From the Guidelines
For poorly controlled asthma without elevated biomarkers, consider a trial of omalizumab (Xolair) as the first-line biologic therapy, given its mechanism of action and potential benefits in reducing airway inflammation and hyperresponsiveness, as supported by the 2019 study by the aaaai mast cell disorders committee work group report 1. When initiating omalizumab, it is essential to start with weight-based dosing every 2-4 weeks via subcutaneous injection, typically 150-375 mg depending on weight and baseline IgE. Before initiating therapy, perform baseline spirometry and assess symptom control using validated questionnaires like ACT or ACQ. The mechanism of omalizumab involves blocking free IgE and downregulating high-affinity IgE receptors on inflammatory cells, potentially addressing inflammatory pathways not reflected in standard biomarker testing, as noted in the study 1. Key points to consider when using omalizumab include:
- Monitoring treatment response after 4-6 months, looking for reduced exacerbations, improved symptom control, and decreased rescue medication use
- Considering alternative biologics like dupilumab (Dupixent) if omalizumab fails, which targets IL-4/IL-13 pathways and may work independently of traditional biomarkers
- Recognizing that omalizumab may still benefit patients through its action on IgE-mediated pathways that contribute to airway inflammation and hyperresponsiveness, despite the absence of elevated markers like eosinophils, periostin, or FeNO.
From the Research
Biologic Markers for Poorly Controlled Asthma
- In patients with poorly controlled asthma and no elevated markers, several biologic markers can be considered, including:
- These biologic markers are associated with different asthma endotypes, and identifying the correct endotype is crucial for effective treatment 3, 4, 5
Treatment Options
- Omalizumab is a therapeutic agent for bronchial asthma that targets IgE, and is considered an option for patients with severe allergic asthma 2
- Benralizumab, an anti-IL-5R monoclonal antibody, has been shown to be effective in reducing disease-related morbidity and hospitalizations due to asthma exacerbations in patients with higher systemic eosinophil burden and higher doses of inhaled corticosteroids 3
- Mepolizumab and dupilumab are also effective in reducing exacerbation rates and improving lung function in patients with eosinophilic asthma 5
Comparative Efficacy
- A Bayesian network meta-analysis compared the efficacy of mepolizumab, benralizumab, and dupilumab in individuals with severe eosinophilic asthma, and found minimal differences in efficacy and safety between the three biologics 5
- Benralizumab and mepolizumab were more effective in improving the NP endoscopic score and the blood eosinophil count, while omalizumab had a greater effect on nasal pruritus 4