Severe asthma is traditionally classified into either high or low T-helper cell type 2 (T2) subtypes. T2-high asthma, which is characterised by allergic inflammation and elevated eosinophil levels, has seen significant advances in treatment and disease management with the advent of biological therapies. However, T2-low asthma, which lacks the characteristic biomarkers that are associated with T2-high asthma, remains underdiagnosed and underserved. Experts interviewed by leading data and analytics company GlobalData emphasise the challenges in diagnosing T2-low asthma due to the absence of reliable biomarkers, leading to delayed treatments for many patients. Recent studies have shown the need for better diagnostic tools, as current methods fail to distinguish T2-low asthma from other forms, hindering effective treatment decisions (Kankaanranta, 2023).
Although biologic therapies have revolutionised the treatment of T2-high asthma, T2-low asthma remains largely neglected. Many key opinion leaders (KOLs) interviewed by GlobalData stressed the lack of biologic therapies specifically targeting T2-low asthma. Current biologic treatments focus primarily on eosinophilic or allergic inflammation, leaving patients with non-eosinophilic or neutrophilic asthma with limited options. In the broader treatment landscape, competitors such as Areteia Therapeutics’ dexpramipexole, which has potential applications beyond eosinophilic asthma, and AstraZeneca’s Breztri, currently approved for chronic obstructive pulmonary disease but being explored for asthma, are noteworthy. Additionally, Sanofi’s dual interleukin-13 and thymic stromal lymphopoietin antibodies have garnered attention for their potential to address complex asthma phenotypes, including T2-low cases. As such, advanced strategies such as multi-omics analyses and precision medicine, hold promise for identifying novel therapeutic targets, offering the potential to significantly improve outcomes for this underserved group (Fouka et al, 2022).
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A significant barrier to effective treatment is the diagnostic challenge. In Japan, experts note that biomarkers such as eosinophils and immunoglobulin E are commonly used to diagnose asthma subtypes, but these markers are ineffective for diagnosing T2-low asthma, complicating early detection. It has also been noted that without reliable biomarkers, many patients with T2-low asthma remain undiagnosed and untreated (Kankaanranta, 2023). As asthma prevalence continues to rise globally- particularly in regions with high pollution – the urgency for more accurate diagnostic tools and therapies becomes clear.
Along with diagnostic hurdles, treatment adherence remains a significant challenge. One US KOL notes that despite the availability of biologics, adherence is often compromised by issues such as inhaler technique, high medication costs, and inconsistent use. This aligns with findings indicating widespread inhaler misuse, where many patients fail to use their medications correctly despite multiple instructions. Improving patient education on proper inhaler use and ensuring better access to treatments are essential to enhancing asthma control and preventing exacerbations.
In conclusion, T2-low asthma represents a critical unmet need in asthma management. Despite significant progress in treating T2-high asthma, patients with T2-low asthma continue to lack effective therapies. More research is needed to identify reliable biomarkers and develop targeted treatments for this population. Additionally, enhancing diagnostic methods, improving patient education, and increasing adherence to treatments will be essential for improving outcomes for all asthma patients, particularly those with T2-low asthma.
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