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    Clinical Trial Results:
    A multicenter, randomized, double-blind, phase III trial to evaluate the safety, immunogenicity, and efficacy of MSB11022 compared with Humira® in patients with moderately to severely active rheumatoid arthritis

    Summary
    EudraCT number
    2016-002852-26
    Trial protocol
    CZ   GB   HU   DE   LT   BG  
    Global end of trial date
    27 Aug 2018

    Results information
    Results version number
    v2(current)
    This version publication date
    26 Jan 2020
    First version publication date
    13 Jul 2019
    Other versions
    v1
    Version creation reason
    • New data added to full data set
    Sponsor scientific responsible changed

    Trial information

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    Trial identification
    Sponsor protocol code
    MS200588-0004
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03052322
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Fresenius Kabi SwissBioSim GmbH
    Sponsor organisation address
    Route de Crassier 23 – Bâtiment A3, Eysins, Switzerland, 1262
    Public contact
    Eugenia Kunina, Fresenius Kabi SwissBioSim GmbH, +41 79 1093376, eugenia.kunina@fresenius-kabi.com
    Scientific contact
    Eugenia Kunina, Fresenius Kabi SwissBioSim GmbH, +41 79 1093376, eugenia.kunina@fresenius-kabi.com
    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
    27 Aug 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Aug 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study is to evaluate the safety profile of MSB11022- modified buffer and stabilizer compared to Humira® in subjects with moderately to severely active Rheumatoid Arthritis (RA).
    Protection of trial subjects
    Subject protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    31 Jan 2017
    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
    Bulgaria: 61
    Country: Number of subjects enrolled
    Czech Republic: 52
    Country: Number of subjects enrolled
    Germany: 15
    Country: Number of subjects enrolled
    Hungary: 23
    Country: Number of subjects enrolled
    Poland: 135
    Country: Number of subjects enrolled
    United Kingdom: 2
    Worldwide total number of subjects
    288
    EEA total number of subjects
    288
    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)
    241
    From 65 to 84 years
    47
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Subjects were randomized in 1:1 ratio to receive either MSB11022 or EU-Humira for 48 weeks.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    MSB11022
    Arm description
    Subjects received MSB11022 subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
    Arm type
    Experimental

    Investigational medicinal product name
    MSB11022
    Investigational medicinal product code
    MSB11022
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received MSB11022 subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.

    Arm title
    EU-Humira
    Arm description
    Subjects received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
    Arm type
    Active comparator

    Investigational medicinal product name
    EU-Humira
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.

    Number of subjects in period 1
    MSB11022 EU-Humira
    Started
    143
    145
    Completed
    122
    113
    Not completed
    21
    32
         Death
    -
    2
         Protocol deviation
    1
    -
         Lack of efficacy
    1
    2
         Other un-specified
    1
    2
         Adverse events
    6
    13
         Consent withdrawn by subject
    10
    9
         Lost to follow-up
    2
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MSB11022
    Reporting group description
    Subjects received MSB11022 subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.

    Reporting group title
    EU-Humira
    Reporting group description
    Subjects received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.

    Reporting group values
    MSB11022 EU-Humira Total
    Number of subjects
    143 145 288
    Age categorical
    Units: Subjects
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    53.9 ± 11.9 54.0 ± 11.0 -
    Sex: Female, Male
    Units: Subjects
        Female
    108 119 227
        Male
    35 26 61
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0
        Asian
    0 2 2
        Native Hawaiian or Other Pacific Islander
    0 0 0
        Black or African American
    0 0 0
        White
    142 143 285
        More than one race
    0 0 0
        Unknown or Not Reported
    1 0 1
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    3 1 4
        Not Hispanic or Latino
    140 144 284
        Unknown or Not Reported
    0 0 0

    End points

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    End points reporting groups
    Reporting group title
    MSB11022
    Reporting group description
    Subjects received MSB11022 subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.

    Reporting group title
    EU-Humira
    Reporting group description
    Subjects received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.

    Primary: Percentage of Subjects with Treatment-emergent Adverse Events of Special Interest (AESI)

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    End point title
    Percentage of Subjects with Treatment-emergent Adverse Events of Special Interest (AESI) [1]
    End point description
    Adverse event (AE) was defined as any untoward medical occurrence in subjects, which does not necessarily have causal relationship with treatment. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. Hypersensitivity was the pre-defined TEAE of special Interest for this study. The percentage of subjects with treatment emergent AESIs (hypersensitivity) were reported. The Safety Analysis Set included all randomized subjects who received at least one dose of study treatment.
    End point type
    Primary
    End point timeframe
    Up to Week 52
    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: Only descriptive data was planned to be reported for this endpoint.
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Percentage of subjects
        number (confidence interval 95%)
    4.2 (1.6 to 8.9)
    5.5 (2.4 to 10.6)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Achieved American College of Rheumatology 20 Response (ACR20) at Week 12

