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    Clinical Trial Results:
    An international prospective, double-blind, placebo-controlled phase III RCT in which patients with moderate to severe psoriasis vulgaris are treated with s.c. methotrexate using an optimized treatment schedule

    Summary
    EudraCT number
    		 2012-002716-10
    Trial protocol
    		 DE   GB   NL  
    Global end of trial date
    07 Apr 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 Jun 2022
    First version publication date
    24 Jun 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    165-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Dermatologikum Hamburg
    Sponsor organisation address
    Stephansplatz 5, Hamburg, Germany, 20354
    Public contact
    Prof. Dr. med. Kristian Reich, Dermatologikum Hamburg, +49 4035107579,
    Scientific contact
    Prof. Dr. med. Kristian Reich, Dermatologikum Hamburg, +49 4035107579,
    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
    10 Feb 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    13 May 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Apr 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is to evaluate the efficacy of subcutaneous application of MTX in patients with moderate to severe psoriasis compared to placebo as determined by the number of patients reaching the primary endpoint PASI 75 after a 16 week treatment phase in the two study arms.
    Protection of trial subjects
    Informed consent of subject was obtained in accordance with § 40 I 3 No. 3 Lit. b), II 1 AMG and § 40 I 3 No. 3 Lit. c). IIa 1&2 AMG by each investigator prior to inclusion of each patient to the study. The nature, objective and importance of the study, the possible benefits and disadvantages or risks, and the study procedures were explained to each subject orally and in writing. The subjects were informed that their participation was voluntary, that they were free to withdraw from the study at any time, and that choosing not to participate would not impact on the subject’s care or future treatment. Subjects were also informed that, by signing the ICF, they explicitly permitted authorised representatives of the sponsor and regulatory authorities to access study-related personal data to the extent permitted by the applicable law(s) and/or regulations without violating the confidentiality of the subject. Subjects were also informed that their consent to access their data could not be revoked. Each subject was given sufficient time to read and discuss the ICF with the investigator prior to giving his/her written consent. Prior to study entry and any study-related examination, informed consent was documented by the subject’s dated signature. The subject was then given a copy of the information sheet and his/her signed ICF. The ICF was retained by the investigator as part of the study records. The terms and date of consent were also documented in the Case Report Form (CRF).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    22 Feb 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    United Kingdom: 11
    Country: Number of subjects enrolled
    Germany: 108
    Worldwide total number of subjects
    120
    EEA total number of subjects
    109
    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)
    112
    From 65 to 84 years
    8
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 142 subjects were screened at 13 sites; 120 subjects were eligible and were randomized (13 sites: 11 in Germany, 0 in France, 1 in the Netherlands and 1 in the United Kingdom) to receive MTX/MTX or placebo/MTX. Study started on 22-FEB-2013 with the first subject randomization and was completed on 13-MAY-2015 with the last patient visit.

    Pre-assignment
    Screening details
    		 A total of 142 subjects were screened; 22 of them did not meet inclusion/exclusion criteria, requested consent withdrawal or were lost to follow-up. Main inclusion criteria: Adult patients; MTX naïve; moderate to severe plaques psoriasis for at least 6 months with or without psoriatic arthritis; use of highly effective contraception methods.

    Period 1
    Period 1 title
    Double-blind treatment phase
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    The trial was performed in a double-blind manner up to week 16. All study medication was supplied in identical packages. From week 16 commercial product was handed out to the patients with an additional label “for clinical study use only”. Patients of both arms remained blind to the identity of treatment from the time of randomisation until an interim database lock up to and including week 16 of their treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MTX/MTX group
    Arm description
    		 From week 0 to week 16: The starting dose and regular maintenance dose was 17.5 mg MTX /0.35 mL NaCl (0.9%) solution (placebo) administered once weekly (every 7 days). However, if PASI 50 was not reached at week 8 the dosage was increased to 22.5 mg MTX per week or 0.45 mL placebo. The primary endpoint was assessed after 16 weeks of treatment. If a patient showed a decrease of leukocytes, lymphocytes, erythrocytes or platelet counts of 30% at Day 5 after the first administration of MTX compared with baseline, the patient was to be withdrawn from treatment.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Methotrexate (MTX)
    Investigational medicinal product code
    Other name
    metex®, Metoject®
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Methotrexate (metex®/Metoject®) subcutaneously (s.c.) injected into the abdomen once weekly. The starting and regular maintenance dose was 17.5 mg per week. If PASI 50 was not reached at week 16, the dose was to be increased to 22.5 mg per week.

