A Study to Compare Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) Monotherapy in Adults With Rheumatoid Arthritis (RA) Who Have Not Previously Taken Methotrexate

* Duration of symptoms consistent with RA for ≥ 6 weeks who also fulfill the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA. * Naïve to Methotrexate (MTX) or, if already on MTX, have received no more than 3 weekly MTX doses with requirement to complete a 4-week MTX washout before the first dose of study drug. * Participants with prior exposure to conventional synthetic disease-modifying anti-rheumatic drugs(csDMARDs) other than MTX may be enrolled if completed the washout period. * Participant meets both of the following minimum disease activity criteria: -≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits. * high sensitivity C reactive protein (hsCRP) ≥ 5 mg/L (central lab, upper limit of normal \[ULN\] 2.87 mg/L at Screening Visit. * Greater than or equal to 1 bone erosion on x-ray (by local reading) OR in the absence of documented bone erosion, both positive rheumatoid factor (RF) and positive anti-cyclic citrullinated peptide (anti CCP) autoantibodies are required at Screening. * Stable dose of non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, oral corticosteroids (equivalent to prednisone ≤ 10 mg/day), or inhaled corticosteroids for stable medical conditions are allowed but must have been at a stable dose ≥ 1 week prior to the first dose of study drug.

* Intolerant to Methotrexate (MTX). * Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib). * Prior exposure to any biologic disease-modifying anti-rheumatic drugs (bDMARDs). * History of any arthritis with onset prior to age 17 years or current diagnosis, inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia \[currently with active symptoms\]. Current diagnosis of secondary Sjogren's Syndrome is permitted. * Has been treated with intra-articular, intramuscular, intravenous, trigger point or tender point, intra-bursa, or intra-tendon sheath corticosteroids in the preceding 8 weeks prior to the first dose of study drug.