A Study to Assess Adverse Events and Change in Disease Activity Comparing Oral Upadacitinib to Subcutaneous Dupilumab in Children From 2 to Less Than 12 Years of Age With Moderate to Severe Atopic Dermatitis

Eligibility Criteria

• * A minimum weight of 10 kg and weight and height \> 5th percentile for their age according to local standard growth charts at the Baseline Visit.
• * Atopic Dermatitis (AD), according to Hanifin and Rajka criteria, with onset of symptoms at least 6 months prior to Baseline.
• * Eczema Area and Severity Index (EASI) score \>= 16; vIGA-AD score \>= 3 (Note: In countries where dupilumab is only approved for severe AD, subjects to be included in the Randomized Cohort should have severe AD \[vIGA-AD = 4\]); \>= 10% Body Surface Area of AD involvement at the Baseline Visit; and Baseline weekly average of daily Worst Itch Scale (WIS) or Worst Scratch/Itch numerical rating scale (WSI-NRS) \>= 4.
• * Participant must satisfy at least one of the following criteria (Note: More than 1 criterion may apply to an individual participant. All applicable criteria for each individual participant should be reported):
• * To be included in the Randomized Cohort (Note: Participants must have severe AD \[vIGA-AD = 4\] in countries where dupilumab is approved only for severe AD.):
• 1. \[For all countries except US\] Documented history of inadequate response or intolerance to TCS and/or TCI OR for whom use of one or more of these topical treatments is medically inadvisable (e.g., high disease burden, Scoring Atopic Dermatitis (SCORAD) \> 50, EASI score \> 21, or vIGA-AD \> 3).
• 2. For dupilumab-naïve participants: History of inadequate response to a systemic therapy for AD other than dupilumab or oral corticosteroids or for whom the available systemic treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks).
• 3. History of inadequate response to 2 or more courses of oral corticosteroid therapy given for \>= 14 days within 6 months prior to Screening or history of oral corticosteroid rebound, defined as recurrence of AD symptoms within 4 months after its discontinuation.
• 4. For dupilumab-exposed participants: Prior exposure to dupilumab without documented history of inadequate response or intolerance (i.e., discontinuation of dupilumab for a non-medical reason, such as, but not limited to, non-coverage or loss of coverage for the drug by health insurance, or other logistic challenges \[not safety- or efficacy-related\] precluding the participants continued access to dupilumab).
• * To be included in the Dupi-IR/Dupi-Medically Inadvisable Cohort:
• * Previous inadequate response or intolerance to dupilumab OR
• * Dupilumab is medically inadvisable (e.g., allergy to a component of dupilumab, etc.) AND a documented history of inadequate response or intolerance to TCS and/or TCI.
• * Current or past history of other active skin diseases (e.g., psoriasis or Netherton syndrome or lupus erythematosus) or skin infections (bacterial, fungal, or viral) requiring systemic treatment within 4 weeks of the Baseline Visit or which would interfere with the appropriate assessment of AD lesions.
• * Have used topical treatments for AD (except for topical emollient treatments) including but not limited to TCS, TCI, or topical phosphodiesterase type 4 (PDE-4) inhibitors, within 7 days of the Baseline Visit or any the following prohibited concomitant AD treatments within the specified timeframes below prior to the Baseline Visit:
• * Systemic therapy for AD, including but not limited to corticosteroids, methotrexate, cyclosporine, azathioprine, PDE-4 inhibitors, interferon-γ, and mycophenolate mofetil within 4 weeks;
• * Dupilumab within 8 weeks;
• * Targeted biologic treatments (other than dupilumab) within 5 half-lives (if known) or within 12 weeks, whichever is longer;
• * Phototherapy treatment, laser therapy, tanning booth, or extended sun exposure that could affect disease severity or interfere with disease assessments within 4 weeks.
• * Known history of retinal detachment, previous cataract surgery, previous significant ocular trauma, or a known congenital ocular abnormality.
• * For Randomized Cohort: diagnosed active parasitic infection; suspected or high risk of parasitic infection, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization.