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    Clinical Trial Results:
    A Phase 3, Multicenter Study to Evaluate the Long-Term Safety and Efficacy of Baricitinib in Patients with Rheumatoid Arthritis

    Summary
    EudraCT number
    2012-003686-17
    Trial protocol
    IT   SK   CZ   BE   PL   SE   GB   HU   AT   DK   DE   PT   NL   ES   LV   LT   GR   SI   HR   FR  
    Global end of trial date
    12 Nov 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    27 Nov 2021
    First version publication date
    27 Nov 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    I4V-MC-JADY
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01885078
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Trial Number: 14060
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 877 CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 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
    12 Nov 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Nov 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to evaluate the long-term safety and tolerability of baricitinib.
    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
    Participants may continue to receive the background non-investigational, open-label conventional disease-modifying antirheumatic drugs (cDMARD), nonsteroidal anti-inflammatory drug (NSAID), corticosteroid, and other analgesic therapies they were receiving at completion of the originating study.
    Evidence for comparator
    -
    Actual start date of recruitment
    27 Jun 2013
    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
    Korea, Republic of: 72
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    Poland: 156
    Country: Number of subjects enrolled
    Portugal: 11
    Country: Number of subjects enrolled
    Slovakia: 27
    Country: Number of subjects enrolled
    Slovenia: 5
    Country: Number of subjects enrolled
    Spain: 86
    Country: Number of subjects enrolled
    Sweden: 3
    Country: Number of subjects enrolled
    United Kingdom: 26
    Country: Number of subjects enrolled
    Croatia: 9
    Country: Number of subjects enrolled
    Austria: 17
    Country: Number of subjects enrolled
    Belgium: 41
    Country: Number of subjects enrolled
    Czechia: 56
    Country: Number of subjects enrolled
    Denmark: 5
    Country: Number of subjects enrolled
    France: 36
    Country: Number of subjects enrolled
    Germany: 36
    Country: Number of subjects enrolled
    Greece: 8
    Country: Number of subjects enrolled
    Hungary: 60
    Country: Number of subjects enrolled
    Italy: 27
    Country: Number of subjects enrolled
    Latvia: 8
    Country: Number of subjects enrolled
    Lithuania: 21
    Country: Number of subjects enrolled
    United States: 488
    Country: Number of subjects enrolled
    Canada: 47
    Country: Number of subjects enrolled
    Argentina: 430
    Country: Number of subjects enrolled
    Australia: 32
    Country: Number of subjects enrolled
    Brazil: 30
    Country: Number of subjects enrolled
    India: 71
    Country: Number of subjects enrolled
    Israel: 27
    Country: Number of subjects enrolled
    China: 208
    Country: Number of subjects enrolled
    Japan: 328
    Country: Number of subjects enrolled
    Mexico: 214
    Country: Number of subjects enrolled
    Romania: 21
    Country: Number of subjects enrolled
    Russian Federation: 122
    Country: Number of subjects enrolled
    South Africa: 56
    Country: Number of subjects enrolled
    Taiwan: 81
    Country: Number of subjects enrolled
    Switzerland: 7
    Country: Number of subjects enrolled
    Turkey: 3
    Worldwide total number of subjects
    2876
    EEA total number of subjects
    634
    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)
    2358
    From 65 to 84 years
    517
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    The modified intent to treat (mITT) analysis set includes all enrolled participants who received at least one dose of study drug.

    Pre-assignment
    Screening details
    Participants who completed an originating study: I4V-MC-JADZ (NCT01711359), I4V-MC-JADV (NCT017103580, I4V-MC-JADX (NCT01721057), I4V-MC-JADW (NCT01721044), I4V-MC-JADA (NCT01185353), or I4V-MC-JAGS (NCT02265705) were eligible for enrollment into study JADY.

    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
    JADZ 4 mg Baricitinib
    Arm description
    4 mg Baricitinib administered orally once daily.
    Arm type
    Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    LY3009104
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    4 mg Baricitinib administered orally once daily.

    Arm title
    JADV 4 mg Baricitinib
    Arm description
    4 mg Baricitinib administered orally once daily.
    Arm type
    Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    LY3009104
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    4 mg Baricitinib administered orally once daily.

    Arm title
    JADX 2 mg Baricitinib
    Arm description
    2 mg Baricitinib administered orally once daily
    Arm type
    Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    LY3009104
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    2 mg Baricitinib administered orally once daily.

    Arm title
    JADX 4 mg Baricitinib
    Arm description
    4 mg Baricitinib administered orally once daily.
    Arm type
    Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    LY3009104
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    4 mg Baricitinib administered orally once daily.

    Arm title
    JADW 2 mg Baricitinib
    Arm description
    2 mg Baricitinib administered orally once daily.
    Arm type
    Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    LY3009104
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    2 mg Baricitinib administered orally once daily.

    Arm title
    JADW 4 mg Baricitinib
    Arm description
    4 mg Baricitinib administered orally once daily.
    Arm type
    Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    LY3009104
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    4 mg Baricitinib administered orally once daily.

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    LY3009104
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    4 mg Baricitinib administered orally once daily.

    Arm title
    JAGS 4 mg Baricitinib
    Arm description
    4 mg Baricitinib administered orally once daily.
    Arm type
    Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    LY3009104
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    4 mg Baricitinib administered orally once daily.

    Arm title
    JADA 4 mg Baricitinib
    Arm description
    4 mg Baricitinib administered orally once daily.
    Arm type
    Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    LY3009104
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    4 mg Baricitinib administered orally once daily.

    Number of subjects in period 1
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Started
    451
    1090
    180
    403
    117
    331
    221
    83
    Received at Least One Dose of Study Drug
    451
    1090
    180
    403
    117
    331
    221
    83
    Completed
    19
    64
    49
    120
    27
    81
    0
    55
    Not completed
    432
    1026
    131
    283
    90
    250
    221
    28
         Protocol deviation
    3
    5
    -
    3
    1
    6
    -
    -
         Death
    13
    33
    5
    9
    2
    10
    3
    2
         Physician decision
    19
    21
    5
    12
    9
    24
    4
    3
         Unknown
    -
    -
    -
    1
    -
    -
    -
    -
         Lack of efficacy
    12
    33
    10
    23
    24
    58
    9
    5
         Adverse event, non-fatal
    52
    136
    30
    73
    17
    72
    24
    5
         Consent withdrawn by subject
    72
    131
    25
    63
    15
    34
    17
    10
         Sponsor decision
    245
    648
    49
    90
    20
    38
    162
    3
         Lost to follow-up
    16
    19
    7
    9
    2
    8
    2
    -
    Period 2
    Period 2 title
    Step-down
    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
    No

    Arm title
    2 mg Baricitinib Step-down
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    LY3009104
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    2 mg Baricitinib administered orally once daily in the Step-down period.

    Arm title
    4 mg Baricitinib Step-down
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    LY3009104
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    4 mg Baricitinib administered orally once daily in the Step-down period.

    Number of subjects in period 2
    2 mg Baricitinib Step-down 4 mg Baricitinib Step-down
    Started
    592
    594
    Completed
    523
    533
    Not completed
    69
    61
         Protocol deviation
    1
    1
         Death
    4
    3
         Physician decision
    7
    2
         Lack of efficacy
    1
    -
         Adverse event, non-fatal
    29
    38
         Consent withdrawn by subject
    25
    15
         Lost to follow-up
    1
    1
         Sponsor decision
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Treatment Period
    Reporting group description
    All participants who received at least one dose of study drug.

