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    Clinical Trial Results:
    A 24-Week Multicenter, Randomized, Open-Label, Parallel-Group Study Comparing the Efficacy and Safety of Ixekizumab to Fumaric Acid Esters and Methotrexate in Patients With Moderate-to-Severe Plaque Psoriasis Who Are Naive to Systemic Treatment With an Extension Period

    Summary
    EudraCT number
    		 2015-002649-69
    Trial protocol
    		 DE  
    Global end of trial date
    14 Nov 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Nov 2018
    First version publication date
    28 Nov 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    I1F-EW-RHBZ
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02634801
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 16190
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Nov 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Nov 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main purpose of this study is to evaluate the efficacy and safety of ixekizumab compared to fumaric acid esters (FAE) and methotrexate (MTX) in participants with moderate-to-severe plaque psoriasis who are naive to systemic treatment.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Jan 2016
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 3 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 162
    Worldwide total number of subjects
    162
    EEA total number of subjects
    162
    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)
    154
    From 65 to 84 years
    8
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Treatment Period (Weeks 0 to 24), Extension Period (Weeks 24 to 36) followed by post-treatment follow-up period occurring from last treatment visit (week 36), or Early Termination Visit (ETV) up to a minimum of 12 weeks following that visit.

    Pre-assignment
    Screening details
    		 Not applicable

    Period 1
    Period 1 title
    Treatment Period (Weeks 0 to 24)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ixekizumab
    Arm description
    		 160 milligrams (mg) ixekizumab given as two subcutaneous injections (SC) followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ixekizumab
    Investigational medicinal product code
    Other name
    LY2439821
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    160 mg ixekizumab given as two subcutaneous (SC )injection followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. In extension period at week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.

    Arm title
    		 Fumaric Acid Esters
    Arm description
    		 Starting dose of 105 mg Fumaric Acid Esters (FAE) given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Fumaric Acid Esters
    Investigational medicinal product code
    Other name
    Fumaderm initial; FAE
    Pharmaceutical forms
    Gastro-resistant tablet
    Routes of administration
    Oral use
    Dosage and administration details
    FAE was administered as oral tablets. After starting oral FAE 105 mg (Fumaderm initial; until exhaustion of the package), FAE 215 mg (Fumaderm) was given orally immediately thereafter.

    Arm title
    		 Methotrexate
    Arm description
    		 7.5 mg starting dose up to 30 mg Methotrexate (MTX) given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Methotrexate
    Investigational medicinal product code
    Other name
    Lantarel
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    MTX was administered as oral tablets, starting with 7.5 mg/week, with a stepwise increase in dosage of 5 mg to 7.5 mg/week until a dose of 15 mg/week was reached.

    Number of subjects in period 1
    		Ixekizumab Fumaric Acid Esters Methotrexate
    Started
    54
    54
    54
    Received at Least 1 Dose of Study Drug
    54
    52
    52
    Completed
    50
    23
    49
    Not completed
    4
    31
    5
         Consent withdrawn by subject
    -
    8
    3
         Adverse event, non-fatal
    2
    20
    -
         Lost to follow-up
    2
    1
    1
         Lack of efficacy
    -
    2
    -
         Protocol deviation
    -
    -
    1
    Period 2
    Period 2 title
    Extension Period (Weeks 24 to 36)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ixekizumab
    Arm description
    		 160 milligrams (mg) ixekizumab given as two subcutaneous injections (SC) followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ixekizumab
    Investigational medicinal product code
    Other name
    LY2439821
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    160 mg ixekizumab given as two subcutaneous (SC )injection followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. In extension period at week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.

    Arm title
    		 Fumaric Acid Esters
    Arm description
    		 Starting dose of 105 mg Fumaric Acid Esters (FAE) given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Fumaric Acid Esters
    Investigational medicinal product code
    Other name
    Fumaderm initial; FAE
    Pharmaceutical forms
    Gastro-resistant tablet
    Routes of administration
    Oral use
    Dosage and administration details
    FAE was administered as oral tablets. After starting oral FAE 105 mg (Fumaderm initial; until exhaustion of the package), FAE 215 mg (Fumaderm) was given orally immediately thereafter.

    Arm title
    		 Methotrexate
    Arm description
    		 7.5 mg starting dose up to 30 mg Methotrexate (MTX) given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Methotrexate
    Investigational medicinal product code
    Other name
    Lantarel
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    MTX was administered as oral tablets, starting with 7.5 mg/week, with a stepwise increase in dosage of 5 mg to 7.5 mg/week until a dose of 15 mg/week was reached.

    Number of subjects in period 2 [1]
    		Ixekizumab Fumaric Acid Esters Methotrexate
    Started
    48
    19
    31
    Completed
    45
    18
    29
    Not completed
    3
    1
    2
         Consent withdrawn by subject
    1
    1
    1
         Adverse event, non-fatal
    -
    -
    1
         Lost to follow-up
    1
    -
    -
         Missing
    1
    -
    -
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Participants who discontinued previous periods had option to enter post treatment followup period.
    Period 3
    Period 3 title
    Followup
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Ixekizumab
    Arm description
    		 160 milligrams (mg) ixekizumab given as two subcutaneous injections (SC) followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ixekizumab
    Investigational medicinal product code
    Other name
    LY2439821
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    160 mg ixekizumab given as two subcutaneous (SC )injection followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. In extension period at week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.

    Arm title
    		 Fumaric Acid Esters
    Arm description
    		 Starting dose of 105 mg Fumaric Acid Esters (FAE) given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Fumaric Acid Esters
    Investigational medicinal product code
    Other name
    Fumaderm initial; FAE
    Pharmaceutical forms
    Gastro-resistant tablet
    Routes of administration
    Oral use
    Dosage and administration details
    FAE was administered as oral tablets. After starting oral FAE 105 mg (Fumaderm initial; until exhaustion of the package), FAE 215 mg (Fumaderm) was given orally immediately thereafter.

    Arm title
    		 Methotrexate
    Arm description
    		 7.5 mg starting dose up to 30 mg Methotrexate (MTX) given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Methotrexate
    Investigational medicinal product code
    Other name
    Lantarel
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    MTX was administered as oral tablets, starting with 7.5 mg/week, with a stepwise increase in dosage of 5 mg to 7.5 mg/week until a dose of 15 mg/week was reached.

    Number of subjects in period 3
    		Ixekizumab Fumaric Acid Esters Methotrexate
    Started
    41
    26
    46
    Completed
    36
    18
    38
    Not completed
    5
    8
    8
         Consent withdrawn by subject
    1
    2
    5
         Physician decision
    -
    -
    1
         Adverse event, non-fatal
    1
    5
    -
         Lost to follow-up
    3
    1
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Ixekizumab
    Reporting group description
    		 160 milligrams (mg) ixekizumab given as two subcutaneous injections (SC) followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.

    Reporting group title
    Fumaric Acid Esters
    Reporting group description
    		 Starting dose of 105 mg Fumaric Acid Esters (FAE) given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.

    Reporting group title
    Methotrexate
    Reporting group description
    		 7.5 mg starting dose up to 30 mg Methotrexate (MTX) given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.

    Reporting group values
    		 Ixekizumab Fumaric Acid Esters Methotrexate Total
    Number of subjects
    		 54 54 54 162
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 44.3 ( 13.84 ) 43.1 ( 14.16 ) 38.7 ( 12.90 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 12 11 18 41
        Male
    		 42 43 36 121
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0
        Asian
    		 1 0 3 4
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        Black or African American
    		 0 0 0 0
        White
    		 43 44 42 129
        More than one race
    		 10 10 9 29
        Unknown or Not Reported
    		 0 0 0 0
    Region of Enrollment
    Units: Subjects
        Germany
    		 54 54 54 162

    End points

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    End points reporting groups
    Reporting group title
    Ixekizumab
    Reporting group description
    		 160 milligrams (mg) ixekizumab given as two subcutaneous injections (SC) followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.

    Reporting group title
    Fumaric Acid Esters
    Reporting group description
    		 Starting dose of 105 mg Fumaric Acid Esters (FAE) given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.

    Reporting group title
    Methotrexate
    Reporting group description
    		 7.5 mg starting dose up to 30 mg Methotrexate (MTX) given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
    Reporting group title
    Ixekizumab
    Reporting group description
    		 160 milligrams (mg) ixekizumab given as two subcutaneous injections (SC) followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.

    Reporting group title
    Fumaric Acid Esters
    Reporting group description
    		 Starting dose of 105 mg Fumaric Acid Esters (FAE) given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.

    Reporting group title
    Methotrexate
    Reporting group description
    		 7.5 mg starting dose up to 30 mg Methotrexate (MTX) given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
    Reporting group title
    Ixekizumab
    Reporting group description
    		 160 milligrams (mg) ixekizumab given as two subcutaneous injections (SC) followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.

    Reporting group title
    Fumaric Acid Esters
    Reporting group description
    		 Starting dose of 105 mg Fumaric Acid Esters (FAE) given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.

    Reporting group title
    Methotrexate
    Reporting group description
    		 7.5 mg starting dose up to 30 mg Methotrexate (MTX) given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.

    Primary: Percentage of Participants with a ≥75% Improvement in Psoriasis Area and Severity Index (PASI 75) at Week 24

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    End point title
    		 Percentage of Participants with a ≥75% Improvement in Psoriasis Area and Severity Index (PASI 75) at Week 24
    End point description
    The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). Analysis Population Description (APD): All randomized participants who had a post-baseline measurement for PASI 75. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.
    End point type
    Primary
    End point timeframe
    Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    54
    54
    54
    Units: Percentage of Participants
        number (not applicable)
    90.7
    22.2
    70.4
    Statistical analysis title
    		 PASI 75
    Comparison groups
    Fumaric Acid Esters v Ixekizumab
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Fisher exact
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    4.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.46
         upper limit
    		 6.77
    Statistical analysis title
    		 PASI 75
    Comparison groups
    Ixekizumab v Methotrexate
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0137
    Method
    		 Fisher exact
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.06
         upper limit
    		 1.56

    Secondary: Percentage of Participants with a ≥90% Improvement in Psoriasis Area and Severity Index (PASI 90) from Baseline

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    End point title
    		 Percentage of Participants with a ≥90% Improvement in Psoriasis Area and Severity Index (PASI 90) from Baseline
    End point description
    The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). APD: All randomized participants who had a post-baseline measurement for PASI 90. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    54
    54
    54
    Units: Percentage of Participants
        number (not applicable)
    79.6
    9.3
    38.9
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a 100% Improvement in Psoriasis Area and Severity Index (PASI 100) from Baseline

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    End point title
    		 Percentage of Participants with a 100% Improvement in Psoriasis Area and Severity Index (PASI 100) from Baseline
    End point description
    The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). APD: All randomized participants who had a post-baseline measurement for PASI 100. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    54
    54
    54
    Units: Percentage of Participants
        number (not applicable)
    40.7
    3.7
    13.0
    No statistical analyses for this end point

    Secondary: Change from baseline in PASI Total Score

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    End point title
    		 Change from baseline in PASI Total Score
    End point description
    The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). LS mean change from baseline in PASI was calculated using Analysis of Covariance (ANCOVA) with modified Baseline- Observation- Carried Forward (mBOCF) and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for PASI.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    54
    50
    52
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -16.68 (-18.46 to -14.91)
    -4.93 (-6.78 to -3.09)
    -14.61 (-16.42 to -12.80)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Static Physician Global Assessment (sPGA) (0,1) and ≥2 Point Improvement from Baseline among those with sPGA Score ≥3 at Baseline

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    End point title
    		 Percentage of Participants with a Static Physician Global Assessment (sPGA) (0,1) and ≥2 Point Improvement from Baseline among those with sPGA Score ≥3 at Baseline
    End point description
    The sPGA is the physician's determination of the participant's Psoriasis (Ps) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of "0" or "1" with at least a 2-point improvement from baseline. APD: All randomized participants with baseline sPGA >=3 & received at least 1 dose of study drug and had a post-baseline measurement for sPGA. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    52
    53
    52
    Units: Percentage of Participants
        number (not applicable)
    86.5
    13.2
    51.9
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving DLQI (0,1)

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    End point title
    		 Percentage of Participants Achieving DLQI (0,1)
    End point description
    The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "not at all," "a lot," and "very much," with corresponding scores of 1, 2, and 3, respectively, and unanswered ("not relevant") responses scored as "0." Totals range from 0 to 30 (less to more impairment), and a 5-point change from baseline is considered clinically relevant. APD: All randomized participants who had a post-baseline measurement for DLQI. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    54
    54
    54
    Units: Percentage of Participants
        number (not applicable)
    63.0
    14.8
    37.0
    No statistical analyses for this end point

    Secondary: Change from Baseline on Dermatology Life Quality Index (DLQI) Total Score

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    End point title
    		 Change from Baseline on Dermatology Life Quality Index (DLQI) Total Score
    End point description
    The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "not at all," "a lot," and "very much," with corresponding scores of 1, 2, and 3, respectively, and unanswered ("not relevant") responses scored as "0." Totals range from 0 to 30 (less to more impairment), and a 5-point change from baseline is considered clinically relevant. LS mean change from baseline in DLQI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for DLQI. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    52
    49
    49
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -13.08 (-14.56 to -11.61)
    -5.37 (-6.88 to -3.86)
    -12.81 (-14.32 to -11.29)
    No statistical analyses for this end point

    Secondary: Change from Baseline in Body Surface Area (BSA) Affected by Psoriasis

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    End point title
    		 Change from Baseline in Body Surface Area (BSA) Affected by Psoriasis
    End point description
    The percentage involvement of psoriasis on each participant's body surface area was assessed by the investigator on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand including palm, fingers and thumb. LS mean change from baseline in BSA was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for BSA. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    54
    50
    52
    Units: % Body Surface Affected
        least squares mean (confidence interval 95%)
    -20.64 (-23.21 to -18.08)
    -5.26 (-7.93 to -2.60)
    -18.46 (-21.08 to -15.85)
    No statistical analyses for this end point

    Secondary: Change from Baseline in Palmoplantar Psoriasis Severity Index (PPASI) Total Score

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    End point title
    		 Change from Baseline in Palmoplantar Psoriasis Severity Index (PPASI) Total Score
    End point description
    The Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 (no PPASI) to 72 (most severe PPASI). The PPASI was only assessed if participants have palmoplantar psoriasis at baseline. LS mean change from baseline in PPASI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for PPASI. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    12
    14
    9
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -7.23 (-10.88 to -3.59)
    -2.45 (-6.03 to 1.13)
    -3.77 (-8.10 to 0.56)
    No statistical analyses for this end point

    Secondary: Change from Baseline in Psoriasis Scalp Severity Index (PSSI) Total Score

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    End point title
    		 Change from Baseline in Psoriasis Scalp Severity Index (PSSI) Total Score
    End point description
    The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (<10%) to 6 (90%-100%) with a total score ranging from 0 (less severity) to 72 (more severity). LS mean change from baseline in PSSI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for Psoriasis Scalp. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    40
    39
    40
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -20.85 (-23.63 to -18.06)
    -6.76 (-9.58 to -3.94)
    -18.56 (-21.35 to -15.78)
    No statistical analyses for this end point

    Secondary: Patient Benefit Index (PBI) overall benefit score

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    End point title
    		 Patient Benefit Index (PBI) overall benefit score
    End point description
    The PBI assessment consists of 2 steps: before treatment, every patient defines his/her treatment needs according to a standardized list (Patient Needs Questionnaire [PNQ]). After treatment, the patient rates the degree of benefits achieved (Patient Benefits Questionnaire [PBQ]). 25 items are rated on a 5-point scale with values from 0 (not at all) to 4 (very), allowing for “did not apply to me” (5) and missing. For each treatment goal the PNQ importance is derived by dividing the respective PNQ item by the sum of all PNQ items. The weighted sum of each PBQ item with its respective PNQ importance yields the PBI score. LS mean was calculated using ANCOVA with LOCF and with a term for treatment. APD: All randomized participants who received at least 1 dose of study drug and had a baseline PBI questionnaire such that postbaseline PBI assessments can be valid (nonmissing).
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    43
    41
    50
    Units: units on a scale
        least squares mean (confidence interval 95%)
    3.42 (2.99 to 3.84)
    2.33 (1.81 to 2.84)
    2.66 (2.23 to 3.10)
    No statistical analyses for this end point

    Secondary: Change from Baseline on Itch Numeric Rating Scale (NRS) Score

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    End point title
    		 Change from Baseline on Itch Numeric Rating Scale (NRS) Score
    End point description
    The Itch NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing “no itch” and 10 representing “worst itch imaginable.” Overall severity of a participant's itching from psoriasis (Ps) is indicated by circling the number that best describes the worst level of itching in the past 24 hours. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for Itch NRS score. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    53
    50
    52
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -5.25 (-5.89 to -4.61)
    -1.50 (-2.15 to -0.84)
    -4.40 (-5.05 to -3.76)
    No statistical analyses for this end point

    Secondary: Change from Baseline on the Skin Pain Visual Analog Scale (VAS)

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    End point title
    		 Change from Baseline on the Skin Pain Visual Analog Scale (VAS)
    End point description
    The pain VAS is a participant-administered single-item scale designed to measure Skin pain from Psoriasis using a 100 millimeter (mm) horizontal VAS. Overall severity of participant's skin pain from Psoriasis is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no pain) to 100 mm (pain as severe as you can imagine). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for skin pain VAS. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    53
    50
    52
    Units: Millimeter (mm)
        least squares mean (confidence interval 95%)
    -33.83 (-39.46 to -28.20)
    -7.20 (-12.99 to -1.42)
    -28.29 (-33.98 to -22.60)
    No statistical analyses for this end point

    Secondary: Change from Baseline on Quick Inventory of Depressive Symptomatology-Self Report (16 items) (QIDS-SR16)

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    End point title
    		 Change from Baseline on Quick Inventory of Depressive Symptomatology-Self Report (16 items) (QIDS-SR16)
    End point description
    QIDS-SR16 is a participant-administered, 16-item instrument intended to assess the existence and severity of symptoms of depression. A participant is asked to consider each statement as it relates to the way they have felt for the past 7 days and rate each on a 4-point scale: 0 (best) to 3 (worst). The sum of the 16 items corresponding to 9 depression domains [sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance (initial, middle and late insomnia or hypersomnia), decrease/increase in appetite/weight, and psychomotor agitation/retardation] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity. Whereas 0-5 indicates no symptoms. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for QIDS-SR16.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    51
    49
    50
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -2.16 (-3.00 to -1.32)
    -1.01 (-1.89 to -0.14)
    -2.50 (-3.37 to -1.64)
    No statistical analyses for this end point

    Secondary: Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS)

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    End point title
    		 Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS)
    End point description
    The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, lower scores = more disability, higher scores = less disability and better health. In this study, the SF-36 acute version was used, which has a 1-week recall period. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for SF36 PCS score.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    50
    48
    49
    Units: units on a scale
        least squares mean (confidence interval 95%)
    4.45 (2.29 to 6.60)
    0.57 (-1.64 to 2.77)
    4.01 (1.83 to 6.19)
    No statistical analyses for this end point

    Secondary: Change from Baseline in 36-Item Short Form Health Survey (SF-36) Mental Component Summary (MCS) Scores

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    End point title
    		 Change from Baseline in 36-Item Short Form Health Survey (SF-36) Mental Component Summary (MCS) Scores
    End point description
    The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, lower scores = more disability, higher scores = less disability and better health. In this study, the SF-36 acute version was used, which has a 1-week recall period. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for SF36 MCS score.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    50
    48
    49
    Units: units on a scale
        least squares mean (confidence interval 95%)
    7.13 (4.99 to 9.27)
    3.39 (1.19 to 5.59)
    6.99 (4.80 to 9.17)
    No statistical analyses for this end point

    Secondary: Change from Baseline on Patient’s Global Assessment (PatGA) of Disease Severity

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    End point title
    		 Change from Baseline on Patient’s Global Assessment (PatGA) of Disease Severity
    End point description
    The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for PatGA. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    54
    50
    50
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -3.12 (-3.47 to -2.78)
    -0.87 (-1.23 to -0.51)
    -2.39 (-2.75 to -2.04)
    No statistical analyses for this end point

    Secondary: Change from Baseline on the Psoriasis Skin Appearance Bothersomeness (PSAB) total score

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    End point title
    		 Change from Baseline on the Psoriasis Skin Appearance Bothersomeness (PSAB) total score
    End point description
    PSAB measure is a 3-item scale designed to measure the degree of bothersomeness of skin appearance due to Ps in participants with Ps. Participants are asked to indicate on 3 numeric rating scales (NRS) from 0 (not at all bothered) to 10 (extremely bothered) how bothered they are by any redness or discoloration, thickness, and scaling or flaking on their skin due to Ps. The scores from the 3 NRS items are summed for a total score ranging from 0 to 30, where 0 indicating no bothersomeness and 30 indicating greater bothersomeness. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for PSAB. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    52
    47
    48
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -19.87 (-22.38 to 17.36)
    -5.18 (-7.82 to -2.54)
    -15.05 (-17.67 to -12.43)
    No statistical analyses for this end point

    Secondary: Change from Baseline on the Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA-CLIN) Total Score

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    End point title
    		 Change from Baseline on the Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA-CLIN) Total Score
    End point description
    NAPPA is a clinical and participant-reported outcomes tool, and consists of 3 components: a questionnaire assessing nail-specific quality of life NAPPA-QoL (Nail Assessment in Psoriasis and Psoriatic Arthritis Quality of Life), a 2-part questionnaire assessing participant relevant needs and treatment benefits NAPPA-PBI (Nail Assessment in Psoriasis and Psoriatic Arthritis – Patient Benefit Index), and a clinical assessment of objective finger nail psoriasis severity NAPPA-CLIN. Sum of all assessed finger and toes ranging between 0 (no involvement) to 16 (worst involvement). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who had palmoplantar, scalp, or nail involvement at baseline. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    35
    29
    27
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -6.58 (-8.12 to -5.04)
    -0.14 (-1.91 to 1.62)
    -3.41 (-5.30 to -1.52)
    No statistical analyses for this end point

    Secondary: Change from Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D) + Bolt On UK population-based index score

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    End point title
    		 Change from Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D) + Bolt On UK population-based index score
    End point description
    The European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of a descriptive system of the respondent's health which comprises the following 5 dimensions: 1) mobility 2) self-care 3) usual activities 4) pain/discomfort 5) anxiety/depression. The EQ-5D-5L health states were converted into a single summary index by applying a crosswalk using a United Kingdom (UK) Population value set to each of the levels in each dimension. This produced participant-level index scores between -0.594 and 1.0 (worse to better health). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for EQ-5D 5L Index.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    52
    47
    50
    Units: units on a scale
        least squares mean (confidence interval 95%)
    0.15 (0.11 to 0.20)
    0.04 (-0.01 to 0.09)
    0.15 (0.10 to 0.20)
    No statistical analyses for this end point

    Secondary: Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D 5L) "Bolt On" - Psoriasis (PSO) index score

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    End point title
    		 Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D 5L) "Bolt On" - Psoriasis (PSO) index score
    End point description
    The European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of a descriptive system of the respondent's health which comprises the following 5 dimensions: 1) mobility 2) self-care 3) usual activities 4) pain/discomfort 5) anxiety/depression. The Bolt On PSO is an addition to the EQ-5D-5L that consists of 2 dimensions specific to psoriatic disease: 6) skin irritation (itching) and 7) self-confidence. Index scores for the Bolt On PSO range from 0.0042 to 1.0 (worse to better health). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for EQ-5D 5L "Bolt On" PSO-Index.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    52
    46
    50
    Units: units on a scale
        least squares mean (confidence interval 95%)
    0.15 (0.12 to 0.18)
    0.05 (0.01 to 0.08)
    0.13 (0.10 to 0.16)
    No statistical analyses for this end point

    Secondary: Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D 5L) "Bolt On" - Visual Analog Scale Score

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    End point title
    		 Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D 5L) "Bolt On" - Visual Analog Scale Score
    End point description
    The EQ-5D 5L is a standardized measure of health status that includes a descriptive system of the respondent's health and a rating of his/her current health state using a 0 (worst health imaginable)- to 100 (best health imaginable)-millimeter (mm) Visual Analog Scale (VAS). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for EQ-5D 5L + Bolt on VAS.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    52
    48
    50
    Units: Millimeter (mm)
        least squares mean (confidence interval 95%)
    16.91 (12.23 to 21.59)
    6.08 (1.21 to 10.96)
    13.91 (9.14 to 18.69)
    No statistical analyses for this end point

    Secondary: Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Absenteeism score

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    End point title
    		 Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Absenteeism score
    End point description
    The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for WPAI-PSO absenteeism score.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    26
    30
    39
    Units: units on a scale
        least squares mean (confidence interval 95%)
    3.08 (-3.79 to 9.96)
    -1.26 (-7.69 to 5.17)
    0.06 (-5.49 to 5.62)
    No statistical analyses for this end point

    Secondary: Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Presenteeism Score

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    End point title
    		 Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Presenteeism Score
    End point description
    The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for WPAI-PSO Presenteeism score.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    29
    32
    39
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -22.70 (-28.73 to -16.66)
    -5.29 (-11.10 to 0.52)
    -20.32 (-25.51 to -15.13)
    No statistical analyses for this end point

    Secondary: Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Impairment in Activities Performed Outside of Work

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    End point title
    		 Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Impairment in Activities Performed Outside of Work
    End point description
    The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for WPAI-PSO.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    53
    50
    48
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -28.23 (-33.99 to -22.47)
    -3.45 (-9.38 to 2.47)
    -23.57 (-29.58 to -17.55)
    No statistical analyses for this end point

    Secondary: Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Overall Work Impairment Score

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    End point title
    		 Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Overall Work Impairment Score
    End point description
    The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment. APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for WPAI-PSO.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    25
    30
    38
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -18.20 (-26.29 to -10.11)
    -6.20 (-13.66 to 1.27)
    -19.80 (-26.31 to -13.29)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Positive Responses to Neck/Face Psoriasis Question

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    End point title
    		 Percentage of Participants with Positive Responses to Neck/Face Psoriasis Question
    End point description
    Studying psoriasis involvement in the face, neck, and the genitals is of considerable interest for participants. These are locations that bear high potential for stigmatization and/or psychological distress, and, hence, effects in those regions are assumed to heavily influence participant's quality of life. Following set of binary questions were asked to check the satisfaction of participants. 1) Does the participant currently have visible psoriasis on face/neck? (Yes/No) 2) Does the participant currently have psoriasis on the genital area? (Yes/No). APD: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for binary questions. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    33
    34
    36
    Units: Percentage of Participants
        number (not applicable)
    81.8
    26.5
    66.7
    No statistical analyses for this end point

    Secondary: Percentage of Participants positive responses to genital psoriasis question

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    End point title
    		 Percentage of Participants positive responses to genital psoriasis question
    End point description
    Studying psoriasis involvement in the face, neck, and the genitals is of considerable interest for participants. These are locations that bear high potential for stigmatization and/or psychological distress, and, hence, effects in those regions are assumed to heavily influence participant's quality of life. Following set of binary questions were asked to check the satisfaction of participants. 1) Does the patient currently have visible psoriasis on face/neck? (Yes/No) 2) Does the patient currently have psoriasis on the genital area? (Yes/No) The genital area includes the labia majora (hair-bearing), labia minora modified mucus membrane, and perineum in female patients; and the penis glans, penis – shaft, and scrotum in male patients. APD:All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for binary questions. Participants who did not meet the clinical response criteria or had missing data were considered NRI analys
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    20
    24
    24
    Units: Percentage of participants
        number (not applicable)
    85.0
    29.2
    75.0
    No statistical analyses for this end point

    Secondary: Mean adherence on medication and satisfaction with therapy (STAQ)

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    End point title
    		 Mean adherence on medication and satisfaction with therapy (STAQ)
    End point description
    STAQ is a 38 item questionnaire that was developed by shortening and adapting the Topical Treatment Adherence Questionnaire (TTAQ) for administration to participants under systemic therapy. The following STAQ items are of special interest for this study. 1) STAQ item 13 (The treatment does not affect my sex life) 2) STAQ item 16 (I am enjoying life again as a result of the treatment) 3) STAQ item 20 (The side effects of the treatment were acceptable) 4) STAQ item 31 (I am satisfied with the efficacy of the treatment) 5) STAQ item 32 (I am satisfied with the tolerability of the treatment) 6) STAQ item 35 (The positive aspects of the treatment outweigh the negative ones). The STAQ items are on a 4-point Likert scale with scores between 0 (strong disagreement) and 3 (strong agreement). LS mean was calculated using ANCOVA with term for treatment. APD: All randomized participants who received at least 1 dose of study drug and had a post-baseline measurement for STAQ.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Ixekizumab Fumaric Acid Esters Methotrexate
    Number of subjects analysed
    49
    22
    48
    Units: units on a scale
    least squares mean (confidence interval 95%)
        STAQ item 13|
    2.84 (2.68 to 3.00)
    2.75 (2.51 to 2.99)
    2.78 (2.61 to 2.94)
        STAQ item 16|
    2.82 (2.60 to 3.04)
    2.00 (1.68 to 2.32)
    2.43 (2.20 to 2.66)
        STAQ item 20|
    2.76 (2.51 to 3.01)
    2.00 (1.66 to 2.34)
    2.42 (2.17 to 2.66)
        STAQ item 31|
    2.88 (2.68 to 3.08)
    2.09 (1.79 to 2.39)
    2.29 (2.09 to 2.50)
        STAQ item 32|
    2.86 (2.66 to 3.05)
    1.95 (1.66 to 2.25)
    2.50 (2.30 to 2.70)
        STAQ item 35|
    2.80 (2.58 to 3.02)
    2.14 (1.82 to 2.46)
    2.53 (2.31 to 2.75)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Entire Study
    Adverse event reporting additional description
    All randomized participants.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Ixekizumab-Treatment Period
    Reporting group description
    		 -

    Reporting group title
    Fumaric Acid Esters-Treatment Period
    Reporting group description
    		 -

    Reporting group title
    Methotrexate-Treatment Period
    Reporting group description
    		 -

    Reporting group title
    Fumaric Acid Esters-Extension Period
    Reporting group description
    		 -

    Reporting group title
    Methotrexate-Extension Period
    Reporting group description
    		 -

    Reporting group title
    Ixekizumab-Extension Period
    Reporting group description
    		 -

    Reporting group title
    Follow-up period
    Reporting group description
    		 -

    Serious adverse events
    		 Ixekizumab-Treatment Period Fumaric Acid Esters-Treatment Period Methotrexate-Treatment Period Fumaric Acid Esters-Extension Period Methotrexate-Extension Period Ixekizumab-Extension Period Follow-up period
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 54 (1.85%)
    3 / 52 (5.77%)
    1 / 52 (1.92%)
    1 / 19 (5.26%)
    4 / 31 (12.90%)
    3 / 48 (6.25%)
    4 / 113 (3.54%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    anogenital warts
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    1 / 31 (3.23%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    invasive lobular breast carcinoma
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pancreatic neuroendocrine tumour
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    atrioventricular block complete
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    sciatica
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    1 / 113 (0.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    lymphadenopathy
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    1 / 113 (0.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    abdominal pain
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    colitis
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastritis erosive
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    hepatic cirrhosis
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    1 / 113 (0.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    tonsillar hypertrophy
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    1 / 31 (3.23%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    intervertebral disc protrusion
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    osteoarthritis
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    2 / 31 (6.45%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    erysipelas
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastroenteritis
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    1 / 113 (0.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    infected dermal cyst
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Ixekizumab-Treatment Period Fumaric Acid Esters-Treatment Period Methotrexate-Treatment Period Fumaric Acid Esters-Extension Period Methotrexate-Extension Period Ixekizumab-Extension Period Follow-up period
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    37 / 54 (68.52%)
    39 / 52 (75.00%)
    38 / 52 (73.08%)
    15 / 19 (78.95%)
    18 / 31 (58.06%)
    24 / 48 (50.00%)
    0 / 113 (0.00%)
    Vascular disorders
    flushing
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    13 / 52 (25.00%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    19
    0
    0
    0
    0
    0
    haematoma
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    fatigue
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    4 / 54 (7.41%)
    3 / 52 (5.77%)
    8 / 52 (15.38%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    4
    3
    14
    1
    0
    0
    0
    injection site erythema
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    2 / 19 (10.53%)
    3 / 31 (9.68%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    10
    13
    0
    0
    injection site pruritus
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    1 / 31 (3.23%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    3
    1
    0
    0
    injection site reaction
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    7 / 54 (12.96%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    3 / 19 (15.79%)
    6 / 31 (19.35%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences all number
    23
    0
    0
    6
    31
    9
    0
    injection site swelling
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    2 / 19 (10.53%)
    3 / 31 (9.68%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    10
    9
    0
    0
    Respiratory, thoracic and mediastinal disorders
    bronchial hyperreactivity
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    cough
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    1 / 54 (1.85%)
    2 / 52 (3.85%)
    1 / 52 (1.92%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences all number
    1
    2
    1
    1
    0
    1
    0
    oropharyngeal pain
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    3 / 54 (5.56%)
    1 / 52 (1.92%)
    1 / 52 (1.92%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences all number
    3
    1
    1
    1
    0
    1
    0
    Investigations
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    1 / 31 (3.23%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    gamma-glutamyltransferase increased
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    3 / 52 (5.77%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    weight increased
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    2 / 31 (6.45%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    0
    Injury, poisoning and procedural complications
    arthropod bite
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    3 / 52 (5.77%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    0
    Nervous system disorders
    dizziness
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    2 / 54 (3.70%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences all number
    2
    0
    1
    1
    0
    1
    0
    headache
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    7 / 54 (12.96%)
    4 / 52 (7.69%)
    9 / 52 (17.31%)
    1 / 19 (5.26%)
    2 / 31 (6.45%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences all number
    7
    4
    12
    1
    2
    1
    0
    Blood and lymphatic system disorders
    lymphopenia
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    5 / 52 (9.62%)
    2 / 52 (3.85%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    5
    2
    1
    0
    0
    0
    Ear and labyrinth disorders
    middle ear inflammation
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    vertigo
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    2 / 54 (3.70%)
    3 / 52 (5.77%)
    3 / 52 (5.77%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    2
    3
    5
    0
    0
    0
    0
    Gastrointestinal disorders
    abdominal pain upper
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    2 / 54 (3.70%)
    19 / 52 (36.54%)
    6 / 52 (11.54%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences all number
    2
    26
    6
    0
    0
    1
    0
    diarrhoea
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    1 / 54 (1.85%)
    24 / 52 (46.15%)
    6 / 52 (11.54%)
    1 / 19 (5.26%)
    1 / 31 (3.23%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences all number
    1
    29
    6
    1
    1
    1
    0
    dyspepsia
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    flatulence
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    3 / 52 (5.77%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    3
    0
    1
    0
    0
    0
    nausea
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    1 / 54 (1.85%)
    3 / 52 (5.77%)
    5 / 52 (9.62%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    1
    4
    14
    1
    0
    0
    0
    oral mucosal eruption
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    vomiting
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    3 / 52 (5.77%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    alopecia
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    2 / 54 (3.70%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 19 (0.00%)
    2 / 31 (6.45%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    2
    0
    1
    0
    2
    0
    0
    dermatitis
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    eczema
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    2 / 19 (10.53%)
    2 / 31 (6.45%)
    2 / 48 (4.17%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    2
    2
    4
    0
    ingrowing nail
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    nail psoriasis
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    night sweats
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    xanthelasma
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    2 / 54 (3.70%)
    0 / 52 (0.00%)
    4 / 52 (7.69%)
    0 / 19 (0.00%)
    2 / 31 (6.45%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences all number
    2
    0
    6
    0
    2
    1
    0
    back pain
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    1 / 54 (1.85%)
    2 / 52 (3.85%)
    5 / 52 (9.62%)
    0 / 19 (0.00%)
    0 / 31 (0.00%)
    3 / 48 (6.25%)
    0 / 113 (0.00%)
         occurrences all number
    1
    2
    5
    0
    0
    3
    0
    bursitis
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    2 / 31 (6.45%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    musculoskeletal pain
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    myalgia
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    2 / 19 (10.53%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    1
    4
    0
    0
    0
    pain in extremity
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    1 / 54 (1.85%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    1 / 31 (3.23%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences all number
    1
    1
    0
    1
    1
    1
    0
    Infections and infestations
    bronchitis
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    1 / 54 (1.85%)
    1 / 52 (1.92%)
    1 / 52 (1.92%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    2 / 48 (4.17%)
    0 / 113 (0.00%)
         occurrences all number
    1
    1
    1
    1
    0
    2
    0
    gastroenteritis
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    1 / 54 (1.85%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 19 (0.00%)
    2 / 31 (6.45%)
    2 / 48 (4.17%)
    0 / 113 (0.00%)
         occurrences all number
    1
    1
    0
    0
    2
    2
    0
    impetigo
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    nasopharyngitis
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    20 / 54 (37.04%)
    9 / 52 (17.31%)
    18 / 52 (34.62%)
    6 / 19 (31.58%)
    10 / 31 (32.26%)
    18 / 48 (37.50%)
    0 / 113 (0.00%)
         occurrences all number
    23
    13
    21
    7
    15
    25
    0
    sinusitis
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 52 (1.92%)
    1 / 52 (1.92%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    0
    tinea pedis
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    2 / 54 (3.70%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    2 / 19 (10.53%)
    0 / 31 (0.00%)
    1 / 48 (2.08%)
    0 / 113 (0.00%)
         occurrences all number
    2
    0
    1
    2
    0
    1
    0
    tooth infection
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Metabolism and nutrition disorders
    hyperlipidaemia
    alternative dictionary used: MedDRA 19.1
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 19 (5.26%)
    0 / 31 (0.00%)
    0 / 48 (0.00%)
    0 / 113 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Nov 2015
    Amendment (b): Amended to include a statement on dose reduction for fumaderm and methotrexate.
    07 Apr 2016
    Amendment (c): Amended to provide outcome description and scale details for Columbia Suicide Severity Rating Scale and Quick Inventory of Depressive Symptomatology-Self Report (16 items) (QIDS-SR16).
    07 Jun 2016
    Amendment (d): Amended study design at Week 24.

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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