Biologic Therapy in Severe Asthma
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Direct answer
Biologic therapy in severe asthma uses monoclonal antibodies that block specific type 2 inflammatory pathways, such as IgE, IL-5, IL-4 receptor alpha or thymic stromal lymphopoietin. Each agent is matched to a phenotype, using blood eosinophil count, fractional exhaled nitric oxide and allergic status. Biologics are added only when asthma stays uncontrolled despite high-dose inhaled corticosteroid plus a long-acting bronchodilator, after adherence and inhaler technique are confirmed.
What you must remember
- Omalizumab: anti-IgE therapy for allergic asthma with raised total IgE, dosed by body weight and serum IgE level.
- Mepolizumab: anti-IL-5 therapy for eosinophilic asthma, usually with a blood eosinophil count of 150 cells per microlitre or more.
- Reslizumab: anti-IL-5 given intravenously, reserved for eosinophilic disease.
- Benralizumab: anti-IL-5 receptor alpha antibody that depletes eosinophils, given subcutaneously.
- Dupilumab: blocks IL-4 and IL-13 signalling; suits raised eosinophils or FeNO and co-existing nasal polyps or atopic dermatitis.
- Tezepelumab: anti-TSLP antibody acting upstream, used across several phenotypes, including low eosinophil disease.
- Biomarkers: blood eosinophils and FeNO, with a level of about 25 ppb or more in adults, support type 2 inflammation.
Matching the biologic to the phenotype
A 38-year-old woman with allergic asthma has four exacerbations in a year despite high-dose inhaled steroid and a long-acting bronchodilator. Her total IgE, blood eosinophil count and FeNO are checked before any target is chosen, because each drug works on a different pathway.
| Agent | Target | Best-fit phenotype |
|---|---|---|
| Omalizumab | IgE | Allergic, raised total IgE |
| Mepolizumab | IL-5 | Eosinophilic, count of 150 or more |
| Reslizumab | IL-5 | Eosinophilic, given intravenously |
| Benralizumab | IL-5 receptor alpha | Eosinophilic, depleting |
| Dupilumab | IL-4 receptor alpha | Type 2 high, raised FeNO |
| Tezepelumab | TSLP | Broad, including low eosinophil disease |
Blood eosinophils and FeNO are the practical markers in everyday practice, while total IgE is needed for omalizumab dosing and eligibility. Her raised IgE and allergic sensitisation point to omalizumab, but a raised eosinophil count would instead favour mepolizumab or benralizumab if IgE were normal. Response is judged over several months, using exacerbation rates, oral steroid use and lung function, and therapy is stopped if no benefit appears.
Where the exam tests the phenotype trap
Biologics are targeted drugs, so the examiner tests whether the choice follows the biology rather than habit.
- Trap: starting a biologic as first-line add-on in mild asthma Correct: biologics are reserved for severe asthma uncontrolled on high-dose inhaled steroid plus a second controller.
- Trap: choosing omalizumab for a non-allergic eosinophilic patient Correct: omalizumab targets IgE, so mepolizumab or benralizumab suits eosinophilic disease without allergy.
- Trap: assuming a normal eosinophil count rules out type 2 disease Correct: FeNO can still be raised, and dupilumab may then be considered.
Adherence, inhaler technique and trigger control are checked before any biologic is started.
Frequently asked questions
Which biologic is the only anti-IgE drug used in asthma?
Omalizumab is the only anti-IgE monoclonal antibody used in asthma, binding free IgE and reducing mast cell activation. It suits allergic asthma with raised total IgE, and its dose depends on body weight and the serum IgE level.
What blood eosinophil count favours mepolizumab in severe asthma?
Mepolizumab is generally used for eosinophilic asthma with a blood eosinophil count of 150 cells per microlitre or more at initiation. Eosinophil counts and exacerbation history guide the choice, and response is reviewed after several months of treatment.
Why is FeNO measured before starting dupilumab for asthma?
Fractional exhaled nitric oxide is a marker of type 2 airway inflammation, and a raised level in adults, often 25 ppb or more, supports dupilumab use. Dupilumab is more likely to work when FeNO is raised, and eosinophil count and allergic disease add further support.
How is response to a biologic judged in severe asthma?
Response to a biologic is judged by fewer exacerbations, reduced oral steroid use, better symptom control and improved lung function over several months. Therapy is continued only when a clear benefit is documented, and the review is repeated periodically.