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    End point title
    Percentage of Subjects Who Achieved American College of Rheumatology 20 Response (ACR20) at Week 12
    End point description
    ACR 20 Response: >= 20 percent improvement in swollen joint count (66 joints) & tender joint count (68 joints) & >=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS) ; 0-10 millimeter [mm], 0=no pain & 10=worst possible pain), patient's global assessment of disease activity by using VAS (scale ranges from 0 to 100 mm, [0 mm=no pain & 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, subjects's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). Derived HAQ-DI ranges from 0= no difficulty & 3= inability to perform task) & acute-phase marker. Intent-To-Treat Analysis Set included all subjects randomly allocated to treatment, based on intent to treat “as randomized” principle. Here "Number of subjects analyzed" signifies those who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    142
    141
    Units: Percentage of Subjects
        number (confidence interval 95%)
    79.6 (72.0 to 85.9)
    80.9 (73.4 to 86.9)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Positive Anti-Drug Antibodies (ADAs) Status to Adalimumab

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    End point title
    Percentage of Subjects with Positive Anti-Drug Antibodies (ADAs) Status to Adalimumab
    End point description
    Percentage of subjects with positive anti-Drug antibodies (ADAs) status to Adalimumab were reported. The Safety Analysis Set included all randomized subjects who received at least one dose of study treatment. Here "n" signifies those subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, 4, 12, 24, 36 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Percentage of Subjects
    number (not applicable)
        Baseline (n= 142, 144)
    7.7
    4.2
        Week 2 (n= 143, 145)
    20.3
    15.2
        Week 4 (n= 141, 141)
    29.8
    21.3
        Week 12 (n= 142, 140)
    54.2
    48.6
        Week 24 (n= 139, 133)
    71.9
    61.7
        Week 36 (n= 124, 121)
    66.9
    65.3
        Week 52 (n= 120, 119)
    60.8
    62.2
    No statistical analyses for this end point

    Secondary: Anti-Drug Antibodies (ADAs) Titer Levels for Adalimumab

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    End point title
    Anti-Drug Antibodies (ADAs) Titer Levels for Adalimumab
    End point description
    Titer was defined as the degree to which the antibody-serum sample could be diluted and still contained detectable amounts of antibody. Anti-Drug Antibodies (ADAs) Titers for adalimumab was reported. Data was collected using validated bioanalytical method. The Safety Analysis Set included all randomized subjects who received at least one dose of study treatment. Here "number of subject analyzed" signifies those who were evaluable for this endpoint and "n" signifies those subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, 4, 12, 24, 36 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    115
    104
    Units: Titer
    median (full range (min-max))
        Baseline (n= 11, 6)
    4.0 (1 to 512)
    1.5 (1 to 8)
        Week 2 (n= 29, 22)
    4.0 (1 to 32768)
    12.0 (1 to 1024)
        Week 4 (n= 42, 30)
    6.0 (1 to 16384)
    6.0 (1 to 512)
        Week 12 (n= 77, 68)
    16.0 (1 to 4096)
    16.0 (1 to 16384)
        Week 24 (n= 100, 82)
    16.0 (1 to 32768)
    24.0 (1 to 131072)
        Week 36 (n= 83, 79)
    16.0 (1 to 32768)
    16.0 (1 to 131072)
        Week 52 (n= 73, 74)
    16.0 (1 to 16384)
    12.0 (1 to 32768)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Confirmed Neutralizing Antibodies (NAb) Status to Adalimumab

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    End point title
    Percentage of Subjects with Confirmed Neutralizing Antibodies (NAb) Status to Adalimumab
    End point description
    Percentage of subjects with confirmed neutralizing antibodies status to Adalimumab were reported. The Safety Analysis Set included all randomized subjects who received at least one dose of study treatment. Here "Number of subjects analyzed" signifies those subjects who were evaluable for this endpoint and "n" signifies those subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, 4, 12, 24, 36 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    115
    104
    Units: Percentage of Subjects
    number (not applicable)
        Baseline (n= 11, 6)
    45.5
    50.0
        Week 2 (n= 29, 22)
    31.0
    40.9
        Week 4 (n= 42, 30)
    33.3
    30.0
        Week 12 (n= 77, 68)
    33.8
    38.2
        Week 24 (n= 100, 82)
    27.0
    29.3
        Week 36 (n= 83, 79)
    24.1
    29.1
        Week 52 (n= 73, 74)
    32.9
    39.2
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 2, 4, 8, 24 and 52

