A Study to Compare Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) Monotherapy in Adults With Rheumatoid Arthritis (RA) Who Have Not Previously Taken Methotrexate
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Placebo to Upadacitinib; Methotrexate; Placebo to Methotrexate; Upadacitinib
Intervention description: Tablet; Oral; Capsule or Tablet; Oral; Capsule or Tablet; Oral; Tablet; Oral
Intervention MeSH terms: Methotrexate; Upadacitinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants were to be randomized in a 1:1:1 ratio to treatment Groups 2, 3, and 4 below, except for participants from Japan, who were to be randomized in a 2:1:1:1 ratio to Groups 1, 2, 3, and 4:
Group 1: Upadacitinib 7.5 mg QD monotherapy (Japan only)
Group 2: Upadacitinib 15 mg QD monotherapy (43 countries, including Japan)
Group 3: Upadacitinib 30 mg QD monotherapy (43 countries, including Japan)
Group 4: MTX monotherapy (43 countries, including Japan)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1002.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Musculoskeletal disease; Arthritis; Joint disease; Anti-inflammatory agents; Antirheumatic agents; ABT-494; Upadacitinib

Summary:

      The objectives of Period 1 were the following:

        -  To compare the safety and efficacy of upadacitinib 7.5 mg once daily (QD) monotherapy
           (for participants in Japan only), 15 mg QD monotherapy, and 30 mg QD monotherapy versus
           weekly methotrexate monotherapy for the treatment of signs and symptoms of RA in
           methotrexate-naïve adults with moderately to severely active RA;

        -  To compare the efficacy of upadacitinib 15 mg QD monotherapy and upadacitinib 30 mg QD
           monotherapy versus weekly methotrexate monotherapy for prevention of structural
           progression in methotrexate-naïve adults with moderately to severely active RA.

      The objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of
      upadacitinib 7.5 mg QD (for participants in Japan only), 15 mg QD, and 30 mg QD in adults
      with RA who have completed Period 1.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.