Tezepelumab in Canadian Adults With Severe Chronic Rhinosinusitis With Nasal Polyps: A Subgroup Analysis of the Phase 3 WAYPOINT Trial.

Importance

Tezepelumab, a monoclonal antibody targeted against thymic stromal lymphopoietin, was recently approved in Canada for the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). Its effectiveness specifically in the Canadian setting has not been evaluated.

Objective

To analyze the efficacy and safety of tezepelumab in Canadian patients enrolled in the WAYPOINT trial and contextualize the findings with respect to the Canadian healthcare environment.

Design

Post hoc analysis of a multinational, parallel-group, randomized, placebo-controlled, Phase 3 trial.

Participants

Forty-nine Canadian adult patients with severe uncontrolled CRSwNP.

Setting

Subgroup of Canadian patients enrolled in the WAYPOINT trial.

Intervention

Tezepelumab 210 mg (n = 25) or placebo (n = 24) administered subcutaneously every 4 weeks for 52 weeks. MAIN OUTCOME MEASURES The co-primary endpoints were change from baseline to week 52 in endoscopic total nasal polyp score (NPS) and patient-reported bi-weekly nasal congestion score (NCS).

Results

The Canadian cohort had higher numbers of patients with asthma and nonsteroidal anti-inflammatory drug-exacerbated respiratory disease than in the full study population. Objective and subjective signs and symptoms of CRSwNP were significantly improved with tezepelumab compared with placebo in the Canadian cohort, including both co-primary endpoints (least squares mean difference vs placebo [95% confidence interval]: total NPS, -2.53 [-3.33 to -1.73], P < .0001; mean NCS, -1.10 [-1.62 to -0.58], P < .0001) and all secondary efficacy endpoints in the overall population. The magnitude of clinical benefit was similar in the Canadian cohort versus the full study population, with less frequent use of rescue therapy (nasal polyp surgery and/or systemic corticosteroids) compared to placebo. The safety profile of tezepelumab was consistent in the Canadian cohort as in the full study population. There were no serious adverse events (AEs) or discontinuations due to AEs in the Canadian cohort.

Conclusions

Tezepelumab is an effective and safe treatment for severe uncontrolled CRSwNP in a patient population that is reflective of the Canadian clinical landscape. RELEVANCE The multinational WAYPOINT trial findings are relevant to patients with CRSwNP routinely seen in Canadian clinical practice, supporting their applicability in the Canadian healthcare context. TRIAL REGISTRY WAYPOINT ClinicalTrials.gov number, NCT04851964.