Combination of allergen-specific immunotherapy with biologics in severe asthma: contra-intuitive or rational?

Although numbers vary, most patients with severe asthma have eosinophilic asthma. Many of them have the allergic asthma endotype, particularly those with concomitant allergic rhinitis (AR). Allergen immunotherapy (AIT) is the only disease-modifying therapy offering long-term effectiveness for allergic respiratory disorders, including asthma, but it is contraindicated in patients with uncontrolled disease. Patients with severe asthma often have frequent exacerbations, making them poor candidates for AIT. However, after approximately 6 to 12 months on biologic therapy, many patients become exacerbation-free and obtain good symptom control and even improved lung function. Thus, in these patients, add-on AIT, subcutaneous or sublingual, is possible. Importantly, AIT could contribute to achieving clinical remission in severe asthma with biologic therapy, that even may be sustained after cessation of treatment. In a few landmark trials of AIT added to biologics (omalizumab, dupilumab, or tezepelumab), mechanisms were also studied, unveiling the additional benefit of these combinations in enhancing not only safety and tolerability, but possibly also efficacy. We present a summary of clinical trials combining immunotherapy with aeroallergens with biologic therapy in patients with respiratory allergy and discuss the cons and pros of AIT in patients with severe allergic asthma who received biological therapy, concluding that this combination could benefit many of these patients.