Lung function trajectories in a cohort of patients with moderate-to-severe asthma who initiated mepolizumab, omalizumab, and dupilumab therapy

Rationale: Prebronchodilator forced expiratory volume in one second (FEV1) is an independent predictor of asthma exacerbations and mortality. We sought to describe the lung function trajectories of a clinical cohort of patients who received omalizumab, mepolizumab, or dupilumab.

Methods: We identified 194 monoclonal antibody-naïve adult patients with moderate to severe asthma who initiated omalizumab, mepolizumab, or dupilumab between 2010 and 2022 at Mass General Brigham in Boston, MA using the electronic health records (EHR). Generalized additive mixed models were used to estimate the FEV1 trajectory during the 24 months before and the 36 months after biologic initiation. ‘Responders’ were defined as patients with an improvement in FEV1 or a decrease in FEV1 of ≤0.5% per year. The Kaplan-Meier estimator was used to assess time to maximum post-initiation FEV1 in responders. All models were adjusted for age, sex, body mass index, smoking status, baseline exacerbation rate, and eosinophil counts.

Results: Seventy-five patients initiated mepolizumab, 66 omalizumab, and 53 dupilumab. The rate of FEV1 change was stable from before to after biologic initiation in mepolizumab (-27 mL/yr.) and omalizumab patients (+27 mL/yr.). The individuals who initiated dupilumab showed a reversal of FEV1 decline in the first two years, -82 mL/yr. to +51 mL/yr., after which the effect wore off. Fifty-five percent of the mepolizumab group were responders, 59% of omalizumab, and 72% of dupilumab. The time to maximum post-initiation FEV1 in responders was 6 months for omalizumab, 10 months for mepolizumab, and 15 months for dupilumab. The FEV1 improvement was sustained for over 12 months in 55% of dupilumab responders, 41% of mepolizumab, and in 23% of omalizumab responders.

Conclusions: In this EHR-based study, mepolizumab, omalizumab, and dupilumab had beneficial effects on FEV1 improvement with distinct post-initiation trajectories and duration of sustained effects.