    Arm title
    		 Placebo/MTX group
    Arm description
    		 From week 0 to week 16: The starting dose and regular maintenance dose was 17.5 mg MTX /0.35 mL NaCl (0.9%) solution (placebo) administered once weekly (every 7 days). However, if PASI 50 was not reached at week 8 the dosage was increased to 22.5 mg MTX per week or 0.45 mL placebo. The primary endpoint was assessed after 16 weeks of treatment. If a patient showed a decrease of leukocytes, lymphocytes, erythrocytes or platelet counts of 30% at Day 5 after the first administration of MTX compared with baseline, the patient was to be withdrawn from treatment.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Matching placebo (0.9% NaCl solution) s.c. injected into the abdomen once weekly (until week 16).

    Number of subjects in period 1
    		MTX/MTX group Placebo/MTX group
    Started
    91
    29
    Completed
    77
    22
    Not completed
    14
    7
         Consent withdrawn by subject
    -
    2
         Adverse event, non-fatal
    10
    4
         Lost to follow-up
    2
    -
         discovery of patient ineligibility
    1
    -
         Lack of efficacy
    1
    1
    Period 2
    Period 2 title
    Open-label treatment phase
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    The trial was performed in a double-blind manner up to week 16. All study medication was supplied in identical packages. From week 16 commercial product was handed out to the patients with an additional label “for clinical study use only”. Patients of both arms remained blind to the identity of treatment from the time of randomization until an interim database lock up to and including week 16 of their treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MTX/MTX group
    Arm description
    		 From week 16 to week 52: MTX/MTX: Patients stayed on their dose in the MTX/MTX. However, if at week 24 patients were receiving 17.5 mg MTX but PASI 75 was not yet reached the dosage was increased to 22.5 mg MTX per week. If patients had already been dosed with 22.5 mg MTX per week at week 24 and PASI 50 was not yet reached, patients were excluded from treatment.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Methotrexate (MTX)
    Investigational medicinal product code
    Other name
    metex®, Metoject®
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Commercial product was used. Patients stayed on their dose. If PASI 75 was not reached in patients receiving 17.5 mg at week 24, the dose was to be increased to 22.5 mg per week.

    Arm title
    		 Placebo/MTX group
    Arm description
    		 From week 16 to week 52: Placebo/MTX: From week 16 to week 52, patients received MTX according to the fixed dose schedule of the MTX/MTX (starting dose 17.5 mg with the possibility of up-titration after 8 weeks, i.e., at week 24). However, patients who reached PASI 75 under placebotreatment after 16 weeks were dosed with neither placebo nor MTX until relapse. After relapse, patients received a starting dose of 17.5 mg MTX as described above.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Methotrexate (MTX)
    Investigational medicinal product code
    Other name
    metex®, Metoject®
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Commercial product was used. Patients stayed on their dose. If PASI 75 was not reached in patients receiving 17.5 mg at week 24, the dose was to be increased to 22.5 mg per week.

    Number of subjects in period 2
    		MTX/MTX group Placebo/MTX group
    Started
    77
    22
    Completed
    56
    15
    Not completed
    21
    7
         Consent withdrawn by subject
    2
    1
         Adverse event, non-fatal
    9
    4
         Lost to follow-up
    1
    2
         discovery of patient ineligibility
    2
    -
         Lack of efficacy
    7
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    MTX/MTX group
    Reporting group description
    		 From week 0 to week 16: The starting dose and regular maintenance dose was 17.5 mg MTX /0.35 mL NaCl (0.9%) solution (placebo) administered once weekly (every 7 days). However, if PASI 50 was not reached at week 8 the dosage was increased to 22.5 mg MTX per week or 0.45 mL placebo. The primary endpoint was assessed after 16 weeks of treatment. If a patient showed a decrease of leukocytes, lymphocytes, erythrocytes or platelet counts of 30% at Day 5 after the first administration of MTX compared with baseline, the patient was to be withdrawn from treatment.