    Reporting group values
    Treatment Period Total
    Number of subjects
    2876 2876
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    2358 2358
        From 65-84 years
    517 517
        85 years and over
    1 1
    Gender categorical
    Units: Subjects
        Female
    2262 2262
        Male
    614 614
    Race
    Units: Subjects
        American Indian or Alaska Native
    143 143
        Asian
    781 781
        Native Hawaiian or Other Pacific Islander
    1 1
        Black or African American
    64 64
        White
    1859 1859
        More than one race
    23 23
        Unknown or Not Reported
    5 5
    Region of Enrollment
    Units: Subjects
        United States
    488 488
        Czechia
    56 56
        Portugal
    11 11
        Russia
    122 122
        Greece
    8 8
        South Korea
    72 72
        Latvia
    8 8
        Sweden
    3 3
        Austria
    17 17
        Netherlands
    1 1
        China
    208 208
        Poland
    156 156
        Brazil
    30 30
        Slovenia
    5 5
        Slovakia
    27 27
        France
    36 36
        Lithuania
    21 21
        Croatia
    9 9
        Argentina
    430 430
        Romania
    21 21
        Hungary
    60 60
        Japan
    328 328
        United Kingdom
    26 26
        Switzerland
    7 7
        India
    71 71
        Spain
    86 86
        Canada
    47 47
        Turkey
    3 3
        Belgium
    41 41
        Taiwan
    81 81
        Denmark
    5 5
        South Africa
    56 56
        Italy
    27 27
        Mexico
    214 214
        Israel
    27 27
        Australia
    32 32
        Germany
    36 36
    Subject analysis sets

    Subject analysis set title
    2 mg Baricitinib
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    2 mg Baricitinib administered orally once daily.

    Subject analysis set title
    4 mg Baricitinib
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    4 mg Baricitinib administered orally once daily.

    Subject analysis sets values
    2 mg Baricitinib 4 mg Baricitinib
    Number of subjects
    297
    2579
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    236
    2122
        From 65-84 years
    61
    456
        85 years and over
    0
    1
    Age continuous
    Units:
        
    ±
    ±
    Gender categorical
    Units: Subjects
        Female
    231
    2031
        Male
    66
    548
    Race
    Units: Subjects
        American Indian or Alaska Native
    7
    136
        Asian
    56
    725
        Native Hawaiian or Other Pacific Islander
    0
    1
        Black or African American
    16
    48
        White
    217
    1642
        More than one race
    1
    22
        Unknown or Not Reported
    0
    5
    Region of Enrollment
    Units: Subjects
        United States
    91
    397
        Czechia
    3
    53
        Portugal
    2
    9
        Russia
    10
    112
        Greece
    2
    6
        South Korea
    9
    63
        Latvia
    0
    8
        Sweden
    0
    3
        Austria
    3
    14
        Netherlands
    1
    0
        China
    0
    208
        Poland
    20
    136
        Brazil
    0
    30
        Slovenia
    0
    5
        Slovakia
    3
    24
        France
    6
    30
        Lithuania
    0
    21
        Croatia
    2
    7
        Argentina
    12
    412
        Romania
    2
    19
        Hungary
    8
    52
        Japan
    7
    321
        United Kingdom
    4
    22
        Switzerland
    0
    7
        India
    16
    55
        Spain
    15
    71
        Canada
    11
    36
        Turkey
    1
    2
        Belgium
    3
    38
        Taiwan
    23
    58
        Denmark
    2
    3
        South Africa
    0
    56
        Italy
    6
    21
        Mexico
    13
    201
        Israel
    6
    21
        Australia
    6
    26
        Germany
    4
    32

    End points

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    End points reporting groups
    Reporting group title
    JADZ 4 mg Baricitinib
    Reporting group description
    4 mg Baricitinib administered orally once daily.

    Reporting group title
    JADV 4 mg Baricitinib
    Reporting group description
    4 mg Baricitinib administered orally once daily.

    Reporting group title
    JADX 2 mg Baricitinib
    Reporting group description
    2 mg Baricitinib administered orally once daily

    Reporting group title
    JADX 4 mg Baricitinib
    Reporting group description
    4 mg Baricitinib administered orally once daily.

    Reporting group title
    JADW 2 mg Baricitinib
    Reporting group description
    2 mg Baricitinib administered orally once daily.

    Reporting group title
    JADW 4 mg Baricitinib
    Reporting group description
    4 mg Baricitinib administered orally once daily.

    Reporting group title
    JAGS 4 mg Baricitinib
    Reporting group description
    4 mg Baricitinib administered orally once daily.

    Reporting group title
    JADA 4 mg Baricitinib
    Reporting group description
    4 mg Baricitinib administered orally once daily.
    Reporting group title
    2 mg Baricitinib Step-down
    Reporting group description
    -

    Reporting group title
    4 mg Baricitinib Step-down
    Reporting group description
    -

    Subject analysis set title
    2 mg Baricitinib
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    2 mg Baricitinib administered orally once daily.

    Subject analysis set title
    4 mg Baricitinib
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    4 mg Baricitinib administered orally once daily.

    Primary: Number of Participants Who Experienced Adverse Events (AEs) or Serious AE

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    End point title
    Number of Participants Who Experienced Adverse Events (AEs) or Serious AE [1]
    End point description
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (i.e., abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Non-serious AEs are reported at a threshold of 5%. An SAE is an AE from this study that results in any of the following: death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability/incapacity, congenital anomaly/birth defect, considered significant by the investigator for any other reason A summary of serious adverse events (SAEs) and other non-serious adverse events (AEs), regardless of causality, were reported in the Reported Adverse Events module.
    End point type
    Primary
    End point timeframe
    Baseline through 84 Months Analysis Population Description (APD): All enrolled participants who received at least 1 dose of study drug and did not discontinue the study for the reason 'Lost to Follow-up' at the first postbaseline visit in study JADY.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical comparison was not conducted on safety outcome measure.
    End point values
    2 mg Baricitinib Step-down 4 mg Baricitinib Step-down 2 mg Baricitinib 4 mg Baricitinib
    Number of subjects analysed
    592
    594
    297
    2579
    Units: Count of participants
        Adverse Events
    270
    315
    234
    153
        Serious Adverse Events
    164
    178
    127
    518
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR20

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    End point title
    Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR20
    End point description
    ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) * 100 APD: All enrolled participants who received at least one dose of study drug and completed at least 48 weeks in study JADY.
    End point type
    Secondary
    End point timeframe
    Year 1, 3 and 5 after entry into JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    274
    210
    78
    Units: Percentage of Participants
    number (confidence interval 95%)
        Year 1
    92.6 (89.7 to 94.7)
    88.4 (86.3 to 90.2)
    79.3 (72.6 to 84.7)
    79.5 (75.1 to 83.3)
    72.3 (62.9 to 80.1)
    70.8 (65.2 to 75.9)
    86.7 (81.4 to 90.6)
    75.6 (65.1 to 83.8)
        Year 3
    78.3 (74.1 to 82.0)
    76.6 (73.9 to 79.1)
    71.6 (64.4 to 77.9)
    70.5 (65.6 to 74.9)
    57.4 (47.7 to 66.6)
    55.8 (49.9 to 61.6)
    73.8 (67.5 to 79.3)
    71.8 (61.0 to 80.6)
        Year 5
    67.3 (62.7 to 71.6)
    65.6 (62.6 to 68.4)
    60.4 (52.8 to 67.4)
    56.0 (50.9 to 61.0)
    50.5 (40.9 to 60.0)
    43.1 (37.3 to 49.0)
    24.8 (19.4 to 31.0)
    60.3 (49.2 to 70.4)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR50