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    End point title
    Percentage of Subjects Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 2, 4, 8, 24 and 52
    End point description
    ACR 20 Response: defined as greater than or equal to (>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, subjects's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP). ITT Analysis Set was used. Here "n" signifies those subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Week 2, 4, 8, 24 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Week 2 (n= 143, 145)
    30.0 (22.55 to 38.32)
    29.7 (22.36 to 37.80)
        Week 4 (n= 142, 144)
    52.1 (43.58 to 60.56)
    52.8 (44.29 to 61.15)
        Week 8 (n= 142, 144)
    71.1 (62.93 to 78.42)
    72.9 (64.89 to 79.98)
        Week 24 (n= 139, 133)
    88.5 (81.98 to 93.28)
    83.3 (75.86 to 89.25)
        Week 52 (n= 122, 119)
    81.8 (73.78 to 88.24)
    86.4 (78.92 to 92.05)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Achieved American College of Rheumatology 50 (ACR50) Response at Week 2, 4, 8, 12, 24 and 52

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    End point title
    Percentage of Subjects Who Achieved American College of Rheumatology 50 (ACR50) Response at Week 2, 4, 8, 12, 24 and 52
    End point description
    ACR 50 Response is defined as greater than or equal to (>=) 50 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=50 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, subjects's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP). ITT Analysis Set was used. Here "n" signifies those subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Week 2, 4, 8, 12, 24 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Week 2 (n= 143, 145)
    6.4 (2.9 to 11.9)
    6.2 (2.9 to 11.5)
        Week 4 (n= 142, 144)
    17.6 (11.7 to 24.9)
    19.4 (13.3 to 26.9)
        Week 8 (n= 142, 144)
    40.8 (32.7 to 49.4)
    34.7 (26.9 to 43.1)
        Week 12 (n= 142, 141)
    54.2 (45.7 to 62.6)
    51.1 (42.5 to 59.6)
        Week 24 (n= 139, 133)
    65.5 (56.9 to 73.3)
    60.6 (51.7 to 68.9)
        Week 52 (n= 122, 119)
    64.5 (55.3 to 72.9)
    66.1 (56.8 to 74.6)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Achieved American College of Rheumatology 70 (ACR70) Response at Week 2, 4, 8, 12, 24 and 52

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    End point title
    Percentage of Subjects Who Achieved American College of Rheumatology 70 (ACR70) Response at Week 2, 4, 8, 12, 24 and 52
    End point description
    ACR 70 Response is defined as greater than or equal to (>=) 70 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=70 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, subjects's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP). ITT Analysis Set was used. Here "n" signifies those subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Week 2, 4, 8, 12, 24 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Week 2 (n= 143, 145)
    0.7 (0.0 to 3.9)
    0.7 (0.0 to 3.8)
        Week 4 (n= 142, 144)
    4.9 (2.00 to 9.9)
    2.8 (0.8 to 6.9)
        Week 8 (n= 142, 144)
    14.8 (9.4 to 21.7)
    12.5 (7.6 to 19.0)
        Week 12 (n= 142, 141)
    26.8 (19.7 to 34.8)
    19.9 (13.6 to 27.4)
        Week 24 (n= 139, 133)
    33.8 (26.0 to 42.3)
    35.6 (27.5 to 44.4)
        Week 52 (n= 122, 119)
    39.7 (30.9 to 48.9)
    42.4 (33.3 to 51.8)
    No statistical analyses for this end point

    Secondary: Change from Baseline in Disease Activity Score Based on a 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 2, 4, 8, 12, 24 and 52

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    End point title
    Change from Baseline in Disease Activity Score Based on a 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 2, 4, 8, 12, 24 and 52
    End point description
    DAS calculated on 28 joints is composite score derived from 4 measures: number of swollen joints, number of tender joints, ESR, Patient’s Global Assessment of Disease Activity on VAS. Overall DAS28 was derived using following formulas from DAS28: DAS28=0.56*√(TJC28)+0.28*√(SJC28) +0.014*GH+0.70*ln(ESR). Where: TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, ln(ESR) = natural log of ESR, GH = general health component of DAS (ie, Patient’s Global Assessment of Disease Activity, assessed using scale of 1-100 where 100 is maximal activity; For analyses, GH divided by 10 & converted to a 0.5 scale, i.e., 0, 0.5, 1, 1.5. DAS28-ESR of >5.1 implies active disease, <3.2 low disease activity, & <2.6 remission. Change of 1.2(twice measurement error)= significant change of disease activity state. Overall score ranges from 0-10 where higher score means more severe disease. ITT Analysis Set used. Here “n”= subjects evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, 4, 8, 12, 24 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Change at Week 2 (n= 140, 145)
    -0.9 ± 0.9
    -0.7 ± 0.9
        Change at Week 4 (n= 141, 144)
    -1.4 ± 1.1
    -1.2 ± 1.0
        Change at Week 8 (n= 142, 144)
    -1.9 ± 0.9
    -1.7 ± 1.1
        Change at Week 12 (n= 142, 141)
    -2.4 ± 1.1
    -2.1 ± 1.2
        Change at Week 24 (n= 138, 132)
    -2.7 ± 1.0
    -2.3 ± 1.2
        Change at Week 52 (n= 121, 118)
    -2.8 ± 1.1
    -2.5 ± 1.1
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52

