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Dupilumab Reduces Airway Inflammation, Mucus Plugs in Asthma Patients

— VESTIGE trial highlights use of imaging to measure new clinical endpoints

MedpageToday

Dupilumab (Dupixent), an interleukin (IL)-4/IL-13-blocking antibody, significantly reduced nitric oxide levels compared to placebo and reduced mucus plug scores by as early as 4 weeks, according to a multinational postmarketing study reported at the recent American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting.

In this exclusive 鶹ý video, investigator Njira Lugogo, MD, of the University of Michigan in Ann Arbor, discusses the results of the phase IV VESTIGE study and its focus on imaging and new novel endpoints.

Following is a transcript of her remarks:

The VESTIGE study was presented at AAAAI this year, and it's quite interesting actually. I found this study quite fascinating because it was focused on imaging outcomes. And more and more in asthma we are starting to appreciate the importance of chest CT imaging at measuring new novel endpoints for patients who are being treated with biologics.

So in VESTIGE, the primary outcome was looking at the proportion of patients who have a reduction in exhaled nitric oxide levels and the second outcome of interest was looking at mucus plug scoring.

And so what this study showed is that dupilumab significantly reduces nitric oxide levels compared to placebo, and in addition, significantly reduces the mucus plug scores by as early as 4 weeks.

And just to give you a little bit of context about mucus plug scores, because most people aren't really familiar with it; it's not used clinically. There are 20 subsegmental airways. In order to have a score of 20, you have to have fully plugged every airway, basically. Nobody ever has very high scores like that. And then it requires manual counting by two radiologists who have to both agree that particular subsegmental airways are plugged. And then they basically give you a count. And so a change of 4 is a pretty significant reduction in the mucus plug scores in this particular study.

In addition to the mucus plug scores, the study actually used FRI [functional respiratory imaging], which is a new technique that looks at volumes in the lungs. And they were able to actually see improvements in lung volumes, and at the same time, concomitant reductions in airway resistance with this novel measure. And so the mucus plug scores actually had a corollary change in how much air trapping was present and also how much resistance was present in the patient's airway.

And the takeaway from this for clinicians is I think we're pushing the envelope every time in asthma care. Certainly all of us know that dupilumab reduces nitric oxide levels, which is quite important. But we are starting to see some clinically meaningful changes in imaging in patients with severe asthma. And I personally believe that in the future, once mucus plug scores can be calculated in a more automated fashion, we may actually be using this as a clinical endpoint for patients that we are treating with biologics.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.