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RA-BEGIN: A Study in Participants With Moderate to Severe Rheumatoid Arthritis

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01711359
Collaborator
(none)
588
Enrollment
154
Locations
3
Arms
33
Duration (Months)
3.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
588 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Active-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib (LY3009104) in Patients With Moderately to Severely Active Rheumatoid Arthritis Who Have Had Limited or No Treatment With Disease-Modifying Antirheumatic Drugs
Study Start Date :
Nov 1, 2012
Actual Primary Completion Date :
Feb 1, 2015
Actual Study Completion Date :
Aug 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Baricitinib + MTX

Baricitinib 4 milligram (mg) administered orally once daily through Week 52. Participants received methotrexate (MTX) orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.

Drug: Baricitinib
Administered orally
Other Names:
  • LY3009104

    • Drug: Methotrexate
    Administered orally

    Drug: Folic Acid
    Administered orally every day
    Experimental: Baricitinib

    Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.

    Drug: Baricitinib
    Administered orally
    Other Names:
  • LY3009104

    • Drug: MTX Placebo
    MTX placebo administered orally once weekly.

    Drug: Folic Acid
    Administered orally every day
    Active Comparator: MTX

    MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.

    Drug: Methotrexate
    Administered orally

    Drug: Baricitinib Placebo
    Baricitinib placebo administered orally once daily.

    Drug: Folic Acid
    Administered orally every day

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20) [Week 24]

      ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). "ACR20 Responder" is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity using visual analog scale (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain due to arthritis, and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and participants who discontinued study or drug or were rescued before analysis time point were deemed non-responders.

    Secondary Outcome Measures

    1. Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20) [Week 52]

      ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). "ACR20 Responder" is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity using visual analog scale (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain due to arthritis, and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and participants who discontinued study or drug or were rescued before analysis time point were deemed non-responders.

    2. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score [Baseline, Week 24]

      HAQ-DI assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area are averaged to calculate the HAQ-DI score, which ranges from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicates an improvement in the participant's condition.

    3. Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP) [Baseline, Week 24]

      Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using the following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.

    4. Change From Baseline in the Modified Total Sharp Score (mTSS) [Baseline, Week 24]

      X-rays of the hands/wrists and feet were scored for structural progression as measured using the mTSS (van der Heijde 2000). This methodology quantified the extent of bone erosions and joint space narrowing for 44 and 42 joints, with higher scores representing greater damage. The mTSS at a time point is the sum of the erosion (range from 0 to 280) and JSN (range from 0 to 168) scores, for a maximum score of 448.

    5. Percentage of Participants Who Achieved a Simplified Disease Activity Index (SDAI) Score ≤3.3 [Week 24]

      SDAI is a tool for measurement of disease activity in RA that integrates TJC28, SJC28, acute phase response using C-reactive protein (milligrams per liter), Patient's Global Assessment of Disease Activity using VAS centimeters (cm), and Physician's Global Assessment of Disease Activity using VAS (cm). The SDAI is calculated by summing the values of the 5 components. Lower scores indicated less disease activity. An index-based definition of remission occurs with an SDAI score ≤3.3.

    6. Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response [Week 12, Week 24, Week 52]

      ACR50 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR50 Responder" is a participant who has at least 50% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinued study or drug or were rescued before analysis time point were deemed non-responders.

    7. Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response [Week 12, Week 24, Week 52]

      ACR70 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR70 Responder" is a participant who has at least 70% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinued study or drug or were rescued before analysis timepoint were deemed non-responders.

    8. Change From Baseline in Clinical Disease Activity Index (CDAI) Score [Baseline, Week 24; Baseline, Week 52]

      The CDAI is a tool for measurement of disease activity in RA that does not require a laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). The CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity. A negative change from baseline indicates improvement in condition.

    9. Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) [Baseline, Week 24; Baseline, Week 52]

      DAS28 consisted of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), erythrocyte sedimentation rate (ESR) (millimeters per hour), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using the following formula: DAS28-ESR=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.70*natural log(ESR)+0.014*Patient's Global VAS. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.

    10. Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission [Week 12, Week 24, Week 52]

      The ACR/EULAR definitions of RA remission include a "Boolean-based definition". The Boolean-based definition of remission occurs when all 4 of the following criteria are met at the same visit: TJC28 ≤1, SJC28 ≤1, acute phase response using C-reactive protein (milligrams per deciliter) ≤1, Patient's Global Assessment of Disease Activity using VAS (cm) ≤1.

    11. Change From Baseline in Joint Space Narrowing and Bone Erosion Scores [Baseline, Week 24; Baseline, Week 52]

      X-rays of the hands/wrists and feet were assessed for joint space narrowing (JSN) and bone erosions. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, is scored from 0 to 4, with 0 indicating no (normal) JSN and 4 indicating complete loss of joint space, bony ankylosis or luxation. JSN scores ranged from 0-168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing. The bone erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints of the feet. Each joint is scored according to the surface area involved from 0 to 5 for hand joints and 0 to 10 for the foot joints, with 0 indicating no erosion and the highest score (5 for the hand and 10 for the foot) indicating extensive loss of bone from more than one half of the articulating bone. Erosion scores ranged from 0 (no erosion) to 280 (high erosion).