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    End point title
    Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR50
    End point description
    ACR 50 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Percentage of participants achieving ACR20 response = (number of ACR50 responders) / (number of participants analyzed) * 100
    End point type
    Secondary
    End point timeframe
    Year 1, 3 and 5 after entry into JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    274
    210
    78
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    80.0 (75.9 to 83.5)
    67.7 (64.8 to 70.5)
    58.0 (50.5 to 65.2)
    58.2 (53.1 to 63.1)
    45.5 (36.2 to 55.2)
    43.8 (38.0 to 49.7)
    69.0 (62.5 to 74.9)
    43.6 (33.1 to 54.6)
        Year 3
    67.8 (63.2 to 72.1)
    61.6 (58.6 to 64.5)
    49.7 (42.3 to 57.2)
    53.3 (48.2 to 58.3)
    43.6 (34.3 to 53.3)
    36.5 (31.0 to 42.3)
    59.0 (52.3 to 65.5)
    43.6 (33.1 to 54.6)
        Year 5
    59.9 (55.1 to 64.5)
    52.7 (49.7 to 55.7)
    44.4 (37.1 to 51.9)
    43.2 (38.2 to 48.3)
    37.6 (28.8 to 47.4)
    32.1 (26.9 to 37.9)
    18.6 (13.9 to 24.4)
    37.2 (27.3 to 48.3)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR70

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    End point title
    Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR70
    End point description
    ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) * 100
    End point type
    Secondary
    End point timeframe
    Year 1, 3 and 5 after entry into JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    274
    210
    78
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    61.3 (56.6 to 65.9)
    45.7 (42.7 to 48.8)
    34.9 (28.1 to 42.4)
    35.8 (31.1 to 40.8)
    28.7 (20.8 to 38.2)
    25.9 (21.1 to 31.4)
    42.9 (36.4 to 49.6)
    26.9 (18.3 to 37.7)
        Year 3
    54.4 (49.6 to 59.1)
    44.1 (41.1 to 47.7)
    35.5 (27.9 to 37.5)
    32.5 (27.9 to 37.5)
    24.8 (17.4 to 34.0)
    21.5 (17.1 to 26.8)
    35.2 (29.1 to 41.9)
    21.8 (14.1 to 32.2)
        Year 5
    48.2 (43.5 to 53.0)
    39.1 (36.1 to 42.1)
    28.4 (22.1 to 35.6)
    28.4 (24.0 to 33.2)
    23.8 (16.5 to 32.9)
    18.2 (14.1 to 23.2)
    12.9 (9.0 to 18.1)
    19.2 (12.0 to 29.3)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining a Disease Activity Score (DAS28) High-Sensitivity C-Reactive Protein (hsCRP) ≤3.2

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    End point title
    Percentage of Participants Maintaining a Disease Activity Score (DAS28) High-Sensitivity C-Reactive Protein (hsCRP) ≤3.2
    End point description
    Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count-28 (TJC28), swollen joint count-28 (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). 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 from 1.0-9.4, where lower scores indicated less disease activity, and remission was DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition. APD: All enrolled participants who received at least one dose of study drug and completed at least 48 weeks in study JADY.
    End point type
    Secondary
    End point timeframe
    Year 1, 3 and 5 after entry into JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    274
    210
    78
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    81.9 (77.9 to 85.3)
    71.9 (69.0 to 74.5)
    66.3 (58.9 to 73.0)
    68.6 (63.7 to 73.1)
    50.5 (40.9 to 60.0)
    51.1 (45.2 to 57.0)
    72.4 (66.0 to 78.0)
    59.0 (47.9 to 69.2)
        Year 3
    71.8 (67.3 to 75.9)
    65.5 (62.5 to 68.3)
    59.2 (51.6 to 66.3)
    59.3 (54.2 to 64.2)
    47.5 (38.1 to 57.2)
    41.6 (35.9 to 47.5)
    61.0 (54.2 to 67.3)
    60.3 (49.2 to 70.4)
        Year 5
    61.1 (56.3 to 65.6)
    58.9 (55.9 to 61.9)
    46.7 (39.4 to 54.3)
    50.0 (44.9 to 55.1)
    44.6 (35.2 to 54.3)
    34.3 (28.9 to 40.1)
    21.0 (16.0 to 27.0)
    53.8 (42.9 to 64.5)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining a Disease Activity Score (DAS28) High-Sensitivity C-Reactive Protein (hsCRP) <2.6

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    End point title
    Percentage of Participants Maintaining a Disease Activity Score (DAS28) High-Sensitivity C-Reactive Protein (hsCRP) <2.6
    End point description
    DAS28 consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), ESR (millimeters per hour), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using 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. Total scores ranged from 1.0-9.4, where lower scores indicated less disease activity. APD: All enrolled participants who received at least one dose of study drug and completed at least 48 weeks in study JADY.
    End point type
    Secondary
    End point timeframe
    Year 1, 3 and 5 after entry into JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    274
    210
    78
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    65.6 (61.0 to 70.0)
    52.3 (49.3 to 55.4)
    50.9 (43.4 to 58.3)
    46.2 (41.1 to 51.3)
    34.7 (26.1 to 44.3)
    32.8 (27.6 to 38.6)
    52.4 (45.6 to 59.0)
    44.9 (34.3 to 55.9)
        Year 3
    59.9 (55.1 to 64.5)
    51.0 (47.9 to 54.0)
    43.8 (36.5 to 51.3)
    43.2 (38.2 to 48.3)
    31.7 (23.4 to 41.3)
    26.3 (21.4 to 31.8)
    38.6 (32.2 to 45.3)
    35.9 (26.1 to 47.0)
        Year 5
    51.1 (46.3 to 55.8)
    44.0 (41.0 to 47.0)
    36.1 (29.2 to 43.6)
    37.7 (32.9 to 42.8)
    29.7 (21.7 to 39.2)
    26.6 (21.8 to 32.2)
    13.3 (9.4 to 18.6)
    43.6 (33.1 to 54.6)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission Response

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    End point title
    Percentage of Participants Maintaining American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission Response
    End point description
    Boolean-based definition of remission, all 4 criteria below must be met: tender joint count (TJC28 ) <=1, swollen joint count (SJC28) <=1, hsCRP <=1 milligram per deciliter (mg/dL), Patient Global Assessment of Disease Activity using visual analog scale (VAS) <=1 cm.
    End point type
    Secondary
    End point timeframe
    Year 1, 3, and 5 after entry into JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    274
    210
    78
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    30.5 (26.3 to 35.1)
    20.8 (18.4 to 23.4)
    17.8 (12.7 to 24.2)
    17.8 (14.2 to 22.0)
    8.9 (4.8 to 16.1)
    9.5 (6.6 to 13.5)
    17.1 (12.6 to 22.8)
    12.8 (7.1 to 22.0)
        Year 3
    30.8 (26.6 to 35.4)
    20.3 (18.0 to 22.9)
    16.6 (11.7 to 22.9)
    15.0 (11.7 to 19.1)
    9.9 (5.5 to 17.3)
    8.0 (5.4 to 11.9)
    11.9 (8.2 to 17.0)
    15.4 (9.0 to 25.0)
        Year 5
    26.5 (22.5 to 30.9)
    17.7 (15.5 to 20.1)
    13.6 (9.2 to 19.6)
    14.2 (11.0 to 18.2)
    6.9 (3.4 to 13.6)
    7.3 (4.8 to 11.0)
    5.2 (2.9 to 9.1)
    15.4 (9.0 to 25.0)
    No statistical analyses for this end point

    Secondary: Change From Baseline of Originating Study in Modified Total Sharp Score (mTSS)