    Reporting group title
    Placebo/MTX group
    Reporting group description
    		 From week 0 to week 16: The starting dose and regular maintenance dose was 17.5 mg MTX /0.35 mL NaCl (0.9%) solution (placebo) administered once weekly (every 7 days). However, if PASI 50 was not reached at week 8 the dosage was increased to 22.5 mg MTX per week or 0.45 mL placebo. The primary endpoint was assessed after 16 weeks of treatment. If a patient showed a decrease of leukocytes, lymphocytes, erythrocytes or platelet counts of 30% at Day 5 after the first administration of MTX compared with baseline, the patient was to be withdrawn from treatment.

    Reporting group values
    		 MTX/MTX group Placebo/MTX group Total
    Number of subjects
    		 91 29 120
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 0 0 0
        From 65-84 years
    		 84 28 112
        85 years and over
    		 7 1 8
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 45.9 ± 12.9 44.4 ± 10.8 -
    Gender categorical
    Units: Subjects
        Female
    		 26 4 30
        Male
    		 65 25 90
    Race
    Units: Subjects
        White
    		 89 28 117
        Asian
    		 2 0 2
        Other
    		 0 1 1
    Employment status
    Units: Subjects
        Full-time employee
    		 51 22 73
        Part-time employee
    		 13 0 13
        Retired
    		 10 2 12
        Student
    		 2 1 3
        Other
    		 15 4 19
    Health insurance
    Units: Subjects
        Compulsory
    		 75 27 102
        Private
    		 8 0 8
        Other
    		 8 2 10
    Vascular disorders
    Units: Subjects
        Hypertension
    		 27 7 34
        Arteriosclerosis
    		 1 0 1
        Deep vein thrombosis
    		 1 0 1
        Varicose vein
    		 1 0 1
        None
    		 61 22 83
    Metabolism and nutrition disorders
    Units: Subjects
        Hypercholesterolaemia
    		 2 4 6
        Hyperlipidaemia
    		 2 3 5
        Obesity
    		 2 1 3
        Type 2 diabetes mellitus
    		 2 1 3
        Diabetes mellitus
    		 2 0 2
        Dyslipidaemia
    		 1 0 1
        Fructose intolerance
    		 1 0 1
        Glucose tolerance impaired
    		 0 1 1
        Gout
    		 0 1 1
        Hyperuricaemia
    		 1 0 1
        Iron deficiency
    		 1 0 1
        Lactose intolerance
    		 1 0 1
        None
    		 76 18 94
    Nervous system disorders
    Units: Subjects
        Migraine
    		 9 1 10
        Headache
    		 5 1 6
        Cerebrovascular accident
    		 2 0 2
        Cerebral ischaemia
    		 0 1 1
        Narcolepsy
    		 1 0 1
        Sciatica
    		 1 0 1
        Tension headache
    		 0 1 1
        VIIth nerve paralysis
    		 1 0 1
        None
    		 72 25 97
    Psychiatric disorders
    Units: Subjects
        Depression
    		 9 3 12
        Attention deficit/hyperactivity disorder
    		 1 0 1
        Panic disorder
    		 0 1 1
        Sleep disorder
    		 1 0 1
        None
    		 80 25 105
    Respiratory, thoracic and mediastinal disorders
    Units: Subjects
        Asthma
    		 4 3 7
        Chronic obstructive pulmonary disease
    		 1 1 2
        Emphysema
    		 1 0 1
        Pharyngeal erythema
    		 1 0 1
        Pulmonary sarcoidosis
    		 0 1 1
        Rhinitis allergic
    		 1 0 1
        Sleep apnoea syndrome
    		 1 0 1
        None
    		 82 24 106
    Cardiac disorders
    Units: Subjects
        Myocardial infarction
    		 1 3 4
        Coronary artery disease
