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CRSwNP treatment landscape
The Evolving CRSwNP Treatment Landscape: Emerging Targeted Biologic Therapies and What Lies Ahead

Released: November 17, 2025

Thomas S. Higgins
Thomas S. Higgins, MD, MSPH, MBA
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Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly a disease resulting from type 2 inflammation. This pathway is driven by specific immune cells and signaling molecules, such as interleukin (IL)-4, IL-5, and IL-13.

IL-5 is the cytokine that promotes eosinophil recruitment, maturation, and survival, which is a hallmark of the inflammatory process for severe nasal polyps. In turn, IL-4 and IL-13 have many different functions. But their primary role is driving IgE production and goblet cell hyperplasia, which leads to the development of thick, tenacious mucus and severe tissue edema. IL-13, in particular, is important in the formation of nasal polyps; it is central to the subepithelial remodeling and fibrosis that occurs during the physical growth of these polyps in the sinonasal cavity. 

The Evolving CRSwNP Treatment Landscape
Tezepelumab is a newly approved TSLP blocker indicated as an add-on maintenance therapy for patients aged 12 years or older with inadequately controlled CRSwNP. Today, it is difficult to say exactly how this novel agent will change the current treatment landscape for CRSwNP. But because of the significance of the inflammatory process in this disease, I think tezepelumab will have a significant impact.

As researchers continue to look at the benefit regarding targeting downstream mediators like IL-5 and IL-13 and blocking these to reduce inflammation, they can also begin evaluating upstream mediators. For example, the particular role of the epithelium and the leakiness/inflammatory effect of the epithelium—where CRSwNP starts. That produces the alarmins that start the inflammatory response in the first place. Therefore, with tezepelumab, we now are looking more at the initial response at the epithelial layer and determining how to further optimize the management of CRSwNP at this step. This is what differentiates its mechanism of action from that of dupilumab, which is an IL-4Rα antagonist, blocking IL-4 and IL-13, and mepolizumab, which is an IL-5 antagonist.

Medical Therapy vs Endoscopic Sinus Surgery
Deciding between medical therapy and surgery is an important decision that should be based on patients’ clinical findings and shared decision-making in terms of where they are in their journey with CRSwNP. For instance, if patients present with mild symptoms and small nasal polyps, maybe initial medical management with first-line therapy (ie, topical intranasal corticosteroids, oral corticosteroids, and/or nasal saline irrigation) is ideal. In this case, healthcare professionals (HCPs) should follow up with patients over time.

I think it is critical to follow the disease state and see where that inflammatory process takes each patient. This is because HCPs will need to look at next steps once patients’ disease becomes severe, and they have nasal polyps filling up their nose and sinuses. At this point, surgery and biologic therapy will be needed to control CRSwNP.

The role for endoscopic sinus surgery (ESS) is important because it addresses the burden of disease by removing the nasal polyps and improving sinus function. In evaluating the cost-effectiveness of CRSwNP treatments, it is shown that ESS is the most cost-effective treatment strategy vs medical therapy for long-term disease management. In addition, a recent analysis found that upfront ESS is a more cost-effective treatment strategy than dupilumab for CRSwNP.

There are key considerations regarding ESS for use as a diagnostic component. You want to ensure that patients truly have nasal polyps and not tumors or infections. Remember that nasal polyps are not just edema, but they also are components of fibrosis. Sometimes removing that burden of disease can help patients with CRSwNP.

For many patients, their disease can be controlled with topical intranasal corticosteroids after ESS. But for others,  the nasal polyps can return, and their disease can become refractory to first-line treatment. That is why HCPs must follow up with patients over time, and this is where biologic therapies are extremely helpful. Biologic therapies are crucial for treating recalcitrant disease and controlling inflammation.

Furthermore, HCPs should listen to patients to understand their symptoms, even if they feel better after ESS. That is because ESS does not completely control the inflammatory cascade of CRSwNP and their symptoms. HCPs want to look at patients’ ability to smell and level of congestion to identify when biologic therapy is needed to control their disease.

Comorbidity Management
Another critical component of care is determining which treatments for CRSwNP work best, especially considering any present comorbidities. In particular, among patients with aspirin-exacerbated respiratory disease or severe asthma, their comorbidity can help indicate the severity of their CRSwNP and the type 2 inflammation that is occurring in their body. For these patients, HCPs must look at the unified airway disease and ensure that gets adequately treated.

If considering surgery for patients with severe asthma, one thing that HCPs need to make sure of is that they are surgical candidates. If patients have ongoing asthmatic exacerbations and you cannot do anesthesia safely, then that is a significant factor that should play a role in your decision-making.

HCPs should also monitor the number of systemic corticosteroids that patients are receiving. It is well known that there are severe adverse events associated with ongoing corticosteroid use, and patients can receive prescriptions for these therapies in many different places—from the emergency department and urgent care to primary care, otolaryngology, or immunology and allergy. Multiple HCPs could be providing corticosteroids to patients, so we must keep on top of that. In particular, patients with asthma are likely to need corticosteroids, so that is why HCPs need to look at it from a comorbidity standpoint. Furthermore, these patients may be candidates for biologic therapy sooner than other patients.

Future Directions in CRSwNP
I think the research will be looking into a more precise way of managing type 2 inflammation. Maybe we will have biomarker-driven biologic therapy selection, as more agents are approved and become available for patients. I hope one day we can look at specific types of CRSwNP and use biomarkers to help us decide what the best biologic therapy is for each patient or what the best treatment is for their individual condition. We are seeing emerging therapies that target many different areas of the inflammatory cascade—from the epithelial layer to the signaling pathways that affect the causes of the inflammation. So finding out which biologic therapy best fits each patient and their condition is the next step.

I also think that we may see combinations of biologic therapies emerge because they have different targets. There may be a role for those with severe type 2 inflammation to use combined therapies to induce increased benefit if proven so.

Your Thoughts
Are you using biologic therapy to treat your patients with CRSwNP? You can get involved in the conversation by answering the poll question and posting a comment below.

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In what percentage of your patients with CRSwNP are you using biologic therapies?

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