A Study in Participants With Moderate to Severe Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Baricitinib; Methotrexate; Baricitinib Placebo; MTX Placebo; Folic Acid
Intervention description: Administered orally; Administered orally; Baricitinib placebo administered orally once daily.; MTX placebo administered orally once weekly.; Administered orally every day
Intervention MeSH terms: Folic Acid; Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 588.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether baricitinib therapy alone is noninferior to
      methotrexate (MTX) therapy alone in the treatment of moderate to severe active rheumatoid
      arthritis (RA) in those who have had limited or no treatment with MTX and are naive to other
      conventional or biologic disease-modifying antirheumatic drugs (DMARDs).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a diagnosis of adult-onset rheumatoid arthritis (RA) as defined by American
             College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) 2010 Criteria
             for the Classification of RA

          -  Have documented history of positive rheumatoid factor and/or cyclic citrullinated
             peptide (CCP) antibody test

          -  Have moderately to severely active RA defined as the presence of at least 6/68 tender
             joints and at least 6/66 swollen joints

          -  Have a C-reactive protein (CRP) or high-sensitivity C-reactive protein (hsCRP)
             measurement ≥1.2 times the upper limit of normal (ULN)

          -  Have had limited or no treatment with methotrexate (MTX)

        Exclusion Criteria:

          -  Have received conventional disease-modifying antirheumatic drugs (DMARDs) other than
             MTX (eg, gold salts, cyclosporine, leflunomide, azathioprine, hydroxychloroquine,
             sulfasalazine or any other immunosuppressives)

          -  Are currently receiving corticosteroids at doses >10 mg per day of prednisone (or
             equivalent) or have been receiving an unstable dosing regimen of corticosteroids
             within 2 weeks of study entry or within 6 weeks of planned randomization

          -  Have started treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or have
             been receiving an unstable dosing regimen of NSAIDs within 2 weeks of study entry or
             within 6 weeks of planned randomization

          -  Have started a new physiotherapy treatment for RA in the 2 weeks prior to study entry

          -  Have ever received any biologic DMARD

          -  Have received interferon therapy within 4 weeks prior to study entry or are
             anticipated to require interferon therapy during the study

          -  Have received any parenteral corticosteroid administered by intramuscular or
             intravenous (IV) injection within 2 weeks prior to study entry or within 6 weeks prior
             to planned randomization or are anticipated to require a parenteral injection of
             corticosteroids during the study

          -  Have had 3 or more joints injected with intraarticular corticosteroids or hyaluronic
             acid within 2 weeks prior to study entry or within 6 weeks prior to planned
             randomization

          -  Have active fibromyalgia that, in the investigator's opinion, would make it difficult
             to appropriately assess RA activity for the purposes of this study

          -  Have a diagnosis of any systemic inflammatory condition other than RA, such as, but
             not limited to, juvenile chronic arthritis, spondyloarthropathy, Crohn's disease,
             ulcerative colitis, psoriatic arthritis, active vasculitis, or gout (Participants with
             secondary Sjogren's syndrome are not excluded.)

          -  Have a diagnosis of Felty's syndrome

          -  Have had any major surgery within 8 weeks of study entry or will require major surgery
             during the study that, in the opinion of the investigator in consultation with Lilly
             or its designee, would pose an unacceptable risk to the participant

          -  Have experienced any of the following within 12 weeks of study entry: myocardial
             infarction, unstable ischemic heart disease, stroke, or New York Heart Association
             Stage IV heart failure

          -  Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal,
             endocrine, hematological, neurological, or neuropsychiatric disorders or any other
             serious and/or unstable illness that, in the opinion of the investigator, could
             constitute a risk when taking investigational product or could interfere with the
             interpretation of data

          -  Are largely or wholly incapacitated permitting little or no self care, such as, being
             bedridden or confined to a wheelchair

          -  Have an estimated Glomerular Filtration Rate (eGFR) based on the most recent available
             serum creatinine using the Modification of Diet in Renal Disease (MDRD) method of <40
             milliliter per minute per 1.73 m^2 (mL/min/1.73 m^2)

          -  Have a history of chronic liver disease with the most recent available aspartate
             aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times the ULN or the
             most recent available total bilirubin ≥1.5 times the ULN

          -  Have a history of, lymphoproliferative disease; or have signs or symptoms suggestive
             of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or
             have active primary or recurrent malignant disease; or have been in remission from
             clinically significant malignancy for <5 years

          -  Have been exposed to a live vaccine within 12 weeks prior to planned randomization or
             are expected to need/receive a live vaccine during the course of the study (with the
             exception of herpes zoster vaccination)

          -  Have a current or recent clinically serious viral, bacterial, fungal, or parasitic
             infection

          -  Have had symptomatic herpes zoster infection within 12 weeks prior to study entry

          -  Have a history of disseminated/complicated herpes zoster (eg, multidermatomal
             involvement, ophthalmic zoster, central nervous system involvement, postherpetic
             neuralgia)

          -  Are immunocompromised and, in the opinion of the investigator, are at an unacceptable
             risk for participating in the study

          -  Have a history of active hepatitis B virus (HBV), hepatitis C virus (HCV), or human
             immunodeficiency virus (HIV)

          -  Have screening laboratory test values, including thyroid-stimulating hormone (TSH),
             outside the reference range for the population or investigative site that, in the
             opinion of the investigator, pose an unacceptable risk for the participant's
             participation in the study

          -  Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the
             investigator or the sponsor, are clinically significant and indicate an unacceptable
             risk for the participant's participation in the study

          -  Have symptomatic herpes simplex at the time of study enrollment

          -  Have evidence of active or latent tuberculosis (TB)