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Biologics for Chronic Rhinosinusitis With Nasal Polyps

Author Taylor Spurgeon-Hess covers Biologics for Chronic Rhinosinusitis With Nasal Polyps on BackTable ENT

Taylor Spurgeon-Hess • Feb 27, 2022 • 222 hits

In the past, patients with chronic rhinosinusitis (CRS) who were unresponsive to steroids and surgery often found themselves out of options in terms of symptom improvement. Today, biologics for chronic rhinosinusitis with nasal polyps can provide drastic improvement when administered as a last line treatment. While not all patients with CRS may be eligible candidates for biologics treatment with one of three monoclonal antibodies approved for the condition, those who qualify often report significant improvement with minimal side effects. Learn more about the conversations otolaryngologists are having about this new CRS treatment.

This article features excerpts from the BackTable ENT Podcast. We’ve provided the highlight reel in this article, and you can listen to the full podcast below.

The BackTable ENT Brief

• The approved biologics for chronic rhinosinusitis include three monoclonal antibodies: dupilumab, mepolizumab, and omalizumab.

• Only type 2 inflammation can be targeted by the biologics for chronic rhinosinusitis with nasal polyps. Patient responsiveness to steroids best indicates this mechanism of inflammation.

• Patients might benefit from biologics as a last-line treatment, with frequency and quantity of injections ranging from 1-3 injections every 2-4 weeks.

• Some research reports side effects including cornea problems, arthralgias, and headache, but often patients report an injection site reaction or no side effects at all.

An MRI scan used to determine candidacy for treatment with biologics for chronic rhinosinusitis with nasal polyps

Table of Contents

(1) Biologics for Chronic Rhinosinusitis Basics

(2) Determining Candidacy for Biologics Treatment

(3) Discussing Biologics with Patients: Medication Administration & Insurance Coverage

(4) Side Effects of Dupilumab, Mepolizumab & Omalizumab

Biologics for Chronic Rhinosinusitis Basics

The list of indications that biologics can treat continues to increase, and, in addition to various conditions such as thyroid eye disease, asthma, skin conditions, and ulcerative colitis, has recently come to include chronic rhinosinusitis with nasal polyps. The three major monoclonal antibodies used to treat CRS are dupilumab, mepolizumab, and omalizumab. Each targets various interleukins and/or anti-IgE in order to decrease the underlying inflammation causing CRS. While these drugs generally provide excellent results, they are expensive and still considered the last line of treatment.

[Ashley Agan MD]
Laying the groundwork for immunomodulators, biologics, what are we talking about as far as this class of medications? How do they work? How is it different than our typical kind of traditional toolkit of what we use to treat allergies?

[Matthew Ryan MD]
So I'll jump in on that one. Dr. Agan, the biologics are monoclonal antibodies that are available for the treatment of a variety of conditions. And we know about many of them through TV ads, because there's a lot of direct-to-consumer marketing being done for these monoclonal antibody therapies that can treat a range of conditions, everything from thyroid eye disease to ulcerative colitis to psoriasis, asthma, skin conditions, and now finally nasal polyp disease.

And they are very different from small molecule pharmaceutical agents that really had been the mainstay of our medical treatment approach, throughout the history of medicine. Small molecules are much easier to produce. Their dosing is in a lot of ways simpler. They can be given orally. I guess, one big distinction with these monoclonal antibody therapies, the biologics, is that they have to be administered parenterally. Usually that's intramuscular though. There are some IV preparations as well. I say intramuscular, I meant subcutaneous actually, right Dr. Damask? Yeah. So they can't be taken orally because they are essentially antibodies.

[Gopi Shah MD]
And Dr. Damask, you've been using this, you said for about the last five years of your practice, for what patients, like what indications have you been using it for in your practice?

[Cecelia Damask MD]
My gateway, I guess, to biologics and what I started with was different skin conditions. So I've been using biologics for chronic spontaneous urticaria for patients who had failed management with high doses of antihistamines to suppress their urticaria. I've been using it for other skin conditions like atopic dermatitis. So patients who have failed management with various topical steroids or calcineurin inhibitors. I have used it a lot for asthma, for allergic asthma, as well as for eosinophilic asthma or asthma that is corticosteroid dependent. And then I have a few patients that I have on biologics for EGPA or what we used to Churg-Strauss. And then most recently I have patients on biologic specifically just for nasal polyps.

[Ashley Agan MD]
For most patients, would you say traditional therapy is still the mainstay and that biologics are really more of a next tier, like when things aren't working or is this something we should be thinking about earlier?

[Matthew Ryan MD]
I would say that for most conditions, the biologics are the last line of therapy. And the reason that we see so many TV ads is because the biologics are very expensive medications. There's a lot of money involved in this. And so, in general for most chronic health conditions for which we have a biologic available, the traditional or standard therapies are really what we rely on. And so it's a select niche group of patients for whom a biologic is appropriate. And that's to some extent, I think function of the cost of these therapies. That's something that we have to consider when we're making decisions about whether or not we want to start a patient on a biologic. What are your thoughts, Cecilia?

[Cecelia Damask MD]
I agree. These are patients who we have tried traditional therapy, whether for asthma, that's doing inhaled corticosteroids or adding on a long acting beta agonist or a LAMA, and these patients are failing and requiring other systemic therapy, like systemic steroids multiple times a year to control their asthma. Then that's someone I would consider for a biologic and same with our nasal polyp patients, it’s someone who has failed other management and the biologics, at least in their PI they're listed as being add-on for maintenance therapy that have failed with intranasal corticosteroid.

Listen to the Full Podcast

Biologics for Nasal Polyps: What’s the Role? with Dr. Cecelia Damask and Dr. Matthew Ryan on the BackTable ENT Podcast)
Ep 46 Biologics for Nasal Polyps: What’s the Role? with Dr. Cecelia Damask and Dr. Matthew Ryan
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Determining Candidacy for Biologics Treatment

To determine whether or not a patient may benefit from biologics for chronic rhinosinusitis with nasal polyps, the phenotype and endotype of the disease must be assessed. Phenotype refers to the observable characteristics of the disease, while endotype refers to the underlying mechanism of the disease. Only type 2 mediated inflammation can be targeted by monoclonal antibodies. The best indicator of T2-mediated disease is steroid responsiveness; if a patient responds well to steroids, it is likely they will also respond to biologics for nasal polyps.

[Matthew Ryan MD]
So what are the phenotypes, Cecilia, of chronic rhinosinusitis?

[Cecelia Damask MD]
Well, can we back up and talk maybe a little bit about endotypes first and just about what is T2 versus non-T2.

[Matthew Ryan MD]

[Cecelia Damask MD]
So when we think about trying to break things down and we look at things that are T2 mediated or non-T2 mediated, things that are T2 mediated can be mediated by different cell types or different cytokines. Like the interleukin four, interleukin five, interleukin 13, and once we identify someone is potentially having a T2 endotype then we can break them down into different phenotypes.

[Matthew Ryan MD]
And Dr. Agan to get to your question, since we're talking about inflammatory endotypes, the biologics that we have available for treatment of CRS with polyps are specific for those type two cytokines, IL-4 and 13, IL-5 and IgE. And so, I think if we're trying to decide who a biologics for, we want to try to identify a type two endotype and maybe in our discussion, we'll get to that.

But I wanted you to talk about phenotypes, Dr. Damask. The phenotypes of CRS. How's that different from endotype?

[Cecelia Damask MD]
So a phenotype is something that you can observe. It's an observable characteristic, whereas an endotype is a mechanism of how something happened. So a phenotype is something that we could look in and say, oh, we see polyps, or we don't see polyps. But in terms of CRS with NP, different phenotypes would be something like CCAD or AFRS or eosinophilic CRS.

[Ashley Agan MD]
So how do we stratify patients into whether they're a T2 endotype so that we can know, okay, they're a candidate for biologics? Should we be getting labs? Is it based on what our clinical exam looks like? How do we know?

[Cecelia Damask MD]
So I think there are some things that we can see in clinic that might clue us in to someone being a type two patient. And then yes, there are laboratory studies or pathology specimen, but we're not going to have that available to us in a clinical setting. But I think biggest indicators is if someone is steroid responsive. And so if they have a good response to a steroid, then that is someone who most likely has T2 mediated disease.

[Ashley Agan MD]
And does a Medrol dose pack count? Are we talking like a larger dos of prednisone, any steroid?

[Cecelia Damask MD]
Any steroid. Someone that’s steroid responsive most likely has some T2 mediated disease.

[Matthew Ryan MD]
And the other thing I look at Dr. Agan is, if someone does have a history of allergic rhinitis or has a history of asthma, I think those can, sort of point to a type two. There are some labs that I will draw. So I'll get a total serum IgE and I'll get a CBC with diff to look at the peripheral eosinophil count. And in general, if I see really high total serum IgE, or I see a really high peripheral eosinophil count, that makes me think type two. That's not set in stone by any means. I will say for some of the clinical trials of these biologics, they did have certain thresholds for, let's say, an eosinophil count to be accepted into the trial because these agents, some of them, Dr. Damask, I think, can tell us more precisely, but some of them are specifically for CRS with nasal polyps, with an eosinophilic component.

[Cecelia Damask MD]
Definitely for the trials for asthma, they had to have certain cutoffs of peripheral eosinophil levels to be involved in the trials. For omalizumab, for nasal polyps, they did have to have a minimum IgE level of 30 or above, but for the dupilumab and for the Mepo trials, there was no minimum requirement of peripheral eosinophilia. However, when they have done post hoc analysis and looked at response, like in the Mepo trial, they saw that patients who– post hoc, so this is not in the actual trial, but this is analysis afterwards– patients who had peripheral eosinophils over 300, they had a larger improvement in their nasal polyp score or improvement in less need for systemic steroids if their peripherally eosinophils were over 300.

[Matthew Ryan MD]
So that's an interesting thing, so that these trials enrolled people that perhaps didn't have type two inflammation as the etiology of their polyps and for us as clinicians, if we want to get the best results, we need to try to specifically identify those patients who have type two inflammation as the driver and in those folks we can see dramatic improvement.

So there are a variety of other forms of nasal polyp disease that are not type two. So you can think about cystic fibrosis as a great example. So in cystic fibrosis, the development of nasal polyps in those patients is not necessarily driven by abnormal eosinophilic inflammation going on. And so their problem oftentimes is as a consequence of disrupted mucociliary clearance, they have colonization with various bacteria that promote inflammation and a CF patient doesn't necessarily get that great of a benefit with nasal polyps. Do they, or with steroids, do they Dr. Shah?

[Gopi Shah MD]
No, I mean, we traditionally think that they're oral steroid resistant. The polyps don't respond as well. That being said, in terms of topical steroids, we will recommend Flonase or sometimes Pulmicort rinses topically.

[Matthew Ryan MD]
So that's just an example of case of nasal polyps that’s not steroid responsive and type two mediated, and we see the same pattern in adults. That can be sometimes a challenge, but we do see adults with nasal polyps, but they don't respond well to steroids. If you look at them endoscopically, sometimes you'll see some creamy white pus interdigitating among the polyps. It's very different from AFS where we see eosinophilic mucin. So there are some clinical clues. But I think as Dr. Damask mentioned the trial of steroids and assessing steroid treatment responses, a great way to identify the type two polyps.

[Ashley Agan MD]
It also sounds like it would be helpful too, to screen and ask about things like asthma and, skin things, you know, like asking you, do you also happen to have a atopic dermatitis and asthma because if that's positive as well, it sounds like you're leaning more towards, okay, this is a type two patient.

[Cecelia Damask MD]

Discussing Biologics with Patients: Medication Administration & Insurance Coverage

If systemic steroids fail to treat a patient’s condition, biologics may be considered as the next step. Based on the patient's needs and choice of drug, the treatment may be self-administered or administered in-office to allow for patient monitoring. The number and frequency of injections can range from one to three injections every two to four weeks. Each biologics company has a “hub” responsible for collecting baseline patient information and conducting a benefits investigation to determine insurance coverage. Generally, the out-of-pocket costs for commercial payers remain minimal but the medications can be out of reach for Medicare patients. Biologic medications require special handling and must be ordered and filled through a specialty pharmacy.

