A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Adults With Rheumatoid Arthritis Who Are on a Stable Dose of Methotrexate and Who Have an Inadequate Response to Methotrexate
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Placebo for Adalimumab; Adalimumab; Placebo for Upadacitinib; Upadacitinib
Intervention description: Administered by subcutaneous injection once every other week; Administered by subcutaneous injection once every other week; Tablets taken orally once a day; Tablets taken orally once a day
Intervention MeSH terms: Adalimumab; Upadacitinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1629.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Musculoskeletal disease; Arthritis; Joint disease; Anti-inflammatory agents; Antirheumatic agents

Summary:

      The purpose of this study was to assess efficacy, including inhibition of radiographic
      progression, and safety with upadacitinib versus placebo and versus an active comparator,
      adalimumab, in adults with with moderately to severely active rheumatoid arthritis (RA) who
      are on a stable background of methotrexate (MTX and who have an inadequate response to MTX.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult male or female, at least 18 years old.

          -  Diagnosis of RA for greater than or equal to 3 months.

          -  Subjects must have been on oral or parenteral methotrexate (MTX) therapy greater than
             or equal to 3 months and on a stable prescription of greater than or equal to 15 to 25
             mg/week (or greater than or equal to 10 mg/week in subjects intolerant of MTX at doses
             greater than or equal to 12.5 mg/week) for at least 4 weeks prior to the first dose of
             study drug. In addition all subjects should take a dietary supplement of folic acid or
             folinic acid throughout the study participation.

          -  Meets the following minimum disease activity criteria: greater than or equal to 6
             swollen joints (based on 66 joint counts) and greater than or equal to 6 tender joints
             (based on 68 joint counts) at Screening and Baseline Visits.

          -  At least one of the following at Screening: greater than or equal to 3 bone erosions
             on x-ray OR greater than or equal to 1 bone erosion and a positive rheumatoid factor
             OR greater than or equal to 1 bone erosion and a positive anti-cyclic citrullinated
             peptide autoantibodies.

          -  Subjects with prior exposure to only one biological disease-modifying anti-rheumatic
             drugs (bDMARD) (except adalimumab) may be enrolled (up to 20% of total study
             population) if they have documented evidence of intolerance to the bDMARD or limited
             exposure (less than 3 months), but required washout periods need to be satisfied.

          -  Except for MTX, subject must have discontinued all conventional synthetic
             disease-modifying anti-rheumatic drugs (csDMARDs).

        Exclusion Criteria:

          -  Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to
             tofacitinib, baricitinib, and filgotinib).

          -  Subjects who have been exposed to adalimumab or who are considered inadequate
             responders to bDMARD therapy as determined by the Investigator.

          -  History of inflammatory joint disease other than RA. History of secondary Sjogren's
             Syndrome is permitted.