Targeted Medicine and Biological Therapies Fighting Type 2 Inflammation in Patients With Asthma

In a recent review, Imran Howell, University of Oxford, UK, and colleagues sought to understand the impact of biological therapies and targeted medicines for type 2 inflammation in patients with asthma. Biological therapies target specific symptoms of type 2 inflammation in asthma and reduce a patient’s reliance on oral corticosteroids (OCS). This treatment also fills the gap in care for patients with severe asthma that respond poorly to previously administered treatments such as OCS or inhaled corticosteroids.

Dr Howell described how treatment for type 2 inflammation changed from regulating asthma to a role that is more complex, with a focus on protection of the patient and tissue repair. Type 2 immunity is a wound healing mechanism and a parasite defense. He further defines patients with asthma’s airways as experiencing chronic inflammation and immune cells such as eosinophils, neutrophils, lymphocytes, dendritic cells (DCS), innate lymphoid cells (ILCS), and mast cells being affected. As a result of inflammation, a patient’s airway narrows, becomes hyperresponsive, blocked by mucous, and remodels.

Epithelial cells are the first line of defense against pathogens, allergens, and chemical irritants in the lungs. Alarmins like IL-33, thymic stromal lymphopoietin (TSLP), and IL-25 release epithelial cytokines in response to damage by using toll-like receptors or protease-activated receptors. This response contributes to the symptoms of patients with asthma. IL-25 and IL-33 cause symptoms like airway hyperresponsiveness and disease severity. DCS contributes to allergic asthma, where patients have an allergic response to inhalation of house dust mites, animal dander, or pollen. IL-4 and IL-13 have a powerful role to play in asthma as they affect almost every cell. The 4 receptor chains in IL-4R complexes (IL-4Rα, γ chain, IL-13Rα1, and IL-13Rα2) contribute to allergic asthma and hyperresponsiveness. Finally, eosinophils that develop in bone marrow contribute to the airway remodeling symptom that occurs in asthma.

OCS proves to be effective in the treatment of asthma attacks since 1956. Modern asthma treatments typically involve ICS. ICS reduces cytokines, Th2 cells, mast cells, macrophages, DCS, and eosinophils. 10% of adults with asthma do not respond well to ICS and OCS. Thus, biological therapies are necessary to fill this gap. The first antibody to be approved was omalizumab. This therapy reduced the cellular activation and inflammatory mediator release that can lead to an allergic asthma response. However, clinical evidence is inconsistent, and Dr Howell explained that it is best for young patients with allergic asthma. In anti-IL-5 treatment, it reduced the blood eosinophils in patients with severe eosinophilic asthma. Mepolizumab and reslizumab target IL-5, and benralizumab targets IL-5Rα, demonstrating a significant improvement in function of the lungs, asthma symptoms, and patient quality of life. Anti-IL13 antibodies such as tralokinumab and lebrikizumab have not shown a significant efficacy in reduction of eosinophils for patients with asthma. However, dupilumab has shown consistent efficacy in improvement of symptoms. Newer therapies such as tezepelumab and astegolimab are undergoing phase 2 and 3 clinical trials for approval for treatment.

“Future research should also delve into the causes and mechanisms of asthma attacks. We know that viral infection is often implicated, but why they do not always lead to an attack and the impact of viral infections on the lower airway immunopathology in type 2-high asthma are not well understood,” wrote study authors.

Dr Howell concluded that asthma treatments have significantly changed and improved over the years. In the past, patients were unable to acquire the treatments that they have access to now. He stressed the importance of asthma diagnosis and target treatment.

Reference:

Howell I, Howell A, Pavord ID. Type 2 inflammation and biological therapies in asthma: Targeted medicine taking flight. J Exp Med. 2023;220(7):e20221212. doi:10.1084/jem.20221212.