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    End point title
    Percentage of Subjects with Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
    End point description
    Disease Activity Score calculated on 28 joints is composite score derived from 4 measures: number of swollen joints (out of 28), -number of tender joints (out of 28), -Erythrocyte sedimentation rate (ESR), -Patient’s Global Assessment of Disease Activity on visual analog scale (VAS). Overall disease activity score DAS28 was derived using following formulas from DAS28: DAS28=0.56*√(TJC28)+0.28*√(SJC28) + 0.014*GH+0.70*ln(ESR). Where: -TJC28 = 28 joint count for tenderness, -SJC28 = 28 joint count for swelling, -ln(ESR) = natural logarithm of ESR, -GH = general health component of DAS (ie, Patient’s Global Assessment of Disease Activity, assessed using scale of 1 to 100 where 100 is maximal activity; For analyses, GH was divided by 10 and converted to a 0.5 scale, i.e., 0, 0.5, 1, 1.5. DAS28-ESR of >5.1 implies active disease, <3.2 low disease activity, and <2.6 remission. ITT Analysis Set used. Here "n" = subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Week 2, 4, 8, 12, 24, and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Low Disease Activity: Week 2 (n= 143, 145)
    10.0 (5.6 to 16.2)
    8.3 (4.4 to 14.0)
        Low Disease Activity: Week 4 (n= 142, 144)
    20.6 (14.2 to 28.2)
    16.0 (10.4 to 23.0)
        Low Disease Activity: Week 8 (n= 142, 144)
    33.1 (25.4 to 41.5)
    33.3 (25.7 to 41.7)
        Low Disease Activity: Week 12 (n= 142, 141)
    46.5 (38.1 to 55.0)
    42.6 (34.3 to 51.2)
        Low Disease Activity: Week 24 (n= 139, 133)
    55.1 (46.4 to 63.5)
    53.8 (44.9 to 62.5)
        Low Disease Activity: Week 52 (n= 122, 119)
    57.0 (47.7 to 65.9)
    56.8 (47.3 to 65.9)
        Remission: Week 2 (n= 143, 145)
    3.6 (1.2 to 8.1)
    2.1 (0.4 to 5.9)
        Remission: Week 4 (n= 142, 144)
    7.8 (3.9 to 13.5)
    6.9 (3.4 to 12.4)
        Remission: Week 8 (n= 142, 144)
    18.3 (12.3 to 25.7)
    16.0 (10.4 to 23.0)
        Remission: Week 12 (n= 142, 141)
    29.6 (22.2 to 37.8)
    24.1 (17.3 to 32.0)
        Remission: Week 24 (n= 139, 133)
    31.2 (23.6 to 39.6)
    34.1 (26.1 to 42.8)
        Remission: Week 52 (n= 122, 119)
    40.5 (31.7 to 49.8)
    36.4 (27.8 to 45.8)
    No statistical analyses for this end point

    Secondary: Change from Baseline in Simplified Disease Activity Index (SDAI) Total Score at Week 2, 4, 8, 12, 24, and 52

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    End point title
    Change from Baseline in Simplified Disease Activity Index (SDAI) Total Score at Week 2, 4, 8, 12, 24, and 52
    End point description
    SDAI is numerical sum of 5 parameters: tender & swollen joint count, Patient’s & Physician’s Global Assessment of Disease Activity (VAS) & level of C-reactive protein (CRP) (mg/dL), normal<1 mg/dL. SDAI was calculated based on following formula: SDAI = 28 joint count for swelling (SJC28) + 28 joint for tenderness (TJC28)+GH+PGA+CRP Where: GH =general health component of DAS (i.e. Patient’s Global Assessment of Disease Activity, assessed using scale of 1 to 100, here 100 is maximal activity. GH was divided by 10 & converted to 0.5 scale (0, 0.5, 1, 1.5).-PGA = Physician’s Global Assessment of Disease Activity assessed using scale of 1 to 100 where 100 is maximal activity. For analyses, PGA was divided by 10 & converted to 0.5 scale (0, 0.5, 1, 1.5). where [0-0.25=0, [0.25-0.75]=0.5, [0.76-1.25]=1. Total score range was 0-86 & lower score indicates less disease activity. ITT Analysis Set used. Here "n" signifies subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, 4, 8, 12, 24, and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Change at Week 2 (n= 139, 145)
    -11.5 ± 10.6
    -9.1 ± 10.0
        Change at Week 4 (n= 140, 140)
    -18.0 ± 11.3
    -16.0 ± 10.9
        Change at Week 8 (n= 141, 144)
    -24.0 ± 10.6
    -21.4 ± 11.0
        Change at Week 12 (n= 140, 141)
    -27.9 ± 10.8
    -24.7 ± 10.9
        Change at Week 24 (n= 136, 131)
    -31.4 ± 11.2
    -27.8 ± 10.6
        Change at Week 52 (n= 118, 118)
    -31.5 ± 11.6
    -29.1 ± 10.8
    No statistical analyses for this end point

