Program to Assess Adverse Events and Change in Disease Activity of Oral Upadacitinib in Adult Participants With Moderate to Severe Systemic Lupus Erythematosus

Inclusion Criteria: * Clinical diagnosis of systemic lupus erythematosus (SLE) at least 24 weeks prior to screening as defined by the 2019 European Alliance of Associations for Rheumatology (EULAR)/ American College of Rheumatology (ACR) classification criteria for SLE. * At Screening, must have at least one of the following: * antinuclear antibody (ANA) positive (titer \>= 1:80) * anti-double stranded deoxyribonucleic acid (dsDNA) positive * anti-Smith positive * Hybrid systemic lupus erythematosus disease activity index (hSLEDAI) \>= 6, of which \>= 4 points are clinical (not based on laboratory criteria), independently reviewed by the MCDR at Screening. Clinical hSLEDAI score (not based on laboratory criteria) must be re-confirmed as \>= 4 at the Baseline visit. Lupus headache or organic brain syndrome do not count towards the hSLEDAI points required for eligibility but should be documented on the hSLEDAI if present. * Physician's Global Assessment (PhGA) \>= 1 during screening period. * On stable background treatment for \>= 60 days prior to Baseline (with the exception of oral corticosteroid \[OCS\], which must be at a stable dose for \>=14 days prior to Baseline) with * antimalarial(s) \[hydroxychloroquine \<= 400 mg daily, chloroquine \<= 500 mg daily, quinacrine \<= 100 mg daily\]; * and/or prednisone (or prednisone-equivalent) (\<= 20 mg daily); * and/or no more than 1 of the following: azathioprine (\<= 150 mg daily), 6-mercaptopurine (\<= 150 mg daily), mycophenolate mofetil (\<= 2 g daily), mycophenolate sodium \<= 1,440 mg/day, leflunomide (\<= 20 mg daily), cyclosporine, tacrolimus, voclosporin (\<= 23.7 mg twice daily), methotrexate (\<= 25 mg weekly), or mizoribine (\<= 150 mg daily). Exclusion Criteria: * Class III/IV lupus nephritis that was treated with induction therapy within the 6 months prior to Screening. * Active neuropsychiatric SLE (excluding lupus headache) within the 6 months prior to Screening. * SLE overlap syndromes including, but not limited to, rheumatoid arthritis, systemic sclerosis, polymyositis, dermatomyositis, or mixed connective tissue disease (Sjögren's syndrome is permitted). * Antiphospholipid syndrome and prior unprovoked venous or arterial thrombosis who are not on stable and adequate anticoagulation. * Two or more episodes of herpes zoster, or one or more episodes of disseminated herpes zoster or herpes zoster ophthalmicus. * History of malignancy, except for successfully treated non-melanoma skin cancer or localized carcinoma in situ of the cervix. * Pregnancy, breastfeeding, or considering becoming pregnant during the study. * Clinically relevant or significant ECG abnormalities at Screening. * Planned elective surgery that would impact study procedures or assessments through the completion of the Week 52 assessments. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.