    12. Change From Baseline in Duration of Morning Joint Stiffness [Baseline, Week 52]

      Participants reported the duration of their morning joint stiffness (MJS) in hours and minutes. The participants were asked about their duration of morning joint stiffness on the day prior to the study visit to capture actual symptoms, since the participant may have had an atypical morning routine on the day of the study visit. If morning joint stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. A decrease in duration of morning joint stiffness indicated an improvement in the participant's condition.

    13. Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS) [Baseline, Week 24; Baseline Week 52]

      Participants rated their tiredness by selecting a number from 0 to 10 that best described their worst tiredness during the last 24 hours, where 0 represents "no tiredness" and 10 represents "as bad as you can imagine".

    14. Change From Baseline in Worst Joint Pain Numeric Rating Scale (NRS) [Baseline, Week 24; Baseline Week 52]

      Participants rated their joint pain by selecting a number from 0 to 10 that best described their worst joint pain during the last 24 hours, where 0 represents "no pain" and 10 represents "pain as bad as you can imagine".

    15. Change From Baseline in Mental Component Score (MCS) and Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) [Baseline, Week 24; Baseline Week 52]

      The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (MCS and PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning.

    16. Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores [Baseline, Week 24; Baseline Week 52]

      European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. One component consists of a descriptive system of the respondent's health comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1. A higher score indicates better health state.

    17. Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) [Baseline, Week 24; Baseline Week 52]

      A second component of the EQ-5D-5L is a self-perceived health score which is assessed using a VAS that ranges from 0 to 100 millimeter (mm), where 0 indicates the worst health you can imagine and 100 indicates the best health you can imagine.

    18. Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores [Baseline, Week 24; Baseline Week 52]

      The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a13-item, symptom-specific questionnaire that specifically assesses the participant's self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0 ("Not at all") to 4 ("Very much") for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue.

    19. Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores [Baseline, Week 24; Baseline Week 52]

      The Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. It contains 6 items covering overall work productivity (health), overall work productivity (symptom), impairment of regular activities (health), and impairment of regular activities (symptom). Scores are calculated as impairment percentages. The WPAI-RA yields four types of scores: Absenteeism (work time missed), Presenteeism (impairment at work), Work productivity loss (overall work impairment), and Activity impairment.

    20. Population Pharmacokinetics (PK): Peak Concentration at Steady State (Cmax,ss) of Baricitinib [Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 24; Week 32; Pre-dose]

    21. Population PK: Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib [Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 24; Week 32; Pre-dose]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 m2 (mL/min/1.73 m2)

    • 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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Glendale Arizona United States 85304
    2 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Mesa Arizona United States 85202
    3 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Peoria Arizona United States 85381
    4 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Phoenix Arizona United States 85037
    5 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. El Cajon California United States 92020
    6 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Lakewood California United States 90712
    7 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Palm Desert California United States 92260
    8 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Tustin California United States 92780
    9 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Upland California United States 91786
    10 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Boulder Colorado United States 80304
    11 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Trumbull Connecticut United States 06611
    12 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Lewes Delaware United States 19958
    13 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Boynton Beach Florida United States 33472
    14 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Naples Florida United States 34102
    15 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Orlando Florida United States 32806
    16 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Palm Harbor Florida United States 34684
    17 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Plantation Florida United States 33324
    18 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Tampa Florida United States 33614
    19 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Venice Florida United States 34292
    20 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Vernon Hills Illinois United States 60061
    21 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Indianapolis Indiana United States 46260
    22 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Cumberland Maryland United States 21502
    23 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Grand Rapids Michigan United States 49546
    24 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Lansing Michigan United States 48910
    25 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Flowood Mississippi United States 39232
    26 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Saint Louis Missouri United States 63141
    27 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Freehold New Jersey United States 07728
    28 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Toms River New Jersey United States 08755
    29 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Albuquerque New Mexico United States 87102
    30 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Hartsdale New York United States 10530
    31 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Middleburg Heights Ohio United States 44130
    32 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Oklahoma City Oklahoma United States 73103
    33 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Tulsa Oklahoma United States 74135
    34 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Portland Oregon United States 97239
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    137 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Santurce Puerto Rico 00909
    138 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Moscow Russian Federation 115522
    139 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Ryazan Russian Federation 390026
    140 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Ulyanovsk Russian Federation 432063
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    151 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. London Greater London United Kingdom SE1 9RT
    152 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Basingstoke Hampshire United Kingdom RG24 9NA
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    154 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. North Shields Tyneside United Kingdom NE29 8NH

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01711359
    Other Study ID Numbers:
    • 14062
    • I4V-MC-JADZ
    First Posted:
    Oct 22, 2012
    Last Update Posted:
    Sep 19, 2019
    Last Verified:
    Sep 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:
    Arthritis
    Arthritis, Rheumatoid
    Folic Acid
    Methotrexate

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Participants who did not respond (nonresponders) to study drug were eligible for rescue treatment beginning at Week 24. Nonresponders were defined as lack of improvement of at least 20% in both tender joint count and swollen joint count.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description Methotrexate (MTX) administered orally once weekly with dose ranging from 10 to 20 milligram (mg) per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Period Title: Treatment Period
    STARTED 213 160 215
    Received at Least One Dose of Study Drug 210 159 215
    Rescued 26 7 6
    COMPLETED 161 136 173
    NOT COMPLETED 52 24 42
    Period Title: Treatment Period
    STARTED 25 15 28
    COMPLETED 0 0 0
    NOT COMPLETED 25 15 28

    Baseline Characteristics

    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX Total
    Arm/Group Description Methotrexate (MTX) administered orally once weekly with dose ranging from 10 to 20 milligram (mg) per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Total of all reporting groups
    Overall Participants 210 159 215 584
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    50.5
    (13.4)
    50.9
    (13.0)
    48.5
    (13.5)
    49.9
    (13.4)
    Sex: Female, Male (Count of Participants)
    Female
    148
    70.5%
    121
    76.1%
    156
    72.6%
    425
    72.8%
    Male
    62
    29.5%
    38
    23.9%
    59
    27.4%
    159
    27.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    11
    5.2%
    10
    6.3%
    20
    9.3%
    41
    7%
    Asian
    60
    28.6%
    44
    27.7%
    61
    28.4%
    165
    28.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    10
    4.8%
    5
    3.1%
    10
    4.7%
    25
    4.3%
    White
    128
    61%
    98
    61.6%
    123
    57.2%
    349
    59.8%
    More than one race
    1
    0.5%
    2
    1.3%
    1
    0.5%
    4
    0.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    Argentina
    41
    19.5%
    29
    18.2%
    33
    15.3%
    103
    17.6%
    Austria
    1
    0.5%
    1
    0.6%
    1
    0.5%
    3
    0.5%
    Belgium
    6
    2.9%
    10
    6.3%
    11
    5.1%
    27
    4.6%
    Brazil
    8
    3.8%
    3
    1.9%
    9
    4.2%
    20
    3.4%
    Canada
    5
    2.4%
    5
    3.1%
    7
    3.3%
    17
    2.9%
    Germany
    5
    2.4%
    5
    3.1%
    4
    1.9%
    14
    2.4%
    Greece
    0
    0%
    0
    0%
    1
    0.5%
    1
    0.2%
    India
    18
    8.6%
    12
    7.5%
    17
    7.9%
    47
    8%
    Italy
    8
    3.8%
    2
    1.3%
    4
    1.9%
    14
    2.4%
    Japan
    36
    17.1%
    29
    18.2%
    39
    18.1%
    104
    17.8%
    Mexico
    12
    5.7%
    14
    8.8%
    20
    9.3%
    46
    7.9%
    Portugal
    1
    0.5%
    0
    0%
    2
    0.9%
    3
    0.5%
    Russian Federation
    11
    5.2%
    13
    8.2%
    12
    5.6%
    36
    6.2%
    South Africa
    7
    3.3%
    4
    2.5%
    9
    4.2%
    20
    3.4%
    Korea, Republic of
    4
    1.9%
    1
    0.6%
    2
    0.9%
    7
    1.2%
    Sweden
    3
    1.4%
    0
    0%
    1
    0.5%
    4
    0.7%
    United Kingdom
    7
    3.3%
    3
    1.9%
    4
    1.9%
    14
    2.4%
    United States
    37
    17.6%
    28
    17.6%
    39
    18.1%
    104
    17.8%
    Duration of Rheumatoid Arthritis (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    0.2
    0.2
    0.2
    0.2
    Tender Joint Count of 68 evaluable joints (number of joints) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [number of joints]
    26.5
    (14.8)
    26.4
    (14.1)
    27.7
    (14.5)
    26.9
    (14.5)
    Swollen Joint Count of 66 evaluable joints (number of joints) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [number of joints]
    16.4
    (10.6)
    16.1
    (9.2)
    16.3
    (9.5)
    16.3
    (9.8)
    High sensitivity C-reactive protein (milligrams per liter (mg/L)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [milligrams per liter (mg/L)]
    22.34
    (21.78)
    23.75
    (26.24)
    24.27
    (29.42)
    23.44
    (25.98)

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)
    Description ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). "ACR20 Responder" is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity using visual analog scale (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain due to arthritis, and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and participants who discontinued study or drug or were rescued before analysis time point were deemed non-responders.
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    Modified Intent-to-Treat (mITT) population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using nonresponder imputation (NRI).
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 210 159 215
    Number [Percent of participants]
    61.9
    29.5%
    76.7
    48.2%
    78.1
    36.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Methotrexate, Baricitinib
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Noninferiority is concluded if the lower bound of the 95% CI for the difference in response rate is >-12%
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Newcombe-Wilson method
    Estimated Value 14.8
    Confidence Interval (2-Sided) 95%
    5.5 to 24.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimation Parameter: Newcombe-Wilson method without continuity correction for difference in the response rate (Baricitinib minus Methotrexate).
    2. Secondary Outcome
    Title Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)
    Description ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). "ACR20 Responder" is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity using visual analog scale (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain due to arthritis, and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and participants who discontinued study or drug or were rescued before analysis time point were deemed non-responders.
    Time Frame Week 52

    Outcome Measure Data

    Analysis Population Description
    Modified Intent-to-Treat (mITT) population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using nonresponder imputation (NRI).
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 210 159 215
    Number [Percent of participants]
    55.7
    26.5%
    73.0
    45.9%
    72.6
    33.8%
    3. Secondary Outcome
    Title Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
    Description HAQ-DI assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area are averaged to calculate the HAQ-DI score, which ranges from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicates an improvement in the participant's condition.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using modified baseline observation carried forward (mBOCF).
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 210 159 215
    Mean (Standard Deviation) [units on a scale]
    -0.73
    (0.71)
    -1.01
    (0.74)
    -0.92
    (0.74)
    4. Secondary Outcome
    Title Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP)
    Description Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using the following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mBOCF.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 210 159 215
    Mean (Standard Deviation) [units on a scale]
    -2.01
    (1.51)
    -2.74
    (1.39)
    -2.82
    (1.58)
    5. Secondary Outcome
    Title Change From Baseline in the Modified Total Sharp Score (mTSS)
    Description X-rays of the hands/wrists and feet were scored for structural progression as measured using the mTSS (van der Heijde 2000). This methodology quantified the extent of bone erosions and joint space narrowing for 44 and 42 joints, with higher scores representing greater damage. The mTSS at a time point is the sum of the erosion (range from 0 to 280) and JSN (range from 0 to 168) scores, for a maximum score of 448.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-baseline assessments. Missing values due to discontinuation of study, rescue, or missing data were imputed using linear extrapolation (LE).
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 191 152 198
    Mean (Standard Deviation) [units on a scale]
    0.64
    (1.81)
    0.43
    (1.18)
    0.32
    (1.14)
    6. Secondary Outcome
    Title Percentage of Participants Who Achieved a Simplified Disease Activity Index (SDAI) Score ≤3.3
    Description SDAI is a tool for measurement of disease activity in RA that integrates TJC28, SJC28, acute phase response using C-reactive protein (milligrams per liter), Patient's Global Assessment of Disease Activity using VAS centimeters (cm), and Physician's Global Assessment of Disease Activity using VAS (cm). The SDAI is calculated by summing the values of the 5 components. Lower scores indicated less disease activity. An index-based definition of remission occurs with an SDAI score ≤3.3.
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 210 159 215
    Number [percentage of participants]
    10.5
    5%
    22.0
    13.8%
    22.8
    10.6%
    7. Secondary Outcome
    Title Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
    Description ACR50 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR50 Responder" is a participant who has at least 50% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinued study or drug or were rescued before analysis time point were deemed non-responders.
    Time Frame Week 12, Week 24, Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 210 159 215
    Week 12
    32.9
    15.7%
    54.7
    34.4%
    60.0
    27.9%
    Week 24
    43.3
    20.6%
    59.7
    37.5%
    63.3
    29.4%
    Week 52
    37.6
    17.9%
    57.2
    36%
    61.9
    28.8%
    8. Secondary Outcome
    Title Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
    Description ACR70 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR70 Responder" is a participant who has at least 70% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinued study or drug or were rescued before analysis timepoint were deemed non-responders.
    Time Frame Week 12, Week 24, Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 210 159 215
    Week 12
    15.7
    7.5%
    30.8
    19.4%
    33.5
    15.6%
    Week 24
    21.4
    10.2%
    42.1
    26.5%
    39.5
    18.4%
    Week 52
    25.2
    12%
    42.1
    26.5%
    46.0
    21.4%
    9. Secondary Outcome
    Title Change From Baseline in Clinical Disease Activity Index (CDAI) Score
    Description The CDAI is a tool for measurement of disease activity in RA that does not require a laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). The CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity. A negative change from baseline indicates improvement in condition.
    Time Frame Baseline, Week 24; Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using modified last observation carried forward (mLOCF).
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 200 157 208
    Week 24
    -22.12
    (16.12)
    -28.20
    (13.96)
    -29.86
    (14.05)
    Week 52
    -21.95
    (18.07)
    -28.94
    (14.58)
    -30.72
    (14.87)
    10. Secondary Outcome
    Title Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)
    Description DAS28 consisted of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), erythrocyte sedimentation rate (ESR) (millimeters per hour), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using the following formula: DAS28-ESR=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.70*natural log(ESR)+0.014*Patient's Global VAS. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.
    Time Frame Baseline, Week 24; Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 203 159 209
    Week 24
    -2.20
    (1.53)
    -2.76
    (1.45)
    -3.06
    (1.46)
    Week 52
    -2.32
    (1.77)
    -2.84
    (1.57)
    -3.22
    (1.48)
    11. Secondary Outcome
    Title Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission
    Description The ACR/EULAR definitions of RA remission include a "Boolean-based definition". The Boolean-based definition of remission occurs when all 4 of the following criteria are met at the same visit: TJC28 ≤1, SJC28 ≤1, acute phase response using C-reactive protein (milligrams per deciliter) ≤1, Patient's Global Assessment of Disease Activity using VAS (cm) ≤1.
    Time Frame Week 12, Week 24, Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 210 159 215
    Week 12
    5.7
    2.7%
    13.8
    8.7%
    14.4
    6.7%
    Week 24
    8.6
    4.1%
    18.9
    11.9%
    16.3
    7.6%
    Week 52
    11.4
    5.4%
    17.0
    10.7%
    20.9
    9.7%
    12. Secondary Outcome
    Title Change From Baseline in Joint Space Narrowing and Bone Erosion Scores