    		 1 1 2
        Atrial fibrillation
    		 1 0 1
        Extrasystoles
    		 0 1 1
        Tachycardia
    		 0 1 1
        None
    		 88 23 111
    Prior medication: antipsoriatics
    Units: Subjects
        Antipsoriatics for topical use
    		 37 9 46
        Antipsoriatics for systemic use
    		 27 8 35
        None
    		 27 12 39
    Prior medication: corticosteroids
    Units: Subjects
        Corticosteroids
    		 33 14 47
        None
    		 58 15 73
    Concomitant medication: antiinflammatory and antirheumatic products
    Units: Subjects
        Antiinflammatory and antirheumatic products
    		 37 8 45
        None
    		 54 21 75
    Concomitant medication: analgesics
    Units: Subjects
        Other analgesics and antipyretics
    		 24 11 35
        Antimigraine preparations
    		 3 0 3
        Opioids
    		 2 0 2
        None
    		 62 18 80
    Concomitant medication: agents acting on the renin-angiotensin system
    Units: Subjects
        ACE Inhibitors, plain
    		 9 8 17
        Angiotensin II antagonists, plain
    		 14 0 14
        ACE inhibitors, combinations
    		 1 1 2
        None
    		 67 20 87
    Concomitant medication: antibacterials for systemic use
    Units: Subjects
        Macrolides, lincosamides and streptogramins
    		 7 6 13
        Beta-lactam antibacterials, penicillins
    		 8 2 10
        Other beta-lactam antibacterials
    		 2 2 4
        Quinolone antibacterials
    		 3 1 4
        Tetracyclines
    		 4 0 4
        None
    		 67 18 85
    Concomitant medication: drugs for acid related disorders
    Units: Subjects
        Drugs for peptic ulcer / gastro-oesophageal reflux
    		 7 7 14
        Antacids
    		 1 1 2
        None
    		 83 21 104
    Concomitant medication: lipid modifying agents
    Units: Subjects
        Lipid modifying agents, plain
    		 4 6 10
        Lipid modifying agents, combinations
    		 1 0 1
        None
    		 86 23 109
    Baseline PGA
    Units: Subjects
        Mild
    		 6 0 6
        Mild to moderate
    		 11 7 18
        Moderate
    		 39 12 51
        Moderate to severe
    		 24 9 33
        Severe
    		 11 1 12
    Psoriatic nail
    Units: Subjects
        Yes
    		 62 22 84
        No
    		 29 6 35
        Missing
    		 0 1 1
    Patients suffering from psoriatic arthritis (PsA)
    Units: Subjects
        Yes
    		 11 2 13
        No
    		 80 27 107
    PsA type (multiple choice)
    Units: Subjects
        Spinal involvement
    		 1 0 1
        Multiple small joints affected
    		 7 1 8
        Dactylitis
    		 4 1 5
        Enthesitis
    		 0 0 0
        Arthritis mutilans
    		 0 0 0
        None
    		 79 27 106
    PsA severity rating
    Units: Subjects
        Mild
    		 4 1 5
        Moderate
    		 7 1 8
        None
    		 80 27 107
    Height (cm)
    Units: centimetre
        arithmetic mean (standard deviation)
    		 175.0 ± 9.5 178.4 ± 9.0 -
    Weight (kg)
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    		 92.0 ± 18.6 96.7 ± 20.9 -
    BMI (kg/m2)
    Units: kilogram(s)/square metre
        arithmetic mean (standard deviation)
    		 30.0 ± 6.1 30.2 ± 6.1 -
    Baseline median PASI
    Units: percent
        arithmetic mean (standard deviation)
    		 15.4 ± 5.9 15.4 ± 5.3 -
    Baseline BSA
    Units: square metre
        arithmetic mean (standard deviation)
    		 20.0 ± 11.8 19.6 ± 12.5 -
    Subject analysis sets

