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Improving Outcomes in CRSwNP
Improving Outcomes in CRSwNP: Understanding Disease Pathogenesis and the Emerging Role of Biologics

Released: June 27, 2025

Expiration: June 26, 2026

Anju Peters
Anju Peters, MD, MSCI
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Key Takeaways
  • Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition that often occurs via the type 2 inflammation pathway.
  • Although systemic corticosteroids and endoscopic sinus surgery are mainstay treatment options, patients continue to face increased risk of disease recurrence.
  • Biologic therapies are revolutionizing the treatment landscape for CRSwNP by offering significant improvements in disease and symptom burden.

For most of the Western population, chronic rhinosinusitis with nasal polyps (CRSwNP) occurs due to the type 2 inflammation response. The most relevant components comprise the epithelium and several types of cells. When the epithelial barrier is disrupted, many think that the epithelium as an immune-related organ that releases alarmins—priming the type 2 inflammation response we see in CRSwNP. Then the innate type 2 lymphoid cells (ILC2) release the interleukin (IL)-4, IL-5, and IL-13 cytokines. These are the classic cytokines associated with type 2 inflammation. IL-4 is important for promoting B-cell switching to immunoglobulin E (IgE) production; IL-5 is important for eosinophil activation, recruitment, and survival; and IL-13 is involved in mucus secretion, barrier dysfunction, and some tissue remodeling.

B-cells not only lead to local IgE production, but this local IgE activates mast cells which may then act as a reservoir for bacteria like Staphylococcus aureus. It is thought that a superantigen effect may play a role in CRSwNP pathology. Furthermore, IgE autoantibodies are produced and play a role in the inflammation and persistence of disease. Eosinophils are a hallmark in CRSwNP type 2 inflammation and they can release toxic granules that can cause damage, epithelial disruption, and persistent inflammation. Finally, the ILC2s that produce the classic cytokines seen in CRSwNP type 2 inflammation further induce the persistent inflammation seen with this disease.

Immune Profile of CRSwNP vs CRSsNP
There are similarities and differences in the immune profiles of patients with CRSwNP vs those with chronic rhinosinusitis without nasal polyps (CRSsNP). In terms of disease endotyping, type 2 inflammation is present in 87% of patients with CRSwNP compared with 55% of patients with CRSsNP in the United States. But CRSwNP is different from CRSsNP in that there is increased type 2 inflammation with CRSwNP. That means that we should see more type 2 helper T (Th2) cells, B-cells, and eosinophils in patients with CRSwNP. Also, a thickened basement membrane is more likely in patients with CRSsNP.

The other key difference between these 2 diseases is the response to therapy. Patients with CRSwNP respond well to systemic corticosteroids, while the role of this therapy is not clear in CRSsNP. Similarly, type 2–targeted biologics work well in patients with CRSwNP, including those with the most severe form of disease (ie, the aspirin-exacerbated respiratory disease subpopulation). In contrast, CRSsNP is associated with less type 2 inflammation. Therefore, these patients do not respond as well to systemic steroids or biologics that target this inflammatory pathway.

Furthermore, patients with CRSwNP are more likely to have comorbidities like asthma and allergic rhinitis. CRSsNP is associated with asthma, but not as frequently as CRSwNP. This is important because the treatment landscape is evolving toward more personalized therapies that target specific endotypes. If healthcare professionals (HCPs) know that type 2 inflammation is much more prevalent in CRSwNP, then they should use biologics that target this pathway. For CRSsNP, studies are needed to determine if these biologics provide benefit to patients.

Why Do Nasal Polyps Occur?
It is not known why nasal polyps form. I suspect epigenetics play a role, and maybe patients’ microbiome plays a role, too. I mentioned previously that patients may have a reservoir of S aureus and its superantigens, as enterotoxins are thought to play a role in the occurrence of nasal polyps. But it is hard to say. One hypothesis states that the type 2 inflammation seen in the Western population promotes excessive fibrin deposition and loss of fibrinolysis. There are some good studies on that idea, suggesting that type 2 inflammation involves the coagulation cascade. There also is some evidence that asthma may play a role, while other reasons for nasal polyp formation may include epithelial barrier dysfunction that allows the penetration of allergens, viruses, and other microbes to induce type 2 inflammation.

