Switching biologicals in severe asthma

Switching between biologicals in patients with severe asthma can be considered in case of poor response to treatment (including exacerbations, symptom control, and lung function), side effects, and if patients are pregnant or breastfeeding. With the increasing number of available products, switching between biologicals will become part of common daily clinical practice and so far, combining type2-targeted biologicals seems safe and effective [1]. With increasing insights, more differentiated treatment algorithms and long-term safety and efficacy evaluations will follow in the near future.

Currently, 5 biologicals are available for the treatment of severe asthma: omalizumab (anti-IgE), mepolizumab, reslizumab, and benralizumab (anti-IL-5/5Rα), and dupilumab (anti-IL-4Rα). Possible switches include switching to another biological with a similar or different mode of action or to combine two different modes of action following case reports showing a good clinical response without safety issues. It is important to check that patients fulfil eligibility criteria for a new biological either on or before the current biological if a switch is considered. Most likely, a wash-out period is not necessary when switching biologicals. It needs to be noted that in earlier days only omalizumab was available; many patients who would have been better candidates for anti-IL-5/5R/4R were treated with omalizumab. Presently, these patients may qualify for switching to another biological (e.g. anti-IL-5/5Rα or anti-IL-4Rα). Regarding benralizumab, this biological induces a more complete depletion of eosinophils than mepolizumab which may offer superior clinical effectiveness in some patients with pronounced eosinophilia. However, this requires close monitoring given the potential downside of eosinophil depletion. Furthermore, physicians need to be aware of possible (often transient) increases in blood eosinophils when patients are switched from anti-IL-5/5R to dupilumab [2].

1. Ortega G, et al. Ann Allergy Asthma Immunol. 2019 Sep;123(3):309-311.
2. Lehtimäki L. Switching biologics, how and when? Nordic Lung Congress 2022, 01–03 June, Copenhagen, Denmark.

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