    Subject analysis set title
    Modified intent-to-treat (mITT) set (MTX/MTX)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The modified intent-to-treat (mITT) set comprises all patients who received the study treatment (MTX or placebo) at least once. Patients were analysed according to the treatment they were assigned to at randomisation. A non-responder imputation (NRI) was done for the primary efficacy parameter.

    Subject analysis set title
    Modified intent-to-treat (mITT) set (Placebo/MTX)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The modified intent-to-treat (mITT) set comprises all patients who received the study treatment (MTX or placebo) at least once. Patients were analysed according to the treatment they were assigned to at randomisation. A non-responder imputation (NRI) was done for the primary efficacy parameter.

    Subject analysis sets values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects
    91
    29
    Age categorical
    Units: Subjects
        In utero
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
        Newborns (0-27 days)
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
        Children (2-11 years)
    0
    0
        Adolescents (12-17 years)
    0
    0
        Adults (18-64 years)
    0
    0
        From 65-84 years
    84
    28
        85 years and over
    7
    1
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    45.9 ± 12.9
    44.4 ± 10.8
    Gender categorical
    Units: Subjects
        Female
    26
    4
        Male
    65
    25
    Race
    Units: Subjects
        White
    89
    28
        Asian
    2
    0
        Other
    0
    1
    Employment status
    Units: Subjects
        Full-time employee
    51
    22
        Part-time employee
    13
    0
        Retired
    10
    2
        Student
    2
    1
        Other
    15
    4
    Health insurance
    Units: Subjects
        Compulsory
    75
    27
        Private
    8
    0
        Other
    8
    2
    Vascular disorders
    Units: Subjects
        Hypertension
    27
    7
        Arteriosclerosis
    1
    0
        Deep vein thrombosis
    1
    0
        Varicose vein
    1
    0
        None
    61
    22
    Metabolism and nutrition disorders
    Units: Subjects
        Hypercholesterolaemia
    2
    4
        Hyperlipidaemia
    2
    3
        Obesity
    2
    1
        Type 2 diabetes mellitus
    2
    1
        Diabetes mellitus
    2
    0
        Dyslipidaemia
    1
    0
        Fructose intolerance
    1
    0
        Glucose tolerance impaired
    0
    1
        Gout
    0
    1
        Hyperuricaemia
    1
    0
        Iron deficiency
    1
    0
        Lactose intolerance
    1
    0
        None
    76
    18
    Nervous system disorders
    Units: Subjects
        Migraine
    9
    1
        Headache
    5
    1
        Cerebrovascular accident
    2
    0
        Cerebral ischaemia
    0
    1
        Narcolepsy
    1
    0
        Sciatica
    1
    0
        Tension headache
    0
    1
        VIIth nerve paralysis
    1
    0
        None
    72
    25
    Psychiatric disorders
    Units: Subjects
        Depression
    9
    3
        Attention deficit/hyperactivity disorder
    1
    0
        Panic disorder
    0
    1
        Sleep disorder
    1
    0
        None
    80
    25
    Respiratory, thoracic and mediastinal disorders
    Units: Subjects
        Asthma
    4
    3
        Chronic obstructive pulmonary disease
    1
    1
        Emphysema
    1
    0
        Pharyngeal erythema
    1
    0
        Pulmonary sarcoidosis
    0
    1
        Rhinitis allergic
    1
    0
        Sleep apnoea syndrome
    1
    0
        None
    82
    24
    Cardiac disorders
    Units: Subjects
        Myocardial infarction
    1
    3
        Coronary artery disease
    1
    1
        Atrial fibrillation
    1
    0
        Extrasystoles
    0
    1
        Tachycardia
    0
    1
        None
    88
    23
    Prior medication: antipsoriatics
    Units: Subjects
        Antipsoriatics for topical use
    37
    9
        Antipsoriatics for systemic use
    27
    8
        None
    27
    12
    Prior medication: corticosteroids
    Units: Subjects
        Corticosteroids
    33
    14
        None
    58
    15
    Concomitant medication: antiinflammatory and antirheumatic products
    Units: Subjects
        Antiinflammatory and antirheumatic products
    37
    8
        None
    54
    21
    Concomitant medication: analgesics
    Units: Subjects
        Other analgesics and antipyretics
    24
    11
        Antimigraine preparations
    3
    0
        Opioids
    2
    0
        None
    62
    18
    Concomitant medication: agents acting on the renin-angiotensin system
    Units: Subjects
        ACE Inhibitors, plain
    9
    8
        Angiotensin II antagonists, plain
    14
    0
        ACE inhibitors, combinations
    1
    1
        None
    67
    20
    Concomitant medication: antibacterials for systemic use
    Units: Subjects
        Macrolides, lincosamides and streptogramins
    7
    6
        Beta-lactam antibacterials, penicillins
    8
    2
        Other beta-lactam antibacterials
    2
    2
        Quinolone antibacterials
    3
    1
        Tetracyclines
    4
    0
        None
    67
    18
    Concomitant medication: drugs for acid related disorders
    Units: Subjects
        Drugs for peptic ulcer / gastro-oesophageal reflux
    7
    7
        Antacids
    1
    1
        None
    83
    21
    Concomitant medication: lipid modifying agents
    Units: Subjects
        Lipid modifying agents, plain
    4
    6
        Lipid modifying agents, combinations
    1
    0
        None
    86
    23
    Baseline PGA
    Units: Subjects
        Mild
    6
    0
        Mild to moderate
    11
    7
        Moderate
    39
    12
        Moderate to severe
    24
    9
        Severe
    11
    1
    Psoriatic nail
    Units: Subjects
        Yes
    62
    22
        No
    29
    6
        Missing
    0
    1
    Patients suffering from psoriatic arthritis (PsA)
    Units: Subjects
        Yes
    11
    2
        No
    80
    27
    PsA type (multiple choice)
    Units: Subjects
        Spinal involvement
    1
    0
        Multiple small joints affected
    7
    1
        Dactylitis
    4
    1
        Enthesitis
    0
    0
        Arthritis mutilans
    0
    0
        None
    79
    27
    PsA severity rating
    Units: Subjects
        Mild
    4
    1
        Moderate
    7
    1
        None
    80
    27
    Height (cm)
    Units: centimetre
        arithmetic mean (standard deviation)
    175.0 ± 9.5
    178.4 ± 9.0
    Weight (kg)
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    92.0 ± 18.6
    96.7 ± 20.9
    BMI (kg/m2)
    Units: kilogram(s)/square metre
        arithmetic mean (standard deviation)
    30.0 ± 6.1
    30.2 ± 6.1
    Baseline median PASI
    Units: percent
        arithmetic mean (standard deviation)
    15.4 ± 5.9
    15.4 ± 5.3
    Baseline BSA
    Units: square metre
        arithmetic mean (standard deviation)
    20.0 ± 11.8
    19.6 ± 12.5

    End points

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    End points reporting groups
    Reporting group title
    MTX/MTX group
    Reporting group description
    		 From week 0 to week 16: The starting dose and regular maintenance dose was 17.5 mg MTX /0.35 mL NaCl (0.9%) solution (placebo) administered once weekly (every 7 days). However, if PASI 50 was not reached at week 8 the dosage was increased to 22.5 mg MTX per week or 0.45 mL placebo. The primary endpoint was assessed after 16 weeks of treatment. If a patient showed a decrease of leukocytes, lymphocytes, erythrocytes or platelet counts of 30% at Day 5 after the first administration of MTX compared with baseline, the patient was to be withdrawn from treatment.

    Reporting group title
    Placebo/MTX group
    Reporting group description
    		 From week 0 to week 16: The starting dose and regular maintenance dose was 17.5 mg MTX /0.35 mL NaCl (0.9%) solution (placebo) administered once weekly (every 7 days). However, if PASI 50 was not reached at week 8 the dosage was increased to 22.5 mg MTX per week or 0.45 mL placebo. The primary endpoint was assessed after 16 weeks of treatment. If a patient showed a decrease of leukocytes, lymphocytes, erythrocytes or platelet counts of 30% at Day 5 after the first administration of MTX compared with baseline, the patient was to be withdrawn from treatment.
    Reporting group title
    MTX/MTX group
    Reporting group description
    		 From week 16 to week 52: MTX/MTX: Patients stayed on their dose in the MTX/MTX. However, if at week 24 patients were receiving 17.5 mg MTX but PASI 75 was not yet reached the dosage was increased to 22.5 mg MTX per week. If patients had already been dosed with 22.5 mg MTX per week at week 24 and PASI 50 was not yet reached, patients were excluded from treatment.

    Reporting group title
    Placebo/MTX group
    Reporting group description
    		 From week 16 to week 52: Placebo/MTX: From week 16 to week 52, patients received MTX according to the fixed dose schedule of the MTX/MTX (starting dose 17.5 mg with the possibility of up-titration after 8 weeks, i.e., at week 24). However, patients who reached PASI 75 under placebotreatment after 16 weeks were dosed with neither placebo nor MTX until relapse. After relapse, patients received a starting dose of 17.5 mg MTX as described above.

    Subject analysis set title
    Modified intent-to-treat (mITT) set (MTX/MTX)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The modified intent-to-treat (mITT) set comprises all patients who received the study treatment (MTX or placebo) at least once. Patients were analysed according to the treatment they were assigned to at randomisation. A non-responder imputation (NRI) was done for the primary efficacy parameter.