What we do know is that recurrence of nasal polyps is much more likely in those who have more type 2 involvement with eosinophilic inflammation. The JESREC study looked at patients with prior endoscopic sinus surgery and what they called “eosinophilic chronic rhinosinusitis,” and those with higher eosinophil counts had recurrence occur sooner than the others. There is other literature suggesting that patients with mixed inflammation (eg, type 2 and neutrophilic inflammationor increased B-cells) may have a higher risk for recurrence of nasal polyps.

The Evolving Treatment Landscape for CRSwNP
The treatment for CRSwNP has completely changed over the last few years due to the introduction of biologics. Historically, after patients got diagnosed with CRSwNP, they would be treated with saline irrigation and topical intranasal corticosteroids, which are still a mainstay treatment option. Then they may receive systemic corticosteroids for persistent disease, but these agents only provide temporary relief. It is unfortunate that patients with CRSwNP often receive many courses or long-term courses of systemic corticosteroids, which leads to a higher incidence of adverse events.

If patients’ disease does not respond well to corticosteroids, they become candidates for endoscopic sinus surgery. This surgery is effective, but a study found that up to 40% of patients see their nasal polyps recur. When this happens, patients may end up receiving many of these surgeries in their lifetime. Certain patient subgroups, especially those with more severe disease, often receive more than 1 surgery on a routine basis and continue treatment with systemic corticosteroids.

The management is evolving now that many HCPs agree that a multidisciplinary approach to care is valuable. If patients undergo surgery for their nasal polyps but their disease is coming back, HCPs should then consider biologic therapy. In those with asthma—especially severe asthma—aspirin-exacerbated respiratory disease, or allergic sinusitis, HCPs can consider starting them on a biologic at the time of or prior to surgery. In general, if CRSwNP recurs after 1 surgery, then a type 2 inflammation–targeted biologic is warranted. These include dupilumab, which blocks the IL-4 receptor alpha subunit; mepolizumab, which blocks IL-5; and omalizumab, which blocks IgE.

There are others currently being studied. For example, tezepelumab blocks thymic stromal lymphopoietin and has positive data published. It significantly reduced nasal polyp size and nasal congestion severity/symptoms compared with surgery and systemic corticosteroids. There is also depemokimab, a long-acting IL-5 inhibitor that requires treatment every 6 months. It significantly reduced patients’ total nasal polyp score and was well tolerated compared with placebo. These agents are revolutionizing the way we manage our patients. They do much better with biologics, as the need for systemic corticosteroids and repeat surgeries decreases. These people symptomatically do so much better: their congestion, sense of smell, and asthma improve.

Patients on biologic therapy for CRSwNP must be monitored. This includes ensuring the treatment is effective and safe for each patient. If patients do not have efficacy with a biologic, then HCPs should change the therapy or stop it altogether. The “EUFOREA paper” offers guidance on when to stop a biologic therapy. In my practice, I monitor patients in clinic to determine if they have symptom improvement. I use a validated tool like SNOT-22 to have patients report on a scale of zero to 10 how much better they are doing. I ask them at baseline and at every visit. I also ask them if their sense of smell and nasal congestion are improved because these are the 2 symptoms that I have seen bother patients the most. I also ask if they have or are experiencing any side effects. That is the mainstay of how I follow patients on biologic therapies. Another way to monitor patients is to do an endoscopy. In addition, if patients have asthma, you can monitor their treatment response with their asthma because many of them will start de-escalation of therapy, and I think this is important.

I typically see my patients for their first follow-up at 3 months and their second at 6 months. I then monitor them every 6 months, but many do not come back to the clinic within that time frame. Sometimes I see them a year or so later. Often in these cases, my clinic will call them and tell them that we cannot refill their prescription until we see them for follow-up. That has become the biggest issue with using biologics for both asthma and nasal polyps in my practice. Patients will stop following up until they really need it.

Your Thoughts
How often do you prescribe biologic therapy to your patients with CRSwNP? You can get involved in the conversation by answering the polling question and posting a comment below.

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