Podcast Transcript: Managing Nasal Polyps: Treatments & Insights

[Dr. Agan]:
Now we have that patient who, just going back to the primary pilot patient who saw you in clinic, it's been about six weeks. They did the steroids, they did the rinses, they did the antibiotics. They've come back to you with a scan, and they're feeling better. What's your next step? How do you counsel patients, and how do comorbidities play a role, like comorbidities such as asthma or significant allergies, if they do have those?

[Dr. Citardi]:
Okay. I think a lot depends on the CT scan. We want to make sure the sinuses are safe, meaning there's no mucocoele, no bony erosion, nothing crazy going on. Assuming the scan shows "safe sinuses," we can just talk about, I think, what the likely disease course is. We would keep them on the topical treatment that they're on and see how they do. If they lose the progress that they made, there would be some escalation. Then talk about that escalation. Could be surgery if it's soon. It could just be another round of prednisone in two years.

Really depends on what it is, what happens, and what their prerogatives are. That's the general thing. Most of the time, most patients will be better after that initial treatment. If they're not better, symptomatically they're the same, then they're just going to go to surgery, I think. Because the surgery just allows essentially a complete reboot and you're starting fresh and just lowering the disease burden so much that topical steroids or steroid delivery devices can control the patient's symptoms.

[Dr. Agan]:
Do you have like a number of rounds of steroids in a year or every certain number of months that you're like, "Okay, we're doing it too often, and maybe we should do surgery?" They respond, but then the polyps returns so quickly. Do you have anything like that in your experience that you follow?

[Dr. Citardi]:
It depends on the type of symptoms between the flare-ups. If a patient's requiring steroids like four or five times a year, let's say, they're basically never asymptomatic. If it's like once a year or once every two years, then they're getting large periods of being symptom-free. It's that duration of being symptom-free that drives it. If I treat the patient, they get better for a few weeks, and then three weeks later, they say, "I'm getting worse again," I'm likely to recommend surgery just to escalate to that, just to break the cycle. At that point, patients are sort of on the program, understand this is a chronic disease process, understand the role of topical steroids, and they're great surgical candidates because they're likely to sustain the postoperative treatment.

[Dr. Agan]:
If patients with allergies or AERD or asthma, with those other comorbidities, how that might change your management for the patient with polyps?

[Dr. Citardi]:
Those are three separate items, three separate buckets. When you say allergy, I am thinking of type one IgE-mediated hypersensitivity. I don't think that plays a large role in nasal polyps. Part of it is just intuitive. Think about it. If your nose is full of polyps, you have no aeroallergen exposure because there's no aeroallergens getting into your nose to trigger it. When you look at what we know about polyp mechanisms, it's not really IgE mediated in the sinus lining. I don't think that's super relevant.
Now, there are patients with whom you reduce the polyp burden and suddenly the nasal lining is exposed and can get aeroallergen reactivity. That's relatively easy to treat because you're going to have them on a topical steroid anyhow. You're getting it into the sinuses. It's going to get into the nasal lining as well. You have it covered. As far as AERD, that is a marker for much more difficult to treat disease, both from an asthma standpoint and from a sinus standpoint. I will tell patients point blank upfront that we're going to need to be much more aggressive with this. We can expect just more difficult to control the problem.

Now, what's interesting about that, sometimes you do the standard treatments like this and those patients just cruise right through it. You can't really predict with 100% certainty that every AERD patient is going to fail. I've been surprised occasionally over the years how well some of them do. We will talk about aspirin desensitization in those patients. That's difficult to get, but I've had some patients who do really well with that. I'm a little bit concerned that's sort of a dying art in terms of a lot of allergists don't really want to bother with it anymore. Then in the AERD patients, too, I'm more likely to bring up biologics sooner because they just have more recalcitrant asthma and more recalcitrant sinus disease.

I wouldn't launch that to start with. I think you mentioned asthma as well. Sorry for rambling on here. For asthma, I treat a lot of asthma. Most of these patients have an inhaler. There aren't many people and many pulmonologists or allergists who want to treat asthma, it seems like. The pulmonologists are focused on running the ICUs and their clinic practice is sort of an afterthought, like a side gig or something. These patients can't get anybody to manage their asthma. I'll prescribe their inhalers, occasionally adjust the dose, give refills because they can't get their pulmonologist to do the refills because it's a pretty simple thing to do.
If they're not responding well to that, then I have to escalate and get a pulmonologist involved directly. For the routine maintenance, I think as ENTs, we can we can manage that.

