Dr Surya Bhatt Highlights NOTUS Trial Findings, Promising Dupilumab Results

Surya Bhatt, MD, MSPH, medical director of the Pulmonary Function and Exercise Physiology Lab at the University of Alabama at Birmingham, explained that the phase 3 NOTUS trial results highlighted challenges in diagnosing chronic obstructive pulmonary disease (COPD) with type 2 inflammation. He also noted that dupilumab shows promise in treating this COPD phenotype.

Bhatt discussed these topics further at the American Thoracic Society 2024 International Conference, where he presented the phase 3 NOTUS trial results.

Transcript

The NOTUS trial focused on patients with COPD and type 2 inflammation. Can you discuss the challenges of identifying and diagnosing this specific COPD subtype?

The 2 ways of identifying type 2 inflammation right now are by checking blood eosinophils and making sure that the blood eosinophils are above a certain threshold, currently accepted at 300 cells per microliter.

The second way to diagnose type 2 inflammation is by using the fractional exhaled nitric oxide, or FeNO. If it's above a certain threshold, you can detect type 2 inflammation, but that was not an entry criteria in the clinical trials that were performed.

The challenges with blood eosinophils are that they're not frequently on the top of everybody's mind in COPD practice right now compared to asthma, but that is likely to change. Eosinophils are already recommended by the GOLD [Global Initiative for Chronic Obstructive Lung Disease] committee, the GOLD report, to check often, to make sure that patients are being prescribed inhaled corticosteroids appropriately because people with high blood eosinophils are more likely to respond to inhaled corticosteroids.

Because there is a wide range over which they can be responsive, and because of the limited treatment options, people have not been checking blood eosinophils as often as they should. I think with new treatments coming through and becoming available, that is likely to change, and I also see a lot of colleagues already checking blood eosinophils more often.

The challenges with fractional exhaled nitric oxide is that it's not very widely available, unlike blood eosinophils, which are easy to check. So, I think that we need to do more in terms of making the FeNO testing available.

The NOTUS and BOREAS trials focused on the use of dupilumab for patients with COPD and type 2 inflammation. Do you think dupilumab has the potential to be helpful for other COPD phenotypes in the future? If so, what kinds?

It should be remembered that the target right now is a specific endotype of type 2 inflammation as indicated by blood eosinophils. The specific phenotype that was tested in the trials, phenotype meaning the external characteristics of the disease manifestation, was one of frequent exacerbations.

I think there is data from asthma, which may be applicable to COPD, that there are other phenotypes that can also be potentially be impacted by dupilumab and other biologics. If you think about the asthma studies, there are studies showing that using dupilumab can decrease the number of mucus plugs, it can decrease wall area thickness, it can potentially decrease the ventilation defects on MRI imaging.

So, all these are modifiable targets and potentially disease modifiers, and the hope is that this will translate into COPD. There are also now studies showing associations between type 2 inflammation and emphysema, but it needs to be studied as to whether dupilumab can impact this and COPD.