Advances in Biologic Therapies for Allergic Diseases: Current Trends, Emerging Agents, and Future Perspectives

Abstract

Biologic therapies have revolutionized the treatment of severe allergic diseases, including asthma, atopic dermatitis (AD), chronic spontaneous urticaria (CSU), chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic gastrointestinal diseases (EGIDs), and allergic rhinitis (AR). These molecularly targeted agents provide significant benefits for patients unresponsive to conventional treatments by addressing underlying immune mechanisms, particularly type 2 inflammation driven by cytokines such as IL-4, IL-5, and IL-13. Recent advancements include biologics targeting alarmins like thymic stromal lymphopoietin (TSLP) and IL-33, which may address both type 2 and non-type 2 inflammation, broadening their therapeutic scope. Despite their effectiveness, biologics remain expensive, posing socioeconomic challenges, and there are concerns regarding long-term safety and inter-individual variability in responses. Promising innovations such as bispecific antibodies and ultra-long-acting agents are under investigation, alongside digital health tools like remote biomarker monitoring and AI-driven decision support systems, which aim to enhance personalized care. However, disparities in access, particularly for underserved populations, underscore the need for policy reforms and affordable biosimilars. This review synthesizes recent findings and emerging trends, highlighting the evolving role of biologics in transforming allergic disease management and offering insights into future research directions.

Keywords: allergic rhinitis; allergy; asthma; atopic dermatitis; biologics; chronic rhinosinusitis; cytokines; monoclonal antibodies; spontaneous urticaria.

Figure 1

Cytokine network and biologics targeting inflammatory pathways in asthma. This Figure illustrates the role of key cytokines and immune cells involved in asthma pathogenesis, particularly the interplay between T2 and non-T2 inflammatory responses following exposure to allergens, viruses, and pollutants. Alarmins, such as thymic stromal lymphopoietin (TSLP) and IL-33, are released from the respiratory epithelium and initiate the inflammatory cascade by activating various immune cell types, including dendritic cells, Th17 cells, naive CD4 cells, and innate lymphoid cells (ILC2). These pathways drive cytokine production, such as IL-4, IL-5, IL-13, and IL-17, leading to airway inflammation, mucus production, and tissue remodeling. Biologics reviewed in this manuscript are highlighted in black text, with their molecular targets indicated by red dashed lines. Key biologics include those targeting TSLP (tezepelumab, ecleralimab, solrikitug), IL-33 (tozorakimab, itepekimab), IL-5 (mepolizumab, reslizumab, depemokimab), IL-4R (dupilumab, MG-K10, stapokibart, telikibart), IL-33R/ST2 (astegolimab, melrilimab) and IgE (omalizumab). Bispecific antibodies (IBI3002, lunsekimig) and emerging therapies, such as tryptase inhibitors and allergen-specific therapies, are also depicted. For detailed mechanisms and references, please refer to the relevant sections in the text. Symbols for immune cells and molecules are defined on the right panel for clarity.

Figure 2

Cytokine network and biologics targeting inflammatory pathways in atopic dermatitis (AD). This Figure illustrates the key cytokines, immune cells, and therapeutic targets involved in the pathogenesis of AD, highlighting the role of allergens, microbes, and scratching in triggering skin inflammation. Stressful stimuli activate epithelial-derived alarmins, such as thymic stromal lymphopoietin (TSLP), IL-33, and IL-36, which initiate downstream signaling pathways involving immune cells like dendritic cells, Langerhans cells, mast cells, type 2 innate lymphoid cells (ILC2), and Th2 lymphocytes. These pathways drive the release of cytokines, including IL-4, IL-5, IL-13, and IL-31, contributing to skin inflammation, eosinophil recruitment, and pruritus. Biologics and targeted therapies reviewed in the context of AD are labeled in green boxes with white text, with their molecular targets indicated by red dashed lines. Notable agents include anti-IL-4Rα therapies (dupilumab, stapokibart, rademikibart, telikibart), anti-IL-13 signaling therapies (cendakimab, lebrikizumab, tralokinumab, eblasakimab), anti-IL-5R therapies (benralizumab), and anti-IL-31 therapies (nemolizumab). Agents targeting alarmins, such as TSLP (tezepelumab) and IL-33 signaling (itepekimab, melrilimab, PF-06817024), as well as novel anti-IL-36 therapies like spesolimab, are also shown. Additionally, therapies directed at IgE (e.g., ligelizumab, YH35324) and OX40/OX40L pathways (e.g., rocatinlimab, amitlelimab) highlight innovative strategies in AD management. For further details on mechanisms of action and clinical evidence, please refer to the relevant sections of the text. Symbols for immune cells and cytokine receptors are defined in the legend on the right for clarity.