Past smoking does not influence response to biologic therapy in patients with severe asthma

Background: Many patients with severe asthma (SA) have a smoking history. Clinical trials for asthma biologics/monoclonal antibodies (mAb) excluded current smokers (CS) and ex-smokers (ES) with a significant smoking history. The effect of past smoking on mAb outcome in asthma is unclear. Aims: To determine whether smoking history impacts mAb therapy response in SA. Methods: SA patients started on omalizumab (n=101), mepolizumab (n=93) and benralizumab (n=50) before 2021 were retrospectively reviewed. ES were split into <20 pack years (PY) and ≥20PY. mAb response was defined as >50% reduction in exacerbations needing oral steroids or maintenance steroid dose at 12 months, or, for omalizumab clinical improvement at 4 months. Results: Of 252 patients, 134 were NS (53%), 72 ES with <20PY (29%), 38 ES with ≥20PY (15%) and 8 CS (3%). 96/105 (91%) had stopped smoking >5 years ago. Past smoking did not affect response to mAb: positive response in 113/134 (84%) NS, 62/72 (86%) ES with <20PY and 28/38 (74%) ES with ≥20PY. Asthma Control Questionnaire (ACQ) score improved significantly with mAb therapy in NS (2.5 to 1.6, p<0.0001), ES <20PY (2.8 to 2.0, p=0.0008) and ES ≥20PY (2.8 to 2.0, p=0.02) and there was no clinical or statistical difference in 12-month ACQ between the 3 groups. ES with ≥20PY (but not ES with <20PY) had worse lung function compared to NS (post-bronchodilator FEV1/FVC 68% NS, 66% ES <20PY, 56% ES ≥20PY, p=0.0017). Numbers of CS were low but significantly fewer had a positive response to mAb: 2/8 (25%, p=0.002). Conclusion: Almost 50% of SA patients on a mAb had a smoking history. Past smoking history did not impact clinical response to mAb in patients with SA.