[Ashley Agan MD]
So, yeah, I think continuing with this patient that we were kind of using as our example patient, now that they're back, they've had sinus surgery and we're starting to think of biologics. How does that conversation go?

[Gopi Shah MD]
Yeah. What are the side effects? What do you tell them? How do they do it?

[Matthew Ryan MD]
Well, so if our patient with CRS with polyps and asthma goes through the standard treatment paradigm, I do my surgery on them, start them on high dose steroids and they come back one or two months later and they already have polypoid edema filling their ethmoid cavity and they're starting to notice more mucus secretions, maybe their sense of smell goes away again. Then I'm really frustrated because I'm in a situation where I'm having to give them yet again, another round of systemic steroids. And I'm kind of expecting that it's only going to work for a little.

[Cecelia Damask MD]

[Matthew Ryan MD]
And they're going to be back where they started again and ultimately left alone over time. They're going to regrow their polyps and not only lose their sense of smell, but also become congested and they to have nasal airway obstruction. And I certainly, in my practice, have some nice examples of exactly that scenario, where the patient is coming back after surgery every few months, and I'm giving them more and more steroids. And, we know that's not good. And even if the patient doesn't get any side effects from those steroid bursts, it's not a good treatment approach for a disease that could last 10 years or longer. And so that is precisely the patient in whom I will recommend a biologic and prescribe a biologic.

[Ashley Agan MD]
Cecilia, maybe you can elaborate on what that conversation looks like with the patient. And it sounds like that there's going to be a need for insurance pre-authorization regardless. And, you know, as a patient, I'm sure their concerns are gonna be, how much is this going to cost? Am I going to be on this forever? Is it a pill or do I have to inject? All those types of things I'm sure come up.

[Cecelia Damask MD]
So there are multiple factors and different types of biologics that the patients can be put on. So it is an actual long conversation with a patient to try to decide which one. And then even once we decide which one, is this something that is going to be administered in the office so I can monitor you and make sure that you're compliant, or is this something that you're going to self administer at home or someone's going to administer to you?

And then there's questions about frequency in terms of dosing. So one of them dupilumab, for everybody, is every two weeks and NUCALA or mepolizumab for everybody is every four weeks. Omalizumab can be dosed based on their IgE and their weight, and so it can be variable. It can be something that they might get every two weeks, or it could be something that they might get every four weeks. And also with the omalizumab, the number of injections can vary. So some people could get one injection, some people could get three injections every two or four weeks. So there's that discussion about frequency.

And each one of the biologic companies has what I'll call a hub, where you fill out an enrollment form, which basically tells the patient's insurance. It tells some baseline things about the patient. Like they have failed with topical steroids, or they have been on so many bursts of oral steroids. And you sign it kind of like a prescription and the patient signs it saying that they give this hub permission to evaluate the patient's insurance for a benefits investigation. And then that benefits investigation will come back to the office and it will give you information about if the patient has any out-of-pockets, if they have any deductible, how much this would cost. And then also it will tell the office how the patient is to obtain the drug.

So some patients get the drug through what's called a specialty pharmacy. So it's not your local Walgreens or CVS. It's a pharmacy that specializes in taking care of medicines that require special handling because they have to be refrigerated at a, at a certain degree between two to eight degrees Celsius, like our immunotherapy and the specialty pharmacies will coordinate delivery.

Some patients, their insurance, especially our Medicare patients for some of the biologics require what's called “buy and bill.” And so that means the biologic has to be purchased by either your office or by an infusion center and then billed to the insurance. So these hubs are very helpful and we'll sort all that out for you and send it back so that then you know which way the patient would have to go for a particular biologic. And then also what those hubs will do, as long as the patient signs permission for them to do so, they will look into copay assistance or different assistance programs to help the patients. And for all the different manufacturers that are out there, they all have really wonderful copay assistance programs that help the patient, not only for the cost of the drug, but if you do administer in the office for administration in the office as well.

