Joseph Han, MD: SINUS-24 Trial Results

Data results presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2019 Annual Meeting show that monoclonal antibody biologic dupilumab (Dupixent) is beneficial in chronic rhinosinusitis patients with nasal polyps.

The results from the phase 3 SINUS-24 trial—a multicenter, double-blind study involving 276 patients randomized to either subcutaneous 300 mg dupilumab or placebo for 24 weeks—showed treated patients improved significantly nasal polyp and congestion scores.

In an interview with MD Magazine®, study author Joseph Han, MD, Medical Director of the Division of Allergy, Eastern Virginia Medical School, detailed the primary and secondary endpoint findings—and what they mean for patient quality of life.

MD Mag: What were the findings of the SINUS-24 trial?

Han: So, dupilumab is basically a monoclonal antibody that is targeting IL-4. It doesn't target the circulating IL-4, it targets the IL-4 receptor. By targeting the IL-4 receptor, it not only targets IL-4 but also targets IL-13, which is important, because both IL-4 and 13 are very important in the management of, or the creation of nasal polyps.

If we look at the study, there are several endpoints that we looked at. But the two co-primary endpoints were looking at the change of nasal polyps. Traditionally, you would see in these clinical studies looking at nasal polyps, a change of 1 would be clinically significant. If you look at the change in the nasal polyp for the study, it was incredible. It was a change of 2. It is twice of what we would traditionally consider clinically significant, so that was remarkable.

The other thing that we measured was a change in nasal congestion. A lot of these patients came in and they had moderate to severe nasal congestion. By the end of the study, the patients had zero to mild nasal congestion—so they were able to meet the co-primary endpoints for the clinical study. Traditionally, these clinical studies usually have 1 primary endpoint. For sinusitis with nasal polyps, they had 2. That made it much harder to meet. Yet we were able to meet those goals and see what else it could do.

The other things that we measured were secondary endpoints. These endpoints were a quality of life questionnaire called SNOT-22. It's kind of appropriate, right? And it's kind of interesting, because SNOT-22 is probably a measure that has been used most often for the treatment of sinusitis. So when you have a patient with sinusitis, and you have an intervention like surgery or medical treatment, then you can see if there's a change from baseline to at the end of the clinical trial. SNOT-22 is probably the one that's been measured the most. Now, it's probably not the best measure for sinusitis because it can also measure other disease processes such as depression, but it is the one that's most commonly used out there.

That was one of the secondary endpoints. When you measure the secondary endpoints from baseline to the end of this clinical study, there was a change of 30, which is remarkable, because if you look at what the change for the SNOT-22 after surgery, it’s pretty similar. So the question arises: is the effect of dupilumab almost similar to what we would see in patients after surgery? And based on the changes in SNOT-22, that's what it would infer. Now, in order to really compare, you have to compare the 2 together, but based on the change in SNOT-22, that's what it would infer.

We also measured change in smell. And you know, these patients with nasal polyposis, there are 2 symptoms that are part of the most common: nasal congestion changes and smell. If you asked a patient which is more important for them, they would say the change of smell or loss of smell is more important for them. And in this study, we were able to show that the patients now who did not have any sense of smell in the beginning were able to get their sense of smell back, which is remarkable, because that increases our quality of life tremendously. And so, that's what we were able to show with the secondary endpoints.