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    End point title
    Change From Baseline of Originating Study in 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 (JSN) 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. Least Squares Mean (LSM) was calculated using a mixed model for repeated measures (MMRM) with treatment, visit, treatment-by-visit-interactions as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects. APD: All enrolled participants who received at least 1 dose of study drug in JADY with available baseline (from originating study) and at least 1 postbaseline x-ray assessment (collected in JADY) and Year 1 data. Year 1 data not available, 0 participants analyzed. JADW and JADA, 0 participants analyzed due to no data collected in this study
    End point type
    Secondary
    End point timeframe
    Baseline, Year 1, Baseline, Year 3; Baseline, Year 5 N represents treatments arms consecutively which corresponds with listings in the header.
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    387 [2]
    870 [3]
    137 [4]
    301 [5]
    0 [6]
    0 [7]
    203 [8]
    0 [9]
    Units: Score on a scale
    least squares mean (confidence interval 95%)
        Year 1: N=0, N=0, N=0, N=0, N=0, N=0, N=0, N=0
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    ( to )
    ( to )
    9999 (9999 to 9999)
    ( to )
        Year 3:N=387,N=943,N=137,N=301,N=0,N=0,N=203,N=0
    1.03 (0.94 to 1.67)
    1.64 (1.38 to 1.90)
    1.13 (0.61 to 1.66)
    1.13 (0.78 to 1.48)
    ( to )
    ( to )
    1.20 (0.61 to 1.80)
    ( to )
        Year 5:N=349,N=870,N=127,N=276,N=0,N=0,N=0,N=0
    1.64 (1.18 to 2.09)
    2.18 (1.85 to 2.51)
    1.32 (0.69 to 1.96)
    1.58 (1.15 to 2.02)
    ( to )
    ( to )
    9999 (9999 to 9999)
    ( to )
    Notes
    [2] - 9999=Data not available, zero participants analyzed.
    [3] - 9999=Data not available, zero participants analyzed.
    [4] - 9999=Data not available, zero participants analyzed.
    [5] - 9999=Data not available, zero participants analyzed.
    [6] - Zero participants analyzed due to no data collected in this study or originating study.
    [7] - Zero participants analyzed due to no data collected in this study or originating study.
    [8] - 9999 = Data not available, zero participants analyzed.
    [9] - Zero participants analyzed due to no data collected in this study or originating study.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With mTSS Change ≤0

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    End point title
    Percentage of Participants With mTSS Change ≤0
    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 (JSN) 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, with higher scores representing greater damage. APD: All enrolled participants who received at least one dose of study drug. Year 1 data not available, zero participants analyzed. JADW and JADA, zero participants analyzed due to no data collected in this study or originating study.
    End point type
    Secondary
    End point timeframe
    Year 1, 3, and 5 after entry into JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419 [10]
    1034 [11]
    169 [12]
    366 [13]
    0 [14]
    0 [15]
    210 [16]
    0 [17]
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    ( to )
    ( to )
    9999 (9999 to 9999)
    ( to )
        Year 3
    53.5 (48.7 to 58.2)
    53.0 (50.0 to 56.0)
    0.6 (0.1 to 3.3)
    0.8 (0.3 to 2.4)
    ( to )
    ( to )
    0.0 (0.0 to 1.8)
    ( to )
        Year 5
    1.7 (0.8 to 3.4)
    0.6 (0.3 to 1.3)
    0.0 (0.0 to 2.2)
    0.5 (0.1 to 2.0)
    ( to )
    ( to )
    0.0 (0.0 to 1.8)
    ( to )
    Notes
    [10] - 9999 = Data not available, zero participants analyzed.
    [11] - 9999 = Data not available, zero participants analyzed.
    [12] - 9999 = Data not available, zero participants analyzed.
    [13] - 9999 = Data not available, zero participants analyzed.
    [14] - No data collected; zero participants analyzed..
    [15] - No data collected; zero participants analyzed.
    [16] - 9999 = Data not available, zero participants analyzed.
    [17] - No data collected; zero participants analyzed.
    No statistical analyses for this end point

    Secondary: Change From Baseline of Originating Study in Joint Space Narrowing

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    End point title
    Change From Baseline of Originating Study in Joint Space Narrowing
    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. APD: All enrolled participants treated with at least 1 dose of study drug in JADY with available baseline (from originating study) and at least 1 postbaseline x-ray assessment (collected in JADY). JADW and JADA, zero participants analyzed due to no data collected in this study or originating study.
    End point type
    Secondary
    End point timeframe
    Baseline, Year 3; Baseline, Year 5 N represents treatments arms consecutively which corresponds with listings in the header.
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    387
    943
    137
    301
    0 [18]
    0 [19]
    203 [20]
    0 [21]
    Units: Score on a scale
    least squares mean (confidence interval 95%)
        Year 1: N=0, N=0, N=0, N=0, N=0, N=0, N=0, N=0
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    ( to )
    ( to )
    9999 (9999 to 9999)
    ( to )
        Year 3:N=387,N=943,N=137,N=301,N=0,N=0,N= 203,N=0
    0.45 (0.26 to 0.63)
    0.72 (0.59 to 0.86)
    0.54 (0.25 to 0.83)
    0.44 (0.24 to 0.63)
    ( to )
    ( to )
    0.52 (0.23 to 0.82)
    ( to )
        Year 5:N=349, N-870,N=127,N=276, N=0, N=0, N=0,N=0
    0.59 (0.36 to 0.83)
    1.00 (0.84 to 1.17)
    0.68 (0.34 to 1.02)
    0.60 (0.37 to 0.83)
    ( to )
    ( to )
    9999 (9999 to 9999)
    ( to )
    Notes
    [18] - No data collected; zero participants analyzed.
    [19] - No data collected; zero participants analyzed.
    [20] - 9999=Data not available, zero participants analyzed.
    [21] - No data collected; zero participants analyzed.
    No statistical analyses for this end point

    Secondary: Change From Baseline of Originating Study in Duration of Morning Stiffness

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    End point title
    Change From Baseline of Originating Study in Duration of Morning 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. APD: All enrolled participants who received at least one dose of study drug in JADY and had evaluable morning stiffness data. There were no baseline data for JADX
    End point type
    Secondary
    End point timeframe
    Baseline, Year1 ; Baseline, Year 3; Baseline, Year 5 N represents treatments arms consecutively which corresponds with listings in the header.
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    450
    633
    0 [22]
    0 [23]
    110
    308
    221
    78
    Units: Minutes
    arithmetic mean (standard deviation)
        Yr 1:N=450,N-633,N=0,N=0,N=110,N=308,N=221,N=78
    -102.72 ± 155.27
    -73.53 ± 144.22
    ±
    ±
    -75.07 ± 139.00
    73.88 ± 149.55
    -68.74 ± 148.34
    -37.12 ± 61.34
        Yr 3:N=387,N=556,N=0,N=0,N=81,N=222,N=192,N-69
    -112.41 ± 159.78
    -77.78 ± 141.01
    ±
    ±
    -84.60 ± 127.80
    -67.79 ± 154.05
    -90.61 ± 147.70
    -47.13 ± 52.97
        Yr 5:N=330,N=470,N=0,N=0,N=70,N-169,N=128,N=57
    -111.45 ± 164.74
    -82.48 ± 137.23
    ±
    ±
    88.37 ± 146.73
    -91.57 ± 163.88
    -92.75 ± 125.39
    -45.89 ± 60.43
    Notes
    [22] - No data collected; zero participants analyzed.
    [23] - No data collected; zero participants analyzed.
    No statistical analyses for this end point

    Secondary: Change From Baseline of Originating Study in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Health State Scores (UK)

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    End point title
    Change From Baseline of Originating Study in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Health State Scores (UK)
    End point description
    The European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The first component is 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. APD: All enrolled participants who received at least 1 dose of study drug and had evaluable EQ-5D-5L data. EQ-5D-5L data was not collected during the JADA originating study, zero participants analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Year 1; Baseline, Year 3; Baseline, Year 5
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    450
    1088
    171
    383
    108
    305
    221
    0 [24]
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Yr1:N=450,N=1088,N=171,N=383,N=108,N=305,N=221,N=0
    0.28 ± 0.26
    0.23 ± 0.24
    0.19 ± 0.26
    0.20 ± 0.23
    0.21 ± 0.22
    0.19 ± 0.24
    0.20 ± 0.26
    ±
        Yr3:N=386,N=952,N=146,N=309,N=80,N=219,N=190,N=0
    0.33 ± 0.24
    0.24 ± 0.25
    0.20 ± 0.26
    0.21 ± 0.26
    0.21 ± 0.22
    0.22 ± 0.25
    0.24 ± 0.24
    ±
        Yr5:N=330,N=820,N=122,N=264,N=70,N=169,N=127,N=0
    0.35 ± 0.24
    0.26 ± 0.26
    0.19 ± 0.25
    0.20 ± 0.26
    0.21 ± 0.22
    0.22 ± 0.30
    0.25 ± 0.26
    ±
    Notes
    [24] - Zero participants analyzed; data not collected.
    No statistical analyses for this end point

