Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) now have more biologic treatment options than ever before. These medications target specific parts of the immune system that contribute to chronic inflammation, nasal congestion, loss of smell, and the growth of nasal polyps.
But with several biologics available—and additional treatments being studied—an increasingly important question is:
Which biologic works best for nasal polyps?
A major 2026 study published in the Journal of Allergy and Clinical Immunology (JACI) attempted to answer that question by comparing seven different biologic medications:
- Dupilumab (Dupixent)
- Tezepelumab (Tezspire)
- Omalizumab (Xolair)
- Mepolizumab (Nucala)
- Benralizumab (Fasenra)
- Depemokimab (Exdensur)
- Stapokibart
The results provide some of the clearest evidence so far regarding how these treatments may compare.
What Is Chronic Rhinosinusitis With Nasal Polyps?
Chronic rhinosinusitis with nasal polyps is a persistent inflammatory condition affecting the nose and sinuses. Patients may experience:
- Severe nasal congestion
- Reduced or completely lost sense of smell
- Nasal drainage
- Facial pressure
- Difficulty breathing through the nose
- Recurrent sinus problems
- Poor sleep and reduced quality of life
Nasal polyps are inflammatory growths that develop inside the nasal and sinus passages.
Many patients with severe nasal polyps also have other inflammatory conditions, particularly asthma and aspirin-exacerbated respiratory disease (AERD).
Traditionally, treatment has included corticosteroid nasal sprays, sinus rinses, short courses of oral corticosteroids, and endoscopic sinus surgery. Unfortunately, polyps can return even after surgery.
Biologic medications have dramatically changed our ability to treat some of these difficult cases.
What Did the JACI Study Compare?
Researchers performed a systematic review and network meta-analysis involving 15 randomized clinical trials and 3,642 patients with severe CRSwNP.
Instead of looking only at whether each medication worked better than placebo, the researchers used statistical methods to indirectly compare the medications with one another.
Two of the most important measurements were:
Nasal Polyp Score (NPS): an endoscopic measurement of how much polyp tissue is present.
Nasal Congestion Score (NCS): a measurement of how severely patients experience nasal blockage.
The investigators looked at results at approximately 20 to 24 weeks and again at 48 to 56 weeks.
They also examined other important outcomes, including:
- Sense of smell
- SNOT-22 quality-of-life scores
- Formal smell testing
- Sinus CT findings
- Need for oral corticosteroids
- Need for additional sinus surgery
- Adverse effects
Which Biologics Performed Best?
The study identified three treatments that stood out:
Dupilumab
Dupilumab blocks signaling from the inflammatory cytokines IL-4 and IL-13 through inhibition of the IL-4 receptor alpha pathway.
Dupilumab performed extremely well across multiple outcomes and at both shorter- and longer-term follow-up.
At 20 to 24 weeks, dupilumab produced greater improvements in nasal polyp and congestion scores than several of the other biologics.
At 48 to 56 weeks, dupilumab was again among the strongest-performing treatments.
Importantly, dupilumab has a substantial amount of clinical experience behind it for nasal polyps and is FDA-approved for inadequately controlled CRSwNP.
Tezepelumab
Tezepelumab targets thymic stromal lymphopoietin (TSLP), an inflammatory signaling molecule that sits relatively early in the inflammatory cascade.
At 48 to 56 weeks, tezepelumab and dupilumab produced greater reductions in nasal polyp scores and nasal congestion than depemokimab, mepolizumab, and benralizumab.
The researchers did not find a statistically significant difference between tezepelumab and dupilumab for the main nasal polyp and congestion outcomes.
Tezepelumab is particularly interesting because targeting TSLP may suppress several downstream inflammatory pathways rather than targeting only one cytokine or cell type.
Stapokibart
Stapokibart also targets the IL-4 receptor alpha pathway, making its mechanism similar in concept to dupilumab.
At 20 to 24 weeks, stapokibart and dupilumab produced some of the largest reductions in nasal polyp size and nasal congestion.
The analysis found no significant difference between stapokibart and dupilumab for these primary outcomes at this time point.
However, the study did not have analyzable stapokibart data at the 48- to 56-week time point, which makes long-term comparisons more difficult.
Stapokibart is also not currently an FDA-approved treatment for CRSwNP in the United States.
How Did the Other Biologics Perform?
Omalizumab
Omalizumab targets IgE and has been used for allergic asthma for many years. It is also FDA-approved for nasal polyps.
Omalizumab clearly improves nasal polyps and symptoms compared with placebo, but in this analysis it generally did not achieve the same magnitude of improvement seen with the leading treatments.
It may still be a very reasonable choice for certain patients, particularly when other IgE-mediated diseases are important considerations.
Mepolizumab
Mepolizumab blocks IL-5, a major cytokine involved in eosinophil development and survival.
Mepolizumab is FDA-approved for CRSwNP and has demonstrated reductions in nasal polyp burden and the need for additional sinus surgery.
