Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   41470   clinical trials with a EudraCT protocol, of which   6815   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    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

    Summary
    EudraCT number
    2012-002324-32
    Trial protocol
    BE   SE   DE   GB   PT   AT   IT   GR  
    Global end of trial date
    26 Aug 2015

    Results information
    Results version number
    v2(current)
    This version publication date
    07 Mar 2018
    First version publication date
    26 Mar 2017
    Other versions
    v1
    Version creation reason
    • Correction of full data set
    Revision Required

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    14062
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01711359
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Trial Alias: I4V-MC-JADZ , Trial Number: 14062
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon - Fri 9 AM - 5 PM EST , Eli Lilly and Company, 1 877-CTLilly,
    Scientific contact
    Available Mon - Fri 9 AM - 5 PM EST , Eli Lilly and Company, 1 877-285-4559,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Aug 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Aug 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    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).
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    09 Nov 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 103
    Country: Number of subjects enrolled
    Austria: 3
    Country: Number of subjects enrolled
    Belgium: 27
    Country: Number of subjects enrolled
    Brazil: 20
    Country: Number of subjects enrolled
    Canada: 17
    Country: Number of subjects enrolled
    Germany: 14
    Country: Number of subjects enrolled
    Greece: 1
    Country: Number of subjects enrolled
    India: 47
    Country: Number of subjects enrolled
    Italy: 14
    Country: Number of subjects enrolled
    Japan: 104
    Country: Number of subjects enrolled
    Mexico: 46
    Country: Number of subjects enrolled
    Portugal: 3
    Country: Number of subjects enrolled
    Russian Federation: 36
    Country: Number of subjects enrolled
    South Africa: 20
    Country: Number of subjects enrolled
    Korea, Republic of: 7
    Country: Number of subjects enrolled
    Sweden: 4
    Country: Number of subjects enrolled
    United Kingdom: 14
    Country: Number of subjects enrolled
    United States: 104
    Worldwide total number of subjects
    584
    EEA total number of subjects
    80
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    501
    From 65 to 84 years
    83
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    All started participants received at least one dose of study drug.

    Pre-assignment
    Screening details
    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.

    Period 1
    Period 1 title
    Treatment Period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Methotrexate
    Arm 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. All started participants received at least one dose of study drug.
    Arm type
    Active comparator

    Investigational medicinal product name
    Methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    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.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants 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.

    Investigational medicinal product name
    Folic Acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Folic acid administered orally every day.

    Arm title
    Baricitinib
    Arm 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.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Baricitinib 4 mg administered orally once daily through Week 52. Participants will receive MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    Other name
    LY3009104
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Baricitinib 4 mg administered orally once daily through Week 52. Participants will receive MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.

    Investigational medicinal product name
    Folic Acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Folic acid administered orally every day.

    Arm title
    Baricitinib + MTX
    Arm description
    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.
    Arm type
    Experimental

    Investigational medicinal product name
    Methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Baricitinib 4 milligram (mg) administered orally once daily through Week 52. Participants will receive methotrexate (MTX) orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    Other name
    LY3009104
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Baricitinib 4 milligram (mg) administered orally once daily through Week 52. Participants will receive methotrexate (MTX) orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.

    Investigational medicinal product name
    Folic Acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Folic acid administered orally every day.

    Number of subjects in period 1
    Methotrexate Baricitinib Baricitinib + MTX
    Started
    210
    159
    215
    Rescued
    26 [1]
    7 [2]
    6 [3]
    Completed
    161
    136
    173
    Not completed
    49
    23
    42
         Physician decision
    4
    3
    2
         Lack of efficacy
    13
    2
    2
         Adverse event, serious fatal
    3
    -
    -
         Entry Criteria Not Met
    1
    -
    -
         Adverse event, non-fatal
    8
    10
    24
         Consent withdrawn by subject
    18
    7
    13
         Sponsor Decision
    1
    -
    -
         Lost to follow-up
    1
    1
    1
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Participants who were nonresponders based on tender/swollen joint count were entered into the rescue milestone calculation.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Participants who were nonresponders based on tender/swollen joint count were entered into the rescue milestone calculation.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Participants who were nonresponders based on tender/swollen joint count were entered into the rescue milestone calculation.
    Period 2
    Period 2 title
    Follow Up
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Methotrexate - Follow-up
    Arm description
    No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Baricitinib - Follow-up
    Arm description
    No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Baricitinib + MTX - Follow-up
    Arm description
    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.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2 [4]
    Methotrexate - Follow-up Baricitinib - Follow-up Baricitinib + MTX - Follow-up
    Started
    25
    15
    28
    Completed
    25
    15
    28
    Notes
    [4] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Includes participants who entered the post-treatment follow-up period

