A Study to Observe How Adolescent Patients With Severe Atopic Dermatitis Despite Less Extensive Skin Lesions (Eczema Area and Severity Index Score < 16) Respond to Dupilumab Treatment

Primary outcomes

1. Physician assessment: Percentage (%) change from baseline in Eczema Area and Severity Index (EASI) score at Week 4, Week 16 and Week 52

   Time frame: Baseline, Weeks 4, 16 and 52

   EASI measures the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicating greater severity of AD.

   EASI-50: ≥ 50% reduction in score from baseline; EASI-75: ≥ 75% reduction in score from baseline; EASI-90: ≥ 90% reduction in score from baseline.

2. Physician assessment: Percentage (%) of participants with EASI-50 at 4, 16, 52 weeks

   Time frame: Weeks 4, 16, 52

   EASI measures the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicating greater severity of AD.

   EASI-50: ≥ 50% reduction in score from baseline; EASI-75: ≥ 75% reduction in score from baseline; EASI-90: ≥ 90% reduction in score from baseline.

3. Physician assessment: Percentage (%) of participants with EASI-75 at 4, 16, 52 weeks

   Time frame: Weeks 4, 16, 52

   EASI measures the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicating greater severity of AD.

   EASI-50: ≥ 50% reduction in score from baseline; EASI-75: ≥ 75% reduction in score from baseline; EASI-90: ≥ 90% reduction in score from baseline.

4. Physician assessment: Percentage (%) of participants with EASI-90 at 4, 16, 52 weeks

   Time frame: Weeks 4, 16, 52

   EASI measures the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicating greater severity of AD.

   EASI-50: ≥ 50% reduction in score from baseline; EASI-75: ≥ 75% reduction in score from baseline; EASI-90: ≥ 90% reduction in score from baseline.

5. Participant assessment: Change from baseline in Patient Oriented Eczema Measure (POEM) score at 4, 16, 52 weeks

   Time frame: Baseline, Weeks 4, 16, 52

   The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms on a scale ranging from 0 to 4 (0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, 4 = all days). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). Higher scores indicate more severe disease and poor quality of life.

6. Participant assessment: Percentage (%) of participants with a ≥ 6-point improvement from baseline in POEM score at 4, 16, 52 weeks

   Time frame: Baseline, Weeks 4, 16, 52

   The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms on a scale ranging from 0 to 4 (0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, 4 = all days). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). Higher scores indicate more severe disease and poor quality of life.

7. Percentage (%) of participants with adverse events

   Time frame: Baseline to Week 52

8. Participant assessment: Percentage (%) change from baseline in Peak Pruritus Numerical Rating Scale (PP-NRS) at 4, 16, 52 weeks

   Time frame: Baseline, Weeks 4, 16 and 52

   The PP-NRS is a single item 0-10 numeric rating scale assessing peak pruritus (itch) associated with AD during the past 24 hours, with 0 = no itch and 10 = worst itch imaginable.

9. Participant assessment: Percentage (%) of participants with a ≥4-point improvement from baseline in PP-NRS at 4, 16, 52 weeks

   Time frame: Baseline, Weeks 4, 16 and 52

   The PP-NRS is a single item 0-10 numeric rating scale assessing peak pruritus (itch) associated with AD during the past 24 hours, with 0 = no itch and 10 = worst itch imaginable.

10. Participant assessment: Percentage (%) of participants with a PP-NRS score of 0, 1 to 3, and 4 to 6 at 4, 16, 52 weeks (only patients with baseline PP-NRS ≥ 7

    Time frame: Weeks 4, 16 and 52

    The PP-NRS is a single item 0-10 numeric rating scale assessing peak pruritus (itch) associated with AD during the past 24 hours, with 0 = no itch and 10 = worst itch imaginable.

11. Participant assessment: Percentage (%) change from baseline in Sleep Disturbance Numerical Rating Scale (SD-NRS) at 4, 16, 52 weeks

    Time frame: Baseline, Weeks 4, 16 and 52

    The SD-NRS is a single item 0-10 numeric rating scale assessing sleep disturbance associated with AD, with 0 being "no sleep loss related to the symptoms of atopic dermatitis" and 10 being "I did not sleep at all, due to the symptoms of atopic dermatitis".

12. Participant assessment: Percentage (%) change from baseline in Children's Dermatology Life Quality Index (CDLQI) at 4, 16, 52 weeks

    Time frame: Baseline, Weeks 4, 16 and 52

    The CDLQI is a validated questionnaire designed to measure the impact of skin disease on the Quality of Life. The higher the score, the greater the impact is on the quality of life.

