Dupilumab in Japanese Patients With Chronic Rhinosinusitis With Nasal Polyp (SINUS-M52)

The NPS was the sum of right and left nostril scores as assessed by central video recordings of nasal endoscopy (NE). For each nostril, NPS was graded based on polyp size: Grade 0:No polyps; Grade 1:Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate; Grade 2:Polyps reaching below the lower border of the middle turbinate; Grade 3:Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate; Grade 4:Large polyps causing complete obstruction of the inferior nasal cavity. Score ranged from 0-8; higher scores indicated more severity. The baseline value was defined as the last available value before first study treatment administration.

The NPS was the sum of right and left nostril scores as assessed by central video recordings of NE. For each nostril, NPS was graded based on polyp size: Grade 0:No polyps; Grade 1:Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate; Grade 2:Polyps reaching below the lower border of the middle turbinate; Grade 3:Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate; Grade 4:Large polyps causing complete obstruction of the inferior nasal cavity. Score ranged from 0-8; higher scores indicated more severity. For participants who discontinued for other reasons, missing data are imputed using multiple imputation techniques assuming missing at random, and non-missing data collected after treatment discontinuation were used in the analysis. The baseline value was defined as the last available value before first study treatment administration.

The NC was assessed by the participant using a diary on a daily basis from Visit 1 and throughout the study on a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms). It was scored as a reflective score (evaluation of symptom severity over the past 24 hours) by the participants. The score ranged from 0-3; higher scores indicated more severity. The baseline value was defined as the last available value before first study treatment administration. For participants who discontinued for other reasons, missing data are imputed using multiple imputation techniques assuming missing at random, and non-missing data collected after treatment discontinuation were used in the analysis. The baseline value was defined as the last available value before first study treatment administration.

The LMK system is based on localization with points given for degree of opacification: 0 = normal, 1 = partial opacification, 2 = total opacification. These points were applied to the maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus on each side. The osteomeatal complex (OC) was graded as 0 = not occluded or 2 = occluded. The total score was the sum of scores from each side and ranged from 0 (normal) to 24 (more opacified); higher score indicated more severe disease. For participants who discontinued for other reasons, missing data are imputed using multiple imputation techniques assuming missing at random, and non-missing data collected after treatment discontinuation were used in the analysis. The baseline value was defined as the last available value before first study treatment administration.

The TSS was the sum of participant-assessed nasal symptom scores for nasal congestion and/or obstruction, decreased/loss of sense of smell and rhinorrhea (average of the non-missing anterior/posterior nasal discharge). On a daily basis from Visit 1 and throughout the study, participants used a diary to respond to the morning individual rhinosinusitis symptom questions using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms). Total score ranged from 0 (no symptoms) to 9 (severe symptoms). Higher score indicated more severe symptoms. For participants who discontinued for other reasons, missing data are imputed using multiple imputation techniques assuming missing at random, and non-missing data collected after treatment discontinuation were used in the analysis. The baseline value was defined as the last available value before first study treatment administration.

The severity of loss of smell was reported by the participants using the nasal symptom diary with a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms), higher score indicated more severe symptoms. For participants who discontinued for other reasons, missing data are imputed using multiple imputation techniques assuming missing at random, and non-missing data collected after treatment discontinuation were used in the analysis. The baseline value was defined as the last available value before first study treatment administration.

The VAS for rhinosinusitis was used to evaluate the total disease severity. Rhinosinusitis was divided into mild, moderate and severe based on total severity VAS score (0 to 10 centimeters [cm] where mild: VAS 0 to 3; moderate: VAS >3 to 7 and severe: VAS >7 to 10). The participants were asked to indicate on a VAS the answer to the question: "How troublesome are your symptoms of your rhinosinusitis?" The range of the VAS was from 0 (not troublesome) to 10 (worst thinkable troublesome), where higher score indicated worse disease. For participants who discontinued for other reasons, missing data were imputed using multiple imputation techniques assuming missing at random, and non-missing data collected after treatment discontinuation were used in the analysis. The baseline value was defined as the last available value before first study treatment administration.

An Adverse Event (AE) was defined as any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during TE period which was defined as the period from the time of first dose of study treatment until the last visit in the study. Serious adverse events (SAE) were defined as any untoward medical occurrence 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, was a medically important event. Data reported is till the end of 24-week treatment period.