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Methotrexate
    Reporting 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. All started participants received at least one dose of study drug.

    Reporting group title
    Baricitinib
    Reporting 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.

    Reporting group title
    Baricitinib + MTX
    Reporting group description
    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.

    Reporting group values
    Methotrexate Baricitinib Baricitinib + MTX Total
    Number of subjects
    210 159 215 584
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    50.5 ± 13.4 50.9 ± 13 48.5 ± 13.5 -
    Gender, Male/Female
    Units: participants
        Female
    148 121 156 425
        Male
    62 38 59 159
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    11 10 20 41
        Asian
    60 44 61 165
        Native Hawaiian or Other Pacific Islander
    0 0 0 0
        Black or African American
    10 5 10 25
        White
    128 98 123 349
        More than one race
    1 2 1 4
        Unknown or Not Reported
    0 0 0 0
    Region of Enrollment
    Units: Subjects
        Argentina
    41 29 33 103
        Austria
    1 1 1 3
        Belgium
    6 10 11 27
        Brazil
    8 3 9 20
        Canada
    5 5 7 17
        Germany
    5 5 4 14
        Greece
    0 0 1 1
        India
    18 12 17 47
        Italy
    8 2 4 14
        Japan
    36 29 39 104
        Mexico
    12 14 20 46
        Portugal
    1 0 2 3
        Russian Federation
    11 13 12 36
        South Africa
    7 4 9 20
        Korea, Republic of
    4 1 2 7
        Sweden
    3 0 1 4
        United Kingdom
    7 3 4 14
        United States
    37 28 39 104
    Duration of Rheumatoid Arthritis
    Units: years
        median (inter-quartile range (Q1-Q3))
    0.2 (0.1 to 0.6) 0.2 (0.1 to 1.1) 0.2 (0.1 to 1) -
    Tender Joint Count of 68 evaluable joints
    Units: number of joints
        arithmetic mean (standard deviation)
    26.5 ± 14.8 26.4 ± 14.1 27.7 ± 14.5 -
    Swollen Joint Count of 66 evaluable joints
    Units: number of joints
        arithmetic mean (standard deviation)
    16.4 ± 10.6 16.1 ± 9.2 16.3 ± 9.5 -
    High sensitivity C-reactive protein
    Units: milligrams per liter (mg/L)
        arithmetic mean (standard deviation)
    22.34 ± 21.78 23.75 ± 26.24 24.27 ± 29.42 -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Methotrexate
    Reporting 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. All started participants received at least one dose of study drug.

    Reporting group title
    Baricitinib
    Reporting 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.

    Reporting group title
    Baricitinib + MTX
    Reporting group description
    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.
    Reporting group title
    Methotrexate - Follow-up
    Reporting group description
    No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.

    Reporting group title
    Baricitinib - Follow-up
    Reporting group description
    No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.

    Reporting group title
    Baricitinib + MTX - Follow-up
    Reporting group description
    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.

    Subject analysis set title
    Baricitinib
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All randomized participants who received at least 1 dose of study drug with evaluable PK data.

