A Pragmatic Guide to Choosing Biologic Therapies in Severe Asthma

There are now several monoclonal antibody (mAb) therapies ("biologics") available to treat severe asthma. Omalizumab is an anti-IgE mAb and is licensed in severe allergic asthma. Current evidence suggests it may decrease exacerbations by augmenting deficient antiviral immune responses in asthma. Like all other biologics, clinical efficacy is greatest in those with elevated T2 biomarkers. Three biologics target the interleukin (IL)-5-eosinophil pathway, including mepolizumab and reslizumab that target IL-5 itself, and benralizumab that targets the IL-5 receptor (IL-5R-α). These drugs all reduce the exacerbation rate in those with raised blood eosinophil counts. Mepolizumab and benralizumab have also demonstrated steroid-sparing efficacy. Reslizumab is the only biologic that is given intravenously rather than by the subcutaneous route. Dupilumab targets the IL-4 receptor and like mepolizumab and benralizumab is effective at reducing exacerbation rate as well as oral corticosteroid requirements. It is also effective for the treatment of nasal polyposis and atopic dermatitis. Tezepelumab is an anti-TSLP (thymic stromal lymphopoietin) mAb that has recently completed phase 3 trials demonstrating significant reductions in exacerbation rate even at lower T2 biomarker thresholds. Many patients with severe asthma qualify for more than one biologic. To date, there are no head-to-head trials to aid physicians in this choice. However, analyses have identified certain clinical characteristics that are associated with superior responses to some therapies. The presence of allergic and/or eosinophilic comorbidities, such as atopic dermatitis, nasal polyposis or eosinophilic granulomatosis with polyangiitis, that may additionally benefit by the choice of biologic should also be taken into consideration, as should patient preferences which may include dosing frequency. To date, all biologics have been shown to have excellent safety profiles.