    Description X-rays of the hands/wrists and feet were assessed for joint space narrowing (JSN) and bone erosions. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, is scored from 0 to 4, with 0 indicating no (normal) JSN and 4 indicating complete loss of joint space, bony ankylosis or luxation. JSN scores ranged from 0-168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing. The bone erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints of the feet. Each joint is scored according to the surface area involved from 0 to 5 for hand joints and 0 to 10 for the foot joints, with 0 indicating no erosion and the highest score (5 for the hand and 10 for the foot) indicating extensive loss of bone from more than one half of the articulating bone. Erosion scores ranged from 0 (no erosion) to 280 (high erosion).
    Time Frame Baseline, Week 24; Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-baseline assessment. Missing values due to discontinuation of study, rescue, or missing data were imputed using LE.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 210 159 215
    JSN Week 24
    0.15
    (0.94)
    0.08
    (0.44)
    0.05
    (0.44)
    JSN Week 52
    0.23
    (1.00)
    0.26
    (1.14)
    0.08
    (0.88)
    Bone Erosion Week 24
    0.49
    (1.14)
    0.35
    (0.92)
    0.27
    (0.95)
    Bone Erosion Week 52
    0.80
    (1.80)
    0.55
    (1.48)
    0.33
    (1.21)
    13. Secondary Outcome
    Title Change From Baseline in Duration of Morning Joint Stiffness
    Description Participants reported the duration of their morning joint stiffness (MJS) in hours and minutes. The participants were asked about their duration of morning joint stiffness on the day prior to the study visit to capture actual symptoms, since the participant may have had an atypical morning routine on the day of the study visit. If morning joint stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. A decrease in duration of morning joint stiffness indicated an improvement in the participant's condition.
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 204 159 209
    Median (95% Confidence Interval) [Minutes]
    -40.0
    -55.0
    -60.0
    14. Secondary Outcome
    Title Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS)
    Description Participants rated their tiredness by selecting a number from 0 to 10 that best described their worst tiredness during the last 24 hours, where 0 represents "no tiredness" and 10 represents "as bad as you can imagine".
    Time Frame Baseline, Week 24; Baseline Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 204 159 209
    Week 24
    -2.2
    (2.7)
    -3.0
    (3.1)
    -3.0
    (2.8)
    Week 52
    -2.3
    (2.8)
    -2.9
    (3.1)
    -3.0
    (2.9)
    15. Secondary Outcome
    Title Change From Baseline in Worst Joint Pain Numeric Rating Scale (NRS)
    Description Participants rated their joint pain by selecting a number from 0 to 10 that best described their worst joint pain during the last 24 hours, where 0 represents "no pain" and 10 represents "pain as bad as you can imagine".
    Time Frame Baseline, Week 24; Baseline Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 204 159 209
    Week 24
    -2.8
    (2.5)
    -3.9
    (2.7)
    -3.9
    (2.6)
    Week 52
    -3.0
    (2.8)
    -3.9
    (2.9)
    -4.1
    (2.7)
    16. Secondary Outcome
    Title Change From Baseline in Mental Component Score (MCS) and Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute)
    Description The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (MCS and PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning.
    Time Frame Baseline, Week 24; Baseline Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 202 159 207
    MCS Week 24
    3.4
    (10.8)
    5.9
    (11.7)
    4.6
    (11.6)
    MCS Week 52
    2.4
    (10.9)
    5.8
    (11.9)
    5.0
    (11.5)
    PCS Week 24
    9.4
    (9.2)
    12.5
    (9.1)
    13.2
    (9.6)
    PCS Week 52
    9.4
    (10.1)
    11.6
    (9.6)
    13.3
    (9.8)
    17. Secondary Outcome
    Title Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores
    Description European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. One component consists of a descriptive system of the respondent's health comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1. A higher score indicates better health state.
    Time Frame Baseline, Week 24; Baseline Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 202 159 207
    Index Score (US Algorithm) Week 24
    0.142
    (0.189)
    0.197
    (0.164)
    0.194
    (0.180)
    Index Score (US Algorithm) Week 52
    0.138
    (0.203)
    0.186
    (0.177)
    0.185
    (0.186)
    Index Score (UK Algorithm) Week 24
    0.205
    (0.274)
    0.285
    (0.241)
    0.282
    (0.255)
    Index Score (UK Algorithm) Week 52
    0.197
    (0.294)
    0.271
    (0.258)
    0.268
    (0.266)
    18. Secondary Outcome
    Title Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health)
    Description A second component of the EQ-5D-5L is a self-perceived health score which is assessed using a VAS that ranges from 0 to 100 millimeter (mm), where 0 indicates the worst health you can imagine and 100 indicates the best health you can imagine.
    Time Frame Baseline, Week 24; Baseline Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 202 159 207
    Self-Perceived Health Week 24
    14.5
    (28.3)
    24.1
    (26.0)
    21.4
    (31.4)
    Self-Perceived Health Week 52
    13.6
    (30.1)
    24.5
    (28.7)
    24.5
    (30.6)
    19. Secondary Outcome
    Title Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores
    Description The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a13-item, symptom-specific questionnaire that specifically assesses the participant's self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0 ("Not at all") to 4 ("Very much") for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue.
    Time Frame Baseline, Week 24; Baseline Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 204 159 209
    Week 24
    9.3
    (11.2)
    13.0
    (10.8)
    12.3
    (11.5)
    Week 52
    9.1
    (10.9)
    11.3
    (10.8)
    12.6
    (11.8)
    20. Secondary Outcome
    Title Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
    Description The Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. It contains 6 items covering overall work productivity (health), overall work productivity (symptom), impairment of regular activities (health), and impairment of regular activities (symptom). Scores are calculated as impairment percentages. The WPAI-RA yields four types of scores: Absenteeism (work time missed), Presenteeism (impairment at work), Work productivity loss (overall work impairment), and Activity impairment.
    Time Frame Baseline, Week 24; Baseline Week 52

