Chronic rhinosinusitis with nasal polyps improves with tezepelumab
Key takeaways:
- The need for systemic corticosteroids fell by 88%, and the need for surgery fell by 98%.
- Nasal polyp and congestion scores fell, along with loss of smell and total symptom scores.
SAN DIEGO — Patients with chronic rhinosinusitis with nasal polyps saw improvements across all endpoints with tezepelumab, according to an abstract presented here.
Results were seen as early as 2 and 4 weeks, Joseph K. Han, MD, chief of the division of rhinology and endoscopic sinus and skull base surgery and division of allergy, Eastern Virginia Medical School, said at the 2025 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress.
“When we talk about chronic rhinosinusitis, it really starts with disruption of the chronic epithelium,” Han said during his presentation.
Patients with CRSwNP have elevated levels of thymic stromal lymphopoietin (TSLP), Han said, which is a key driver of inflammation. Tezepelumab (Tezspire; Amgen, AstraZeneca) has been used to block TSLP activity in asthma.
“Current treatments for CRSwNP include intranasal and/or systemic corticosteroids, surgery and biologics,” Han told Healio. “Nasal polyps are most commonly managed with intranasal and/or systemic corticosteroids and surgery, if required, which do not treat the underlying cause of the disease.”
Patients who have more severe disease use oral corticosteroids, Han added, but this approach should be used with caution due to their association with serious systemic side effects.
“Tezepelumab represents a new class of biologic, with a first-in-class mechanism of action (anti-TSLP) that differs from other biologics approved for the treatment of CRSwNP,” Han said.
By acting at the top of the inflammatory cascade, he said, tezepelumab is critical in the initiation and persistence of multiple downstream inflammatory pathways and mediators associated with severe asthma and CRSwNP.
The phase 3 Waypoint study included 408 patients aged 18 years and older with severe, uncontrolled CRSwNP consistent with the need for surgery despite the use of intranasal corticosteroids (INCS).
Patients received 210 mg of subcutaneous tezepelumab (n = 203; mean age, 50.1 years; 62.1% men) or placebo (n = 205; mean age, 49.4; 68.3% men), both every 4 weeks in addition to INCS, for 52 weeks.
In the treatment group, 70.9% had prior nasal polyp surgery, with a mean of 7.71 years since the most recent surgery. In the placebo group, 71.7% had prior nasal polyp surgery, with a mean of 7.68 years since the most recent surgery.
“There really isn’t a big difference between the placebo group and the treatment group,” Han said during his presentation. “They’re very similar.”
Both groups had a mean total endoscopic nasal polyp score (NPS) of 6.1 at baseline. By week 4, Han said, there was a statistical difference between the groups. By week 52, mean total NPS scores fell by 0.39 for the placebo group and by 2.46 for the treatment group for a least square mean difference of –2.07 (95% CI, –2.39 to –1.74; P < .001).
Mean nasal congestion scores at baseline included 2.59 for the treatment group and 2.55 for the placebo group. There was a statistically significant difference between the groups at week 2. At week 52, scores fell by 0.72 for the placebo group and by 1.74 for the treatment group for a least square mean difference of –1.03 (95% CI, –1.2 to –0.86; P < .001).
Also, during the study period, 5.2% of the treatment group required systemic corticosteroids for five events and 18.3% of the placebo group required systemic corticosteroids for 36 events, for an 88% rate reduction with tezepelumab (HR = 0.12; 95% CI, 0.04-0.27; P < .001).
One patient in the treatment group (0.5%) and 42 patients in the placebo group (22.1%) required surgery, including one patient on placebo who required two surgeries, for a 98% rate reduction with tezepelumab (HR = 0.02; 95% CI, 0.0-0.09; P < .001).
Mean loss of smell scores based on Nasal Polyposis Symptom Diary (NPSD) entries included 2.9 for the treatment group and 2.8 for the placebo group at baseline, with a statistical difference between the groups at week 2 and decreases of 0.26 for the placebo group and 1.26 for the treatment group at week 52, for a least square mean difference of 1 (95% CI, –1.18 to –0.83; P < .001).
University of Pennsylvania Smell Identification Test scores included 13.1 for the treatment group and 11.9 for the placebo group at baseline before increasing by 9.31 for the treatment group and falling by 0.15 for the placebo group at week 52, for a least square mean difference of 9.46 (95% CI, 7.82-11.1; P < .001).
Mean baseline scores on the 22-item Sino-nasal Outcome Test included 68.2 for the treatment group and 69.2 for the placebo group, with improvements appearing by week 4. Scores fell by 17.76 for the placebo group and by 45.02 points for the treatment group through week 52 for a least square mean difference of –27.26 (95% CI, –32.32 to –22.21; P < .001).
Total symptom scores in the NPSD entries included 16.3 for the treatment group and 16.4 for the placebo group at baseline, falling by 3.5 for the placebo group and by 10.39 for the treatment group through week 52, for a least square mean difference of –6.89 (95% CI, –8.02 to –5.76; P < .001).
Mean sinus CT Lund-Mackay scores included 18.9 for the treatment group and 18.5 for the placebo group at baseline, falling to 12.47 for the treatment group and 17.69 for the placebo group, for a least square mean difference of –5.72 (95% CI, –6.39 to –5.06; P < .001).
“At baseline, the sinuses were nearly completely opacified,” Han said. “By week 52, there is better aeration.”
The safety profile for both groups was “very similar” as well, Han continued.
“There really isn’t a difference,” he said.
Adverse event rates included 78.3% for the treatment group with 10 serious adverse events and 77.1% with 12 serious adverse events for the placebo group.
Also, the treatment group had 11 cases of CRSwNP exacerbations and one asthma exacerbation, compared with 47 cases of CRSwNP exacerbations and 12 asthma exacerbations in the placebo group, which Han called expected.
Overall, the researchers concluded that patients in the treatment group achieved significant reductions in nasal polyps or nasal congestion by the first endpoint, persisting through 52 weeks, with significant improvements in all the key secondary endpoints.
“The Waypoint results highlight the potential for tezepelumab as a new treatment option for patients with CRSwNP that has demonstrated rapid and sustained improvements in disease symptoms and severity,” Han told Healio.
Han particularly noted the nearly complete elimination of the need for nasal polyp surgery and significant reductions in systemic corticosteroid use as well.
“Significantly, tezepelumab demonstrated unprecedented data by nearly eliminating the need for surgery,” Han said. “This reinforces the first-in-class mode of action of tezepelumab and builds on the efficacy it has shown in severe asthma.”
However, Han cautioned, there have not been any head-to-head trials of tezepelumab against other biologics, so outcomes cannot be directly compared.
“But I am encouraged by any efforts that have the potential to benefit patients with CRSwNP,” Han said. “We are continuing to analyze the data and plan to share future analyses/sub-analyses from the trial with the scientific community.”