    Primary: Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)

    Close Top of page
    End point title
    Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)
    End point 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), participant's assessment of pain, and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders. 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).
    End point type
    Primary
    End point timeframe
    Week 24
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    210
    159
    215
    Units: Percent of participants
    number (not applicable)
        Week 24
    61.9
    76.7
    78.1
    Statistical analysis title
    Statistical Analysis for ACR20
    Comparison groups
    Baricitinib v Methotrexate
    Number of subjects included in analysis
    369
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [1]
    Method
    Parameter type
    Newcombe-Wilson method
    Point estimate
    14.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.5
         upper limit
    24.1
    Notes
    [1] - Noninferiority is concluded if the lower bound of the 95% CI for the difference in response rate is >-12%

    Secondary: Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score

    Close Top of page
    End point title
    Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
    End point 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. 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).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    210
    159
    215
    Units: units on a scale
        arithmetic mean (standard deviation)
    -0.73 ± 0.71
    -1.01 ± 0.74
    -0.92 ± 0.74
    No statistical analyses for this end point

    Secondary: Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP)

    Close Top of page
    End point title
    Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP)
    End point 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. 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    210
    159
    215
    Units: units on a scale
        arithmetic mean (standard deviation)
    -2.01 ± 1.51
    -2.74 ± 1.39
    -2.82 ± 1.58
    No statistical analyses for this end point

    Secondary: Change from Baseline in the modified Total Sharp Score (mTSS)

    Close Top of page
    End point title
    Change from Baseline in the modified Total Sharp Score (mTSS)
    End point description
    X-rays of the hands/wrists and feet were scored for structural progression as measured using the mTSS. 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. 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).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    191
    152
    198
    Units: units on a scale
        arithmetic mean (standard deviation)
    0.64 ± 1.81
    0.43 ± 1.18
    0.32 ± 1.14
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Achieved a Simplified Disease Activity Index (SDAI) Score ≤3.3

    Close Top of page
    End point title
    Percentage of Participants Who Achieved a Simplified Disease Activity Index (SDAI) Score ≤3.3
    End point 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), Participant'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. 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.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    210
    159
    215
    Units: percentage of participants
        number (not applicable)
    10.5
    22
    22.8
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response

    Close Top of page
    End point title
    Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
    End point 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 using visual analog scale (VAS), HAQ-DI, participant's assessment of pain, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders. 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.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24, Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    210
    159
    215
    Units: Percent of participants
    number (not applicable)
        Week 12
    32.9
    54.7
    60
        Week 24
    43.3
    59.7
    63.3
        Week 52
    37.6
    57.2
    61.9
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response

    Close Top of page
    End point title
    Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
    End point description
    ACR70 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR70 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 using visual analog scale (VAS), HAQ-DI, participant's assessment of pain, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders. 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.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24, Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    210
    159
    215
    Units: Percent of participants
    number (not applicable)
        Week 12
    15.7
    30.8
    33.5
        Week 24
    21.4
    42.1
    39.5
        Week 52
    25.2
    42.1
    46
    No statistical analyses for this end point

    Secondary: Change from Baseline in Clinical Disease Activity Index (CDAI) Score

    Close Top of page
    End point title
    Change from Baseline in Clinical Disease Activity Index (CDAI) Score
    End point 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, SJC28, Patient's Global Assessment of Disease Activity using visual analog scale (cm), and Physician's Global Assessment of Disease Activity using visual analog scale (cm). The CDAI is calculated by summing the values of the 4 components. Lower scores indicated less disease activity. 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).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24; Baseline, Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    200
    157
    208
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 24
    -22.12 ± 16.12
    -28.2 ± 13.96
    -29.86 ± 14.05
        Week 52
    -21.95 ± 18.07
    -28.94 ± 14.58
    -30.72 ± 14.87
    No statistical analyses for this end point

    Secondary: Change From Baseline in Disease Activity Score 28–Erythrocyte Sedimentation Rate (DAS28-ESR)

    Close Top of page
    End point title
    Change From Baseline in Disease Activity Score 28–Erythrocyte Sedimentation Rate (DAS28-ESR)
    End point 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. 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24; Baseline, Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    203
    159
    209
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 24
    -2.2 ± 1.53
    -2.76 ± 1.45
    -3.06 ± 1.46
        Week 52
    -2.32 ± 1.77
    -2.84 ± 1.57
    -3.22 ± 1.48
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission

    Close Top of page
    End point title
    Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission
    End point 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. 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.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24, Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    210
    159
    215
    Units: percentage of participants
    number (not applicable)
        Week 12
    5.7
    13.8
    14.4
        Week 24
    8.6
    18.9
    16.3
        Week 52
    11.4
    17
    20.9
    No statistical analyses for this end point