    Secondary: Change From Baseline in Clinical Disease Activity Index (CDAI) Total Score at Week 2, 4, 8, 12, 24 and 52

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    End point title
    Change From Baseline in Clinical Disease Activity Index (CDAI) Total Score at Week 2, 4, 8, 12, 24 and 52
    End point description
    Clinical Disease Activity Index (CDAI) is a composite index (without acute-phase reactant) for assessing disease activity. CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA. Where, -GH = general health component of DAS (i.e., Patient’s Global Assessment of Disease Activity, assessed using a scale of 1 to 100 where 100 is maximal activity; GH was divided by 10 & converted to a 0.5 scale, i.e., 0, 0.5, 1, 1.5 etc. where [0-0.25] = 0,[0.25-0.75] = 0.5, [0.76-1.25] = 1, etc.). -PGA = Physician’s Global Assessment of Disease Activity assessed using a scale of 1 to 100 where 100 is maximal activity. PGA was divided by 10 & converted to a 0.5 scale, ie, 0, 0.5, 1, 1.5 etc. where [0-0.25] = 0, [0.25-0.75] = 0.5, [0.76-1.25] = 1. CDAI ranges from 0 to 76. Lower score indicates less disease activity. ITT Analysis Set used. Here "n"= subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, 4, 8, 12, 24 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Change at Week 2 (n= 139, 145)
    -10.8 ± 10.3
    -8.5 ± 9.9
        Change at Week 4 (n= 141, 144)
    -17.4 ± 11.2
    -15.2 ± 10.7
        Change at Week 8 (n= 141, 144)
    -23.5 ± 10.6
    -20.6 ± 10.9
        Change at Week 12 (n= 141, 141)
    -27.4 ± 10.5
    -24.1 ± 10.7
        Change at Week 24 (n= 138, 132)
    -30.8 ± 10.9
    -27.1 ± 10.7
        Change at Week 52 (n= 120, 118)
    -31.1 ± 11.2
    -28.5 ± 10.6
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission at Week 2, 4, 8, 12, 24 and 52

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    End point title
    Percentage of Subjects With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission at Week 2, 4, 8, 12, 24 and 52
    End point description
    According to Boolean-based definition of remission of ACR/EULAR, a Subjects must satisfy all of the following: tender joint count <= 1, swollen joint count <= 1, CRP <= 1 mg/dL, and Patient’s Global Assessment of Disease Activity <= 1 (0 to 10 VAS). Physician’s Global Assessment of Disease Activity (PGA) was assessed on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition. Here "n" signifies those subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Week 2, 4, 8, 12, 24 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Week 2 (n= 143, 145)
    0.7 (0.0 to 3.9)
    0.0 (0.0 to 2.5)
        Week 4 (n= 142, 144)
    0.7 (0.0 to 3.9)
    1.4 (0.8 to 5.1)
        Week 8 (n= 142, 144)
    3.5 (1.2 to 8.0)
    4.2 (1.5 to 8.9)
        Week 12 (n= 142, 141)
    5.7 (2.5 to 10.9)
    12.1 (7.2 to 18.6)
        Week 24 (n= 139, 133)
    11.7 (6.8 to 18.3)
    8.4 (4.3 to 14.5)
        Week 52 (n= 122, 119)
    21.0 (14.1 to 29.4)
    13.6 (7.9 to 21.1)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death

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    End point title
    Percentage of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
    End point description
    Adverse event(AE) was defined as any untoward medical occurrence in participants which does not necessarily have causal relationship with treatment. A serious adverse event(SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. All abnormal physical examinations occurring during the study have been reported as Adverse events. TEAEs included both Serious TEAEs and non-serious TEAEs. The Safety Analysis Set included all randomized subjects who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 69
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Percentage of Subjects
    number (not applicable)
        TEAEs
    58.0
    64.1
        Serious TEAEs
    5.6
    9.7
        TEAEs Leading to Death
    0
    0.7
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Clinically Meaningful Differences in Vital Signs

