A Study to Assess Treat-to-Target and Dosing Flexibility of Oral Upadacitinib Tablets in Adult Participants With Moderate to Severe Atopic Dermatitis

* Chronic atopic dermatitis (AD) with onset of symptoms at least 3 years prior to Baseline and participant meets Hanifin and Rajka criteria. * Eczema Area and Severity Index (EASI) score \>= 16, vIGA-AD score \>= 3 and \>= 10% Body Surface Area (BSA) of AD involvement at the Baseline Visit. * Baseline weekly average of daily Worst Pruritus NRS \>= 4. * Candidate for systemic treatment defined as prior use of systemic treatment for AD, OR previous inadequate response to TCS, TCI or PDE-4 inhibitors, OR for whom topical treatments are otherwise medically inadvisable.

* Participants with current or past history of infection including: * Two or more episodes of herpes zoster, or one or more episodes of disseminated herpes zoster; * One or more episodes of disseminated herpes simplex (including eczema herpeticum); * Human immunodeficiency virus (HIV) infection defined as confirmed positive anti-HIV antibody (HIV Ab) test; * Active tuberculosis (TB) or meet TB exclusionary parameters (protocol specified requirements for TB testing); * Japan only: Positive result of beta-D-glucan (screening for Pneumocystis jirovecii infection) or two consecutive indeterminate results of beta-D-glucan during the Screening Period; * Active infection(s) requiring treatment with intravenous anti-infectives within 30 days, or oral/intramuscular anti-infectives within 14 days prior to the Baseline Visit; * Chronic recurring infection and/or active viral infection that, based on the investigator's clinical assessment, makes the participant an unsuitable candidate for the study; * COVID-19 infection: In participants who tested positive for COVID, at least 5 days must have passed since a COVID-19 positive test result for study entry of asymptomatic participants. Participants with mild/moderate COVID-19 infection can be enrolled if fever is resolved without use of antipyretics for 24 hours and other symptoms improved, or if 5 days have passed since the COVID-19 positive test result (whichever comes last). Participants may be rescreened if judged to be in good general health, as determined by the investigator based upon the medical history and physical examination. * Evidence of Hepatitis B virus (HBV) or Hepatitis C virus (HCV). * Any of the following medical diseases or disorders: * Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, and aorto-coronary bypass surgery; * History of an organ transplant which requires continued immunosuppression; * History of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class; * History of gastrointestinal perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk for gastrointestinal perforation per investigator judgment; * Conditions that could interfere with drug absorption including but not limited to short bowel syndrome or gastric bypass surgery; participants with a history of gastric banding/segmentation are not excluded; * History of malignancy except for successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix.