Biologic therapy for asthma involves the use of monoclonal antibodies that target specific inflammatory pathways implicated in the pathogenesis of severe asthma: particularly those driven by type 2 (T2) inflammation.
Biologic therapy for asthma is indicated for patients with severe asthma who are inadequately controlled on standard treatments, such as high-dose inhaled corticosteroids and long-acting beta-agonists.
The currently approved biologics for asthma include: Omalizumab: An anti-IgE antibody used primarily for allergic asthma.
Omalizumab (Xolair)
Targets Immunoglobulin E (IgE), which plays a key role in allergic responses.
Indicated for patients with moderate to severe allergic asthma and high IgE levels.
Mepolizumab, Reslizumab, and Benralizumab: These target IL-5 or its receptor, reducing eosinophilic inflammation.
Mepolizumab (Nucala)Targets interleukin-5 (IL-5), which is involved in the growth and activation of eosinophils. Used for patients with eosinophilic asthma.
Reslizumab Cinqair Also targets IL-5 and is used for eosinophilic asthma. Administered via intravenous infusion.
Benralizumab (Fasenra) Targets the IL-5 receptor and is designed to reduce eosinophils in the blood and lungs.
Approved for eosinophilic asthma as well.
Dupilumab (Dupixent) Inhibits IL-4 and IL-13 signaling, which are key drivers of inflammation in asthma.
Approved for moderate to severe asthma with an emphasis on those with an eosinophilic phenotype or with oral corticosteroid-dependent asthma.
Tezepelumab: Targets thymic stromal lymphopoietin (TSLP), an upstream regulator of multiple inflammatory pathways.
These biologic agents have demonstrated efficacy in reducing asthma exacerbations, improving lung function, and decreasing the need for oral corticosteroids.
The choice of biologic is often guided by the patient’s specific asthma phenotype and biomarkers, such as blood eosinophil counts, serum IgE levels, and fractional exhaled nitric oxide (FeNO).
Biologic therapy for asthma represents a significant advancement in the management of severe asthma, offering targeted treatment options for patients with specific inflammatory profiles.
Asthma is heterogeneous, with several clinical phenotypes that differ according to age of onset of asthma, the presence or absence of allergy, and other coexisting conditions, severity of airflow limitation, frequency of exacerbations, response to treatment and prognosis.
Asthma types have distinct patterns of airway inflammation with predominant granulocyltes in sputum or bronchial biopsy specimens and by means of blood or exhaledbreath biomarkers.
Type 2 high inflammation asthma has eosinophils in airway inflammation associated with increased eosinophilia or elevations of fractional exhaled nitric oxide.
Type 2 low inflammation asthma has neutrophilic asthma and paucigranulocytic asthma characterized by eosinophilic and neutrophilic airway inflammation characterized by mixed granulocytic asthma.
Approximately 50% of cases of mild to moderate asthma and probably a large proportion of cases of severe asthma or type 2 high asthma.
Type 2 cytokines include interleukin 5, interleukin 4, and interleukin 13.
Interleukin 5 promotes proliferation differentiation, activation and survival of eosinophils.
The number of eosinophils in peripheral blood, bronchoalveolar lavage, and bronchial biopsy specimens correlate with the severity of asthma.
Type 2 inflammatory asthma is generally suppressed by glucocorticoids when inhaled steroids are initiated with an immediate decrease in functional exhaled nitric oxide, which is mediated by Interleukin–13, and immediate decrease in blood eosinophil count
In patients with severe asthma, airway eosinophilia persists despite inhaled or oral Glucocorticoids.
The anti—IgE monoclonal antibody omalizumab targets the FC fragment of IgE and reduces free IgG levels in serum and inhibits binding of IgE to its high affinity receptor on mast cells and basophils.
Biologics are typically indicated for patients who:
Have a history of frequent asthma exacerbations despite high-dose inhaled corticosteroids and other controllers.
Have specific biomarkers (e.g., high eosinophil counts or high IgE levels).
Are 12 years of age or older.
Most biologics are administered via injection (subcutaneous or intravenous).
Benefits Reduction in asthma exacerbations. Improved lung function. Decreased need for oral corticosteroids.
Potential side effects can include injection site reactions, increased risk of infections, and allergic reactions.