    Secondary: Change From Baseline in Joint Space Narrowing and Bone Erosion Scores

    Close Top of page
    End point title
    Change From Baseline in Joint Space Narrowing and Bone Erosion Scores
    End point 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). Analysis Population Description: mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24; Baseline, Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    191
    152
    198
    Units: units on a scale
    arithmetic mean (standard deviation)
        JSN Week 24
    0.15 ± 0.94
    0.08 ± 0.44
    0.05 ± 0.44
        JSN Week 52
    0.23 ± 1
    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
    0.8 ± 1.8
    0.55 ± 1.48
    0.33 ± 1.21
    No statistical analyses for this end point

    Secondary: Change From Baseline in Duration of Morning Joint Stiffness

    Close Top of page
    End point title
    Change From Baseline in Duration of Morning Joint Stiffness
    End point 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. 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    204
    159
    209
    Units: Minutes
        median (confidence interval 95%)
    -40 (-55 to -30)
    -55 (-60 to -40)
    -60 (-80 to -50)
    No statistical analyses for this end point

    Secondary: Change from Baseline in Worst Tiredness Numeric Rating Scale (NRS)

    Close Top of page
    End point title
    Change from Baseline in Worst Tiredness Numeric Rating Scale (NRS)
    End point 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". 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24; Baseline Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    204
    159
    209
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 24
    -2.2 ± 2.7
    -3 ± 3.1
    -3 ± 2.8
        Week 52
    -2.3 ± 2.8
    -2.9 ± 3.1
    -3 ± 2.9
    No statistical analyses for this end point

    Secondary: Change From Baseline in Worst Joint Pain Numeric Rating Scale (NRS)

    Close Top of page
    End point title
    Change From Baseline in Worst Joint Pain Numeric Rating Scale (NRS)
    End point 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". 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24; Baseline Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    204
    159
    209
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 24
    -2.8 ± 2.5
    -3.9 ± 2.7
    -3.9 ± 2.6
        Week 52
    -3 ± 2.8
    -3.9 ± 2.9
    -4.1 ± 2.7
    No statistical analyses for this end point

    Secondary: 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)

    Close Top of page
    End point 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)
    End point 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. 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24; Baseline Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    202
    159
    207
    Units: units on a scale
    arithmetic mean (standard deviation)
        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 ± 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
    No statistical analyses for this end point

    Secondary: Change From Baseline in European Quality of Life–5 Dimensions–5 Level (EQ-5D-5L) scores

    Close Top of page
    End point title
    Change From Baseline in European Quality of Life–5 Dimensions–5 Level (EQ-5D-5L) scores
    End point description
    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. 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24; Baseline Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    202
    159
    207
    Units: units on a scale
    arithmetic mean (standard deviation)
        Index Score (US Algorithm) Week 24
    0.142 ± 0.189
    0.197 ± 0.164
    0.194 ± 0.18
        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
    No statistical analyses for this end point

    Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) Scores

    Close Top of page
    End point title
    Change From Baseline in Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) Scores
    End point description
    The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a 13-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. 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24; Baseline Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    204
    159
    209
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 24
    9.3 ± 11.2
    13 ± 10.8
    12.3 ± 11.5
        Week 52
    9.1 ± 10.9
    11.3 ± 10.8
    12.6 ± 11.8
    No statistical analyses for this end point

    Secondary: Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores

    Close Top of page
    End point title
    Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
    End point 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. 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24; Baseline Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    210
    159
    215
    Units: Percentage of Impairment
    arithmetic mean (standard deviation)
        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 ± 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
    No statistical analyses for this end point

    Secondary: Population Pharmacokinetics (PK): Peak Concentration at Steady State (Cmax,ss) of Baricitinib

    Close Top of page
    End point title
    Population Pharmacokinetics (PK): Peak Concentration at Steady State (Cmax,ss) of Baricitinib
    End point description
    Analysis population description: all randomized participants who received at least 1 dose of study drug with evaluable PK data.
    End point type
    Secondary
    End point timeframe
    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
    End point values
    Baricitinib
    Number of subjects analysed
    355
    Units: nanomole/Liter (nmol/L)
        geometric mean (geometric coefficient of variation)
    135 ± 23.1
    No statistical analyses for this end point

