Idiopathic pulmonary fibrosis (IPF) is a deadly disease with a poor prognosis,1 involving disabling symptoms and progressive loss of lung function.2 IPF affects around 100,000 people in the US, and millions worldwide.2 Incidence and prevalence are rising globally, a trend that predates COVID-19.3 The two U.S. Food and Drug Administration (FDA)-approved treatments slow IPF disease progression but do not stop or reverse lung fibrosis, and are poorly tolerated by a substantial number of patients.2 This leaves a pressing need for improved therapies, and for novel approaches to demonstrate their value. Biomarkers have potential to improve clinical trials by enabling tracking of outcomes of most importance to patients, as well as by identifying subpopulations that may respond differently to therapies (Sidebar 1) Biomarkers for IPF are related to processes including alveolar epithelial cell dysfunction, immune dysregulation, fibroproliferation, fibrogenesis, and extracellular matrix remodeling4 (Sidebar 2).
Based on published data5, the Prognostic Lung Fibrosis Consortium (PROLIFIC) has selected 12 potential prognostic, blood-based protein biomarkers to help predict which pulmonary fibrosis patients might respond to a particular therapy. These include markers of:
Biomarkers are essential tools for personalized patient management in IPF, such as early detection, diagnosis, prognosis, therapy selection, and research outcomes. IPF biomarker research would aim to identify patients at risk of developing IPF, classify the disease subtype and severity, the subpopulation that may respond differently to therapies, predict the disease course and progression, select the most suitable therapeutic modality, monitor its response, and identify novel treatment targets that can improve the quality of life and survival of IPF patients. Biomarkers once validated would serve as clinical endpoints in clinical trials, some of which must be of meaningful clinical importance to patients. Patient surveys are a helpful source of information on clinical trial outcomes that matter most. For example, for IPF patients, control of chronic cough may of more clinical significance than the FVC decline which is currently the main outcome in trial. Equally, the ability to walk further (as measured by the six-minute walk test) may need to focus on clinically meaningful . Patients are also keen to understand their prognosis, and how likely they are to respond to medications. Efforts can then be made to align outcome metrics with this patient feedback.
Three key learnings on the potential role of biomarkers
Based on IPF studies to date, lessons learned fall into three categories:
Exciting advances are taking place in IPF clinical research, with multiple resources being combined in clinical trials, including digital technologies, various imaging modalities, and genetic testing. With patient needs firmly at the center of decision-making, these resources hold promise to help solve the puzzle of this poorly understood yet devastating disease.
1 Du K, Zhu Y, Mao R. et al. Medium-long term prognosis prediction for idiopathic pulmonary fibrosis patients based on quantitative analysis of fibrotic lung volume, Respir Res 23, 372 (2022).
2 Podolanczuk AJ, Richeldi L, Martinez FJ. The Future of Clinical Trials in Idiopathic Pulmonary Fibrosis, JAMA. 2023;329(18):1554–1555. doi:10.1001/jama.2022.23955
3 Pergolizzi JV Jr, LeQuang JA, Varrassi M, Breve F, Magnusson P, Varrassi G. What Do We Need to Know About Rising Rates of Idiopathic Pulmonary Fibrosis? A Narrative Review and Update. Adv Ther. 2023 Apr;40(4):1334-1346. doi: 10.1007/s12325-022-02395-9. Epub 2023 Jan 24. PMID: 36692679; PMCID: PMC9872080.
4 Biomarkers Definitions Working Group.. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001 Mar;69(3):89-95. doi: 10.1067/mcp.2001.113989. PMID: 11240971. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230407