-85 years with COPD with moderate-to-severe airflow limitation and type 2 inflammation (screening BEC ≥300 cells/µL) on triple inhaled therapy. Patients received add-on dupilumab 300 mg every 2 weeks or matched placebo up to 52 weeks. Endpoints assessed were least squares mean change from baseline at randomization in St. George’s Respiratory Questionnaire (SGRQ) at Week 52 by log baseline FeNO stratified by baseline BEC <300 and ≥300 cells/μL. Interaction analysis was done using an analysis of covariance penalized model.

Results

A total of 827 patients receiving dupilumab and 818 patients receiving placebo were included. At Week 52, patients with elevated BEC ≥300 cells/µL or FeNO ≥20 ppb at baseline receiving dupilumab reported greater reductions in SGRQ score compared with placebo (Figure). Participants receiving dupilumab vs placebo had progressively greater improvements in SGRQ by increasing FeNO levels, irrespective of baseline BEC (<300 BEC, dupilumab range: −18.2 to − 6.6, placebo range: −7.5 to − 3.0; ≥300 BEC, dupilumab range: −17.1 to − 8.7, placebo range: −6.7 to − 8.6). Interaction analysis indicated a significant non-linear relationship between baseline FeNO and change from baseline in SGRQ with dupilumab at Week 52 compared to placebo for patients across both BEC subgroups (Figure; P=0.026).

Conclusions

At screening all patients had BECs of ≥ 300 cells/µL. We observed a significant relationship between baseline FeNO and reduction in SGRQ total score in dupilumab-treated patients with COPD with baseline BEC <300 and ≥300 cells/μL, indicating that FeNO provides predictive information independent of BEC. Our findings suggest that either elevated type 2 inflammatory biomarker (FeNO or BEC) may be used in clinical practice to help identify additional patients with COPD likely to see an improvement in SGRQ with dupilumab.

This abstract is funded by: Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.