    Secondary: Change From Baseline of Originating Study in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Halth State Scores (US)

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    End point title
    Change From Baseline of Originating Study in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Halth State Scores (US)
    End point description
    The European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The first component is 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. APD: All enrolled participants who received at least 1 dose of study drug and had evaluable EQ-5D-5L data. EQ-5D-5L data was not collected during the JADA originating study, zero participants analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Year 1; Baseline Year 3; Baseline, Year 5 N represents treatments arms consecutively which corresponds with listings in the header.
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    450
    1088
    171
    383
    108
    305
    221
    0 [25]
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Yr1:N=450,N=1088,N=171,N=383,N=108,N=305,N=221,N=0
    0.19 ± 0.18
    0.16 ± 0.17
    0.13 ± 0.18
    0.14 ± 0.16
    0.14 ± 0.15
    0.13 ± 0.16
    0.14 ± 0.18
    ±
        Yr3:N=386,N=952,N=146,N=309,N=80,N=219,N=190,N=0
    0.23 ± 0.17
    0.17 ± 0.17
    0.15 ± 0.18
    0.15 ± 0.18
    0.14 ± 0.15
    0.15 ± 0.17
    0.17 ± 0.17
    ±
        Yr5:N=330,N=820,N=122,N=264,N=70,N=169,N=127,N=0
    0.24 ± 0.16
    0.18 ± 0.18
    0.13 ± 0.17
    0.14 ± 0.18
    0.15 ± 0.15
    0.15 ± 0.20
    0.18 ± 0.18
    ±
    Notes
    [25] - Zero participants analyzed; data not collected.
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining a Clinical Disease Activity Index Score (CDAI) ≤10

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    End point title
    Percentage of Participants Maintaining a Clinical Disease Activity Index Score (CDAI) ≤10
    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 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). The CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity. A negative change from baseline indicates improvement in condition. APD: All enrolled participants who received at least one dose of study drug and completed at least 48 weeks in study JADY.
    End point type
    Secondary
    End point timeframe
    Year 3 and Year 5 after entry into JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    274
    210
    78
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    81.6 (77.6 to 85.0)
    75.3 (72.6 to 77.9)
    68.6 (61.3 to 75.2)
    69.9 (65.1 to 74.4)
    52.5 (42.8 to 61.9)
    50.7 (44.8 to 56.6)
    73.3 (67.0 to 78.9)
    60.3 (49.2 to 70.4)
        Year 3
    73.3 (68.8 to 77.3)
    67.7 (64.8 to 70.5)
    60.4 (52.8 to 67.4)
    60.4 (55.3 to 65.3)
    49.5 (40.0 to 59.1)
    44.5 (38.8 to 50.4)
    61.4 (54.7 to 67.8)
    56.4 (45.4 to 66.9)
        Year 5
    61.6 (56.8 to 66.1)
    61.1 (58.1 to 64.0)
    51.5 (44.0 to 58.9)
    54.6 (49.5 to 59.7)
    44.6 (35.2 to 54.3)
    35.4 (30.0 to 41.2)
    21.9 (16.8 to 28.0)
    56.4 (45.4 to 66.9)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining a Clinical Disease Activity Index Score (CDAI) ≤2.8

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    End point title
    Percentage of Participants Maintaining a Clinical Disease Activity Index Score (CDAI) ≤2.8
    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 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). The CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity. A negative change from baseline indicates improvement in condition. APD: All enrolled participants who received at least one dose of study drug and completed at least 48 weeks in study JADY.
    End point type
    Secondary
    End point timeframe
    Year 3 and Year 5 after entry into JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    274
    210
    78
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    44.9 (40.2 to 49.7)
    28.3 (25.7 to 31.2)
    21.9 (16.3 to 28.7)
    25.1 (21.0 to 29.8)
    16.8 (10.8 to 25.3)
    13.5 (10.0 to 18.1)
    22.9 (17.7 to 29.0)
    14.1 (8.1 to 23.5)
        Year 3
    40.1 (35.5 to 44.9)
    30.0 (27.3 to 32.8)
    21.9 (16.3 to 28.7)
    23.5 (19.4 to 28.1)
    22.8 (15.7 to 31.9)
    15.0 (11.2 to 19.7)
    18.6 (13.9 to 24.4)
    20.5 (13.0 to 30.8)
        Year 5
    33.9 (29.5 to 38.6)
    25.0 (22.5 to 27.8)
    19.5 (14.3 to 26.2)
    22.4 (18.4 to 27.0)
    15.8 (10.0 to 24.2)
    12.8 (9.3 to 17.2)
    8.1 (5.1 to 12.6)
    19.2 (12.0 to 29.3)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining a Health Assessment Questionnaire Disability Index (HAQ-DI) Improvement ≥0.22

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    End point title
    Percentage of Participants Maintaining a Health Assessment Questionnaire Disability Index (HAQ-DI) Improvement ≥0.22
    End point description
    The HAQ-DI questionnaire 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 were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. An improvement of 0.22 or 0.3 points on the HAQ-DI has been identified as a minimal clinically important difference in Rheumatoid Arthritis participants. APD: All enrolled participants who received at least one dose of study drug and completed at least 48 weeks in study JADY.
    End point type
    Secondary
    End point timeframe
    Year 3 and Year 5 after entry into JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    274
    210
    78
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    89.7 (86.5 to 92.3)
    81.4 (78.9 to 83.7)
    78.7 (71.9 to 84.2)
    75.4 (70.7 to 79.5)
    74.3 (65.0 to 81.8)
    69.3 (63.6 to 74.5)
    80.0 (74.1 to 84.8)
    48.7 (37.9 to 59.6)
        Year 3
    75.4 (71.1 to 79.3)
    70.4 (67.6 to 73.1)
    64.5 (57.0 to 71.3)
    63.4 (58.3 to 68.2)
    56.4 (46.7 to 65.7)
    54.4 (48.5 to 60.2)
    68.1 (61.5 to 74.0)
    47.4 (36.7 to 58.4)
        Year 5
    65.2 (60.5 to 69.6)
    58.5 (55.5 to 61.5)
    51.5 (44.0 to 58.9)
    51.4 (46.3 to 56.4)
    50.5 (40.9 to 60.0)
    39.4 (33.8 to 45.3)
    20.0 (15.2 to 25.9)
    39.7 (29.6 to 50.8)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining a Health Assessment Questionnaire Disability Index (HAQ-DI) Improvement ≥0.3

