IPF Progression Insights From Telomere Mutations, MUC5B Polymorphism: Ayodeji Adegunsoye, MD, PhD, MSc

In an interview with The American Journal of Managed Care^® (AJMC^®), Ayodeji Adegunsoye, MD, PhD, MSc, FACP, FCCP, assistant professor of medicine at the University of Chicago, explains how polymorphisms like MUC5B and rare telomere-related gene variants are changing the way clinicians think about disease progression in idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF).

These markers not only influence susceptibility and outcomes but may also predict how patients respond to immunosuppressive therapies, according to Adegunsoye. Although genetic testing is not yet standard in clinical practice, he anticipates its broader integration as evidence and cost-effectiveness continue to grow.

This transcript has been lightly edited; captions were auto-generated.

Transcript

What is the current role of genomic markers in predicting IPF and PPF disease progression?

That's a question that I believe is increasingly important to the management and care of patients with IPF. The genetic landscape in IPF is fast evolving. We have recently discovered that genes like MUC5B polymorphism, which is incredibly common in the general population, has an outsized effect on susceptibility to IPF, disease progression, and even outcomes. But more importantly than the MUC5B polymorphism, is the recent discovery of rare pathogenic variants in telomeres. Telomeres are like the capsule ends of our DNAs that protect the DNA from degradation. Those genes that lead to short telomeres can actually portend poor outcomes. We are realizing that there is a need to test patients who are at risk for short telomeres and also for the possible presence of these rare pathogenic gene variants, because it can influence the disease risk, influence outcomes from the disease, and even now influence who gets better with treatment or not.

How can managed care systems incorporate genetic testing into routine care of pulmonary fibrosis?

We haven't started to see mainstream incorporation of genetic testing into routine care yet. I do believe it's coming, though. The reason I say this is it has a clinical impact on the way we care for patients with pulmonary fibrosis, not just IPF. There aren't standardized genetic panels yet, but there is a recognition that several genes as well as polymorphisms put patients at risk for detrimental outcomes when they get immunomodulatory therapy. Immunosuppression portends worse outcomes, for example, if they have short telomeres with diseases like hypersensitivity pneumonitis or unclassifiable ILD [interstitial lung disease]. I think as we start to learn more and more about the value of this, we're going to see it become much more mainstream. These tests are not exactly very affordable, and so there has been an absolute need to get them done before rolling them out en masse.