Table 2.

Effect of approved biotherapies on pulmonary function tests in allergic and eosinophilic severe asthma (phase III trials)

Phenotype Endotype	Molecule Type	Target	Main inclusion criteria	Effect on respiratory function	Ref
Allergic	Omalizumab Humanised monoclonal antibody	IgE	Severe asthma with high dose ICS Positive SPT to aeroallergen Serum total IgE 30–700 IU/mL	Improved morning PEF +2.8% predicted FEV1 in comparison with placebo	15 106
Eosinophilic	Mepolizumab Humanised monoclonal antibody	Il-5	Severe asthma with high dosage ICS. Peripheral blood eosinophils count≥150/mm3 at screening or ≥300/mm3 during the previous year. + Maintenance treatment with systemic corticosteroids (5–35 mg of prednisone or equivalent)4	Slight improvement of pre-BD and post-BD FEV1 (+98 mL, +138 mL, respectively) in comparison with placebo Statistically non-significant improvement of pre-BD and post-BD FEV1 in the corticosteroid weaning trial	14 151
Eosinophilic	Reslizumab Humanised monoclonal antibody	Il-5	Inadequately controlled asthma despite at least medium dosage ICS. Peripheral blood eosinophils count≥400/mm3	Statistically significant improvement of pre-BD FEV1 in comparison with placebo (+0.11 L LS mean)	152
Eosinophilic	Benralizumab Humanised monoclonal antibody	Il-5 receptor	Severe asthma with high dosage ICS. Baseline peripheral blood eosinophils count≥300/mm3	Statistically significant improvement of pre-BD FEV1 in comparison with placebo in SIROCCO and CALIMA studies (+159 mL and +116 mL, respectively, LS mean)	16 153 154
Type-2 inflammation	Dupilumab Fully human monoclonal antibody	Il-4 receptor α	Uncontrolled asthma despite medium to high dosage ICS and up to two controller	Statistically significant improvement of pre-BD FEV1 in comparison with placebo at 12 wks (+130 mL LS mean) and 24 wks (+ 220 mL LS mean).	17 108
Eosinophilic and non-eosinophilic	Tezepelumab Fully human monoclonal antibody	TSLP	Uncontrolled asthma despite medium to high dosage ICS	Statistically significant improvement of pre-BD FEV1 in comparison with placebo at 52 wks (+130 mL LS mean)	110

BD, bronchodilators; FEV1, forced expiratory volume in one second; ICS, inhaled corticosteroid; IgE, immunoglobuline E; IL-5, interleukine 5; LS, least squares; PEF, peak expiratory flow; SPT, skin prick test; TSLP, thymic stromal lymphopoietin; wks, weeks.