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    End point title
    Percentage of Subjects With Clinically Meaningful Differences in Vital Signs
    End point description
    Vital signs including body temperature, respiratory rate, and heart rate (after 5-minute rest) were measured. Percentage of subjects with clinically meaningful abnormalities in vital signs were reported. Clinical meaningful was determined by the investigator. The Safety Analysis Set included all randomized subjects who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Percentage of Subjects
        number (not applicable)
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Clinically Meaningful Differences in Laboratory values

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    End point title
    Percentage of Subjects With Clinically Meaningful Differences in Laboratory values
    End point description
    Laboratory parameters including hematology, urinalysis, and biochemistry analysis were analyzed. The Safety Analysis Set included all randomized subjects who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Percentage of Subjects
        number (not applicable)
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Clinically Significant Abnormal Values for 12-lead Electrocardiogram (ECG) at Week 12, 24, and 52

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    End point title
    Percentage of Subjects With Clinically Significant Abnormal Values for 12-lead Electrocardiogram (ECG) at Week 12, 24, and 52
    End point description
    Percentage of subjects with clinically significant abnormal values for 12-lead electrocardiogram (ECG) at week 12, 24, and 52 were reported. Here "n" signifies those subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Week 12, 24, and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Percentage of Subjects
    number (not applicable)
        Week 12 (n= 142, 141)
    0
    0
        Week 24 (n= 139, 133)
    0
    1.5
        Week 52 (n= 122, 119)
    0
    0.8
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Anti-Nuclear Antibody (ANA) and Anti double-stranded Deoxyribonucleic acid (Anti-dsDNA) at Baseline, Week 24 and 52

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    End point title
    Percentage of Subjects With Anti-Nuclear Antibody (ANA) and Anti double-stranded Deoxyribonucleic acid (Anti-dsDNA) at Baseline, Week 24 and 52
    End point description
    For ANA, positivity is defined as any subject with ANA titer greater than (>) 1:160 and negativity is defined as ANA titer less than (<) 1:160. For anti-ds DNA, positivity is defined as any subject with adsDNA > 15 units per milliliter (U/mL), intermediate category is defined as value between 10 U/mL to 15 U/mL and negativity is defined as adsDNA < 10 U/mL. Percentage of subjects with anti-nuclear antibody (ANA) and anti double-stranded deoxyribonucleic acid (Anti-dsDNA) at baseline, week 24 and 52 were reported. Here "n" signifies those subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Percentage of Subjects
    number (not applicable)
        Baseline: ANA: Negative (n= 143, 145)
    97.2
    95.1
        Baseline: ANA: Positive (n= 143, 145)
    2.8
    4.9
        Week 24: ANA: Negative (n= 138, 131)
    92.0
    91.6
        Week 24: ANA: Positive (n= 138, 131)
    8.0
    8.4
        Week 52: ANA: Negative (n= 118, 111)
    78.8
    84.7
        Week 52: ANA: Positive (n= 118, 111)
    21.2
    15.3
        Baseline: Anti-dsDNA: Negative (n= 141, 141)
    97.9
    98.6
        Baseline: Anti-dsDNA: Intermediate (n= 141, 141)
    1.4
    0.7
        Baseline: Anti-dsDNA: Positive (n= 141, 141)
    0.7
    0.7
        Week 24: Anti-dsDNA: Negative (n= 138, 132)
    95.7
    96.2
        Week 24: Anti-dsDNA: Intermediate (n= 138, 132)
    2.2
    3.0
        Week 24: Anti-dsDNA: Positive (n= 138, 132)
    2.2
    0.8
        Week 52: Anti-dsDNA: Negative (n= 121, 118)
    95.0
    97.5
        Week 52: Anti-dsDNA: Intermediate (n= 121, 118)
    0.8
    1.7
        Week 52: Anti-dsDNA: Positive (n= 121, 118)
    4.1
    0.8
    No statistical analyses for this end point

    Secondary: Health assessment questionnaire disability index (HAQ-DI) Total Score at Baseline, Weeks 12, 24 and 52

