Tezepelumab significantly reduces nasal polyp size and congestion in patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP), according to the results of a new study published in The New England Journal of Medicine.
Patients receiving tezepelumab had lower rates of nasal polyp surgery and systemic glucocorticoid use. Improvements were seen in sinonasal symptoms, including loss of smell and quality of life measures. No new safety concerns were identified.
While biologic therapies targeting type 2 inflammation (e.g., IL-4, IL-5, IL-13, and IgE) have shown varying degrees of success, there remains a need for new treatment options, noted Brian J. Lipworth, MD, of the University of Dundee, United King, and colleagues.
Tezepelumab, a monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), has previously demonstrated efficacy in patients with severe asthma. Given the role of TSLP in the inflammatory cascade of CRSwNP, researchers hypothesized that tezepelumab could be a beneficial treatment. The phase 3 WAYPOINT trial was designed to assess the efficacy and safety of tezepelumab in adults with severe, uncontrolled CRSwNP.
This 52-week, double-blind, randomized, placebo-controlled trial included 408 adult patients with severe CRSwNP across 112 sites in 10 countries. Participants were assigned to receive either tezepelumab (210 mg subcutaneously every 4 weeks) or placebo while continuing standard intranasal glucocorticoid therapy.
The first primary endpoint was total nasal polyp score (TNPS) on endoscopic assessment of severity (range: 0–8, higher scores indicate larger polyps). Mean nasal congestion score (MNCS) was also an endpoint based on patient-reported severity of congestion (range: 0–3, higher scores indicate greater severity).
For TNPS at week 52, tezepelumab demonstrated significant improvement over placebo (-2.07 points vs. placebo), and MNCS improvement (-1.03 points vs. placebo).The improvements were sustained throughout the trial and seen as early as week 4.
Secondary endpoint results included a loss-of-smell score improvement (-1.00 vs. placebo); SNOT-22 quality-of-life improvement (-27.26 vs. placebo); Lund-Mackay sinus opacification score (-5.72 vs. placebo); and total symptom score reduction (-6.89 vs. placebo).
Additionally, fewer patients receiving tezepelumab required nasal polyp surgery (0.5%) compared to placebo (22.1%). The use of systemic glucocorticoids was also lower in the tezepelumab group (5.2% vs. 18.3%).
Adverse event rates were similar between groups (78.3% with tezepelumab vs. 77.1% with placebo), with no new safety concerns identified. Serious adverse events were reported in 4.9% of the tezepelumab group and 5.9% of the placebo group.
The WAYPOINT trial provides strong evidence that tezepelumab effectively reduces nasal polyp size, congestion, and overall symptom burden in patients with severe, uncontrolled CRSwNP. These findings support the potential expanded use of tezepelumab beyond asthma to target CRSwNP at its inflammatory source. Given its steroid-sparing effects and ability to reduce the need for nasal polyp surgery, tezepelumab may become a valuable option for patients with refractory CRSwNP, noted study investigators.
Further studies are warranted to assess its long-term durability, disease modification potential, and real-world effectiveness.
Author disclosures are available in the published study.
