Claus Bachert discusses nasal polyps and current treatment options. Disclosures: Claus Bachert is the PI of the Dupilumab study.
FILMED AT THE EUROPEAN RESPIRATORY SOCIETY (ERS) INTERNATIONAL CONGRESS, SEPTEMBER 2016
Are all nasal polyps alike, or do they have different inflammatory patterns?
00:11 – Actually, nasal polyposis is a heterogeneous disease and they are not alike all over the world, but even not within Europe. We did studies all over the world and it’s very clear that the majority of these patients, certainly in Europe, are so-called type 2 eosinophilic inflammatory disease. But in Asia, they are not. So you have type 2 taking 85% of the patients in Europe and about as little as 15% of the polyp patient population in some parts in Asia. Now in our place, the majority is type 2 mediated, it’s 50% comorbid asthma, and 80% of these patients will have recurrence of disease after surgery if you just look long enough such as 12 years.
What are the current treatment options for patients with nasal polyps?
01:16 – It all starts with topical glucocorticoid steroids to treat these patients. This can be once daily, twice daily. It can be in form of drops. You can add some short courses of oral glucocorticoid steroids over the time, not more than three times a year, that’s the recommendation. And then if that doesn’t control the disease, you go to surgery. Now, as I said, even surgery is not a solution to many of these patients. So about 23% in a European survey of patients with polyposis needed at least four or more surgeries at the time of the interview, and actually they were not at end of life so, it’s even higher than that. So clearly, the surgery is a step, a module in between. After the surgery, you still need further therapy with topical or oral glucocorticoid steroids.
How prevalent is asthma in patients with chronic sinusitis?
02:26 – The prevalence of asthma comorbidity is very dependent on…in which part in the world you are looking at. As I said, in Europe it’s about 50%. It can be as low as 5% in some places in the world. If you select the patients for the most severe eosinophilic type of inflammation, then you will have up to 70% asthma comorbidity. So it’s very much dependent on whom you look at. And about 10% of these patients also have aspirin-exacerbated respiratory disease.
How does the mechanism of action of dupilumab affect the pathogenesis of nasal polyps?
03:13 – As I said, the concern for us is the type 2 inflammation, including cytokines which is IL-4, IL-5 and IL-13. Now dupilumab, is a human monoclonal antibody that binds to the IL-4Rα, and this interferes with IL-4 and IL-13 pathways. In other words, you get an effect on the activation of b cells, of t cells, of eosinophils, mast cells and many other cells. The good thing about this combined thing is that you already target two of these cytokines and you haven’t even targeted the eosinophilic pathway by blocking chemokines locally in the nose, for example; and we have shown that recently. So you’re actually working on IL-4, IL-5 and IL-13 in one way.