Table 1 – Biomarker Tests Recommended For Asthma Phenotyping1
| Test | Comments | ||
| Serum lgE | • Allergic asthma • Aids in identifying allergic triggers that can be avoided |
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| Blood Eosinophils | • TH2-type inflammatory asthma | ||
| Induced sputum | • Considered gold standard test to analyze airway inflammation and inflammatory phenotype • Noninvasive test • Assesses other inflammatory cell levels (i.e. neutrophils) • Widespread use not currently feasible |
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| FeNO | • Used in asthma diagnosis • Assesses eosinophilic airway inflammation, frequency of symptoms, and frequency of use of emergency care • Steroid responsiveness biomarker (high FeNO = more likely to respond to ICS) • Authors recommend testing at diagnosis; if not possible, test patient if not responsive to high-dose ICS + LABA therapy but prior to OCS use |
Abbreviations: FeNO (fractional exhaled nitric oxide); ICS (inhaled corticosteroid); LABA (long-acting β2-agonists); OCS (oral corticosteroids); TH2 (T-helper cell type 2)
Figure 1 – Treatment Algorithm Based on Phenotype of Severe Asthma1
Abbreviations: BT (bronchial thermoplasty)
Table 2 – Treatment Options For Severe Asthma1
| Therapy | Background | Data | Panel Recommendations | ||||||||||||
| Tiotropium | • Maintenance therapy for asthma patients ≥6 years old • Dosed once daily • MOA: airway muscarinic acetylcholine receptor antagonist |
• Superior to doubling dose of ICS; non-inferior to ICS+ LABA therapy in African American patients with uncontrolled asthma • Increases time to severe exacerbations in poorly controlled asthma patients receiving ICS + LABA • Improves FEV1 at 12 weeks in 6-17-year-old severe asthma patients receiving controller therapy • AEs: asthma, bronchitis, peak expiratory flow rate decrease, headache, rhinitis, nasopharyngitis, infection (respiratory tract, viral), tonsillitis |
• Add to high-dose ICS + LABA therapy in uncontrolled asthma patients • Should be used prior to daily OCS therapy, new biologics, and BT • Aim: lung function improvement, symptom control, prevention of exacerbations |
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| Omalizumab | • Treatment of moderate-to-severe persistent asthma in patients ≥6 years old with uncontrolled symptoms despite ICS therapy • Patient must have either a positive skin test reaction or in vitro reactivity to a perennial aeroallergen and serum IgE ≥30 IU/mL |
• Decreased exacerbations by 25% and improved QOL in patients with severe asthma not controlled by high-dose ICS + LABA o Decrease of exacerbations greater in patients with higher TH2 biomarker levels • Effectiveness and safety is sustained long-term in children and adults |
• Should be considered first line for IgE+ allergic severe asthma patients who have failed high-dose ICS + LABA + tiotropium therapy • Use prior to OCS, new biologics, or BT |
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| IL-5 Target Therapies • Mepolizumab, reslizumab: anti-IL-5 antagonist mAb • Benralizumab: eosinophil IL-5 receptor blocker |
Mepolizumab: • Add-on maintenance therapy in severe asthma patients ≥12 years old with an eosinophilic phenotype (≥150 cells/uL at screening or ≥300 cells/uL within 1 year prior to enrollment) |
Mepolizumab: • Efficacy has been demonstrated in patients with severe asthma and eosinophilia in several trials |
• Should be considered first line for eosinophilic severe asthma patients who have failed high-dose ICS + LABA + tiotropium therapy • Use prior to OCS, new biologics, or BT • Can be used for patients with IgE+ with eosinophilia that inadequately responded to omalizumab • No recommendation on which IL-5 agent should be used first |
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Reslizumab: • Add-on maintenance therapy in severe asthma patients ≥18 years old with an eosinophilic phenotype (≥400 cells/uL) |
Reslizumab: • Efficacy has been demonstrated in patients with severe asthma and eosinophilia in several trials |
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Benralizumab: • Add-on maintenance therapy in severe asthma patients ≥12 years old with an eosinophilic phenotype2 • Increased efficacy due to IL receptor blockade, causing luminal depletion of eosinophils |
Benralizumab: • Demonstrated decreased oral maintenance glucocorticoid therapy use and sustained asthma control in severe eosinophilic asthma patients |
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| Macrolide Antibiotics | • Used in patients with poor symptom control who test positive for M pneumoniae and C pneumoniae • MOA unclear; believed to exert therapeutic effect through antimicrobial and anti-inflammatory properties |
• Improved predicted FEV1 percentage and Asthma Control Test scores after 6 months of treatment | • Should be considered in patients with non-TH2 type inflammation asthma | ||||||||||||
| BT | • Used in adult severe asthma patients with uncontrolled symptoms despite ICS and long-acting bronchodilator treatment • Decreases smooth muscle mass in airways by ≥60%, alters collagen deposition, decreases -smooth muscle actin, reduces inflammatory cytokines • Uses the Alair Bronchial Thermoplasty System to deliver thermal energy targeted at different areas of the lung • Conducted in 3 sessions (at 3 week intervals) |
• Asthma Research Intervention (AIR) trial: moderate-to-severe asthma patients experienced a reduction in mild exacerbations and an increase in symptom-free days, asthma control, and QOL vs control at 3 and 12 months • Sham-controlled AIR-2 trial: increase in QOL, and decrease in lost work days, severe exacerbations (32%), and health care usage • 5-year trial follow-ups: sustained reductions in exacerbations and health care resource usage, and no additional decline in lung function was seen • AEs: temporary respiratory-related symptom worsening |
• First option for patients with nonallergic, non-eosinophilic severe asthma with persistent symptoms and variable airflow obstruction after failing therapy with high-dose ICS + LABA + tiotropium • Use prior to OCS or targeted biologic • An alternative treatment option for allergic or eosinophilic asthma patients with an inadequate response to therapy with biologics |
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| Dupilumab | • Currently being investigated • Inhibits signaling of IL-4 and IL-13 cytokines of TH2 cells by binding to the IL-4 receptor |
• Early investigation showed decrease in odds of asthma exacerbations • Phase 2b study: improved FEV1 by 210-260 mL vs placebo and decreased exacerbations by 54-71% in patients with severe asthma despite treatment with medium- to high-dose ICS + LABA • AEs: upper respiratory tract infection, injection site reactions |
• Will likely be considered a therapeutic option for the treatment of eosinophilic and non-eosinophilic, elevated FeNO severe asthma after failing high-dose ICS + LABA + tiotropium and prior to OCS use | ||||||||||||
Abbreviations: AEs (adverse events); BBW (black box warning); BT (bronchial thermoplasty); FeNO (fractional exhaled nitric oxide); FEV1 (forced expiratory volume in 1 second); ICS (inhaled corticosteroid); IgE (immunoglobulin E); IL (interleukin); IV (intravenous); LABA (long-acting β2-agonists); mAb (monoclonal antibody); MOA (mechanism of action); OCS (oral corticosteroids); QOL (quality of life); TH2 (T-helper cell type 2)