However, the JACI analysis generally found stronger improvements with dupilumab and tezepelumab for several major outcomes.
Benralizumab
Benralizumab targets the IL-5 receptor and causes profound depletion of eosinophils.
Although it has demonstrated activity against nasal polyps in clinical trials, it generally ranked below the highest-performing biologics in this analysis.
Benralizumab is FDA-approved for eosinophilic asthma but is not currently FDA-approved specifically for CRSwNP.
Depemokimab
Depemokimab is a newer, long-acting anti-IL-5 biologic.
One of its major potential advantages is convenience because its long duration of action permits much less frequent administration than many currently available biologics.
However, in this nasal polyp analysis, its efficacy generally appeared less impressive than dupilumab, tezepelumab, and stapokibart.
Depemokimab is FDA-approved in the United States for severe eosinophilic asthma, but not currently for CRSwNP.
So Which Biologic Was Number One?
There was not one unquestionable winner.
Instead, the study suggested that three medications formed a leading group:
Dupilumab
Tezepelumab
Stapokibart
At approximately six months, dupilumab and stapokibart appeared particularly effective.
At approximately one year, dupilumab and tezepelumab appeared particularly effective.
Most importantly, the investigators could not demonstrate that stapokibart or tezepelumab was superior to dupilumab at the time points where they could be compared.
Therefore, I would not interpret this study as showing that one medication has definitively replaced the others.
An Important Limitation: These Were Mostly Indirect Comparisons
This is one of the most important points when interpreting network meta-analyses.
Most patients in these studies were not randomized directly between two biologics. Instead, individual biologics were generally compared with placebo in separate clinical trials, and the researchers then used statistical techniques to estimate how the biologics compare with one another.
That is useful, but it is not equivalent to a large head-to-head clinical trial.
The studies may also have enrolled somewhat different populations with differences in disease severity, previous sinus surgery, asthma, eosinophil levels, AERD, corticosteroid use, and other factors.
For that reason, small differences in rankings should not automatically be interpreted as proof that one medication will work better for an individual patient.
My Perspective as an Allergist
The study reinforces something that has become increasingly apparent in clinical practice: not all biologics have the same effect on nasal polyps, even when several medications may work extremely well for asthma.
The biology of severe nasal polyposis is complex.
For many patients, blocking the IL-4/IL-13 pathway appears particularly effective. Dupilumab has consistently demonstrated strong effects on nasal polyp size, congestion, smell, and quality of life.
Tezepelumab is also becoming an important option. By blocking TSLP farther upstream in the inflammatory pathway, it may provide broad suppression of type 2 inflammation, and the results in CRSwNP have been impressive.
Stapokibart is particularly interesting scientifically because its strong results provide additional evidence supporting the importance of IL-4/IL-13 signaling in nasal polyp disease. However, it is not currently an FDA-approved option in the United States.
Choosing a Biologic Is About More Than Rankings
I would not choose a biologic solely because it ranked first or second in a meta-analysis.
Treatment should be individualized.
When selecting a biologic for someone with severe nasal polyps, I consider the entire patient, including:
- Severity of the nasal polyps
- Degree of nasal obstruction
- Loss of smell
- Previous sinus surgeries
- Frequency of oral corticosteroid use
- Presence and severity of asthma
- Blood eosinophil levels
- Total IgE and allergic disease
- Presence of AERD
- Atopic dermatitis or other type 2 inflammatory diseases
- Previous biologic treatment
- Medication dosing frequency
- Insurance coverage and prior authorization requirements
- Patient preference
For example, a patient with severe nasal polyps and significant atopic dermatitis may have different considerations than a patient whose primary accompanying problem is severe eosinophilic asthma.
What About Safety?
Another reassuring finding from the JACI analysis was that overall safety profiles were comparable across the biologics studied.
That does not mean the medications have identical adverse-effect profiles. Each biologic has its own potential risks and monitoring considerations.
Rather, when the randomized trials were analyzed together, the investigators did not find a major safety difference that clearly separated one treatment from the others.
The Future of Nasal Polyp Treatment
The treatment landscape for nasal polyps has changed dramatically.
Years ago, patients with severe recurrent CRSwNP often cycled repeatedly through oral steroids and sinus surgeries.
Today, we can increasingly target the specific inflammatory pathways driving the disease.
The next major step will be direct head-to-head biologic trials that tell us whether one medication is truly more effective than another and, perhaps more importantly, which biomarkers predict that an individual patient will respond best to a particular treatment.
Ultimately, the goal should not simply be to determine the “best biologic.”
The goal is to identify the best biologic for the individual patient.
Reference
Ouranos K, Michael M, Mylona EK, et al. Comparative efficacy of biologic agents for severe chronic rhinosinusitis with nasal polyps: Systematic review and network meta-analysis. Journal of Allergy and Clinical Immunology. 2026;158(4):1047-1057.