Asthma is one of the commonest chronic health conditions, affecting 1 in 15 people in the UK. Four out of 100 people with asthma have severe disease.
Severe asthma is characterised by recurrent exacerbations which impair a patient’s quality of life and lead to additional health problems through severe symptoms, hospital visits and medication side effects.
Novel biologic injections that reduce exacerbations and improve other clinical outcomes are transforming the management of severe asthma. However, response to treatment is only assessed after 12 months and is often variable.
Our ability to predict individual response and disease progression is limited. In addition, NHS pressures mean that only a sixth of eligible patients are able to access biologic treatment in severe asthma, making it increasingly important to maximise the benefits per patient.
The Europe-wide Innovative Medicines Initiative, 3TR, is leading our understanding of differential response to biologic therapies in severe asthma. Leicester is the UK work package lead for 3TR, working closely with 17 academic institutions, 1 SMI (Owlstone), 2 organisations for patient involvement (ELF, EFA), the European Respiratory Society, Sanofi, AstraZeneca and the NIHR Southampton BRC to undertake this work.
3TR has already published fundamental foundation studies that standardise assessment of biologic response across international disease communities; work that will maximise the impact of subsequent analyses.
The 3TR-ABC study is recruiting patients receiving three biologic agents for comprehensive clinico-pathological and multiomic profiling at baseline and across follow up to 3 years.
By integrating in-depth biological characterisation with clinical outcomes and response information we aim to identify biomarkers that will streamline future clinical management. For example, markers that tell us which biologic will work best in an individual, or markers that predict non-response much earlier than at 12 months. This will reduce the time patients spend taking therapies that don’t get them the best results: making sure we get the right drug to the right patient at the right time.
To date, more than 50% of the planned recruitment to 3TR-ABC has been completed, with full recruitment expected by December 2025.
Early/interim analyses are already underway, with annual analyses to follow that evaluate the performance of biomarkers on an individual basis and in combination.
Trial participants and the 60,000 UK severe asthma patients eligible for biologic therapies will benefit from this work, which will reduce inefficiency in current clinical pathways.
Importantly, understanding who is the right patient to treat has the potential to facilitate use of biologic therapies at an earlier stage of disease before long-term damage can occur. This could redefine the population eligible for treatment and profoundly reduce the quality of life and economic burden related to severe asthma in future.
The capacity and capability made possible through the BRC infrastructure award allows the Leicester NIHR BRC to develop and lead on international translational research. The BRC network including the Respiratory Translational Research Collaboration provides the horizontal capability and capacity to ensure delivery of complex translational trials to the highest quality at pace