    Outcome Measure Data

    Analysis Population Description
    mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and an observed value at the time point being summarized.
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX
    Arm/Group Description MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 210 159 215
    Absenteeism Week 24 (n=76, 56, 90)
    -3.6
    (35.5)
    -8.7
    (30.4)
    -7.6
    (26.5)
    Absenteeism Week 52 (n=52, 51, 71)
    -3.0
    (29.2)
    -8.4
    (29.7)
    -7.3
    (21.8)
    Presenteeism Week 24(n=70, 51, 86)
    -19
    (25)
    -26
    (27)
    -32
    (26)
    Presenteeism Week 52 (n=51, 47, 75)
    -26
    (26)
    -27
    (24)
    -33
    (25)
    Work Productivity Loss Week 24 (n=70, 71, 86)
    -17.8
    (30.2)
    -25.6
    (29.1)
    -30.9
    (29.6)
    Work Productivity Loss Week 52 (n=51, 47, 75)
    -24.1
    (30.5)
    -27.6
    (27.3)
    -33.8
    (27.5)
    Activity Impairment Week 24 (n=184, 145, 192)
    -25
    (26)
    -36
    (28)
    -31
    (28)
    Activity Impairment Week 52 (n=141, 131, 172)
    -28
    (27)
    -34
    (27)
    -37
    (27)
    21. Secondary Outcome
    Title Population Pharmacokinetics (PK): Peak Concentration at Steady State (Cmax,ss) of Baricitinib
    Description
    Time Frame Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 24; Week 32; Pre-dose

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug (during study or rescue treatment) with evaluable PK data.
    Arm/Group Title Baricitinib
    Arm/Group Description Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 355
    Geometric Mean (Geometric Coefficient of Variation) [nanomole/Liter (nmol/L)]
    135
    (23.1)
    22. Secondary Outcome
    Title Population PK: Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib
    Description
    Time Frame Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 24; Week 32; Pre-dose