    Subject analysis set title
    Modified intent-to-treat (mITT) set (Placebo/MTX)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The modified intent-to-treat (mITT) set comprises all patients who received the study treatment (MTX or placebo) at least once. Patients were analysed according to the treatment they were assigned to at randomisation. A non-responder imputation (NRI) was done for the primary efficacy parameter.

    Primary: Primary endpoint: PASI 75 Response Rate at Week 16

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    End point title
    		 Primary endpoint: PASI 75 Response Rate at Week 16
    End point description
    The primary efficacy analysis evaluated the proportions (%) of patients achieving a PASI 75 response at week 16. The null hypothesis stated that the difference between the proportions equals zero. The proportions in each treatment arm were provided for the mITT together with 95% CIs according to Clopper and Pearson. The P value of the chi-square test (5% level of significance, two-sided) was presented. The difference between proportions was provided for the mITT together with a 95% Wald CI.
    End point type
    Primary
    End point timeframe
    Difference between treatments in PASI 75 (reduction of Psoriasis Area and Severity Index by ≥75% of baseline value) responder rate after week 16
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        Number of subjects with success
    37
    3
    Statistical analysis title
    		 chi-square test (5% significance level) (mITT set)
    Comparison groups
    Modified intent-to-treat (mITT) set (MTX/MTX) v Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.0026
    Method
    		 Chi-squared
    Confidence interval

    Secondary: PASI 50 Responder Rate at Week 16

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    End point title
    		 PASI 50 Responder Rate at Week 16
    End point description
    End point type
    Secondary
    End point timeframe
    PASI 50 Responder Rate at Week 16.
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        Number of subjects with success
    60
    9
    Statistical analysis title
    		 chi-square test (5% significance level) (mITT set)
    Comparison groups
    Modified intent-to-treat (mITT) set (MTX/MTX) v Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.0009
    Method
    		 Chi-squared
    Confidence interval

    Secondary: PASI 90 Response Rates at week 16

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    End point title
    		 PASI 90 Response Rates at week 16
    End point description
    End point type
    Secondary
    End point timeframe
    PASI 90 Response Rates at week 16.
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        Number of subjects with success
    16
    0
    Statistical analysis title
    		 chi-square test (5% significance level) (mITT set)
    Comparison groups
    Modified intent-to-treat (mITT) set (MTX/MTX) v Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.0153
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Physician’s Global Assessment (PGA) at week 16

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    End point title
    		 Physician’s Global Assessment (PGA) at week 16
    End point description
    End point type
    Secondary
    End point timeframe
    Physician’s Global Assessment (PGA) at week 16.
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: percent
    number (not applicable)
        PGA 0/1 Responder Rate
    25
    2
    No statistical analyses for this end point

    Secondary: Physician’s Global Assessment (PGA) at week 52

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    End point title
    		 Physician’s Global Assessment (PGA) at week 52
    End point description
    End point type
    Secondary
    End point timeframe
    Physician’s Global Assessment (PGA) at week 52
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: percent
    number (not applicable)
        PGA 0/1 Responder Rate
    36
    11
    No statistical analyses for this end point

    Secondary: Body Surface Area (BSA) at week 16

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    End point title
    		 Body Surface Area (BSA) at week 16
    End point description
    End point type
    Secondary
    End point timeframe
    Body Surface Area (BSA) at week 16
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    77
    22
    Units: square metre
        arithmetic mean (standard deviation)
    7.6 ± 7.4
    14.1 ± 9.7
    No statistical analyses for this end point

    Secondary: Body Surface Area (BSA) at week 52

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    End point title
    		 Body Surface Area (BSA) at week 52
    End point description
    End point type
    Secondary
    End point timeframe
    Affected Body Surface Area at week 52
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    56
    15
    Units: square metre
        arithmetic mean (standard deviation)
    3.3 ± 4.5
    3.2 ± 5.7
    No statistical analyses for this end point

    Secondary: Nail Psoriasis Severity Index (NAPSI) at week 16

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    End point title
    		 Nail Psoriasis Severity Index (NAPSI) at week 16
    End point description
    End point type
    Secondary
    End point timeframe
    Patients With at Least One Psoriatic Nail (NAPSI) at week 16
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        Patients With at Least One Psoriatic Nail
    55
    16
        Patients Without Psoriatic Nail
    22
    6
        Missing
    14
    7
    No statistical analyses for this end point

