Clinical studies in asthma usually exclude smokers or ex-smokers with >10 pack-years (PY). Thus the efficiency of biological (BT) in severe smoking asthmatics is unknown.

We analysed the real-life severe asthma registry cohort treated with biological to evaluate the impact of smoking on clinical outcomes.

At week 16 and 52 we analysed exacerbation, lung function, asthma control, biomarkers and compared never-smokers (NS) with (ex)smokers (<10 PY, 10-20 PY, >20 PY). Linear models were fitted for each endpoint. Binary or ordinal logistic regression models were computed for non-linear endpoints.

1129 patients (44,2% males, mean age 53,8, 1,5% active smokers, <10 py (22.9%), 10-20 py (10.3%) and >20 Py (10.6%) received Benralizumab (38,3%), Dupilumab (28,9 %), Mepolizumab (18,3%), Omalizumab (14 %) or Reslizumab (0,53%). ACT improved more in NS at w16 (n=607; p=0.02; +4,2 p. in NS, +3,33 in average smoker (AS), +2,9 if >20 PY (p<0.001), with no difference at w52 (p=0.48). ACQ-5 and miniAQLQ (w52) improved similarly (p=0.094, p=0.1537). The odds of an uncontrolled asthma (w52) in AS compared to NS were 1.04 (p=0.83). FEV1 change (n=431, p=0.2756) and exacerbation rate (n=123, p=0.56) were similar (w52). Rel. diff. NS/AS (w52) was not significant for FVC (p=0.3958), Rtot (p=0.0583), PEF (p=0.137), RV and TLC (p=0.77). FeNO changed (w52) by factor of 0.69 in NS, 0.64 in AS (p<0.001) and 0.69 (p=0.0153) if >20 PY (NS/AS p=0.4799). Rel. diff. between NS and AS was 1.64 (w16; p=0.365) and 1.72 (p=0.486) at w52 for EOS and 0.96 (p=0.909) for total IgE (w52).

After 1 year under BT, AS have similar improvement in asthma control, exacerbations, lung function, FeNO, EOS and total IgE as NS.