Biologic Therapy for Asthma

Biologic therapies are monoclonal antibodies that block specific type 2 inflammatory mediators and are added to optimised inhaled therapy in severe asthma. They cut exacerbations and oral corticosteroid use, and they do not treat acute attacks. They are costly and need a defined phenotype.

Targets. Omalizumab binds free IgE. Mepolizumab and reslizumab bind IL-5, and benralizumab blocks the IL-5 receptor alpha chain. Dupilumab blocks the IL-4 receptor alpha chain, which inhibits IL-4 and IL-13. Tezepelumab blocks thymic stromal lymphopoietin and acts on both allergic and non-allergic disease.

Pharmacokinetics. These are IgG antibodies given by injection with slow absorption, half lives of 3 to 4 weeks and no hepatic or renal adjustment. IgG crosses the placenta mainly after the first trimester.

Differences. No agent has proven superiority over the others, so choice follows phenotype, comorbidity, age and access. Tezepelumab is the option with low eosinophils and low IgE.

Eligibility. Severe asthma uncontrolled despite high dose inhaled corticosteroid with a long acting beta 2 agonist and another controller, shown by 2 or more exacerbations needing oral corticosteroid in 12 months, a hospital admission, or continuous oral corticosteroid use. Confirm the diagnosis first, then adherence, inhaler technique, comorbidity (rhinosinusitis, reflux, obesity, sleep apnoea) and trigger exposure.

Phenotyping. Blood eosinophil count (repeat when off oral corticosteroid, which suppresses it), total IgE, sensitisation to perennial allergens, FeNO, nasal polyps, atopic dermatitis and features of eosinophilic granulomatosis with polyangiitis.

Response. Assess at 4 months and again at 12 months. Count exacerbations, oral corticosteroid dose, symptom score and FEV1. Switch to a different class if there is no response after 4 to 6 months. Stopping leads to loss of benefit in most patients.

Practical points. Keep inhaled therapy and taper oral corticosteroid slowly while watching for adrenal insufficiency. Dual biologic use is not routine.

Region. Eosinophilia may reflect helminth infection, schistosomiasis or strongyloidiasis rather than asthma, so check stool and serology and treat before using the count to choose a drug. Where biologics are unavailable, optimise inhaled therapy, adherence and comorbidity, and use the lowest effective daily oral prednisolone with bone and glucose monitoring.

Hypersensitivity. Anaphylaxis can follow any biologic. Observe after the first doses and keep adrenaline available. Omalizumab and reslizumab carry boxed-warning level anaphylaxis risk.

Infection. Treat helminth infection before starting an anti IL-5 or anti IgE drug. Herpes zoster is reported with mepolizumab.

Eosinophilic disease. Eosinophilia, eosinophilic pneumonia and eosinophilic granulomatosis with polyangiitis can appear when oral corticosteroids are reduced, especially with dupilumab.

Common adverse effects. Injection site reactions, headache, pharyngitis and arthralgia.

Monitoring. Exacerbations, oral corticosteroid dose, FEV1, asthma control scores, blood eosinophils where relevant, and adverse events.

Special groups. Pregnancy: limited data, continue if needed to control disease. Breastfeeding: IgG in milk is poorly absorbed. Children: most agents are licensed from 6 years, and tezepelumab from 12 years. Live vaccines are avoided with some agents. Older adults: no adjustment.

Referral and escalation. Biologic therapy needs a specialist in severe asthma. Refer when control is poor despite medium to high dose combination therapy and confirmed adherence.