Abstract Rationale Traditionally used spirometry parameters, such as forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25 and 75% (FEF25-75%) of forced vital capacity (FVC), may be misleading in informing asthma treatment decisions. Spirometry-derived ratios are better at assessing changes in airway function relevant to asthma control. In particular, FEF25-75% is highly volume dependent, but it may be more valuable when adjusted for the volume as in the ratio FEF25-75%/FVC. We evaluated the effect of dupilumab on spirometry-derived ratios in patients with asthma and assessed the relationship between changes in these ratios and changes in fractional exhaled nitric oxide (FeNO) and eosinophil count. Methods In the phase 4 VESTIGE study (NCT04400318), adults with uncontrolled, type 2 (eosinophils ≥300 cells/µL and FeNO ≥25 ppb), moderate-to-severe asthma received dupilumab 300 mg (n = 72) or placebo (n = 37) every 2 weeks for 24 weeks. We calculated pre-bronchodilator ratios as FEV1/FVC (reflecting large airways) and FEF25-75%/FVC (small airways). We used a penalized regression spline model to evaluate the relationships between changes in these ratios and changes in FeNO and eosinophil count from baseline to Week 24. Results Baseline ratios were similar in the dupilumab and placebo groups but differed significantly in both groups by Week 24. The baseline mean (standard deviation SD) FEV1/FVC ratio was 60.7% (11.5) with dupilumab and 61.8% (13.9) with placebo; at Week 24, dupilumab vs placebo improved the ratio by a least squares mean difference (LSMD) of 6.8% 95% CI: 3.4, 10.2; P0.001. The baseline mean (SD) FEF25-75%/FVC ratio was 34% (24) with dupilumab and 37.8% (25.9) with placebo; at Week 24, dupilumab vs placebo improved by an LSMD of 12.2% 5.2, 19.1; P0.001. As the fold change from baseline at Week 24 in eosinophil count increased (Figure), the value of each spirometry ratio decreased (i.e. lung function worsened) with placebo but was stable with dupilumab. Hence, large and small airway function improved regardless of increasing eosinophil count in patients who received dupilumab but not in those who received placebo. Similarly, both ratios improved from baseline for all fold changes in FeNO for the dupilumab group but not the placebo group. Conclusion Dupilumab vs placebo significantly improved spirometry-derived ratios at Week 24, indicating improved large and small airway function, while the beneficial effect of dupilumab relative to baseline was similar for all patients regardless of their change in eosinophil count. This abstract is funded by: Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.
Shirai et al. (Fri,) studied this question.
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