Impact of smoking on biological treatment response in patients from the German Severe Asthma (GAN) Registry.

Background: Clinical studies of biologics in severe asthma exclude smokers or ex-smokers (ExS) with over 10 pack-years (py). Thus, the effectiveness of this therapy in ex-smokers with severe asthma is not well understood.

Objectives: To assess the impact of smoking on clinical efficiency of biologics in patients with severe asthma from the German Asthma Net (GAN), a comprehensive international registry.

Methods: This analysis included 1129 patients (55.8 % females, mean age 53.82 ± 14.67) from which 56% were never-smokers (NS), while 44% were ExS (<10 py: 22.9%, 10-20 py: 10.3%, >20 py: 10.6%). They received benralizumab (38.3%), dupilumab (28.9%), mepolizumab (18.3%), omalizumab (14%), or reslizumab (0.5%).

Results: Biologic therapy significantly improved asthma control, measured by change in ACT, ACQ-5, and miniAQLQ, lung function, reduced exacerbations and daily oral prednisolone dose in all patients at week 52. Of note, no significant differences in asthma control between NS and ExS at week 52 (P=0.48, 0.09, and 0.15, respectively), were observed. Also, lung function improvement (FEV1, FVC, TLC, PEF, MEF50, P>0.05), reduction in AE (P=0.8) and OCS doses (P=0.15) were comparable in NS and ES. Markers of type 2 inflammation, such as fraction of exhaled nitric oxide (FeNO) and blood eosinophils, decreased in ex-smokers similarly to never-smokers (P=0.29 and P=0.48 respectively).

Conclusion: In summary, ex-smokers with severe asthma experienced similar improvements in asthma control, exacerbations, lung function and biomarkers as NS after one year of biologics, suggesting that severe asthmatics even with a substantial smoking history can benefit from biologic therapy.