Preventative treatments to reduce risk of asthma attacks
| Agent | Patient group/phenotype | Efficacy for attack reduction | Mechanisms for attack reduction | Theranostic biomarker |
| T2-targeted treatment | ||||
| ICS | Asthma (not phenotyped) | Exacerbation rate ↓50% versus placebo99 |
Reduces ‘eosinophilic’ exacerbations
ICS dose titration according to sputum eosinophil count significantly reduces eosinophilic exacerbation frequency but the rate of non-eosinophilic exacerbations was unchanged.69 | Sputum eosinophil count100 |
| Omalizumab | Adults and children with moderate to severe asthma on ICS | Exacerbation odds ↓45% (absolute risk reduction 10%) over 16–60 weeks Meta-analysis (10 studies, n=3261)101 |
Reduces IgE-mediated allergic inflammation blocks IgE–receptor interaction on mast cells, basophils and antigen-presenting cells by selectively binding free IgE.102
Reduces susceptibility to viral exacerbations 30 31 Enhances interferon (IFN)-α responses to rhinovirus (RV) via an unknown mechanism, limiting viral replication and ↓ detection of RV in nasal mucus, ↓ duration and severity of RV infection and ↓ rate of RV-associated illness. | Some evidence suggests that high levels of T2 biomarkers more likely to respond103 though not all studies are concordant104 |
| Mepolizumab (anti-IL-5) | Severe asthma Evidence of eosinophilic airway inflammation | Exacerbation rate ↓ 50%105 |
Reduces ‘eosinophilic’ exacerbations
Exacerbations in mepolizumab patients associated with a lower sputum eosinophil count, fewer symptoms and a reduced OCS treatment response than comparative events in placebo group106 suggesting residual events consistent with ‘non-eosinophilic’ exacerbations. No evidence for specific benefit on viral exacerbations Not assessed in initial phase III studies. No effect on postinfective fall in lung function or loss of asthma control107 in patients with mild asthma experimentally infected with RV. Mepolizumab-treated patients had a significantly enhanced viral load in comparison to placebo group. | Blood eosinophils ≥0.15 x 109/L108 |
| Dupilumab (anti-IL-4/IL-13 receptor) | Moderate to severe asthma and high T2 biomarkers | Exacerbation rate ↓ 50%109 |
No evidence for specific benefit on inflammatory exacerbation subtype
Possible effect on viral exacerbations Trend towards lower rates of viral URTI, bronchitis and influenza in treatment group compared with placebo group. | FeNO109
Blood eosinophils109 |
| Other treatment | ||||
| LAMA, eg, tiotropium | Asthma (not phenotyped) | Exacerbation risk ↓ 33% in addition to ICS110 |
Unclear
? due to effects on airway inflammation/mucus hypersecretion111 | None |
| LABA, eg, formoterol | Asthma (not phenotyped) | Exacerbation risk ↓~50% in addition to ICS112 |
Unclear
?synergistic effect with ICS on allergen-induced airway inflammation.113 | None |
| Leukotriene antagonists (montelukast) | Adults with asthma (not phenotyped) | Exacerbation odds ↓40% (compared with placebo)114 |
Viral exacerbations
Possible selective treatment benefit for viral exacerbations.115 | None |
| Azithromycin | Severe asthma non-eosinophilic subgroup116
Uncontrolled asthma: eosinophilic and non-eosinophilic117 | Exacerbation/ LRTI rate ↓ by 0.6/6 months exacerbation rate ↓ by ~0.8/patient year |
Unclear
Various mechanisms proposed118 including:
| None |
| Self-management plan (monitoring PEFR/symptoms with written action plan) | Adults with asthma (not phenotyped) | Risk of hospitalisation ↓ 36% compared with usual care119 | Based on early recognition of increasing symptoms or reduction in peak flow (figure 3) as trigger to escalate asthma management and reduce clinical severity of ‘peak’ attack. | Not applicable |
| Potential future treatments | ||||
| Tezepelumab (anti-TSLP) | Uncontrolled asthma: T2 high and T2 low subgroups | Exacerbation rate ↓ 62%120 |
No evidence for specific benefit on inflammatory exacerbation subtype
Viral exacerbations Effect on virally induced exacerbations not assessed in trial. In vitro: TSLP released by airway epithelial cells infected by RSV promoting a T2 inflammatory response121 suggesting suppression of this pathway may prove effective. | Effect regardless of T2 biomarker levels |
| Fevipiprant and timapiprant (prostaglandin D2 receptor antagonists) | Unknown (phase III study of fevipiprant in progress) | Fevipiprant significantly ↓ eosinophilic airway inflammation in patients with moderate to severe persistent eosinophilic asthma.122
Timapiprant resulted in a significant ↓ in the rate of respiratory tract infections,123 hence may be effective in reducing viral exacerbations. | ? Sputum eosinophils | |
FeNO, fractional exhaled nitric oxide; ICS, inhaled corticosteroid; IFN-α, interferon α; IL, interleukin; LABA, long-acting β-agonist; LAMA, long acting muscarinic antagonist ; LRTI, lower respiratory tract infection; OCS, oral corticosteroid ; PEFR, peak expiratory flow rate; RSV, respiratory syncytial virus ; RSV, respiratory syncytial virus; RV, rhinovirus; T2, type 2; TSLP, thymic stromal lymphopoietin; URTI, upper respiratory tract infection.