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    End point title
    Percentage of Participants Maintaining a Health Assessment Questionnaire Disability Index (HAQ-DI) Improvement ≥0.3
    End point description
    The HAQ-DI questionnaire 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 were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. An improvement of 0.22 or 0.3 points on the HAQ-DI has been identified as a minimal clinically important difference in Rheumatoid Arthritis participants. APD: All enrolled participants who received at least one dose of study drug and completed at least 48 weeks in study JADY.
    End point type
    Secondary
    End point timeframe
    Year 3 and Year 5 after entry into JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    274
    210
    78
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    85.4 (81.7 to 88.5)
    75.6 (72.9 to 78.1)
    72.8 (65.6 to 78.9)
    69.4 (64.5 to 73.9)
    65.3 (55.7 to 73.9)
    61.7 (55.8 to 67.2)
    75.2 (69.0 to 80.6)
    43.6 (33.1 to 54.6)
        Year 3
    72.6 (68.1 to 76.6)
    64.8 (61.8 to 67.6)
    61.5 (54.0 to 68.5)
    58.5 (53.4 to 63.4)
    50.5 (40.9 to 60.0)
    47.8 (42.0 to 53.7)
    63.8 (57.1 to 70.0)
    38.5 (28.4 to 49.6)
        Year 5
    62.8 (58.0 to 67.3)
    53.4 (50.3 to 56.4)
    46.7 (39.4 to 54.3)
    46.2 (41.1 to 51.3)
    46.5 (37.1 to 56.2)
    35.0 (29.6 to 40.9)
    19.5 (14.7 to 25.4)
    34.6 (25.0 to 45.7)
    No statistical analyses for this end point

    Secondary: Change From Baseline of Originating Study in Bone Erosion Score

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    End point title
    Change From Baseline of Originating Study in Bone Erosion Score
    End point description
    The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints of the feet. The maximum erosion score for a hand joint is 5 and for a foot joint is 10. Thus, the maximal erosion score is 280 for a timepoint (160 for both hands/ wrists and 120 for both 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. The highest score (5 for the hand and 10 for the foot) indicates extensive loss of bone from more than one half of the articulating bone. A score of 0 in either the hand or foot joints indicates no erosion. LSM was calculated using an MMRM model with treatment, baseline value, visit, and the interactions of baseline-by-visit and treatment-by-visit as fixed factors. APD: All enrolled participants treated with at least 1 dose of study drug in JADY with available baseline (from originating study) and at least 1 postbaseline x-ray assessment (collected in JADY).
    End point type
    Secondary
    End point timeframe
    Baseline, Year 1; Baseline, Year 3; Baseline, Year 5 N represents treatments arms consecutively which corresponds with listings in the header. APD: JADW and JADA, zero participants analyzed due to no data collected in this study or originating study.
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    387 [26]
    943 [27]
    137 [28]
    301 [29]
    0 [30]
    0 [31]
    203
    0 [32]
    Units: Score on a sclae
    least squares mean (confidence interval 95%)
        Year 1: N=0, N=0, N=0, N=0, N=0, N=0, N=0, N=0
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    ( to )
    ( to )
    0.00 (0.00 to 0.00)
    ( to )
        Year 3: N=387,N=943,N=137,N=301,N=0,N=0,N=203,N=0
    0.85 (0.63 to 1.08)
    0.92 (0.76 to 1.07)
    0.59 (0.30 to 0.89)
    0.69 (0.49 to 0.89)
    ( to )
    ( to )
    0.68 (0.32 to 1.03)
    ( to )
        Year 5: N=349,N=870,N=127,N=276,N=0,N=0,N=0,N=0
    1.04 (0.77 to 1.32)
    1.18 (0.98 to 1.38)
    0.65 (0.28 to 1.01)
    0.98 (0.74 to 1.23)
    ( to )
    ( to )
    9999 (9999 to 9999)
    ( to )
    Notes
    [26] - 9999 = Data not available, zero participants analyzed.
    [27] - 9999 = Data not available, zero participants analyzed.
    [28] - 9999 = Data not available, zero participants analyzed.
    [29] - 9999 = Data not available, zero participants analyzed.
    [30] - No data collected; zero participants analyzed.
    [31] - No data collected; zero participants analyzed.
    [32] - No data collected; zero participants analyzed.
    No statistical analyses for this end point

    Secondary: Healthcare Resource Utilization

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    End point title
    Healthcare Resource Utilization
    End point description
    Healthcare resource utilization data will be collected by site staff regarding the number of visits to medical care providers such as general practitioners, specialists, physical or occupational therapists, and other nonphysical care providers for services outside of the clinical study; emergency room admissions; hospital admissions; and concomitant medications related to the treatment of Rheumatoid Arthritis (RA). APD: All enrolled participants who received at least one dose of study drug, with access healthcare services outside of the clinical study.
    End point type
    Secondary
    End point timeframe
    Baseline Up to 84 months
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    451
    1090
    180
    403
    117
    331
    221
    83
    Units: Consultations
    number (not applicable)
        Healthcare Consultations
    3134
    11108
    2160
    4573
    2380
    5410
    717
    749
        Emergency Room Consultations
    95
    244
    52
    131
    73
    154
    40
    16
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining a Simplified Disease Activity Index (SDAI) ≤11

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    End point title
    Percentage of Participants Maintaining a Simplified Disease Activity Index (SDAI) ≤11
    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), Patient's Global Assessment of Disease Activity using VAS centimeters (cm), and Physician's Global Assessment of Disease Activity using VAS (cm). The SDAI is calculated by summing the values of the 5 components. Lower scores indicated less disease activity. An index-based definition of remission occurs with an SDAI score ≤3.3. APD: All enrolled participants who received at least one dose of study drug and completed at least 48 weeks in study JADY.
    End point type
    Secondary
    End point timeframe
    Year 1, Year 3, and Year 5 after entry in to JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    274
    210
    78
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    81.6 (77.6 to 85.0)
    75.2 (72.5 to 77.8)
    70.4 (63.1 to 76.8)
    69.1 (64.2 to 73.6)
    53.5 (43.8 to 62.9)
    53.6 (47.7 to 59.5)
    72.4 (66.0 to 78.0)
    59.0 (47.9 to 69.2)
        Year 3
    73.3 (68.8 to 77.3)
    67.8 (64.9 to 70.6)
    60.9 (53.4 to 68.0)
    62.3 (57.2 to 67.1)
    48.5 (39.0 to 58.1)
    44.5 (38.8 to 50.4)
    60.0 (53.3 to 66.4)
    57.7 (46.6 to 68.0)
        Year 5
    61.3 (56.6 to 65.9)
    61.2 (58.2 to 64.1)
    51.5 (44.0 to 58.9)
    53.3 (48.2 to 58.3)
    46.5 (37.1 to 56.2)
    35.4 (30.0 to 41.2)
    23.3 (18.1 to 29.5)
    57.7 (46.6 to 68.0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining a Simplified Disease Activity Index (SDAI) ≤3.3

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    End point title
    Percentage of Participants Maintaining a Simplified Disease Activity Index (SDAI) ≤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), Patient's Global Assessment of Disease Activity using VAS centimeters (cm), and Physician's Global Assessment of Disease Activity using VAS (cm). The SDAI is calculated by summing the values of the 5 components. Lower scores indicated less disease activity. An index-based definition of remission occurs with an SDAI score ≤3.3. APD: All enrolled participants who received at least one dose of study drug and completed at least 48 weeks in study JADY.
    End point type
    Secondary
    End point timeframe
    Year 1, Year 3 and Year 5
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    274
    210
    78
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    45.3 (40.6 to 50.1)
    28.9 (26.2 to 31.8)
    24.3 (18.4 to 31.2)
    23.5 (19.4 to 28.1)
    13.9 (8.4 to 21.9)
    13.1 (9.6 to 17.7)
    22.9 (17.7 to 29.0)
    14.1 (8.1 to 23.5)
        Year 3
    39.9 (35.3 to 44.6)
    29.8 (27.1 to 32.6)
    22.5 (16.8 to 29.4)
    21.6 (17.7 to 26.1)
    19.8 (13.2 to 28.6)
    13.5 (10.0 to 18.1)
    15.7 (11.4 to 21.2)
    21.8 (14.1 to 32.2)
        Year 5
    34.8 (30.4 to 39.5)
    24.7 (22.1 to 27.4)
    20.7 (15.3 to 27.4)
    21.3 (17.4 to 25.8)
    13.9 (8.4 to 21.9)
    11.3 (8.1 to 15.6)
    8.1 (5.1 to 12.6)
    21.8 (14.1 to 32.2)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Relapse Event During the 96-Week Step-Down Period

