Table 2

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

Phenotype
Endotype
Molecule
Type
TargetMain inclusion criteriaEffect on respiratory functionRef
AllergicOmalizumab
Humanised monoclonal antibody
IgESevere 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
EosinophilicMepolizumab
Humanised monoclonal antibody
Il-5Severe 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
EosinophilicReslizumab
Humanised monoclonal antibody
Il-5Inadequately 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
EosinophilicBenralizumab
Humanised monoclonal antibody
Il-5 receptorSevere 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 inflammationDupilumab
Fully human monoclonal antibody
Il-4 receptor αUncontrolled asthma despite medium to high dosage ICS and up to two controllerStatistically 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-eosinophilicTezepelumab
Fully human monoclonal antibody
TSLPUncontrolled asthma despite medium to high dosage ICSStatistically 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.