Dareen Siri, MD, FAAAAI, FACAAI

In closing, thank you to all of you for this rich and informative discussion. You know, my final thought on this is, we talked about nasal polyposis, which is 20% of CRS. But hopefully, in a few years, we'll be talking about CRS without nasal polyps, which is 80% of CRS. And before we completely ended, I'd like to get final thoughts from each of you. Let's start with you, Naveen.

: It's exciting to see what's on the horizon, how we can improve our care. I like what Drew mentioned about the multidisciplinary collaboration. It makes you feel any better, we don't have allergists in our office here, but I agree with you. I think long term, I think that would be a really good treatment model. And above all, I really enjoyed being on the panel today. Thank you, Dr Peters, for including me, and I appreciate all the discussion. And I too, learn something today. So again, thank you.

Thank you, and hey, if it makes you feel any better, we do have a joint clinic and we agree more people should do it. It doesn't have to be brick and mortar if you communicate, it works fine. We do both. Any concluding comments from you, Drew?

You know, I'm always struck at the very beginning, you talked about the prevalence, you know, in 6 to 12% of people. And you know, when you stated a different way that 1 in 8 people have CRS, it's crazy. And I'm always, you know, frustrated when I see a patient who clearly has been suffering for a long time and they show up and its sort of obvious right from the get-go what's going on. And they've just sort of been flying under the radar for some time of years. And I'm really happy to be part of anything that's an increased awareness and get other physicians just to think about looking for this condition.

: I thank you so much for organizing this multidisciplinary discussion. And certainly, regarding some of the patients, since you pointedly asked me about, you know, the vulnerable patients, elderly patients, things like that. You know, it's interesting to think about because we're seeing a lot more of adult-onset atopic dermatitis, adult-onset asthma. And certainly, we know that from several publications that patients over the age of 65, it's like the six most burdensome disease, which is chronic rhinosinusitis. It's not something that is only a disease of the young effect. It's probably more prevalent in the older. And as the population ages, as we think about their vulnerability in terms of medications, their exposures, whether they're in San Diego, or via Chicago, or the Cornfields, you know, what is triggering some of their illness, and some of the sinuses. These are all things that are worth the investigation.

Well, thank you. And thank you everyone for watching this peer exchange. If you enjoyed the content, please subscribe for our E-newsletters to receive upcoming peer exchanges and other great content right in your inbox. Thank you.

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Drs Anju Peters, Naveen Bhandarkar, Andrew White, and Dareen Siri share takeaway thoughts on the management of nasal polyposis.

Final Thoughts on Management of Nasal Polyposis

Drew, what would you think are the biggest challenges or areas of unmet need in treating these patients with CRS with nasal polyps?

: There's a lot of areas where there's still questions. I think, Dareen said, this is the age of the sinuses or something like that, you said. You know, we've had such a huge change in what we have, in terms of treatment, and the ways that we think about these patients, it's sort of like exploded in front of us. And that's even created some of the challenges, you know, now we've got all these options, what do we do with them? Some of the biggest challenges that I would say, and I'd be interested if you agree or disagree, but I think you know, defining like, what's our goal and our endpoint for some of these patients, we want them to feel better. But there's other dimensions to it, because these patients have surgical morbidity or you know, needing repeat surgeries, and they've got asthma, and some of them have NSAID sensitivity. What's our goal, and I think it's probably different with an individual patient. That would be one of the challenges is, you know, like when we take an individual patient in front of us, where do we go with them? I think another challenge now is where's the dividing line between medical and surgical therapy. Where do we sort of decide a patient has failed medical therapy and should go through surgery? And I think that's different in different situations, and the patients sometimes show up in our practices in different stages. That's a big challenge and unmet need is knowing where we advise patients in that. And I would say the other big unmet need or area that we need to focus on is, what if we have biomarkers or certain phenotypes of the disease that we can predict a little bit more about outcome or response to therapy. Because right now, it's sort of just view them all under the same lens. And you know, I think we all have different suspicions, maybe about how to interpret some of the biomarkers, but at the end of the day, we need a lot more information. I would say the biggest challenges that I see more from a scientific standpoint in approaching this.

