Table 2.
Summary on biologic therapies for the treatment of severe asthma and with their clinical effects and confirmed effects on AR.
| Drug | Form | Target | Biological effects | Clinical effects | Effects on airway remodeling | Other fda-approved indications | |
|---|---|---|---|---|---|---|---|
| FDA—approved monoclonal antibodies for treatment of moderate-to-severe asthma | Omalizumab | Humanized IgG1/κ, monoclonal antibody | IgE | ° ↓ circulating total IgE ° Down-regulation of FcεRI receptors on basophils, mast cells, and dendritic cells |
° Improvement of lung function (FEV1) ° Improvement of quality of life (AQLQ) ° Improvement of asthma control (ACT) ° ↓ oral and inhaled corticosteroid use ° Reduction in exacerbation and hospitalization frequency (59) |
° Reduction of production of TNF-α, TGFβ and IL-4 in bronchial epithelial cells (72) ° Prevention of ASM cell remodeling in vitro(73) ° Reduction of airway wall thickness in computed tomography (74, 75) |
° Chronic idiopathic urticaria |
| Mepolizumab | Humanized IgG1/κ, monoclonal antibody | IL-5 | ° Blockage of IL-5/IL-5R binding on eosinophils ° ↓ blood eosinophils ° ↓ sputum eosinophils |
° Reduction in exacerbation frequency vs placebo ° Improvement in AQLQ vs placebo ° No significant effect on FEV1, PEF, PC20(76) |
° Reduction of airway remodeling markers (tenascin, lumican, and procollagen III) and airway eosinophils expressing TGFβ1 in bronchial reticular basement membrane and reduction of TGFβ1 in bronchioalveolar lavage after mepolizumab treatment (77) ° Reduction of AR observed in computed tomography (78) |
NA | |
| Benralizumab | Humanized IgG1/κ, monoclonal antibody | IL-5 Receptor alpha subunit (IL-5Rα) | ° ↓ eosinophils and basophils via antibody dependent cell mediated cytotoxicity (ADCC) | ° Reduction in exacerbation frequency ° No significant effect on FEV1 ° Mixed data on quality of life and asthma symptom scores (79) |
° Decrease in airway smooth muscle mass (predicted using computational modeling approach) (80) | NA | |
| Dupilumab | human IgG4 monoclonal antibody | IL-4 Receptor alpha subunit (IL-4Rα) | ° Blockage of IL-4/IL-4Rα binding ° Blockage of IL-13/ IL-4Rα binding |
° Reduced rate of severe asthma exacerbations and improved lung function (FEV1), asthma control and quality of life (81, 82) | Studies on in vitro or in vivo effects of dupilumab on airway remodeling are currently non-available | ° Eczema ° Moderate-to-severe atopic dermatitis in adolescents ° Chronic rhinosinusitis with nasal polyps |
|
| Resliuzmab | humanized IgG4/κ mAb | IL-5 | ° Blockage of IL-5/IL-5R binding ° ↓ circulating eosinophils ° ↓ sputum eosinophils |
° Reduced exacerbations, improved FEV1, forced vital capacity, the 7-item Asthma Control Questionnaire (83) | Studies on in vitro or in vivo effects of reslizumab on airway remodeling are currently non-available | NA | |
| Drugs investigated (currently or previously) in severe asthma treatment | Secukinumab | human IgG1κ monoclonal antibody | IL-17A | ° Blockage of IL17A -, −17F -, −17A/F heterodimer -, and −17E–(IL-25)/IL-17RA binding | NA | Studies on in vitro or in vivo effects of secukinumab on airway remodeling are currently non-available | ° Plaque psoriasis ° Psoriatic arthritis ° Ankylosing spondylitis ° Discontinued in asthma |
| Brodalumab | human, IgG2 monoclonal antibody | IL-17 receptor A (IL-17RA) | ° Blockage of IL17A -, −17F -, −17A/F heterodimer -, and −17E–(IL-25) /IL-17RA binding | ° No significant improvement in lung function (FEV1) and asthma control in subjects with inadequately controlled moderate to severe asthma (84) | Studies on in vitro or in vivo effects of brodalumab on airway remodeling are currently non-available | Plaque psoriasis | |
| Tralokinumab | Human IgG4 monoclonal antibody | IL-13 | ° Blockage of IL-13/IL-13Rα1 ° Blockage of IL-13/IL-13Rα2 binding |
° Inconsistent effects on annualized asthma exacerbation rate (85)—development of tralokinumab in severe asthma was discontinued by the producer after this study (86) | ° No significant effect on bronchial eosinophilic count ° No significant reduction of airway remodeling in bronchial biopsy features–Airway smooth muscle |
° None available (possibly in atopic dermatitis in the future) (88) ° Discontinued in asthma |
|
| ° No significant improvement of lung function (FEV1) (87) | area, RBM thickness, collagen type IV, periostin, TGFβ and other (87) | ||||||
| Secukinumab | Humanized IgG4 monoclonal antibody | IL-13 | ° Blockage of IL-13/IL-13Rα1 ° Blockage of IL-13/IL-13Rα2 binding |
° Decrease in asthma exacerbations incidence ° Improved lung function (FEV1%) (89) |
° Greater clinical effects (decrease in exacerbation rate and improvement in lung function) in patients with high serum periostin levels – a protein contributing to airway remodeling (90) | ° None available (possibly in atopic dermatitis in the future)(91) ° Discontinued in asthma |
|
| Tezepelumab (AMG 157) | human, IgG2 monoclonal antibody | TSLP | ° Blockage of TSLP/TSLP-receptor binding | ° Inhibition of late allergen-induced asthmatic response (FEV1) (92) ° Reduction of annualized asthma exacerbation rate (93) |
° Studies on in vitro or in vivo effects of tezepelumab on airway remodeling are currently non-available | NA |
The table includes approved and emerging therapies with published human data. NA, none available.