13. Participant assessment: Percentage (%) of participants who achieve a ≥6-point reduction from baseline in CDLQI score at 4, 16, 52 weeks

    Time frame: Baseline, Weeks 4, 16 and 52

    The CDLQI is a validated questionnaire designed to measure the impact of skin disease on the Quality of Life. The higher the score, the greater the impact is on the quality of life.

14. Participant assessment: Percentage (%) of participants with CDLQI Score of 0 to 1, 2 to 6 and ˃ 6 at 4, 16, 52 weeks (only patients with CDLQI ≥ 10 at baseline)

    Time frame: Weeks 4, 16 and 52

    The CDLQI is a validated questionnaire designed to measure the impact of skin disease on the Quality of Life. The higher the score, the greater the impact is on the quality of life.

15. Participant assessment: Percentage (%) change from baseline in Hospital Anxiety and Depression Scale (HADS) at 4, 16, 52 weeks

    Time frame: Baseline, Weeks 4, 16 and 52

    The HADS is a 14-item patient-reported outcomes measure used to assess states of anxiety and depression over the past week. It is comprised of 7 items assessing anxiety and depression respectively. A Total score is out of 42 (21 per subscale). Higher scores indicate greater levels of anxiety and/or depression.

16. Participant assessment: Percentage (%) change from baseline Atopic Dermatitis Control Tool (ADCT) score at 4, 16, 52 weeks

    Time frame: Baseline, Weeks 4, 16 and 52

    ADCT is a six-item patient self-administered instrument designed and validated to assess atopic dermatitis (AD) control. The score ranges from 0-24 with higher scores indicating worsening disease control.

17. Participant assessment: Percentage (%) of participants with ADCT < 7 at 4, 16, 52 weeks

    Time frame: Weeks 4, 16 and 52

    ADCT is a six-item patient self-administered instrument designed and validated to assess atopic dermatitis (AD) control. The score ranges from 0-24 with higher scores indicating worsening disease control.

18. Participant assessment: Percentage (%) change from baseline the Dermatitis Family Impact (DFI) questionnaire at 4, 16, 52 weeks

    Time frame: Baseline, Weeks 4, 16 and 52

    The DFI is a 10-item disease specific questionnaire assessing the impact of having a child with AD on family Quality of Life (QoL). The DFI questions are scored on a four-point Likert scale ranging from 0 to 3, and the total DFI score ranges from 0 to 30. The time frame of reference is the past week, and a higher DFI score indicates greater impairment in family QoL as affected by AD.

19. Physician assessment: Percentage (%) of participants with Physician's Global Assessment (PGA) Face 0 or (/) 1, PGA Feet 0/1, PGA Hands 0/1, PGA Genitals 0/1 and at least a 2-point improvement from baseline at 4, 16, 52 weeks

    Time frame: Baseline, Weeks 4, 16 and 52

    The PGA score is a measure used in clinical practice and clinical trials to assess the severity of a particular disease. The PGA chosen for this study ranges from 0-5 point, and the following categories will be used: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe, 5 = very severe. In this study, the Investigator will be evaluating four PGA scores, including PGA face, PGA feet, PGA hands, and PGA genitalia, in order to assess the severity of the localized lesions in AD patients at baseline and at week 4, 16 and 52.

20. Time to discontinuation and reasons for discontinuation

    Time frame: Baseline up to Week 52

21. Participant assessment: Mean score of Treatment Satisfaction Questionnaire for Medication (TSQM-9) score at 4, 16, 52 weeks

    Time frame: Weeks 4, 16, 52

    The 9-item TSQM (TSQM-9) is a questionnaire to assess treatment satisfaction, with scores ranging between 9 and 59, and lower scores indicating lower satisfaction with treatment.

22. Participant assessment: Percentage (%) change from baseline in Asthma Control Questionnaire (ACQ-6) at 4, 16, 52 weeks in participants with concomitant asthma

    Time frame: Baseline, Weeks 4, 16 and 52

    The ACQ-6 is a questionnaire that consists of six questions on a scale from 0 to 6 of symptoms. The questions are about limitations due to asthma and symptoms in the past week. A lower score corresponds with better asthma control.

23. Participant assessment: Percentage (%) change from baseline in Total Nasal Symptoms Score (TNSS) at 4, 16, 52 weeks in participants with concomitant chronic rhinitis

    Time frame: Baseline, Weeks 4, 16 and 52

    The TNSS is the sum of scores for each of nasal congestion, sneezing, nasal itching, and rhinorrhea using a four-point scale (0-3), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. TNSS is calculated by adding the score for each of the symptoms to a total out of 12.