EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients

The NPS was assessed by the independent physician to grade the extent/severity of nasal polyps based on evaluation by nasal endoscopy. The NPS scores for each nostril was graded based on polyp size from 0 (no polyps) to 4 (large polyps causing complete obstruction of the inferior nasal cavity). The total NPS score was calculated as the sum of right and left nostril scores and ranged from 0 (no polyps) to 8 (large polyps). Higher scores indicated more extensive or severe nasal polyps. Negative change from baseline indicated less severity of nasal polyps. Baseline was defined as the last available valid (non-missing) value up to and including the day of first administration of study treatment.

The UPSIT was a 40-item test to quantitatively assess human olfactory function. The UPSIT test consisted of 4 booklets, each containing 10 odorants with 1 odorant per page. The participant was asked to release the odorant by rubbing the brown-strip (contained odorant microcapsules) with the tip of a pencil and to indicate which of 4 words best described the odor. Thus, each participant received a score out of 40 possible correct answers. The total UPSIT score ranged from 0 (loss of smell/anosmia) to 40 (normal sense of smell/normosmia). Higher scores indicated better olfactory function. Positive change from baseline indicated normal olfactory function. Baseline was defined as the last available valid (non-missing) value up to and including the day of first administration of study treatment.

The nasal symptom diary was designed to assess the severity of chronic rhinosinusitis nasal symptoms daily. These symptoms included nasal congestion (NC)/obstruction, loss of smell, anterior rhinorrhea, and posterior rhinorrhea. The severity of loss of smell was scored by participants using a scale ranged from 0 to 3 (where, 0= no symptoms, 1= mild symptoms, 2= moderate symptoms and 3= severe symptoms that were hard to tolerate, caused interference with activities, or daily living). Higher scores indicated greater symptom severity. Negative change from baseline indicated less severe symptom. Baseline value was calculated by averaging the data collected/recorded from Day -6 to Day 1.

The nasal symptom diary was designed to assess the severity of chronic rhinosinusitis nasal symptoms daily. These symptoms included NC/obstruction, loss of smell, anterior rhinorrhea, and posterior rhinorrhea. The severity of NC was scored by participants using a scale ranged from 0 to 3 (where, 0= no symptoms, 1= mild symptoms, 2= moderate symptoms and 3= severe symptoms that were hard to tolerate, caused interference with activities, or daily living). Higher scores indicated greater symptom severity. Negative change from baseline indicated less severe symptom. Baseline value was calculated by averaging the data collected/recorded from Day -6 to Day 1.

The TSS is a composite score consisted of the following symptoms assessed daily in the morning: NC/obstruction, decreased/loss of sense of smell, and rhinorrhea (average of anterior/posterior nasal discharge). Each item was scored on a scale ranged from 0 to 3 (where, 0= no symptoms, 1= mild symptoms, 2= moderate symptoms and 3= severe symptoms that were hard to tolerate, and caused interference with activities, or daily living). Higher score indicated greater symptom severity. The TSS score was calculated by summing the individual symptom score and ranged from 0 (no symptoms) to 9 (severe symptoms). Higher scores on the TSS indicated greater symptom severity. Negative change from baseline indicated less severe symptom. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.

The SNOT-22 is a patient-reported outcome questionnaire designed to assess the impact of chronic rhinosinusitis on participants' health-related quality of life. The SNOT-22 consisted of 22 items covering symptoms, social/emotional impact, productivity, and sleep consequences of chronic rhinosinusitis. Each item was rated on a 6-point Likert scale response option, score ranged from 0 (no problem) to 5 (problem as bad as it can be). The SNOT-22 total score was the sum of each item score, and it ranged from 0 (no problem) to 110 (problem as bad as it can be). Higher scores indicated greater rhinosinusitis-related health burden, meaning for this parameter lower score indicated better condition. Negative change from baseline indicated improvement in health-related quality of life. Baseline was defined as the last available valid (non-missing) value up to and including the day of first administration of study treatment.

SNOT-22 is a patient-reported outcome questionnaire designed to assess impact of chronic rhinosinusitis on participants' health-related quality of life. SNOT-22 was categorized into 5 domains: Nasal (items 1, 2, 3, 4, 5, 6, 7 and 12); Ear/Facial (items 8, 9, 10 and 11); Sleep (items 13, 14, 15 and 16); Function (items 17, 18 and 19); Emotion (items 20, 21 and 22). Each item of Nasal domain was rated on a 6-point Likert scale ranged from 0 (no problem) to 5 (problem as bad as it can be) with higher score indicated greater rhinosinusitis-related health burden. Total score of Nasal domain was average score of items of nasal domain, and ranged from 0 (no problem) to 5 (problem as bad as it can be), where higher score indicated greater rhinosinusitis-related health burden. Negative change from baseline indicated improvement in health-related quality of life. Baseline was defined as last available valid (non-missing) value up to and including day of first administration of study treatment.

The NPIF evaluation represented a physiologic measure of the air flow through both nasal cavities during forced inspiration. The NPIF is the best validated technique for the evaluation of nasal flow through the nose. Participants were issued an NPIF meter and were instructed on the use of the device and written instructions on the use of the NPIF meter was provided. Higher NPIF values were indicative of better nasal air flow. Positive change from baseline indicated better nasal air flow. Baseline was the mean measurement recorded for the 7 days (Day -6 to Day 1) prior to first dose of study treatment.

The rhinosinusitis severity VAS was used to evaluate the overall severity of the rhinosinusitis. It is a recommended scale to determine the participant's disease severity and to guide the treatment for chronic rhinosinusitis. The participants were asked to answer the following question: "How troublesome are your symptoms of your rhinosinusitis" on a 10-centimeter VAS from 0 (not troublesome) to 10 (worst thinkable troublesome). Higher scores on the VAS score indicated more severe chronic rhinosinusitis. Negative change from baseline indicated less severity of rhinosinusitis. Baseline was defined as the last available valid (non-missing) value up to and including the day of first administration of study treatment.

An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. The TEAEs was defined as an AEs that occurred from the first administration of the study treatment (on Day 1) up to 98 days after the last dose of study treatment administration.