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    End point title
    Health assessment questionnaire disability index (HAQ-DI) Total Score at Baseline, Weeks 12, 24 and 52
    End point description
    The HAQ-DI is a participant-reported questionnaire that is commonly used in RA to measure disease associated disability (assessment of physical function). It consists of several questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. HAQ-DI scores range from 0 to 3. The disability section of the questionnaire scores 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). ITT analysis set was used. Here "n" signifies those subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 12, 24 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 143, 145)
    1.6 ± 0.6
    1.6 ± 0.6
        Week 12 (n= 142, 141)
    1.1 ± 0.6
    1.1 ± 0.6
        Week 24 (n= 139, 132)
    1.0 ± 0.6
    1.0 ± 0.6
        Week 52 (n= 121, 118)
    0.9 ± 0.7
    0.9 ± 0.6
    No statistical analyses for this end point

    Secondary: Short-Form Health Survey- 36 Items (SF-36) at Baseline, Week 12, 24 and 52

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    End point title
    Short-Form Health Survey- 36 Items (SF-36) at Baseline, Week 12, 24 and 52
    End point description
    SF-36: Validated 36-item, patient-reported indication of overall health status not specific to any age, disease/Treatment group. SF-36 questionnaire contains 36 questions pertaining to eight subscales of health status. 8 subscales summarized as relating to either physical health/mental health. Physical component summary (PCS): based primarily on physical functioning, role-physical, bodily pain & general health scales & mental component summary(MCS): vitality, social functioning, role-emotional & mental health scales. Score from mental health, role emotional, social functioning & vitality domains averaged to calculate MCS.Total score range for MCS: 0-100(100=highest level of mental functioning). Score from physical function, role physical, bodily pain & general health domains averaged to calculate PCS. Total score range for PCS: 0-100(100=highest level of physical functioning). ITT analysis set used. Here "n" signifies those subjects who evaluable for this endpoint at specified time.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Units on a scale
    arithmetic mean (standard deviation)
        PCS: Baseline (n= 134, 134)
    30.3 ± 7.6
    30.6 ± 7.8
        PCS: Week 12 (n= 142, 141)
    39.0 ± 7.9
    38.6 ± 8.6
        PCS: Week 24 (n= 139, 132)
    40.5 ± 8.8
    40.9 ± 9.1
        PCS: Week 52 (n= 121, 118)
    41.8 ± 9.5
    41.6 ± 9.3
        MCS: Baseline (n= 134, 134)
    40.9 ± 13.2
    43.4 ± 11.7
        MCS: Week 12 (n= 142, 141)
    47.4 ± 11.3
    48.2 ± 11.3
        MCS: Week 24 (n= 139, 132)
    49.8 ± 10.8
    48.8 ± 10.9
        MCS: Week 52 (n= 121, 118)
    48.0 ± 10.4
    49.3 ± 11.5
    No statistical analyses for this end point

    Secondary: Euro-Quality of Life - 5 dimension-5 levels (EQ-5D-5L) Utility Index Score at Baseline, Week 12, 24 and 52

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    End point title
    Euro-Quality of Life - 5 dimension-5 levels (EQ-5D-5L) Utility Index Score at Baseline, Week 12, 24 and 52
    End point description
    EQ-5D-5L: standardized, participant-rated questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L health state profile & EQ-5D-5L VAS. EQ-5D-5L descriptive system provides a profile of participant’s health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems & extreme problems) that reflect increasing levels of difficulty. Participant was asked to indicate his/her current health state by selecting most appropriate level in each of 5 dimensions. Responses to 5 dimension scores were combined & converted into single preference-weighted health utility index score 0(0.0- worst health state) to 1(1.0- better health state) representing general health status of individual based on UK scoring algorithm. ITT analysis set used. Here "n"= subjects who were evaluable for this endpoint at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 134, 133)
    0.6 ± 0.2
    0.6 ± 0.2
        Week 12 (n= 142, 140)
    0.8 ± 0.1
    0.8 ± 0.1
        Week 24 (n= 139, 132)
    0.8 ± 0.1
    0.8 ± 0.1
        Week 52 (n= 121, 118)
    0.8 ± 0.22
    0.8 ± 0.1
    No statistical analyses for this end point

    Secondary: Euro-Quality of Life - 5 dimension-5 levels (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Baseline, Week 12, 24 and 52

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    End point title
    Euro-Quality of Life - 5 dimension-5 levels (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Baseline, Week 12, 24 and 52
    End point description
    EQ-5D-5L: Standardized, participant-rated questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L health state profile & EQ-5D-5L VAS. EQ-5D-5L descriptive system provides a profile of participant’s health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 5 responses (no problems, slight problems, moderate problems, severe problems & extreme problems) that reflect increasing levels of difficulty. Responses to 5 dimension scores combined & converted into single preference-weighted health utility index score 0(worst health) to 1 (better health). EQ-VAS: Self-rated health status using a vertical VAS. EQ-VAS records participant's perceptions of their own current overall health in range from 0(worst imaginable health)-100(best imaginable health). ITT analysis set used. Here "n" signifies subjects evaluable for this endpoint at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24 and 52
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 134, 133)
    42.4 ± 18.5
    45.4 ± 20.4
        Week 12 (n= 142, 140)
    64.6 ± 19.6
    63.2 ± 20.9
        Week 24 (n= 139, 132)
    66.2 ± 22.2
    65.6 ± 24.3
        Week 52 (n= 121, 118)
    68.8 ± 21.7
    69.0 ± 22.7
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline (Week 4) in Injection Site Pain as Assessed by Visual Analogue Scale (VAS) at Week 6 and 8

