Biologic therapies for severe asthma are among the most heavily tested topics in the SCE Respiratory exam. The field has expanded rapidly — five biologics are now available in the UK — and the exam tests your ability to select the right biologic for the right patient based on phenotype, biomarkers, and NICE technology appraisal eligibility criteria.
When biologics are indicated
Biologics are indicated for severe asthma that remains uncontrolled despite optimised standard therapy — high-dose inhaled corticosteroids, a long-acting beta-agonist, and consideration of additional controllers (LAMA, LTRA, theophylline). BTS/SIGN step 5 and NICE NG80 define the threshold. Before escalating to biologics, you must confirm adherence, inhaler technique, and address modifiable factors (smoking, rhinosinusitis, GORD, occupational triggers).
All biologic prescribing for severe asthma in the UK occurs through specialist severe asthma centres, not in primary care or general respiratory clinics.
The five biologics and their targets
Omalizumab (anti-IgE) was the first biologic approved for severe asthma. It targets circulating IgE, preventing binding to mast cells and basophils. NICE TA278 defines eligibility: proven IgE-mediated allergic asthma, total serum IgE within the dosing range (30 to 1,500 IU/mL), positive skin prick test or specific IgE to a perennial allergen, and severe uncontrolled asthma despite optimised therapy. The dose is calculated from body weight and total IgE level. Omalizumab is administered subcutaneously every 2 to 4 weeks.
Omalizumab is the only biologic for which allergic status (IgE level and allergen sensitisation) is the primary selection criterion. If the vignette describes a patient with high IgE and proven allergic triggers, omalizumab is typically the correct answer.
Mepolizumab (anti-IL-5) targets interleukin-5, the key cytokine driving eosinophil maturation and survival. NICE TA671 defines eligibility: blood eosinophil count of 300 cells per microlitre or more on at least one occasion in the previous 12 months, and at least 4 exacerbations requiring systemic corticosteroids in the previous 12 months, or continuous oral corticosteroid use. The dose is fixed at 100 mg subcutaneously every 4 weeks.
Mepolizumab is the standard first-line anti-eosinophil biologic. When the vignette describes a patient with raised eosinophils and frequent exacerbations, mepolizumab is typically the first choice.
Benralizumab (anti-IL-5 receptor alpha) binds to the IL-5 receptor alpha subunit on eosinophils and induces direct eosinophil apoptosis through antibody-dependent cellular cytotoxicity. The effect is near-complete eosinophil depletion. NICE TA565 sets eligibility criteria similar to mepolizumab — blood eosinophils 300 or more and frequent exacerbations or OCS dependence. The dose is 30 mg subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks.
The every-8-weeks maintenance schedule is a practical advantage for patients who find frequent injections burdensome. In the exam, the distinction between mepolizumab (anti-IL-5 ligand) and benralizumab (anti-IL-5 receptor) is tested — they target the same pathway but through different mechanisms.
Dupilumab (anti-IL-4 receptor alpha) blocks signalling through both IL-4 and IL-13, which drive type 2 inflammation, mucus production, and airway remodelling. NICE TA751 defines eligibility: blood eosinophils 150 or more, and either raised FeNO (25 ppb or more) or OCS dependence. Dupilumab has the broadest eligibility criteria of the eosinophilic biologics because it targets the type 2 inflammatory pathway more broadly than IL-5 alone.
Dupilumab is also licensed for atopic eczema and chronic rhinosinusitis with nasal polyps. When the vignette describes a patient with asthma, eczema, and nasal polyps — the classic type 2 comorbidity triad — dupilumab is the correct answer because it addresses all three conditions.
Tezepelumab (anti-TSLP) targets thymic stromal lymphopoietin, an upstream epithelial cytokine that initiates the inflammatory cascade in asthma. NICE TA880 is the most recent approval. Unlike the other biologics, tezepelumab does not require elevated eosinophils for eligibility — it is effective across both eosinophilic and non-eosinophilic severe asthma phenotypes. This makes it the only biologic option for patients with severe uncontrolled asthma who do not have raised eosinophils or IgE.
When the vignette describes a patient with severe asthma but normal eosinophils and normal IgE, tezepelumab is the answer. Every other biologic requires either raised eosinophils or raised IgE.
How the exam tests this
SCE questions typically present a patient with severe asthma and specific biomarker results, then ask which biologic is most appropriate. The correct answer depends on the eosinophil count, IgE level, FeNO, allergic status, exacerbation frequency, OCS dependence, and comorbidities. You need a decision framework, not just a list of drugs.
A practical framework runs as follows. If allergic asthma with high IgE and perennial sensitisation, consider omalizumab. If eosinophilic asthma with eosinophils 300 or more and frequent exacerbations, consider mepolizumab or benralizumab. If type 2 inflammation with eosinophils and comorbid eczema or nasal polyps, consider dupilumab. If severe asthma without eosinophilic or allergic features, consider tezepelumab.
The exam also tests what happens after starting a biologic. Response assessment occurs at 12 months. If there is no significant improvement (reduction in exacerbations, OCS dose, or symptoms), the biologic should be stopped. Continuation criteria are defined in each NICE TA.
OCS sparing
A key goal of biologic therapy is reducing or eliminating oral corticosteroid dependence. Both mepolizumab and benralizumab have trial evidence for OCS dose reduction in OCS-dependent patients. The exam may present a patient on long-term prednisolone and ask which biologic has the strongest evidence for OCS sparing — the answer depends on the specific trial data, but all anti-IL-5 pathway agents and dupilumab have demonstrated this effect.
iatroX's SCE Respiratory bank includes dedicated biologic therapy questions covering all five agents, eligibility criteria, biomarker-driven selection, response assessment, and NICE TA access. The adaptive algorithm ensures this high-yield topic is weighted proportionally. All included at £29 per month or £99 per year.