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    End point title
    Percentage of Participants with Relapse Event During the 96-Week Step-Down Period
    End point description
    Relapse is defined as CDAI score > 10 in participants originating from JADV, JADW,JADX and JAGS. The time point refers to time to relapse in the step-down period. APD: All enrolled participants who were randomized, were not rescued, and received at least one dose of study drug during the step-down period.
    End point type
    Secondary
    End point timeframe
    Week 0 through Week 96 of Step-down
    End point values
    2 mg Baricitinib Step-down 4 mg Baricitinib Step-down
    Number of subjects analysed
    498
    498
    Units: Percentage of participants
    number (not applicable)
        Week 12
    11.8
    5.4
        Week 24
    26.0
    12.5
        Week 36
    31.0
    18.2
        Week 48
    36.0
    21.1
        Week 60
    41.0
    26.6
        Week 72
    45.1
    29.1
        Week 84
    46.7
    31.0
        Week 96
    47.8
    34.5
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining a DAS28-Erythrocyte Sedimentation Rate (ESR) Score of ≤3.2

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    End point title
    Percentage of Participants Maintaining a DAS28-Erythrocyte Sedimentation Rate (ESR) Score of ≤3.2
    End point description
    DAS28 consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), ESR (millimeters per hour), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using 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. Total scores ranged from 1.0-9.4, where lower scores indicated less disease activity. APD: All enrolled participants who received at least one dose of study drug and completed at least 48 weeks in study JADY.
    End point type
    Secondary
    End point timeframe
    Year 1, 3, and 5 after entry into JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    274
    210
    78
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    61.8 (57.1 to 66.3)
    48.4 (45.3 to 51.4)
    46.2 (38.8 to 53.7)
    48.4 (43.3 to 53.5)
    31.7 (23.4 to 41.3)
    31.8 (26.5 to 37.5)
    41.0 (34.5 to 47.7)
    35.9 (26.1 to 47.0)
        Year 3
    54.4 (49.6 to 59.1)
    46.1 (43.1 to 49.2)
    40.2 (33.1 to 47.8)
    41.0 (36.1 to 46.1)
    22.8 (15.7 to 31.9)
    23.7 (19.1 to 29.1)
    33.8 (27.8 to 40.4)
    37.2 (27.3 to 48.3)
        Year 5
    48.7 (43.9 to 53.5)
    41.3 (38.3 to 44.3)
    36.1 (29.2 to 43.6)
    32.5 (27.9 to 37.5)
    23.8 (16.5 to 32.9)
    21.9 (17.4 to 27.2)
    11.4 (7.8 to 16.4)
    37.2 (27.3 to 48.3)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Maintaining a DAS28-Erythrocyte Sedimentation Rate (ESR) Sore of <2.6

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    End point title
    Percentage of Participants Maintaining a DAS28-Erythrocyte Sedimentation Rate (ESR) Sore of <2.6
    End point description
    DAS28 consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), ESR (millimeters per hour), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using 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. Total scores ranged from 1.0-9.4, where lower scores indicated less disease activity. APD: All enrolled participants who received at least one dose of study drug and completed at least 48 weeks in study JADY.
    End point type
    Secondary
    End point timeframe
    Year 1, 3, and 5 after entry into JADY
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    419
    1034
    169
    366
    101
    241
    210
    78
    Units: Percentage of participants
    number (confidence interval 95%)
        Year 1
    36.8 (32.3 to 41.5)
    29.3 (26.6 to 32.2)
    24.3 (18.4 to 31.2)
    26.8 (22.5 to 31.5)
    20.8 (14.0 to 29.7)
    13.1 (9.6 to 17.7)
    25.2 (19.8 to 31.5)
    15.4 (9.0 to 25.0)
        Year 3
    38.9 (34.4 to 43.7)
    24.7 (22.1 to 27.4)
    24.3 (18.4 to 31.2)
    23.2 (19.2 to 27.8)
    15.8 (10.0 to 24.2)
    10.2 (7.2 to 14.4)
    19.5 (14.7 to 25.4)
    23.1 (15.1 to 33.6)
        Year 5
    31.3 (27.0 to 35.9)
    23.9 (21.4 to 26.6)
    22.5 (16.8 to 29.4)
    19.4 (15.7 to 23.8)
    11.9 (6.9 to 19.6)
    8.8 (6.0 to 12.7)
    7.1 (4.4 to 11.4)
    19.2 (12.0 to 29.3)
    No statistical analyses for this end point

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

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    End point title
    Change From Baseline of Originating Study in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health)
    End point description
    The European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The second component is a self-perceived health score which is assessed using a VAS that ranged from 0 to 100 millimeter (mm), where 0 mm indicated the worst health you can imagine and 100 mm indicated the best health you can imagine. APD: All enrolled participants who received at least 1 dose of study drug and completed at least 48 weeks in study JADY. EQ-5D-5L data was not collected during the JADA originating study, zero participants analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Year 1; Baseline, Year 3; Baseline, Year 5
    End point values
    JADZ 4 mg Baricitinib JADV 4 mg Baricitinib JADX 2 mg Baricitinib JADX 4 mg Baricitinib JADW 2 mg Baricitinib JADW 4 mg Baricitinib JAGS 4 mg Baricitinib JADA 4 mg Baricitinib
    Number of subjects analysed
    450
    1088
    171
    383
    108
    305
    221
    0 [33]
    Units: millimeter(s)
    arithmetic mean (standard deviation)
        Yr1:N=450,N=1088,N=171,N=383,N=108,N=305,N=221,N=0
    24.69 ± 28.50
    19.72 ± 28.17
    15.13 ± 26.78
    18.32 ± 26.35
    20.96 ± 24.53
    14.98 ± 30.21
    18.47 ± 27.31
    ±
        Yr3:N=386,N=952,N=146,N=309,N=80,N=219,N=190,N=0
    28.48 ± 29.88
    22.10 ± 28.02
    16.29 ± 25.37
    16.48 ± 30.24
    23.53 ± 24.70
    18.79 ± 30.03
    21.45 ± 29.64
    ±
        Yr5:N=330,N=820,N=122,N=264,N=70,N=169,N=127,N=0
    31.13 ± 28.15
    23.93 ± 28.45
    13.82 ± 25.59
    19.34 ± 27.48
    26.19 ± 27.09
    23.57 ± 31.67
    27.31 ± 27.19
    ±
    Notes
    [33] - Zero participants analyzed; data not collected.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to 84 months.
    Adverse event reporting additional description
    All enrolled participants who received at least 1 dose of study drug and did not discontinue the study for the reason 'Lost to Follow-up' at the first postbaseline visit in study JADY. Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    2 mg Baricitinib
    Reporting group description
    2 mg Baricitinib administered orally once daily throughout the 84-month treatment period.

    Reporting group title
    4 mg Baricitinib
    Reporting group description
    4 mg Baricitinib administered orally once daily throughout the 84-month treatment period.

    Reporting group title
    2 mg Baricitinib Step-Down
    Reporting group description
    2 mg Baricitinib administered orally once daily throughout the 96-week step-down period.

    Reporting group title
    4 mg Baricitinib Step-Down
    Reporting group description
    4 mg Baricitinib administered orally once daily throughout the 96-week step-down period.