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    End point title
    Mean Change From Baseline (Week 4) in Injection Site Pain as Assessed by Visual Analogue Scale (VAS) at Week 6 and 8
    End point description
    The participant's reported perception of pain was measured on a VAS where the slash drawn by the participant represents pain of increasing intensity. VAS score ranges from 0-10 millimeter [mm], where; 0 mm=no pain and 10 mm=worst possible pain. The first 2 injections was administered by qualified personnel. The next three doses of Investigational Medicinal Products (IMPs) (3-5) will be self-administered by the participant and injection site pain was assessed. Pain was recorded immediately after, 15 minutes after, and 1 hour after the injections received by the participants. The Safety Analysis Set included all randomized subjects who received at least one dose of study treatment. Here "n" signifies those subjects who were evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Immediately, 15 minutes and 1 hour post-injection on Baseline (Week 4), Week 6 and 8
    End point values
    MSB11022 EU-Humira
    Number of subjects analysed
    143
    145
    Units: Millimeter (mm)
    arithmetic mean (standard deviation)
        Week 4: Immediately post-injection (n= 140, 143)
    3.0 ± 8.4
    6.4 ± 14.3
        Week 4: 15 min post-injection (n= 140, 143)
    0.6 ± 2.5
    1.7 ± 7.6
        Week 4: 1 hour post-injection (n= 140, 143)
    0.1 ± 0.6
    0.8 ± 5.6
        Change:Week6:Immediately post-injection(n=140,143)
    -1.4 ± 5.1
    -1.3 ± 10.2
        Change:Week 6:15 min post-injection (n= 140, 143)
    -0.2 ± 2.7
    0.4 ± 3.3
        Change: Week 6:1 hour post-injection (n= 140, 143)
    0.0 ± 0.7
    0.0 ± 2.7
        Change:Week8:Immediately post-injection(n=140,139)
    -1.7 ± 6.5
    -2.3 ± 10.4
        Change:Week 8:15 min post-injection (n= 140, 139)
    -0.3 ± 2.3
    -0.7 ± 4.1
        Change:Week 8: 1 hour post-injection (n= 140, 139)
    -0.1 ± 0.6
    -0.7 ± 5.4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to Week 69
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    MSB11022
    Reporting group description
    Participants received MSB11022 subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.

    Reporting group title
    EU-Humira
    Reporting group description
    Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.

    Serious adverse events
    MSB11022 EU-Humira
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 143 (5.59%)
    15 / 145 (10.34%)
         number of deaths (all causes)
    0
    2
         number of deaths resulting from adverse events
    Investigations
    Mycobacterium tuberculosis complex test positive
         subjects affected / exposed
    1 / 143 (0.70%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Myocardial infarction
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Rheumatoid lung
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 143 (0.70%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Transient global amnesia
         subjects affected / exposed
    1 / 143 (0.70%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    1 / 143 (0.70%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    1 / 143 (0.70%)
    2 / 145 (1.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 143 (0.70%)
    2 / 145 (1.38%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical spinal stenosis
         subjects affected / exposed
    1 / 143 (0.70%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    1 / 143 (0.70%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    1 / 143 (0.70%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    MSB11022 EU-Humira
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    15 / 143 (10.49%)
    34 / 145 (23.45%)
    General disorders and administration site conditions
    Injection site erythema
         subjects affected / exposed
    4 / 143 (2.80%)
    12 / 145 (8.28%)
         occurrences all number
    4
    93
    Injection site pain
         subjects affected / exposed
    2 / 143 (1.40%)
    10 / 145 (6.90%)
         occurrences all number
    2
    25
    Injection site pruritus
         subjects affected / exposed
    1 / 143 (0.70%)
    8 / 145 (5.52%)
         occurrences all number
    1
    55
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    2 / 143 (1.40%)
    8 / 145 (5.52%)
         occurrences all number
    20
    38
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    6 / 143 (4.20%)
    13 / 145 (8.97%)
         occurrences all number
    6
    14

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Jul 2017
    - Administrative and editorial changes were undertaken to correct typographical errors that do not impact the design or execution of the study

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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