From the Guidelines
When addressing biologic therapy failure in severe asthma, a systematic approach is essential, prioritizing reassessment of the patient's phenotype and optimization of background controller therapy to minimize morbidity, mortality, and improve quality of life. This approach should involve reassessing the patient's phenotype to ensure the biologic matches their specific inflammatory pathway, as asthma severity and control are multifaceted and include domains of current impairment and future risk 1. For patients failing anti-IgE therapy (omalizumab), consider switching to an anti-IL5 agent such as mepolizumab (100mg subcutaneously every 4 weeks), benralizumab (30mg subcutaneously every 4 weeks for the first three doses, then every 8 weeks), or reslizumab (3mg/kg IV every 4 weeks).
Key considerations in managing biologic therapy failure include:
- Ensuring proper administration technique, consistent dosing schedule adherence, and adequate treatment duration (at least 4-6 months) to accurately assess treatment response
- Addressing comorbidities that might contribute to persistent symptoms, including GERD, chronic rhinosinusitis, obesity, and vocal cord dysfunction, as these can impact asthma control and severity 1
- Optimizing background controller therapy, ensuring proper inhaler technique and adherence to high-dose inhaled corticosteroids and long-acting beta-agonists, as high doses of inhaled corticosteroids are preferable to systemic corticosteroids due to fewer systemic effects 1
- Considering adding a long-acting muscarinic antagonist like tiotropium to further optimize control
Treatment failure may occur because biologics target specific inflammatory pathways, while severe asthma often involves multiple pathways, and some patients may have non-T2 inflammation not addressed by current biologics. Therefore, a comprehensive approach that considers the patient's overall asthma severity, control, and responsiveness to treatment is crucial in managing biologic therapy failure and improving patient outcomes.
From the Research
Addressing Biologic Therapy Failure in Severe Asthma
- Biologic therapies have revolutionized the management of severe asthma by reducing exacerbations, improving lung function, and enhancing patient quality of life 2.
- The choice of biologic therapy is mainly based on individual patient characteristics, such as the rate of exacerbations, use of systemic corticosteroids, presence of comorbidities, and lung function impairment 2, 3.
- Biomarkers, such as eosinophil threshold, can predict response to biologic therapies, including those targeting the IL-5 pathway 4.
- Multiple biologics are available for clinical use, targeting overlapping phenotypes, including allergic and eosinophilic asthma 5.
- Emerging biologics and small molecule antagonists are being developed to target other pathways of airway inflammation, including T2 low or non-T2 asthma 5.
Biologic Therapies for Severe Asthma
- Anti-IL-5 monoclonal antibodies, such as mepolizumab, reslizumab, and benralizumab, are effective and safe for severe eosinophilic asthma 6, 4.
- These biologics have been shown to improve asthma symptoms, reduce exacerbations, and demonstrate glucocorticoid-sparing effects with an acceptable safety profile 6.
- The importance of finding biomarkers that can predict response to biologic therapies remains an open issue that needs to be further explored 4, 3.
Future Directions
- Head-to-head comparison studies of biologics are needed to determine their efficacy and safety in different patient populations 2, 3.
- Novel biomarkers, including Omics studies, proteomics data, and exhaled breath analyses, may prove useful in predicting response and non-response to biologics 4.
- Future research should focus on identifying new biomarkers and developing therapeutic strategies tailored to each patient's requirements 3.