: Yes, that is one of the biggest questions that I feel we need to answer. Like even today, patient ask how long do I stay on these biologics? And I'm like, hmm. I totally agree with you. And you know, any one of you guys could chime in, what do you guys think are the greatest unmet needs for our patients with nasal polyps? And one thing that you mentioned earlier, Naveen, was the shared decision making and I think, Drew, you talked about it a little bit too, do you guys want to talk a little bit about that? We'll start with you, Naveen.

So shared decision making. They're just talking with the patient on these different treatments, because we've gone over a lot of different options that we have available, but I don't think the decision to start one over the other, depending on the circumstances, all that cut and dry. Sometimes one of those might work better for somebody than another. You know, when it comes to implants, for example, they do have a limited duration, and they do have a certain effort involved in terms of placement. That patient must come in for an episode of care where this implant is placed on one or both sides, or in one or more sinuses for that treatment, and then they last certain duration. And then the question is what happens after that? Do we need to potentially repeat that versus considering something that may be longer term? Like certain topical steroids or even, you know, when to consider a biologic? A lot of that is really to do with what each patient's personal preference might be. If all of those treatments may have similar efficacies.

How about you, Drew? Any comments on unmet needs in terms of CRSsNP?

The things that I think I struggle with, in my practice, you know, some of it is just accessibility of the treatments to the patients. And I recognize that a lot of these therapies have a lot of expense. And that's a frustrating part of our care delivery is that some of the things that we think might work best may not be an option for patients. That's always a consideration. And I think one of the unmet needs. And for some patients, you know, it's the relationship between the allergist and the otolaryngologist, you know, it's still sort of just by definition, they're all in different clinics. And, you know, my dream is to be able to have like a combined clinic where we can all work together. I know that does exist in places, but not where I'm at. But I just think that would be so much better for the patient to just have like, one long visit, and they just sort of all gets hashed out right at the same time. So those are - those would be sort of my things that I think are our areas for improvement.

How about you, Dareen? Any unmet needs you can think of?

Those are certainly great points, I would invite you to come from sunny, beautiful San Diego to visit us from the Cornfields. Because literally the other day, I sat in with a patient who was on a biological drug, who was also on EDS-FLU in an ENT clinic and talked about the pros and cons with my ENT colleague with the patient. That was cool to be able to do that. And then so in a unique area, of course, we have a lot more space than you do, less traffic. And certainly, I can see that being envisioned, very intimately as well at University of California, Irvine, or even Chicago where you know, they work closely together. It really is great to think about these medications that are coming down the pipeline. But certainly, thinking about some questions that we haven't addressed, such as, what about aspirin desensitization? That was a huge push. Is it safer now with ESP on board or biologics on board? I don't know. Is it effective? Is it still needed? What about other things? Allergy immunotherapy in those patients who do have type 2? Is it effective, needed? Those kinds of questions. I would love to know about these questions. It's some of those, as we are treating the patients. And again, they are complex patients with multiple issues to think about, what about some of these additional therapies that we've offered in the past? How needy are they? Or how needed are they? Those are good questions to address.

I totally agree. And maybe we could have a session with Drew, just talking about that stuff to us next time.

Drs Anju Peters, Naveen Bhandarkar, Andrew White, and Dareen Siri review unmet needs and shared decision making in the treatment of nasal polyposis.

Unmet Needs in Nasal Polyposis

What are you guys most excited about in terms of new medication options for patients, nasal polyps, new mechanism of actions, or any new ongoing trials for with polyps, but also for without polyps?

It's crazy how many options have emerged in the last couple of years. I mean, it's hard for us to even keep track of the new therapies that are getting approved. And then, you know, thinking about if this is therapies approved for asthma, would we think it would work for polyps. That's been exciting. And probably over the next few years, we will just sort of stumble upon some other treatments that are going to work amazing, and at the same time probably teach us a lot about polyp disease in general. Because we will probably learn that something works well that we didn't anticipate. One of the things I'm excited about is tezepelumab. Tezepelumab is a monoclonal that's currently approved for asthma. It works at a very high level, sort of at the beginning of where a lot of this inflammation may happen in the mucosa. The target is something that's important, we know in AERD, which is a severe form of polyps that I've been very interested in. It has a lot of promise. I'm particularly excited about that. You know, I think there's a lot of other targets that are interesting. There's anti-siglec-8, which is on mast cells and eosinophils. And there's potential, you know, therapies in development that may target both of those cells. And I'm pretty interested in things that can do both, do double duty on eosinophils and mast cells.