    Secondary: Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib

    Close Top of page
    End point title
    Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib
    End point description
    Analysis population description: all randomized participants who received at least 1 dose of study drug with evaluable PK data.
    End point type
    Secondary
    End point timeframe
    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
    End point values
    Baricitinib
    Number of subjects analysed
    355
    Units: nanomole/Liter (nmol/L)
        geometric mean (geometric coefficient of variation)
    1280 ± 47.2
    No statistical analyses for this end point

    Secondary: Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health)

    Close Top of page
    End point title
    Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health)
    End point 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. 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24; Baseline Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    202
    159
    207
    Units: millimeter(s)
    arithmetic mean (standard deviation)
        Self-Perceived Health (Week 24)
    14.5 ± 28.3
    24.1 ± 26
    21.4 ± 31.4
        Self-Perceived Health (Week 52)
    13.6 ± 30.1
    24.5 ± 28.7
    24.5 ± 30.6
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)

    Close Top of page
    End point title
    Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)
    End point 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 discontinue study or drug or are rescued before analysis time point are deemed non-responders. 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).
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    Methotrexate Baricitinib Baricitinib + MTX
    Number of subjects analysed
    210
    159
    215
    Units: Percent of participants
        number (not applicable)
    55.7
    73
    72.6
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    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.
    Adverse event reporting additional description
    I4V-MC-JADZ
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Baricitinib
    Reporting 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.

    Reporting group title
    Baricitinib + MTX
    Reporting group description
    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.

    Reporting group title
    Methotrexate
    Reporting 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.

    Reporting group title
    Rescue
    Reporting group description
    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.

    Reporting group title
    Baricitinib - Follow-up
    Reporting group description
    No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.

    Reporting group title
    Methotrexate - Follow-up
    Reporting group description
    No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.

    Reporting group title
    Baricitinib + MTX - Follow-up
    Reporting group description
    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.