    Serious adverse events
    2 mg Baricitinib 4 mg Baricitinib 2 mg Baricitinib Step-Down 4 mg Baricitinib Step-Down
    Total subjects affected by serious adverse events
         subjects affected / exposed
    112 / 297 (37.71%)
    517 / 2579 (20.05%)
    164 / 592 (27.70%)
    178 / 594 (29.97%)
         number of deaths (all causes)
    7
    43
    14
    14
         number of deaths resulting from adverse events
    1
    11
    4
    5
    Injury, poisoning and procedural complications
    accident
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ankle fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    brain herniation
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    burns second degree
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    carbon monoxide poisoning
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cervical vertebral fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    colon injury
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    compression fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    contusion
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    crush injury
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    dislocation of vertebra
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    epiphyseal injury
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    face injury
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    fall
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    2 / 297 (0.67%)
    13 / 2579 (0.50%)
    1 / 592 (0.17%)
    3 / 594 (0.51%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 14
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    femoral neck fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    1 / 2579 (0.04%)
    2 / 592 (0.34%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    femur fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    7 / 2579 (0.27%)
    3 / 592 (0.51%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 8
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    fibula fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    foot fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    3 / 2579 (0.12%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hand fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    head injury
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hip fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    5 / 2579 (0.19%)
    2 / 592 (0.34%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    humerus fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    3 / 2579 (0.12%)
    1 / 592 (0.17%)
    3 / 594 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    injury
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    joint dislocation
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    3 / 2579 (0.12%)
    2 / 592 (0.34%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    joint injury
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    keratorhexis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ligament rupture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    lower limb fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    3 / 2579 (0.12%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    lumbar vertebral fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    meniscus injury
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    7 / 2579 (0.27%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 7
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    open globe injury
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    open fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    overdose
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    patella fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pelvic fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    periprosthetic fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    post procedural haematoma
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    post procedural complication
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    post procedural haemorrhage
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    radius fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    rib fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    road traffic accident
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    3 / 2579 (0.12%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    scapula fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    seroma
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    skin wound
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    skull fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    spinal compression fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    6 / 2579 (0.23%)
    1 / 592 (0.17%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    suture rupture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    synovial rupture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    tendon injury
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    tendon rupture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    2 / 592 (0.34%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    thoracic vertebral fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    tibia fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    3 / 2579 (0.12%)
    1 / 592 (0.17%)
    4 / 594 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    toxicity to various agents
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    traumatic arthritis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    upper limb fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    1 / 592 (0.17%)
    2 / 594 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    wound
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    wound dehiscence
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    wrist fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    blood creatine phosphokinase increased
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    2 / 592 (0.34%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    blood glucose increased
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    blood pressure increased
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardiac murmur
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    electrocardiogram t wave inversion
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    electrocardiogram change
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    glomerular filtration rate decreased
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    haemoglobin decreased
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    influenza a virus test positive
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    mycobacterium tuberculosis complex test positive
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    transaminases increased
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    acute coronary syndrome
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    acute left ventricular failure
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    acute myocardial infarction
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    4 / 297 (1.35%)
    7 / 2579 (0.27%)
    1 / 592 (0.17%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    2 / 5
    1 / 7
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 1
    angina pectoris
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    3 / 2579 (0.12%)
    1 / 592 (0.17%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    angina unstable
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    5 / 2579 (0.19%)
    1 / 592 (0.17%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 5
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    aortic valve disease
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    aortic valve incompetence
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    aortic valve stenosis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    arteriosclerosis coronary artery
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    atrial fibrillation
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    4 / 297 (1.35%)
    11 / 2579 (0.43%)
    1 / 592 (0.17%)
    3 / 594 (0.51%)
         occurrences causally related to treatment / all
    0 / 5
    4 / 13
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    atrial tachycardia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    atrioventricular block complete
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    bradycardia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    bundle branch block left
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardiac arrest
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    4 / 2579 (0.16%)
    2 / 592 (0.34%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    cardiac failure
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    1 / 2579 (0.04%)
    1 / 592 (0.17%)
    2 / 594 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    1 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 2
    cardiac failure acute
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardiac failure chronic
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardiac failure congestive
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    3 / 297 (1.01%)
    4 / 2579 (0.16%)
    1 / 592 (0.17%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 4
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    cardio-respiratory arrest
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    chronic left ventricular failure
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    coronary artery disease
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    3 / 2579 (0.12%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    coronary artery occlusion
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    coronary artery stenosis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    mitral valve disease
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    mitral valve incompetence
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    2 / 594 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    myocardial infarction
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    4 / 2579 (0.16%)
    2 / 592 (0.34%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 6
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    myocardial ischaemia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    2 / 592 (0.34%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    palpitations
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pericarditis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    right ventricular failure
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    sinus node dysfunction
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    sinus tachycardia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    stress cardiomyopathy
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    supraventricular tachycardia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ventricular arrhythmia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ventricular fibrillation
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ventricular tachycardia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    congenital central nervous system anomaly
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hydrocele
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed [1]
    0 / 66 (0.00%)
    1 / 548 (0.18%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hypertrophic cardiomyopathy
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    2 / 297 (0.67%)
    3 / 2579 (0.12%)
    2 / 592 (0.34%)
    3 / 594 (0.51%)
         occurrences causally related to treatment / all
    1 / 2
    3 / 4
    0 / 2
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    coagulopathy
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    febrile neutropenia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    leukocytosis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    lymphopenia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    normochromic normocytic anaemia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    normocytic anaemia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pancytopenia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    3 / 2579 (0.12%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    thrombocytopenia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    thrombocytosis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    amyotrophic lateral sclerosis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    autonomic neuropathy
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    basal ganglia haemorrhage
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    central nervous system vasculitis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebellar infarction
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebellar stroke
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebral artery stenosis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebral artery thrombosis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebral haemorrhage
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    cerebral infarction
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    1 / 592 (0.17%)
    2 / 594 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebral microhaemorrhage
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebral thrombosis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebral venous thrombosis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebrospinal fistula
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebrospinal fluid leakage
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebrovascular accident
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebrovascular disorder
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cervical cord compression
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cervical radiculopathy
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    dementia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    depressed level of consciousness
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    dizziness
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    embolic stroke
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    epilepsy
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    haemorrhage intracranial
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    haemorrhagic stroke
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    5 / 2579 (0.19%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    headache
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    1 / 2579 (0.04%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hemiparesis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    intercostal neuralgia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    intracranial aneurysm
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ischaemic cerebral infarction
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ischaemic stroke
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    5 / 297 (1.68%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    leukoencephalopathy
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    loss of consciousness
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    metabolic encephalopathy
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    migraine
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    myelopathy
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    neuralgia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    neuropathy peripheral
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    peripheral sensorimotor neuropathy
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    post herpetic neuralgia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    presyncope
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    radiculopathy
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    sciatica
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    3 / 2579 (0.12%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    seizure
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    sensory disturbance
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    subarachnoid haemorrhage
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    syncope
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    9 / 2579 (0.35%)
    1 / 592 (0.17%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 10
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    thalamus haemorrhage
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    transient ischaemic attack
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    4 / 2579 (0.16%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 4
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    cataract
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    6 / 2579 (0.23%)
    3 / 592 (0.51%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 13
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cataract subcapsular
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    corneal perforation
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    dry age-related macular degeneration
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    glaucoma
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    1 / 592 (0.17%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    keratitis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    macular rupture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ocular hypertension
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    retinal detachment
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    rhegmatogenous retinal detachment
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    conductive deafness
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    deafness unilateral
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    meniere's disease
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    sudden hearing loss
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    vertigo
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    vertigo positional
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    abdominal pain
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    2 / 2579 (0.08%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    abdominal pain upper
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    abdominal wall haematoma
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    anal fistula
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    colitis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    3 / 2579 (0.12%)
    1 / 592 (0.17%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    colitis ischaemic
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    colitis ulcerative
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 2579 (0.00%)
    0 / 592 (0.00%)
    1 / 594 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    dental cyst
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    diarrhoea
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 2579 (0.04%)
    0 / 592 (0.00%)
    0 / 594 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    diverticular perforation
    alternative dictionary used: MedDRA 23.1