Dupilumab for the Treatment of Chronic Spontaneous Urticaria in Patients Who Remain Symptomatic Despite the Use of H1 Antihistamine and Who Are naïve to, Intolerant of, or Incomplete Responders to Omalizumab (LIBERTY-CSU CUPID)

UAS is a validated composite patient-reported outcome (PRO) measure for assessing chronic spontaneous urticaria (CSU) activity. The once daily UAS is the sum of the daily hives severity score (HSS) and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.

Daily HSS was recorded in e-diary. The HSS7 score is the sum of daily HSS ranging from 0 (none) to 3 (more than 50 hives) recorded by a participant at the same time of each day over 7 days with an overall scale of 0 (no hives) to 21 (severe hives). Higher scores indicate greater intensity of hives. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.

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. An ISS7 MID response was defined as >=5 points decrease from baseline after study intervention.

UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. In evaluating urticaria control using UAS7, an UAS7 score of <=6 indicated a well-controlled urticaria.

UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. In evaluating urticaria control using UAS7, an UAS7 score of 0 indicated an absence of both itch and hives and a complete resolution of CSU symptoms.

The UCT assessed urticaria control based on 4 items (severity of pruritus and wheals urticaria symptoms; frequency of treatment being not sufficient; quality-of-life [QoL] impairment; overall urticarial control). Each item was rated on a 5-point Likert-type scale from 0 (no control) to 4 (maximum control). The overall UCT score was the sum of all 4 individual item scores with a range of 0 (no disease control) to 16 (complete disease control). Higher scores indicated greater disease control. LS mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.

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. LS mean is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization.

UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.

UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. In evaluating urticaria control using UAS7, an UAS7 score of <=6 indicated a well-controlled urticaria and an UAS7 score of 0 indicated an absence of both itch and hives and a complete resolution of CSU symptoms.

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. An ISS7 MID response was defined as >=5 points decrease from baseline after study intervention.

Daily HSS was recorded in e-diary. The HSS7 score is the sum of daily HSS ranging from 0 (none) to 3 (more than 50 hives) recorded by a participant at the same time of each day over 7 days with an overall scale of 0 (no hives) to 21 (severe hives). Higher scores indicate greater intensity of hives. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.

The UCT assessed urticaria control based on 4 items (severity of pruritus and wheals urticaria symptoms; frequency of treatment being not sufficient; quality-of-life [QoL] impairment; overall urticarial control). Each item was rated on a 5-point Likert-type scale from 0 (no control) to 4 (maximum control). The overall UCT score was the sum of all 4 individual item scores with a range of 0 (no disease control) to 16 (complete disease control). Higher scores indicated greater disease control. LS mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.

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. Mean is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization.

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. The MID for ISS7 was a change of 5.0 points. Time to first ISS7 MID response (ISS7 >=5) was defined as time to reduction from baseline of 5 points or more. Kaplan-Meier estimate is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization.

The AAS is a diary in which participants document on a daily basis the presence or absence of angioedema during the past 24 hours. If angioedema is present, participants answer 5 additional questions about the time of the day the swelling episode occurred and the severity and impact on daily functioning and appearance this swelling episode has had. Each AAS item is scored between 0 (minimum) and 3 (maximum). The daily AASs range from 0 (no episode) to 15 (severe) points. The AAS7 score is the sum of daily AAS scores reported by a participant at the same time of each day over 7 days, with a range of 0 (no angioedema episodes) to 105 (highest angioedema severity). Higher scores indicate greater angioedema activity. Mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.

The UCT assessed urticaria control based on 4 items (severity of pruritus and wheals urticaria symptoms; frequency of treatment being not sufficient; QoL impairment; overall urticarial control). Each item was rated on a 5-point Likert-type scale from 0 (no control) to 4 (maximum control). The overall UCT score was the sum of all 4 individual item scores with a range of 0 (no disease control) to 16 (complete disease control). Higher scores indicated greater disease control. An UCT score of >=12 (out of maximum 16) indicated a well-controlled urticaria disease status.

The DLQI is an assessment assessing the impact of skin disease on participants' HRQoL over the previous week and contains 10 questions related to symptoms, leisure activities, work/school or holiday time, personal relationships including intimate, the side effects of treatment, and emotional reactions to having a skin disease. The questions (except question 7) were scored on a 4-point Likert scale: 0 (not at all), 1 (a little), 2 (a lot), 3 (very much). Question 7 about work/studying asked whether work/study had been prevented and then (if "No") to what degree the skin condition has been a problem at work/study; the item was again rated on a 3-point Likert scale: 0 (not at all) to 3 (a lot). Total DLQI was calculated by summing the score of each question and ranged from 0 (no impact) to 30 (severe impact). Higher scores indicated poor HRQoL. Mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.

The CDLQI is a validated questionnaire designed to measure the impact of skin disease on children's HRQoL. Participants provide responses to 10 questions (symptoms feelings associated with disease, the impact of the disease on leisure, school or holidays, personal relationships, sleep, and side effects of treatment for the skin disease). The instrument has a recall period of 7 days. 9 of the 10 questions are scored on a 4-point Likert scale ranging from 0 (not at all/question unanswered) to 3 (very much). Question 7 has an additional possible response (prevented school) which is assigned a score of 3 (0 [not at all] to 3 [definitely]). The total CDLQI score is the sum of the score of each question ranging 0 (no impact) to 30 (severe impact). The higher the score, the greater the impact is on the child's HRQoL. Mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.

The PGIC is a 1-item questionnaire that asks the participant to provide the overall self-assessment of change in their CSU on a 7-point scale compared to just before participant started taking the study intervention. Response choices are: 0 (very much better), 1 (moderately better), 2 (a little better), 3 (no change), 4 (a little worse), 5 (moderately worse), 6 (very much worse). Higher score indicate worsening.

The PGIS is a 1-item questionnaire that asks participants to provide the overall self-assessment of their disease severity on a 4-point scale for the past week. Response choices are: 1 (none), 2 (mild), 3 (moderate), 4 (severe). Higher score indicate more severity. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.

Participants receiving OCS as rescue medications for CSU were recorded by the Investigator in e-case report form (eCRF) during the 24-week treatment period. Kaplan-Meier estimate for time to first OCS use is presented.

Percentage of participants receiving OCS as rescue medications for CSU were recorded by the Investigator in eCRF during the 24-week treatment period.

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was 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 disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened or became serious during the TE period.

Blood samples were collected at specified timepoints and ADA samples were assayed using validated methods. Treatment-emergent ADA response was defined as a positive response in the ADA assay post first dose when baseline results were negative or missing. Number of participants with treatment-emergent ADA response is presented.