Asthma remains a very common chronic disease worldwide and poses a huge burden on individuals and societies (García-Marcos et al., 2023; To et al., 2012). It is characterized by variable symptoms including dyspnea, chest tightness, coughing and wheezing and affects both children and adults. Already decades ago, a T helper cell subset (Type 2 helper- (Th2-) cells) was identified that has a distinct cytokine profile leading to recruitment and activation of eosinophils, basophils and mast cells and subsequently resulting in airway inflammation (Mosmann et al., 1986). Th2 lymphocytes are central in allergic asthma reacting to allergen presentation to their antigen-specific T-cell receptors (TCRs). In adult-onset eosinophilic (non-allergic) asthma, type 2 innate lymphoid cells (ILC2) orchestrate inflammation. ILC2s do not express TCRs but are activated by epithelial cytokines (alarmins) that are released upon epithelial stress induced by trigger factors like viral infections. Both, Th2 cells and ILC2 release a typical set of cytokines including interleukin 4 (IL-4), IL-5 and IL-13 resulting in a so-called type-2 inflammation that is driving asthma in allergic, but also eosinophilic phenotypes (Fahy, 2015; Peters et al., 2014; Robinson et al., 2023; Schleich et al., 2014).

Monoclonal antibodies have been developed that specifically interrupt type 2 (T2) inflammation pathways by binding to specific interleukins or their respective receptors. Choice of a specific biological is made depending on asthma phenotype and/or biomarker profiles. Currently, monoclonal antibodies are approved for patients with severe asthma who remain uncontrolled despite moderate to high doses of inhaled corticosteroid (ICS)/ long-acting β₂-agonist -agonist (LABA) and additional controller medication (Chung et al., 2014). These therapies demonstrated significant improvements regarding quality of life, asthma control, lung function, exacerbations and oral corticosteroid (OCS) medication while having a very favorable safety profile with minimal side-effects (Bleecker et al., 2016; Busse et al., 2001; Castro et al., 2015; Castro et al., 2018; FitzGerald et al., 2016; Menzies-Gow et al., 2021; Ortega, Liu, et al., 2014; Pavord et al., 2012; Rabe et al., 2018). Frequently, asthma is associated with other T2 inflammation diseases, such as allergic rhinitis, chronic rhinosinusitis with or without nasal polyps (CRSwNP/CRSsNP), chronic spontaneous urticaria, atopic dermatitis (AD) or eosinophilic esophagitis (EoE). Due to their overlapping pathophysiology, biologics frequently improve comorbidities as well. Thus, comorbidities can be both, a predictor of therapeutic response to biologic therapy, but at the same time also a therapeutic target.

Great therapeutic success with biologics has led to a shift from the therapeutic goal of asthma control, i.e. controlling symptoms over weeks to months to an even more ambitious long-term goal of asthma remission under treatment (Lommatzsch, Criee, et al., 2023). Asthma remission has been defined by an absence of asthma symptoms and exacerbations as well as stabilization of lung function in the absence of OCS use for at least one year (Lommatzsch, Brusselle, et al., 2022; Menzies-Gow et al., 2020). Even though this goal might not be achievable for all patients with severe asthma, a fraction of patients is already achieving this goal under treatment with biologics today (Milger, Suhling, et al., 2023; Thomas et al., 2023).

In this review, we provide an overview of currently available asthma biologics, their mode of action, indications, treatment selection, monitoring and possibility of switching treatment in case of insufficient response. We also discuss available real life-data comparing benefits of biologic therapies in asthma and associated T2 diseases.