Comparative Effectiveness of Tezepelumab versus Dupilumab in Patients with Chronic Rhinosinusitis with Nasal Polyps: A Real-World Study

The primary objective is to compare the efficacy of tezepelumab and dupilumab in achieving clinically meaningful improvement in chronic rhinosinusitis with nasal polyps (CRSwNP) over 12 months. Clinical improvement is defined as a minimum reduction in the nasal polyp score (NPS) by 1 point or a reduction in the sino-nasal outcome test (SNOT)-22 by 8.9 points from baseline. Secondary objectives involve evaluating the following outcomes after one year of treatment:

• Olfactory perception via the Sniffin’Sticks Identification Test (SSIT)-16.
• Respiratory function through forced expiratory volume (FEV1%) and peak nasal inspiratory flow (PNIF).
• Assessment of asthma control using the asthma control test (ACT) and asthma quality of life questionnaire (AQLQ).
• Symptom perception via visual analogue scale (VAS) scores for chronic rhinosinusitis, allergic symptoms, and sense of smell.
• Exploratory analysis of nasal and blood biomarkers, transcriptomics, and microbiome composition.
• Safety and tolerability.

The sponsor did not provide information regarding the total number of participants. The study population consists of adult patients, including both males and females, diagnosed with chronic rhinosinusitis with nasal polyps. Eligible participants must be aged between 18 and 64 years and present with uncontrolled disease according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) criteria. Inclusion requires an indication for biologic treatment based on the investigator's assessment and established reimbursement criteria. The study population is identified as a vulnerable group.

This phase 6 clinical trial is a direct comparison study involving patients with chronic rhinosinusitis with nasal polyps. The research methodology aims to evaluate the efficacy of tezepelumab and dupilumab in a real-world setting. The primary objective is to demonstrate clinical improvement in nasal polyp disease, measured by a minimal reduction in the nasal polyp score or the sino-nasal outcome test between baseline and 12 months. Study procedures involve a screening visit to assess eligibility based on EPOS criteria and reimbursement requirements. Following inclusion, participants undergo one year of therapy with subcutaneous injection of the assigned biologic. Monitoring includes various secondary endpoints such as quality of life parameters, olfactory performance, and changes in the nasal microbiome. The total duration of participant involvement is 12 months, with the overall study period estimated to conclude by June 2028.

The experimental medication consists of dupilumab, provided as a solution for injection in a pre-filled pen. The administered dose is 300 mg via subcutaneous injection.

The experimental medication also includes tezepelumab, administered as a solution for injection in a pre-filled syringe. The dosage is 210 mg delivered through subcutaneous injection.

The primary efficacy assessment for chronic rhinosinusitis with nasal polyps involves evaluating the change in the nasal polyp score (NPS) or the change in the sino-nasal outcome test (SNOT-22) from baseline to 12 months. Clinical meaningfulness is defined as a minimal reduction in NPS by 1 point or a reduction in SNOT-22 by 8.9 points.

Secondary endpoints include the following:

• Percentage of patients categorized by EPOS/EUROFREA criteria as having good-excellent, poor-moderate, or no response during one year of therapy.
• Changes in quality of life (QoL) parameters using the SNOT-22 and EQ-5D-3L, and clinical parameters including NPS and eosinophil cationic protein (ECP).
• Changes in objective olfactory function measured by Sniffin’sticks and subjective olfactory performance via visual analog scale (VAS).
• Changes in peak nasal inspiratory flow (PNIF) or forced expiratory volume in 1 second (FEV1) measured by spirometry.
• Changes in asthma control perception using the asthma control test (ACT) or asthma quality of life questionnaire (AQLQ), and changes in chronic rhinosinusitis (CRS) symptom perception via VAS.
• Evaluation of allergic symptoms using the total respiratory symptom score (TRSS) and allergic sensitization via skin prick test or allergen-specific IgE levels in nasal secretions and serum.
• Assessment of the nasal microbiome through diversity and abundance metrics, and changes in mediator levels determined by OLINK.
• Changes in relative gene expression of oxidative stress response induced genes and routine blood parameters.
• Monitoring of side effects through patient diaries or oral reports.