A Phase 3 Study to Compare Upadacitinib to Abatacept in Subjects With Rheumatoid Arthritis on Stable Dose of Conventional Synthetic Disease- Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response or Intolerance to Biologic DMARDs
Condition: Rheumatoid Arthritis (RA)
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Abatacept; Placebo for abatacept; Upadacitinib; Placebo for upadacitinib
Intervention description: IV infusion; IV infusion; 15 mg extended release tablet; Film-coated tablet
Intervention MeSH terms: Abatacept; 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: 613.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Musculoskeletal Disease; Arthritis; Joint Disease; Anti-inflammatory agents; Antirheumatic agents

Summary:

      The study objective of Period 1 was to compare the safety and efficacy of upadacitinib 15 mg
      once daily (QD) to abatacept on a background of conventional synthetic disease-modifying
      antirheumatic drugs (csDMARDs) for the treatment of signs and symptoms of rheumatoid
      arthritis (RA) in biologic disease-modifying antirheumatic drug (bDMARD)-inadequate response
      or bDMARD-intolerant participants with moderately to severely active RA. The study objective
      of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib
      15 mg QD in participants with RA who had completed Period 1.
    

Eligibility criteria:

        Main Inclusion Criteria:

          -  Diagnosis of rheumatoid arthritis (RA) for ≥ 3 months who also fulfill the 2010
             American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR)
             classification criteria for RA

          -  Participants have been treated for ≥ 3 months prior to the screening visit with ≥ 1
             bDMARD therapy, but continue to exhibit active RA or had to discontinue due to
             intolerability or toxicity, irrespective of treatment duration and have never received
             abatacept prior to the first dose of study drug

          -  Participants have been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥
             4 weeks prior to the first dose of study drug. The following csDMARDs are allowed:
             methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide. A
             combination of up to two background csDMARDs is allowed except the combination of MTX
             and leflunomide

          -  Meets the following criteria: ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6
             tender joints (based on 68 joint counts) at Screening and Baseline Visits and
             high-sensitivity C-reactive protein (hsCRP) ≥ 3 mg/L at Screening

        Main Exclusion Criteria:

          -  Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to
             upadacitinib, tofacitinib, baricitinib and filgotinib)

          -  Prior exposure to abatacept

          -  History of any arthritis with onset prior to age 17 years or current diagnosis of
             inflammatory joint disease other than RA. Current diagnosis of secondary Sjogren's
             Syndrome is permitted

          -  Laboratory values meeting the following criteria within the Screening period prior to
             the first dose of study drug: serum aspartate transaminase > 2 × upper limit of normal
             (ULN); serum alanine transaminase > 2 × ULN; estimated glomerular filtration rate by
             simplified 4-variable Modification of Diet in Renal Disease formula < 40
             mL/minute/1.73 meter (m)^2; total white blood cell count < 2,500/ μL; absolute
             neutrophil count < 1,500/μL; platelet count < 100,000/μL; absolute lymphocyte count <
             800/μL; and hemoglobin < 10 g/dL