: Naveen, would you like to add anything else?

: Yes. The EDS-fluticasone that we have been talking about, which has a current FDA approved indication for polyps. As I think we mentioned earlier has gone through a trial, which met primary endpoints for treatment of chronic sinusitis, which in the FDA view is a separate disease state for whatever it's worth. And I'm excited to see what comes out of that. If approved, it would be the first FDA approved therapy we have for chronic sinusitis. That's very exciting. The second that is ongoing right now is use of a mometasone-eluting implant that can be used prior to surgery and is placed in a specific location in the middle meatus. That's going through trials right now, which may not be available for several months, but is another very exciting thing on the horizon.

How about you, Dareen? Anything you are excited about in terms of new treatment?

: As you discussed at the very beginning, there's this, you know, huge section of patients. The majority who do not have nasal polyps, or perhaps they have nasal polyps and evolution. We just haven't quite recognized them, because they don't have free nasal polyps hanging in their nose. That, to me is the most exciting. Because right now, you know, I'm trying to have to, again, negotiate different medications that will help these patients without an FDA approval. And that that is the number one most exciting part is that now I'll have something that I can treat in the majority of my patients with, and something that is easily accessible, easy to prescribe, those kinds of things. And certainly, there are a lot of other cool medications coming down the pipeline. And in fact, some of the other research, not necessarily about therapies, but just, you know, phenotyping, and endotyping the patients. Kind of like, when you have with asthma and other diseases to see which drugs might work the best for them? Which therapies? Which interventions? And as we understand a bit more about, you know, this age of the sinuses, I think that that's the best part.

A multidisciplinary panel reviews emerging treatment options for nasal polyposis, including EDS-FLU, Tezepelumab, and Rimegepant.

Emerging Treatment Options for Nasal Polyposis

Let's move on to the next question. Dareen, this is for you. You do a lot of clinical trials. How do use clinical trials for patients, who for example, have stopped responding to their current treatment? Do you offer them other clinical trials?

: My answer transitions to some of both of your points, in that, as I discussed, in some of these complicated patients with the excellent ENTs school of medicine in my area. We typically will try one of these biologics for probably about 6 months. I would like to see what you guys are thinking about that as well, and certainly if there's a feeler, we might try a different one. And, funny enough with these medications, unlike asthma, which clearly states this is an add on therapy with biologics, that's not very clear with all the biologics in terms of the use with nasal polyposis, which I find kind of interesting because that the similar inflammation is underlying it. I certainly think that the best success is add on treatment, meaning that we're addressing the underlying inflammation with something like EDS-FLU, as well as the use of biologics. But beyond that, one of the big barriers for us is that all these medications, IL-4, IL-13, anti-IgE, anti-eosinophils, IL-5, is that they are focused on that type 2 inflammation. And the deficit or the lack is that what about those patients who do not have an underlying type 2 inflammation, or a sinophilic inflammation status. And in those patients, perhaps, that where is where the clinical trials may be utilized for them, with some of the newer developing therapies. Or perhaps, they do have that inflammation, but they are still having some lack of symptoms that are being addressed, and really are feeling still some issues. And of course, we've assumed that we've worked these patients up for all the underlying diseases that we're worried about. But we have encountered these patients, you know, similar to some of the other disease states where we've treated them, the polyps have improved. We have much less inflammation, but the patients continue, for example, to have significant facial pain pressure. There are certainly opportunities for them going forward for some newer medications.

Drs Anju Peters and Naveen Bhandarkar, comment on the challenges of using biologic therapies to treat patients with Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP).

Dareen Siri, MD, FAAAAI, FACAAI

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