3TR Asthma Biologics Cohort Study Observing Severe Asthma Patients Starting Biological Therapy Part of the 3TR Consortium for Understanding Treatment Response and Remission

What this Trial Is About

3TR-ABC follows people with severe asthma from the day they start a biologic and keeps following them for three years. It is observational, meaning the study does not decide who gets which drug. Patients begin their biologic through normal clinical channels, according to whatever criteria apply in their country, and the study observes what happens next. The point is to work out why these expensive, highly targeted drugs transform life for some patients and do very little for others. The structure is a platform rather than a single trial. One shared core design sits underneath, and individual studies focused on specific biologics run on top of it, each free to add its own extra measurements while keeping the visit schedule and sampling aligned so results can be pooled. Only patients who have never had a biologic before are enrolled. They are assessed thoroughly at the start, then seen again at 4 weeks, 16 weeks, 52 weeks, and at the 2 and 3 year marks, with additional sampling whenever an exacerbation happens. Some sites collect a core package of samples, others an expanded one. Behind it all is the 3TR Consortium, a collaboration spanning 15 European countries and 69 partners, working across seven immune-driven diseases including asthma, COPD, Crohns disease, ulcerative colitis, multiple sclerosis, lupus, and rheumatoid arthritis. It is the largest immunology project the Innovative Medicines Initiative has funded. The asthma work sits in what the consortium calls work package 8, and its guiding questions are blunt ones what separates a good responder from a non-responder, and can severe asthma actually be pushed into remission rather than merely managed. Participants are sorted after the fact into three groups based on how they did remission, clinical response, and non-response. The blood, tissue, and breath samples collected before anyone started treatment are then compared across those groups, along with how each groups immune activity shifted over time. Healthy volunteers and people with mild or moderate controlled asthma go through the same baseline visit and serve as reference points, giving the researchers a sense of what these markers look like outside of severe disease. Samples feed into multi-omic analysis, which means examining genes, proteins, metabolites and more from the same person to map the biological pathways involved. The main target is a set of baseline markers that predict remission at one year. Remission here has a specific definition an ACQ-5 score below 1.5, lung function after bronchodilator either at or above 80% of predicted or improved by more than 10%, no exacerbations, and no maintenance steroid use across the previous twelve months. The same question is asked again at three years, alongside how marker profiles shift between those who reach remission and those who dont, how each individual response measure behaves, and how physician and patient ratings of treatment benefit compare with the consortiums own composite response measure. Exploratory work applies network and cluster analysis, discriminant methods such as PLSDA, daily FENO readings, and analysis of host and microbiome interaction to hunt for biomarker signatures nobody has identified yet. One cohort within the platform, AIR-BIO-OCT, focuses on patients taking benralizumab and goes a step further into the airway wall itself. Biologics are currently matched to patients through phenotyping that leans on clinical features, oral steroid use, and eosinophil counts in blood, sputum, or lavage fluid. What remains unclear is whether these drugs change airway remodeling, the structural thickening involving smooth muscle and extracellular matrix that tracks with how severe and how persistent the disease becomes. This substudy pairs exhaled breath analysis, using both GC-MS and electronic nose technology to read volatile organic compounds, with omics and with optical coherence tomography imaging, including a polarization-sensitive form of OCT. Endobronchial biopsies alongside the imaging are used to establish whether smooth muscle and matrix actually decrease after six months to a year on benralizumab. The broader hope is a minimally invasive breath-based signature that could flag likely responders before treatment ever starts.

3TR Asthma Biologics Cohort (ABC) Study