Dupilumab SAR231893

The EASI is a composite index with scores ranging from 0 to 72.Higher scores indicates worse condition

The ice cube provocation test is the most frequently used provocation method for cold urticaria (ColdU). A negative ice cube provocation test was defined as the absence of confluent hives/wheal at the entire skin site of exposure after ice cube provocation test. Ice cube was applied on forearm skin for 5 minutes. Provocation test reading time was 10 minutes after removal of ice cube.

The LMK score is used to quantify the degree of opacification of each sinus on CT scan. The CT scan LMK staging system represents the most widely established method of sinus CT scoring. The LMK total score is based on assessment of the CT scan findings for each sinus area (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus plus the osteomeatal complex on each side). The extent of sinus opacification is rated on a 3-point scale ranging from 0 = normal to 2 = total opacification. In addition, the osteomeatal complex is graded as 0 = not occluded or 2 = occluded. The maximum score is 12 per side; total score ranges from 0 (normal) to 24 (more opacified) corresponding to the sum of all sinuses and the osteomeatal complexes bilaterally. Higher score indicate worse outcome; a negative change from baseline indicate improvement. Baseline was defined as the last available value before the first dose of study drug.

Moderate exacerbations were recorded by the Investigator and defined as acute exacerbation of COPD (AECOPD) event that required either systemic corticosteroids (such as intramuscular, intravenous, or oral) and/or antibiotics. Severe exacerbations were also recorded by the Investigator and defined as AECOPD event that required hospitalization or observation for \>24 hours in an emergency department/urgent care facility or resulted in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days. Annualized event rate was the total number of events that occurred during the 52-week treatment period divided by the total number of participant-years followed in the 52-week treatment period.

WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with \>=4 points improvement (reduction) from baseline in WI-NRS scores at Week 12 is reported in this outcome measure.

WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with improvement (reduction) in WI-NRS scores by \>=4 points from Baseline to Week 24 is reported in this outcome measure.

ISS was recorded in e-diary. The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. Least squares (LS) mean is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization.

Absolute change from baseline in pre-bronchodilator FEV1 at Week 12

An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. TEAEs were the AEs that developed or worsened or became serious during the TEAE period (defined as the time from the first dose of the investigational medicinal product \[IMP\] up to 12 weeks after the last dose of the IMP).

An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. TEAEs were the AEs that developed or worsened or became serious during the TEAE period (defined as the time from the first dose of the IMP up to 12 weeks after last dose of the IMP). TEAE event rate was defined as the number of TEAE events per 100 participant-years.

NC symptom severity was assessed by the participants on a daily basis from Visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. Least squares (LS) means and standard error (SE) were obtained from Analysis of covariance (ANCOVA) model described in Statistical Analysis Overview.

NPS: sum of right, left nostril scores, evaluated by nasal endoscopy. For each nostril, NPS was graded based on polyp size from 0 = no polyps to 4 = large polyps causing complete obstruction of inferior nasal cavity; lower score = smaller-sized polyps. Total NPS: sum of right and left nostril scores; ranges from 0 (no polyps) to 8 (large polyps), higher score = more severe disease. NPS was assessed by centralized, blinded, independent review of the nasal endoscopy video recordings. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview.

The CT scan LMK staging system represented the most widely established method of sinus CT scoring. The LMK total score is based on assessment of the CT scan findings for each sinus area (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus on each side). The extent of mucosal opacification is rated on a 3-point scale ranging from 0 = normal to 2 = total opacification. In addition, the ostiomeatal complex is graded as 0 = not occluded or 2 = occluded. The maximum score is therefore 12 per side; total score ranges from 0 (normal) to 24 (more opacified), corresponding to the sum of all sinuses and the ostiomeatal unit. Higher score indicated worse outcome. Baseline was defined as the last available value up to randomization date and prior to the first dose of study medication.

Inflammatory cells i.e. eosinophils were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.

Mucin was identified by staining with Alcian-blue periodic acid-Schiff and/or immunostaining for MUC5AC and then the mucin-positive area was measured and expressed per square millimeter.

Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.

Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.

T-Lymphocytes i.e. CD3 positive cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.

T-helper i.e. CD4 positive lymphocytes were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.