A review published in the International Journal of Molecular Science offers a “unified model” for using key biomarkers to inform biologic treatment strategies in patients with severe eosinophilic asthma.
“[Severe asthma (SA)] is associated with significant morbidity and mortality,” Ilaria Mormile, MD, PhD, and colleagues wrote. “Furthermore, the quality of life of patients with SA is significantly impaired by drug side effects, particularly [oral corticosteroids]. In this view, biological therapies have emerged as steroid-sparing tools to achieve disease control in patients with SA in the long term.”
However, not all patients benefit from biologics, and “the effectiveness of biologic therapy greatly depends on appropriate patient selection, which requires a detailed analysis of patient characteristics, medical history, and the evaluation of multiple biomarkers,” they continued.
“Endo-phenotyping patients with SA is critical for selecting a priori the optimal biologic drug from the wide currently available pharmacological armamentarium.”
In their review, Dr. Mormile and colleagues assessed the role of phenotyping and endotyping in patients with SA, focusing specifically on the impact of eosinophilic inflammation and combinatory biomarkers in the decision-making process for selecting biologic therapies.
Classifying Asthma Based on FeNO & Eosinophil Values
The review focused on the following areas:
› Asthma clinical phenotype and endotype;
› Eosinophils;
› Identifying eosinophilic asthma and combination-use biomarkers;
› Biologics available for severe asthma; and
› Selecting biologic therapy.
Based on their findings, Dr. Mormile and colleagues proposed dividing asthma into four eosinophilic categories: non-eosinophilic asthma; low eosinophilic asthma; eosinophil-associated asthma; and eosinophil-driven asthma (Infographic).
“It should be noted that evidence to support this proposed classification is currently lacking; therefore, it should be considered an eminent-based recommendation rather than evidence-based,” Dr. Mormile and colleagues wrote. “In any case, the categorization into eosinophil-associated and eosinophil-driven asthma may highlight two distinct inflammatory settings. In the former, the presence of eosinophils could represent an epiphenomenon, not necessarily playing a causal role in the underlying inflammatory process of the disease. By contrast, in eosinophil-driven asthma, eosinophils represent the key pathological determinant of the disease process.”
Choosing Treatments Based on Asthma Category
The authors followed this classification with advice for factoring eosinophil grading into choosing a biologic therapy. All the recommendations focus on monoclonal antibodies.
› For patients with non-eosinophilic asthma without allergy, treatment should be based on its ability to target non-T2 inflammation, but other options are available if the patient is allergic.
› In low eosinophilic asthma, the patient presentation can vary. For allergic individuals, they suggest three agents, including one as a first-line choice, and note that non-allergic patients would benefit from other agents, with final selection based on FeNO levels
› In eosinophil-associated asthma, the eosinophilic component is more pronounced. Allergic patients will benefit from various monoclonal antibodies, with specific choices depending on high versus low FeNO levels. Several monoclonal antibodies are beneficial for those with non-allergic eosinophil-associated asthma, with second-line options available in certain situations.
› For eosinophil-driven asthma, where eosinophils can be a primary pathological driver of disease, MAEC and/or FeNO levels should guide treatment selection. For allergic individuals, several monoclonal antibodies are recommended. Non-allergic patients, particularly those with very high eosinophil counts, are likely to benefit from several monoclonal antibodies as first-line therapy and second-line therapies as needed.
› With severe eosinophilia, three monoclonal antibodies are considered the primary therapeutic options, and the researchers noted the importance of ruling out hypereosinophilic syndrome or eosinophilic granulomatosis with polyangiitis.
“Future studies are expected to discriminate between eosinophil-driven asthma and eosinophil-associated asthma,” Dr. Mormile and colleagues wrote. “Meanwhile, the integration of multiple biomarkers, including MAEC, FeNO, and [immunoglobulin E] levels, may off er a refi ned framework for patient classification, enabling tailored therapeutic strategies. Comorbidities such as [chronic rhinosinusitis with nasal polyps], atopic dermatitis, and eosinophilic esophagitis provide additional context for therapy selection, as some biologics address both SA and these associated conditions.”