[Matthew Ryan MD]
So I think for commercial payers there's really minimal out-of-pocket costs for patients. So the companies have arranged it so that it's not painful financially at all for the patient. And the treatments are very expensive, but of course the insurance pays for that. It's a little different with Medicare or Medicaid, because then the copay assistance is not allowed. It's prohibited and so I have found that the biologics can be out of reach for Medicare patients because of what their expected out-of-pocket costs are. But they get back to your question, Dr. Agan, I just tell patients, this is an injection based treatment, kind of like an insulin shot and you can give it yourself at home and It's not that hard to do.

Side Effects of Dupilumab, Mepolizumab & Omalizumab

While generally well-tolerated and often preferred over steroids, monoclonal antibodies can produce various side effects in some patients. In practice, the most commonly reported side effect is a reaction at the injection site. While less common, research shows that dupilumab can cause cornea problems, keratitis, eye irritation and conjunctivitis. For omalizumab, patients reported headache and abdominal pain more frequently than the placebo. Mepolizumab has been shown to cause oropharyngeal pain in some patients. When utilized to treat nasal polyps, arthralgia came up as a side effect for all three.

[Matthew Ryan MD]
And from a side effect standpoint, these agents are, I think, extraordinarily safe. You'll see, on the TV ads, all sorts of disclaimers and warnings, tell your doctor, if you have a parasitic infection, like, okay, I'm going to do that because I know I've got parasites and so I better not start this you know, immunosuppressing biologic agent. So, the one side effect that I know of is dupilumab can cause some cornea problems, some keratitis, eye irritation, conjunctivitis type symptoms in some patients. But that's really the only practical side effect that I feel like doctors need to know about. At least with dupilumab. Now, omalizumab, mepolizumab, now also available for nasal polyps. Do those have any prominent side effects, Dr. Damask that people ought to know about?

[Cecelia Damask MD]
So for all three of them injection site reaction, you know, big surprise, was a frequent or less than 10% reported side effect. But, interesting for all three of them for nasal polyps, arthralgia was seen as a side effect. For NUCALA oropharyngeal pain came up more frequently than placebo. And for omalizumab, abdominal pain and headache also came up more frequently than placebo.

[Matthew Ryan MD]
But what have you seen in your practice, Dr. Damask? Because I've only seen the eye thing with dupilumab.

[Cecelia Damask MD]
I have seen nothing, other than injection site reactions. They have been really well tolerated. And I will say for dupilumab specifically that I will monitor their peripheral eosinophils before I start them and after I start them, because in the trial, there was some unmasking of EGPA in very small percentage, but I still will monitor. And I have not seen that happen in any of my patients.

[Matthew Ryan MD]
So in general, I would say side effect wise, these are better than steroids.

[Cecelia Damask MD]
Yes, absolutely. Oh, absolutely.

Podcast Contributors

Dr. Cecelia Damask discusses Biologics for Nasal Polyps: What’s the Role? on the BackTable 46 Podcast

Dr. Cecelia Damask

Dr. Cecelia Damask is a practicing otolaryngologist in the Orlando, Florida area.

Dr. Matthew Ryan discusses Biologics for Nasal Polyps: What’s the Role? on the BackTable 46 Podcast

Dr. Matthew Ryan

Dr. Ryan is a Professor of Otolaryngology - Head and Neck Surgery at UT Southwestern Medical Center.

Dr. Gopi Shah discusses Biologics for Nasal Polyps: What’s the Role? on the BackTable 46 Podcast

Dr. Gopi Shah

Dr. Gopi Shah is a practicing ENT at UT Southwestern Medical Center in Dallas, TX.

Cite This Podcast

BackTable, LLC (Producer). (2022, February 1). Ep. 46 – Biologics for Nasal Polyps: What’s the Role? [Audio podcast]. Retrieved from

Disclaimer: The Materials available on are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.



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