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug (during study or rescue treatment) with evaluable PK data.
    Arm/Group Title Baricitinib
    Arm/Group Description Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
    Measure Participants 355
    Geometric Mean (Geometric Coefficient of Variation) [nanomole/Liter (nmol/L)]
    1280
    (47.2)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description All enrolled participants including those receiving rescue therapy, with events occurring after rescue accounted separately. Rescue therapy occurred at Week 24 or later, if determined to be nonresponders (lack of improvement of at least 20% in both tender joint count and swollen joint count).
    Arm/Group Title Methotrexate Baricitinib Baricitinib + MTX Rescue Period Methotrexate - Follow-up Baricitinib - Follow-up Baricitinib + MTX - Follow-up
    Arm/Group Description Methotrexate (MTX) administered orally once weekly with dose ranging from 10 to 20 milligram (mg) per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly. Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug. No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug. No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug. Includes participants who were rescued to Baricitinib + MTX.
    All Cause Mortality
    Methotrexate Baricitinib Baricitinib + MTX Rescue Period Methotrexate - Follow-up Baricitinib - Follow-up Baricitinib + MTX - Follow-up
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Methotrexate Baricitinib Baricitinib + MTX Rescue Period Methotrexate - Follow-up Baricitinib - Follow-up Baricitinib + MTX - Follow-up
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 20/210 (9.5%) 12/159 (7.5%) 17/215 (7.9%) 1/39 (2.6%) 0/25 (0%) 0/15 (0%) 0/28 (0%)
    Cardiac disorders
    Atrial fibrillation 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Coronary artery disease 0/210 (0%) 0 1/159 (0.6%) 1 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Myocardial infarction 0/210 (0%) 0 1/159 (0.6%) 1 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Myocardial ischaemia 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Eye disorders
    Cataract 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Gastrointestinal disorders
    Chronic gastritis 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Duodenal ulcer 0/210 (0%) 0 1/159 (0.6%) 1 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Enterocolitis 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Gastric ulcer haemorrhage 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Umbilical hernia 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    General disorders
    Drowning 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Fatigue 0/210 (0%) 0 1/159 (0.6%) 1 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Non-cardiac chest pain 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Oedema peripheral 0/210 (0%) 0 1/159 (0.6%) 1 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Pyrexia 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Hepatobiliary disorders
    Cholecystitis 0/210 (0%) 0 1/159 (0.6%) 1 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Infections and infestations
    Acute hepatitis B 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Bronchitis haemophilus 0/210 (0%) 0 1/159 (0.6%) 1 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Campylobacter gastroenteritis 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Cellulitis 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Diverticulitis 0/210 (0%) 0 1/159 (0.6%) 1 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Escherichia sepsis 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Herpes zoster 2/210 (1%) 2 1/159 (0.6%) 1 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Infectious colitis 0/210 (0%) 0 1/159 (0.6%) 1 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Lung infection 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Meningitis bacterial 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Pneumocystis jirovecii pneumonia 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Pneumonia 1/210 (0.5%) 1 1/159 (0.6%) 1 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Pyelonephritis acute 0/210 (0%) 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Sepsis 1/210 (0.5%) 1 1/159 (0.6%) 1 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Urinary tract infection 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Injury, poisoning and procedural complications
    Fall 2/210 (1%) 2 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Femur fracture 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Overdose 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Spinal compression fracture 2/210 (1%) 2 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Tibia fracture 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Toxicity to various agents 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Wrist fracture 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Investigations
    Lymphocyte count decreased 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Musculoskeletal and connective tissue disorders
    Rheumatoid arthritis 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cervix carcinoma 0/210 (0%) 0 1/159 (0.6%) 1 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Gallbladder adenosquamous carcinoma 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Malignant melanoma 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Nervous system disorders
    Cerebral haemorrhage 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Headache 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Migraine 0/210 (0%) 0 1/159 (0.6%) 1 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Syncope 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Reproductive system and breast disorders
    Genital prolapse 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Chronic obstructive pulmonary disease 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Pneumothorax spontaneous 0/210 (0%) 0 0/159 (0%) 0 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Pulmonary embolism 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Pulmonary fibrosis 1/210 (0.5%) 1 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Other (Not Including Serious) Adverse Events
    Methotrexate Baricitinib Baricitinib + MTX Rescue Period Methotrexate - Follow-up Baricitinib - Follow-up Baricitinib + MTX - Follow-up
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 115/210 (54.8%) 81/159 (50.9%) 129/215 (60%) 21/39 (53.8%) 2/25 (8%) 2/15 (13.3%) 0/28 (0%)
    Blood and lymphatic system disorders
    Anaemia 2/210 (1%) 2 2/159 (1.3%) 2 6/215 (2.8%) 6 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Thrombocytosis 0/210 (0%) 0 4/159 (2.5%) 4 3/215 (1.4%) 3 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Cardiac disorders
    Cardiomegaly 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Left ventricular hypertrophy 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Ear and labyrinth disorders
    Ear pruritus 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Endocrine disorders