    Serious adverse events
    Baricitinib Baricitinib + MTX Methotrexate Rescue Baricitinib - Follow-up Methotrexate - Follow-up Baricitinib + MTX - Follow-up
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 159 (7.55%)
    17 / 215 (7.91%)
    20 / 210 (9.52%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    cervix carcinoma
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed [1]
    1 / 121 (0.83%)
    0 / 156 (0.00%)
    0 / 148 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gallbladder adenosquamous carcinoma
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    malignant melanoma
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    drowning
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    fatigue
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    non-cardiac chest pain
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    oedema peripheral
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pyrexia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    genital prolapse
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    fall
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    2 / 210 (0.95%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    femur fracture
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    overdose
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    spinal compression fracture
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    2 / 210 (0.95%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    tibia fracture
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    toxicity to various agents
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    wrist fracture
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    lymphocyte count decreased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    atrial fibrillation
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    coronary artery disease
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    myocardial infarction
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    myocardial ischaemia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    asthma
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumothorax spontaneous
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pulmonary embolism
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pulmonary fibrosis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    cerebral haemorrhage
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    headache
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    migraine
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    syncope
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    cataract
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    chronic gastritis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    duodenal ulcer
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    enterocolitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastric ulcer haemorrhage
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    umbilical hernia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    acute kidney injury
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    cholecystitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    rheumatoid arthritis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    acute hepatitis b
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    bronchitis haemophilus
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    campylobacter gastroenteritis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cellulitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    diverticulitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    escherichia sepsis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    herpes zoster
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 215 (0.00%)
    2 / 210 (0.95%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    infectious colitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    lung infection
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    meningitis bacterial
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumocystis jirovecii pneumonia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 215 (0.47%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pyelonephritis acute
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 215 (0.47%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    sepsis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    Baricitinib Baricitinib + MTX Methotrexate Rescue Baricitinib - Follow-up Methotrexate - Follow-up Baricitinib + MTX - Follow-up
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    81 / 159 (50.94%)
    129 / 215 (60.00%)
    115 / 210 (54.76%)
    21 / 39 (53.85%)
    2 / 15 (13.33%)
    2 / 25 (8.00%)
    0 / 28 (0.00%)
    Vascular disorders
    hypertension
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    2 / 159 (1.26%)
    13 / 215 (6.05%)
    7 / 210 (3.33%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    13
    7
    1
    0
    0
    0
    Pregnancy, puerperium and perinatal conditions
    pregnancy
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed [2]
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 28 (3.57%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    fatigue
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    3 / 159 (1.89%)
    8 / 215 (3.72%)
    5 / 210 (2.38%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    3
    8
    5
    0
    0
    0
    0
    oedema peripheral
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    1 / 25 (4.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    pyrexia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    5 / 215 (2.33%)
    4 / 210 (1.90%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    6
    5
    0
    0
    0
    0
    Psychiatric disorders
    depression
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    6 / 159 (3.77%)
    2 / 215 (0.93%)
    4 / 210 (1.90%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    6
    2
    4
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    ankle fracture
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    arthropod bite
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    joint injury
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    thermal burn
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    2 / 39 (5.13%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    wrist fracture
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    13 / 215 (6.05%)
    5 / 210 (2.38%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    15
    5
    1
    0
    0
    0
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    7 / 215 (3.26%)
    3 / 210 (1.43%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    8
    3
    1
    0
    0
    0
    blood creatine phosphokinase increased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    4 / 159 (2.52%)
    10 / 215 (4.65%)
    2 / 210 (0.95%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    5
    11
    2
    1
    0
    0
    0
    blood creatinine increased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    liver function test abnormal
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    lymphocyte count increased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    weight increased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    4 / 159 (2.52%)
    1 / 215 (0.47%)
    3 / 210 (1.43%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    4
    1
    3
    0
    0
    0
    0
    Cardiac disorders
    cardiomegaly
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    left ventricular hypertrophy
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    2 / 159 (1.26%)
    6 / 215 (2.79%)
    2 / 210 (0.95%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    6
    2
    0
    0
    0
    0
    thrombocytosis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    4 / 159 (2.52%)
    3 / 215 (1.40%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    4
    3
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    catarrh
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    cough
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    5 / 159 (3.14%)
    6 / 215 (2.79%)
    13 / 210 (6.19%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    7