[Dr. Shah]:
Back to our patient who maybe is a candidate for surgery now, you're starting to think about surgery, what extent of surgery are you doing? Do you ever think about biologics earlier as an alternative to surgery? Is there a patient population that is a conversation?

[Dr. Citardi]:
Let's talk about the surgery first and maybe the biologics issue. I think the important thing about the surgery is the first surgery is probably the most important one. We suspect that's true, especially for allergic fungal sinusitis patients. I think it's true really in general for all of these polyp patients. It has to be comprehensive in terms of making sure that all the sinuses on the involved side that have polyps in them are cleared out, because you really want to get them down to a true polyp-zero state. Because that's your new baseline.

You don't want to have any pockets where there is a nidus of eosinophilic inflammation just blocked off from topical treatments. The surgery, I think, needs to be comprehensive. That doesn't mean that every patient automatically gets a drill out. I think that's overkill and too dysfunctional. Most of these patients with polyps, the frontal recess is expanded by the polyp. It's almost done the work. You just have to spend the time to make sure that all the little compartments are open and cleared out.
We have the technology to do that safely, reasonably well. What the surgery does is set up the patient for post-operative steroid delivery. You can place memetazole implants at the time of surgery as well. The sustained delivery of steroids into the cavity is important. Now, for the biologics question, I think it's an interesting one. Over the past three or four years, there are a couple of patients who were sent to me by allergists in town who were started on biologics, and their request was they wanted their sinuses "cleaned out" so the biologics would work better. They were started on biologics basically the week before I would see them in the office.
In that very small number of patients, the surgery seemed a little bit different in terms of how their eosinophilic mucus looked. It was just a different consistency. It's tough to put into words, but it did look different. The problem with that approach now is there's no data to show that. You choose your favorite biologic, you give them one or two rounds, you do surgery, you're going to take it off, whether that actually improves outcomes. That study in the US will never happen because the people who fund the research do not want to fund only two rounds of a pharma treatment or one round. We're trapped there. It's an interesting idea, but I don't know how far we'll be able to take it.

[Dr. Agan]:
I know you said that for these patients, when they started the biologics one week before the mucin was different, it was hard to explain. Was it thinner, stickier, like less copious, less amount?

[Dr. Citardi]: It looked like it was, in my mind, depleted. It was stringier. It had the consistency. This is a little bit gross, but sort of like a raw bacon in terms of how it came out in the stringy sheets. There's only like three or four patients. It's hard to know exactly what I was looking at.

[Dr. Shah]: Does it make the surgery easier? The corollary would be like using preoperative steroids to decrease inflammation before surgery. Is it easier to suck out?

[Dr. Citardi]: Wasn't easier to suck out. It was easier to grab. Wouldn't go through the suction, you had to grab it. That's an interesting idea. The reality is that because I don't keep patients on long courses of steroids before surgery, we can do the surgery without the steroids. We can do the surgery without the round of the preoperative biologic. Because our techniques have gotten better. The issue with the steroids originally was at a time when your cameras, if you're using a camera versus looking with your eye, the camera was only basically less than DVD quality in video. The picture was dark, and you couldn't tolerate any bleeding.

Now, with 4K cameras, if you use intraoperative topical epi, bleeding and visualization, I think we've checked that box that we can see. We don't need to use preoperative steroids. I don't see what the advantage of offering a very expensive drug, even for one or two doses, is going to give us beyond that, and to show how many extra patients do you need to treat before you actually make a difference? I don't really see the value proposition there based on current technology and currently how we're doing the surgery.

[Dr. Agan]:
Do you think that there are patients who can avoid surgery by using biologics? They just never end up in your office because they were started on biologics, and then their polyps got so much better?

[Dr. Shah]:
Maybe for asthma or for other reason and--

[Dr. Citardi]:
That's a good question, but very hard because it's like an unknowable from an ENT perspective, because we're not seeing those patients. I do think that's happening. Allergists and pulmonologists are prescribing biologics at higher rates than we are as ENTs. There's a whole flow of patients that are no longer coming to our offices. That's a problem for our specialty, a significant problem. Because we fought in the roughly between 1995 to 2005 very strongly as a specialty to control this disease space.
We're losing control over that disease space now. If you look at the indications for the biologics, it doesn't say that patient had prior surgery and has a recurrence. It just says they have polyps above a certain grade. That's the indication. When we have our meetings, we say, "Oh, this is reserved for people who are not doing well after "conventional treatment," which includes surgery." That's not what the FDA indication says. That's not what the allergists say or do. They're capturing those patients and keeping them away from us.

[Dr. Shah]:
Do you think we should be offering it as a first line before surgery?

[Dr. Citardi]:
No, it's ridiculous. I think it's ridiculous because we've gotten really good at it. If you look at how there's a whole issue, it's sort of a separate topic, but how drugs are developed in this country, they are developed to get an indication. It's not really developed in the sense of what role they should play in a chronic disease process. Nobody really looks at that. It's up to the specialty societies to try to do something. The standard things that we rely on are pharma-funded. Pharma is interested in just getting the indication and driving sales. Their interests here do not 100% align with physicians who are responsible for the care of these patients.

[Dr. Shah]:
Dr. Citardi, where do biologics play a role in the management for your patients with polyps?

[Dr. Citardi]:
I think where they play a role is when our "conventional treatments" are failing. Patients have had surgery. They're on topical treatments. They're compliant with those treatments. Then they're still failing. Many of those patients also will have asthma. We also as ENTs, I think we need to step up and own the process because no one wants to see the patient coming back after sinus surgery, and they're just struggling and not doing well. It's sort of frustrating. The reality is, through getting a good history, educating the patient, looking at their endoscopy, and doing debridements in the office, we can come up with regimens that emphasize topical drug delivery and keep those patients off of biologics.
We have to work with the patients who are not doing well. That's hard. It's not fun. The reality is, as ENTs, we prided ourselves when we were doing our residency interviews that we were going to be both physicians in the office and surgeons and be both. If we're true to that, we've got to sort of embrace that part of the practice.
[Dr. Shah]:
Yes. Can you tell us a little bit more about steroid delivery? We all think of topical budesonide. Is there a role for steroid-eluting stents at the time of surgery or in your office, or in your practice?

[Dr. Citardi]:
I'm going to say a strong yes for that because it's a way to get basically steroid to target in a very reproducible way and predictable way. You can think about the standard 370 microgram, PROPEL Mini, PROPEL Contour versus SINUVA, which is a much higher dose. The SINUVA mometasone implant was designed for recurrent polyps after ethmoidectomy for delivery in an office setting. I will offer that to patients quite a bit when they're not doing well. The conversation is basically we can do this procedure in the office, place this dissolvable device versus putting you on a biologic, which is probably an indefinite commitment.

Most patients don't like the idea of an indefinite commitment to an injectable medication. All the studies seem to show that the patients will respond to your favorite biologic, but when you stop the treatment, the symptoms quickly start to return. It's not what we hoped it was going to be. We hoped that you would treat them for a brief period of time. The system would reset, and you'd be done. That's not what it is. They need to be on it continuously.

Now, some of that might be because of how the studies are designed. If you're a pharma wanting an indication for your billion-dollar drug, you don't want to show that you only need a finite treatment course. You want it to be open-ended. All the available data and the anecdotal clinical data shows that when you stop the biologic, the underlying disease process reverts. When you make that choice to patients, many of them will opt for having a mometasone implant done in the office.

[Dr. Agan]:
When they do the implant, they don't have to do budesonide irrigations? The implant's going to do the work for them?

[Dr. Citardi]:
I tell them they should still do the budesonide irrigations. I'm not sure they're as compliant with that as they should be, because you can check when they're asking for refills. What I say is that the implant gets things going. It's not going to be an indefinite presence. It's 90 days, and probably the first 45 are the most important. You open things up again, and then it allows the budesonide to get in. It's sort of the same idea behind the original polyp surgery. Open things up, reduce the disease burden, and then let the topical steroids take over again.

[Dr. Agan]:
Just to play devil's advocate a little bit. To the patient who's saying, "Okay, either I'm going to be needing topical steroids indefinitely, or doing this shot indefinitely," why is one better than the other?

[Dr. Citardi]:
The thing that's most understandable from a patient perspective is the systemic effects. One of the unique things about what we do is that our body space is accessible to the outside world for diagnosis and follow-up evaluation. It's not like asthma or looking in the lungs requires a bronch, or if you're treating the GI tract. It's a whole different game. We have a unique opportunity to sort of assess pretty much everything that's going on. In my mind, it's all about drug to target. We have an accessible target in a way that a lot of our other medical specialties don't.

[Dr. Agan]:
In terms of the steroids, when do you decide when you're going to place a steroid-eluding implant? Which patients are you going to place them in? Is it part of all of your surgeries initially that maybe you'll put a propeller and see how they do, and then they come back and do the SINUVA? How do you decide which one to use?