Tezepelumab and Severe Chronic Rhinosinusitis with Nasal Polyps

Written By Dr. Arthur Lubitz MD

Tezepelumab, a human monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), has demonstrated significant efficacy in treating severe chronic rhinosinusitis with nasal polyps (CRSwNP) in the Phase 3 WAYPOINT trial. This study's findings offer promising therapeutic options for patients with CRSwNP, a condition often associated with severe asthma.

Study Design and Primary Endpoints

The double-blind, multicenter, randomized, placebo-controlled WAYPOINT trial evaluated the efficacy and safety of tezepelumab in adults with severe, uncontrolled CRSwNP. A total of 408 participants were randomized 1:1 to receive subcutaneous injections of either tezepelumab 210 mg or placebo every four weeks for 52 weeks. The co-primary endpoints were the change from baseline in total nasal polyp score (NPS) and the bi-weekly mean nasal congestion score at week 52.

Efficacy Outcomes

At week 52, tezepelumab demonstrated significant improvements compared to placebo in both co-primary endpoints:

  • Total Nasal Polyp Score (NPS): The least squares (LS) mean difference between the tezepelumab and placebo groups was -2.07 (95% confidence interval [CI], -2.39 to -1.74; P<0.001), indicating a substantial reduction in polyp size.

  • Nasal Congestion Score: The LS mean difference was -1.03 (95% CI, -1.20 to -0.86; P<0.001), reflecting a marked alleviation of nasal congestion.

Notably, improvements in both NPS and nasal congestion scores were observed as early as weeks 2 and 4, respectively, and were sustained throughout the treatment period.

Secondary Endpoints

Tezepelumab also achieved significant improvements in key secondary endpoints at week 52:

  • Loss of Smell: The LS mean difference was -1.00 (95% CI, -1.18 to -0.83; P<0.001), indicating enhanced olfactory function.

  • Sino-Nasal Outcome Test (SNOT-22): The LS mean difference was -27.26 (95% CI, -32.32 to -22.21; P<0.001), demonstrating improved disease-specific health-related quality of life.

  • Lund-Mackay Score: The LS mean difference was -5.72 (95% CI, -6.39 to -5.06; P<0.001), reflecting reduced sinus opacification.

  • Total Symptom Score: The LS mean difference was -6.89 (95% CI, -8.02 to -5.76; P<0.001), indicating overall symptom relief.

Importantly, the need for nasal polyp surgery was significantly lower in the tezepelumab group (0.5%) compared to the placebo group (22.1%) (hazard ratio [HR], 0.02; 95% CI, 0.00 to 0.09; P<0.001). Similarly, systemic glucocorticoid use was reduced in the tezepelumab group (5.2%) versus the placebo group (18.3%) (HR, 0.12; 95% CI, 0.04 to 0.27; P<0.001).

Safety Profile

The incidence of adverse events was comparable between the tezepelumab and placebo groups, indicating a favorable safety profile for tezepelumab.

Efficacy in Severe Asthma

Tezepelumab has also shown efficacy in patients with severe, uncontrolled asthma, irrespective of nasal polyp status. In the NAVIGATOR study, tezepelumab treatment resulted in substantial reductions in asthma exacerbations and improvements in lung function, asthma control, and health-related quality of life over 52 weeks compared with placebo. Notably, patients with comorbid nasal polyps experienced clinically meaningful improvements in sino-nasal symptoms, as assessed by the Sino-Nasal Outcome Test (SNOT-22).

Lack of Efficacy in Other Conditions

While tezepelumab has demonstrated efficacy in treating severe asthma and CRSwNP, current evidence does not support its effectiveness in conditions such as urticaria or atopic dermatitis. Further research is necessary to explore its potential in these and other inflammatory diseases.

Conclusion

The Phase 3 WAYPOINT trial underscores tezepelumab's efficacy in reducing nasal polyp size, alleviating nasal congestion, and decreasing the need for surgical intervention and systemic corticosteroid use in patients with severe CRSwNP. These findings, coupled with its established benefits in severe asthma, position tezepelumab as a promising therapeutic option for patients with these challenging respiratory conditions.

If you need to book an appointment for your allergies or asthma, you can book your appointment online, or call (212) 247-7447.

Dr. Arthur Lubitz MD
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