    Hypothyroidism 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Eye disorders
    Scleritis 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Scleromalacia 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Gastrointestinal disorders
    Constipation 3/210 (1.4%) 3 2/159 (1.3%) 3 7/215 (3.3%) 8 0/39 (0%) 0 0/25 (0%) 0 1/15 (6.7%) 1 0/28 (0%) 0
    Abdominal discomfort 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Large intestine polyp 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Stomatitis 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Abdominal pain upper 6/210 (2.9%) 6 3/159 (1.9%) 4 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Diarrhoea 12/210 (5.7%) 15 3/159 (1.9%) 3 5/215 (2.3%) 6 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Dyspepsia 1/210 (0.5%) 1 3/159 (1.9%) 3 8/215 (3.7%) 9 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Gastrooesophageal reflux disease 1/210 (0.5%) 1 0/159 (0%) 0 5/215 (2.3%) 5 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Nausea 13/210 (6.2%) 16 7/159 (4.4%) 7 20/215 (9.3%) 26 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Vomiting 6/210 (2.9%) 6 5/159 (3.1%) 5 5/215 (2.3%) 8 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    General disorders
    Oedema peripheral 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 1/25 (4%) 1 0/15 (0%) 0 0/28 (0%) 0
    Fatigue 5/210 (2.4%) 5 3/159 (1.9%) 3 8/215 (3.7%) 8 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Pyrexia 4/210 (1.9%) 5 1/159 (0.6%) 1 5/215 (2.3%) 6 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Hepatobiliary disorders
    Hepatic function abnormal 5/210 (2.4%) 5 1/159 (0.6%) 1 8/215 (3.7%) 9 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Infections and infestations
    Hepatitis E 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Herpes zoster 0/210 (0%) 0 3/159 (1.9%) 3 5/215 (2.3%) 5 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Nasopharyngitis 17/210 (8.1%) 20 16/159 (10.1%) 21 21/215 (9.8%) 32 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Pharyngitis 4/210 (1.9%) 6 2/159 (1.3%) 2 7/215 (3.3%) 9 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Upper respiratory tract infection 15/210 (7.1%) 15 12/159 (7.5%) 14 16/215 (7.4%) 19 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Vaginal infection 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/28 (3.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Bronchitis 4/210 (1.9%) 4 5/159 (3.1%) 5 9/215 (4.2%) 10 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Gastroenteritis 4/210 (1.9%) 4 10/159 (6.3%) 10 6/215 (2.8%) 6 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Influenza 4/210 (1.9%) 4 7/159 (4.4%) 7 11/215 (5.1%) 11 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Rhinitis 7/210 (3.3%) 7 1/159 (0.6%) 1 2/215 (0.9%) 3 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Sinusitis 5/210 (2.4%) 5 1/159 (0.6%) 1 7/215 (3.3%) 8 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Urinary tract infection 7/210 (3.3%) 7 6/159 (3.8%) 7 14/215 (6.5%) 16 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Vulvovaginal candidiasis 1/148 (0.7%) 1 0/159 (0%) 0 6/156 (3.8%) 8 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Injury, poisoning and procedural complications
    Ankle fracture 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Arthropod bite 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Joint injury 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Thermal burn 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 2/39 (5.1%) 2 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Wrist fracture 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Investigations
    Alanine aminotransferase increased 5/210 (2.4%) 5 1/159 (0.6%) 1 13/215 (6%) 15 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Aspartate aminotransferase increased 3/210 (1.4%) 3 0/159 (0%) 0 7/215 (3.3%) 8 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Blood creatine phosphokinase increased 2/210 (1%) 2 4/159 (2.5%) 5 10/215 (4.7%) 11 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Blood creatinine increased 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Liver function test abnormal 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Lymphocyte count increased 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Weight increased 3/210 (1.4%) 3 4/159 (2.5%) 4 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Metabolism and nutrition disorders
    Hypercholesterolaemia 3/210 (1.4%) 3 4/159 (2.5%) 4 4/215 (1.9%) 4 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Hyperlipidaemia 1/210 (0.5%) 1 3/159 (1.9%) 3 6/215 (2.8%) 6 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Dyslipidaemia 2/210 (1%) 2 2/159 (1.3%) 2 8/215 (3.7%) 8 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 1/25 (4%) 1 0/15 (0%) 0 0/28 (0%) 0
    Back pain 5/210 (2.4%) 5 3/159 (1.9%) 3 9/215 (4.2%) 10 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Muscle spasms 1/210 (0.5%) 2 2/159 (1.3%) 2 7/215 (3.3%) 7 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Rheumatoid arthritis 7/210 (3.3%) 7 3/159 (1.9%) 3 1/215 (0.5%) 1 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Nervous system disorders
    Dizziness 5/210 (2.4%) 6 1/159 (0.6%) 1 3/215 (1.4%) 4 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Headache 3/210 (1.4%) 3 5/159 (3.1%) 6 6/215 (2.8%) 7 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Sciatica 0/210 (0%) 0 4/159 (2.5%) 4 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/28 (3.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Psychiatric disorders
    Depression 4/210 (1.9%) 4 6/159 (3.8%) 6 2/215 (0.9%) 2 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Renal and urinary disorders
    Polyuria 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Catarrh 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Cough 13/210 (6.2%) 14 5/159 (3.1%) 7 6/215 (2.8%) 6 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Sinus congestion 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Skin and subcutaneous tissue disorders
    Eczema asteatotic 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 1/15 (6.7%) 1 0/28 (0%) 0
    Miliaria 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 1/15 (6.7%) 1 0/28 (0%) 0
    Seborrhoeic dermatitis 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 0/39 (0%) 0 0/25 (0%) 0 1/15 (6.7%) 1 0/28 (0%) 0
    Dermatitis 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Petechiae 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Pruritus 0/210 (0%) 0 0/159 (0%) 0 0/215 (0%) 0 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Alopecia 5/210 (2.4%) 5 1/159 (0.6%) 1 6/215 (2.8%) 6 0/39 (0%) 0 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0
    Vascular disorders
    Hypertension 7/210 (3.3%) 7 2/159 (1.3%) 2 13/215 (6%) 13 1/39 (2.6%) 1 0/25 (0%) 0 0/15 (0%) 0 0/28 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01711359
    Other Study ID Numbers:
    • 14062
    • I4V-MC-JADZ
    First Posted:
    Oct 22, 2012
    Last Update Posted:
    Sep 19, 2019
    Last Verified:
    Sep 1, 2019