    6
    14
    1
    0
    0
    0
    sinus congestion
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Nervous system disorders
    dizziness
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    3 / 215 (1.40%)
    5 / 210 (2.38%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    4
    6
    0
    0
    0
    0
    headache
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    5 / 159 (3.14%)
    6 / 215 (2.79%)
    3 / 210 (1.43%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    6
    7
    3
    0
    0
    0
    0
    sciatica
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    4 / 159 (2.52%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    0
    0
    Eye disorders
    scleritis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    scleromalacia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Ear and labyrinth disorders
    ear pruritus
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Gastrointestinal disorders
    abdominal discomfort
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    abdominal pain upper
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    3 / 159 (1.89%)
    1 / 215 (0.47%)
    6 / 210 (2.86%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    4
    1
    6
    0
    0
    0
    0
    constipation
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    2 / 159 (1.26%)
    7 / 215 (3.26%)
    3 / 210 (1.43%)
    0 / 39 (0.00%)
    1 / 15 (6.67%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    3
    8
    3
    0
    1
    0
    0
    diarrhoea
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    3 / 159 (1.89%)
    5 / 215 (2.33%)
    12 / 210 (5.71%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    3
    6
    15
    0
    0
    0
    0
    dyspepsia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    3 / 159 (1.89%)
    8 / 215 (3.72%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    3
    9
    1
    0
    0
    0
    0
    gastrooesophageal reflux disease
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    5 / 215 (2.33%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    5
    1
    0
    0
    0
    0
    large intestine polyp
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    nausea
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    7 / 159 (4.40%)
    20 / 215 (9.30%)
    13 / 210 (6.19%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    7
    26
    16
    0
    0
    0
    0
    stomatitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    vomiting
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    5 / 159 (3.14%)
    5 / 215 (2.33%)
    6 / 210 (2.86%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    5
    8
    6
    0
    0
    0
    0
    Renal and urinary disorders
    polyuria
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Hepatobiliary disorders
    hepatic function abnormal
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    8 / 215 (3.72%)
    5 / 210 (2.38%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    9
    5
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    alopecia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    6 / 215 (2.79%)
    5 / 210 (2.38%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    6
    5
    0
    0
    0
    0
    dermatitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    eczema asteatotic
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    1 / 15 (6.67%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    miliaria
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    1 / 15 (6.67%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    petechiae
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    pruritus
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    purpura
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    seborrhoeic dermatitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    1 / 15 (6.67%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    1 / 25 (4.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    back pain
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    3 / 159 (1.89%)
    9 / 215 (4.19%)
    5 / 210 (2.38%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    3
    10
    5
    1
    0
    0
    0
    muscle spasms
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    2 / 159 (1.26%)
    7 / 215 (3.26%)
    1 / 210 (0.48%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    7
    2
    0
    0
    0
    0
    rheumatoid arthritis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    3 / 159 (1.89%)
    1 / 215 (0.47%)
    7 / 210 (3.33%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    3
    1
    7
    0
    0
    0
    0
    Endocrine disorders
    hypothyroidism
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Metabolism and nutrition disorders
    dyslipidaemia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    2 / 159 (1.26%)
    8 / 215 (3.72%)
    2 / 210 (0.95%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    8
    2
    0
    0
    0
    0
    hypercholesterolaemia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    4 / 159 (2.52%)
    4 / 215 (1.86%)
    3 / 210 (1.43%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    4
    4
    3
    1
    0
    0
    0
    hyperlipidaemia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    3 / 159 (1.89%)
    6 / 215 (2.79%)
    1 / 210 (0.48%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    3
    6
    1
    1
    0
    0
    0
    Infections and infestations
    bronchitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    5 / 159 (3.14%)
    9 / 215 (4.19%)
    4 / 210 (1.90%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    5
    10
    4
    0
    0
    0
    0
    gastroenteritis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    10 / 159 (6.29%)
    6 / 215 (2.79%)
    4 / 210 (1.90%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    10
    6
    4
    0
    0
    0
    0
    hepatitis e
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    herpes zoster
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    3 / 159 (1.89%)
    5 / 215 (2.33%)
    0 / 210 (0.00%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    3
    5
    0
    1
    0
    0
    0
    influenza
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    7 / 159 (4.40%)
    11 / 215 (5.12%)
    4 / 210 (1.90%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    7
    11
    4
    0
    0
    0
    0
    nasopharyngitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    16 / 159 (10.06%)
    21 / 215 (9.77%)
    17 / 210 (8.10%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    21
    32
    20
    1
    0
    0
    0
    pharyngitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    2 / 159 (1.26%)
    7 / 215 (3.26%)
    4 / 210 (1.90%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    9
    6
    1
    0
    0
    0
    rhinitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    2 / 215 (0.93%)
    7 / 210 (3.33%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    3
    7
    0
    0
    0
    0
    sinusitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 159 (0.63%)
    7 / 215 (3.26%)
    5 / 210 (2.38%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    8
    5
    0
    0
    0
    0
    upper respiratory tract infection
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    12 / 159 (7.55%)
    16 / 215 (7.44%)
    15 / 210 (7.14%)
    1 / 39 (2.56%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    14
    19
    15
    1
    0
    0
    0
    urinary tract infection
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    6 / 159 (3.77%)
    14 / 215 (6.51%)
    7 / 210 (3.33%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    7
    16
    7
    0
    0
    0
    0
    vaginal infection
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed [3]
    0 / 159 (0.00%)
    0 / 215 (0.00%)
    0 / 210 (0.00%)
    1 / 28 (3.57%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    vulvovaginal candidiasis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed [4]
    0 / 121 (0.00%)
    6 / 156 (3.85%)
    1 / 148 (0.68%)
    0 / 39 (0.00%)
    0 / 15 (0.00%)
    0 / 25 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    8
    1
    0
    0
    0
    0
    Notes
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA