Effectiveness and Safety of Lebrikizumab Treatment in Adults and Adolescents With Moderate-to-Severe Atopic Dermatitis

The EASI is used to assess the severity and extent of AD; it is a composite index with total score ranging from 0 to 72, with higher values indicating more severe and extensive disease. The severity of erythema, induration/papulation, excoriation, and lichenification will be assessed by the Investigator or trained designee on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. In addition, the extent of AD involvement in each of the 4 body areas will be assessed as a percentage by body area of head/neck, trunk, upper limbs, and lower limbs, and converted to a score of 0 (0%), 1 (0 to 9%), 2 (10 to 29%), 3 (30 to 49%), 4 (50 to 69%), 5 (70 to 89%) and 6 (90 to 100%). Percentage of participants who achieved EASI Total Score <=7, EASI <=5, and EASI <=3 at each visit was reported.

The EASI is used to assess the severity and extent of AD; it is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and or extensive disease. EASI 75 is defined as 75% reduction from baseline in the EASI score. EASI 90 is defined as 90% reduction from baseline in the EASI score. Percentage of participants who achieved EASI 75 and EASI 90 at each visit was reported.

The IGA is an instrument used to globally rate the severity of the participant's AD. It is based on a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate) and 4 (severe), and a score is selected using descriptors that best describe the overall appearance of the lesions at a given time point. The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting (minimal, palpable induration and significant induration). Percentage of participants with an IGA Score of 0 or 1 and a reduction >=2 points from baseline at each visit was reported.

SCORAD is a validated clinical tool for assessing the extent and intensity of AD. There are 3 components: surface involvement, intensity part and subjective assessment. Surface involvement is assessed as proportion of involved surface area segment by segment by applying the rule of 9s. Intensity part of the SCORAD consists of 6 items: erythema, oedema, oozing/crusting, excoriation, lichenification, and dryness. Each item is graded as follows: none (0), mild (1), moderate (2), or severe (3) (for a maximum of 18 total points). Subjective assessment of itch and of sleeplessness is recorded for each symptom using a VAS, where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), for maximum possible score of 20. The score ranges from 0 to 103, with higher values indicating a more extensive and/or severe condition. SCORAD 75 is defined as 75% reduction in SCORAD from baseline. SCORAD 90 is defined as 90% reduction in SCORAD from baseline.

mTLSS combines an evaluation of hand eczema lesions severity including 6 key signs (erythema, desquamation, lichenification/hyperkeratosis, vesiculae, oedema, fissures) and the intensity of pruritus and pain. The seven features of AD of the hands (erythema, scaling, lichenification/hyperkeratosis, vesiculation, oedema, fissures, pruritus/pain) form the composite scale of mTLSS' strength and each one of them scores from (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The scores are summed, extending from a base estimation of 0 (no signs or symptoms) to the most extreme of 21 (more serious disease). Percentage change from baseline was calculated as: ([Observed or imputed value at post-baseline time point (i.e. Visit) - Observed value at Baseline]/Observed value at Baseline) *100.

The Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity score over the past 24 hours, with 0 (No itch) to 10 (Worst itch imaginable). Assessments will be recorded by the participant using an eDiary. Percentage of participants with pruritus NRS >=4 at baseline who achieved >=4-Point improvement in pruritus NRS from baseline at each visit was reported

The DLQI is a 10-item validated questionnaire completed by the participant or caregiver used to assess the impact of skin disease on the participant's QoL during the previous week. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment. Each question is scored from 0=not at all, 1=a little, 2=a lot, and 3=very much, giving a total score ranging from 0 to 30. A high score is indicative of a poor QoL. DLQI scores indicates 0-1 (no effect on patient's life), 2-5 (small effect on patient's life), 6-10 (moderate effect on patient's life), 11-20 (very large effect on patient's life), 21-30 (extremely large effect on patient's life). Percentage of participants who achieved DLQI 0-1 at each visit was reported.

DLQI is a 10-item validated questionnaire completed by the participant or caregiver used to assess the impact of skin disease on the participant's QoL during the previous week. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment. Each question is scored from 0=not at all, 1=a little, 2=a lot, and 3=very much, giving a total score ranging from 0 to 30. High score is indicative of a poor QoL. Percentage of participants with DLQI >=4 at Baseline who achieved >=4-Point improvement in DLQI from baseline at each visit was reported.

cDLQI is validated from adolescents younger than age of 16 years, which is based on a set of 10 questions different from those of the DLQI. The answers to the questions are generally scored on a 4-point scale from 0=not at all or question unanswered, 1=only a little, 2=quite a lot, 3=very much. cDLQI is calculated by summing the score of each question resulting in 0 to 30. Higher the score, the more impairment of the child's life is experienced. Percentage of participants who achieved cDLQI 0-1 at each visit was reported.

cDLQI is validated from adolescents younger than age of 16 years, which is based on a set of 10 questions different from those of the DLQI. The answers to the questions are generally scored on a 4-point scale from 0=not at all or question unanswered, 1=only a little, 2=quite a lot, 3=very much. cDLQI is calculated by summing the score of each question resulting in 0 to 30. Higher the score, the more impairment of the child's life is experienced. Percentage of participants with cDLQI >=6 at baseline who achieved >=6-Point improvement in cDLQI from baseline at each visit was reported.

Sleep loss will be assessed by all participants using a patient-related outcome (PRO) instrument. Participants (and if applicable, with help of parents/caregiver if required) will rate their sleep on a 5-point Likert scale (with scores ranging from 0 [not at all] to 4 [unable to sleep at all]). Assessments will be recorded by the participant using an eDiary.The baseline Sleep-Loss Scale score will be determined based on the average of daily Sleep-Loss Scale scores during the 7 days immediately before the Day 1 or Baseline visit. Percentage of participants with a Sleep-Loss scale of >=2 points at baseline who achieved at least 2-point reduction from baseline at each visit was reported.

The POEM is a 7-item, validated questionnaire completed by the participant (and, if applicable, with help of parents/caregiver if required) to assess disease symptoms. Participants are asked to respond to questions on skin dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping. All answers carry equal weight, with a total possible score ranging from 0 to 28 (answers scored as: No days = 0; 1-2 days = 1; 3-4 days = 2; 5-6 days = 3; every day = 4. A high score is indicative of a poor quality of life. POEM responses are captured weekly using an eDiary. Percentage of participants with POEM >=4 at baseline who achieved >=4-Point improvement in POEM from baseline at each visit was reported.

TEAEs are undesirable events that first occurred or worsened in severity after the date of first IMP injection in the study, and on or prior to the date of the last visit within the treatment period. An SAE are AE, which falls into any of the following categories: death, is life-threatening, requires in-patient hospitalisation or prolongs existing hospitalisation, persistent or significant disability or incapacity, congenital anomaly or birth defect, or any other medically important event that may jeopardise the participant or may require intervention to prevent one of the other above outcomes. Related TEAEs includes events considered related or possibly related to study treatment by the Investigator. The following treatment-emergent AEs are being designated as AESIs: conjunctivitis, herpes simplex or zoster infection and parasitic infections.