    Secondary: Nail Psoriasis Severity Index (NAPSI) at week 52

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    End point title
    		 Nail Psoriasis Severity Index (NAPSI) at week 52
    End point description
    End point type
    Secondary
    End point timeframe
    Patients With at Least One Psoriatic Nail (NAPSI) at week 52.
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        Patients With at Least One Psoriatic Nail
    35
    9
        Patients Without Psoriatic Nail
    19
    6
        Missing
    37
    14
    No statistical analyses for this end point

    Secondary: NAPSI (Short Version) Total Score at week 16

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    End point title
    		 NAPSI (Short Version) Total Score at week 16
    End point description
    End point type
    Secondary
    End point timeframe
    NAPSI (Short Version) Total Score at week 16
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    77
    22
    Units: severity index
        arithmetic mean (standard deviation)
    3.7 ± 3.7
    5.0 ± 4.8
    No statistical analyses for this end point

    Secondary: NAPSI (Short Version) Total Score at week 52

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    End point title
    		 NAPSI (Short Version) Total Score at week 52
    End point description
    End point type
    Secondary
    End point timeframe
    NAPSI (Short Version) Total Score at week 52
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    53
    15
    Units: severity index
        arithmetic mean (standard deviation)
    2.1 ± 3.0
    2.5 ± 3.6
    No statistical analyses for this end point

    Secondary: Psoriatic Arthritis Rating at week 16

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    End point title
    		 Psoriatic Arthritis Rating at week 16
    End point description
    End point type
    Secondary
    End point timeframe
    Psoriatic Arthritis Rating at week 16
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        Slightly improved
    1
    1
        Improved
    1
    0
        Highly improved
    6
    0
        Missing
    83
    28
    No statistical analyses for this end point

    Secondary: Psoriatic Arthritis Rating at week 52

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    End point title
    		 Psoriatic Arthritis Rating at week 52
    End point description
    End point type
    Secondary
    End point timeframe
    Psoriatic Arthritis Rating at week 52
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        Worsened
    1
    0
        Improved
    2
    0
        Highly improved
    3
    1
        Missing
    85
    28
    No statistical analyses for this end point

    Secondary: Dermatology Life Quality Index (DLQI) at week 16

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    End point title
    		 Dermatology Life Quality Index (DLQI) at week 16
    End point description
    End point type
    Secondary
    End point timeframe
    Dermatology Life Quality Index (DLQI) at week 16
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    77
    21
    Units: score
        arithmetic mean (standard deviation)
    3.9 ± 4.9
    8.7 ± 8.4
    No statistical analyses for this end point

    Secondary: Dermatology Life Quality Index (DLQI) at week 52

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    End point title
    		 Dermatology Life Quality Index (DLQI) at week 52
    End point description
    End point type
    Secondary
    End point timeframe
    Dermatology Life Quality Index (DLQI) at week 52
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    56
    15
    Units: score
        arithmetic mean (standard deviation)
    1.8 ± 3.3
    3.1 ± 7.2
    No statistical analyses for this end point

    Secondary: EQ-5D Pain/Discomfort at week 16

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    End point title
    		 EQ-5D Pain/Discomfort at week 16
    End point description
    End point type
    Secondary
    End point timeframe
    EQ-5D Pain/Discomfort at week 16
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        I have no pain or discomfort
    46
    8
        I have slight pain or discomfort
    24
    6
        I have moderate pain or discomfort
    7
    5
        I have severe pain or discomfort
    0
    3
        Missing
    14
    7
    No statistical analyses for this end point

    Secondary: EQ-5D Pain/Discomfort at week 52

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    End point title
    		 EQ-5D Pain/Discomfort at week 52
    End point description
    End point type
    Secondary
    End point timeframe
    EQ-5D Pain/Discomfort at week 52
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        I have no pain or discomfort
    37
    11
        I have slight pain or discomfort
    15
    2
        I have moderate pain or discomfort
    2
    2
        I have severe pain or discomfort
    1
    0
        I have extreme pain or discomfort
    1
    0
        Missing
    35
    14
    No statistical analyses for this end point

    Secondary: EQ-5D Anxiety/Depression at week 16

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    End point title
    		 EQ-5D Anxiety/Depression at week 16
    End point description
    End point type
    Secondary
    End point timeframe
    EQ-5D Anxiety/Depression at week 16
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        I am not anxious or depressed
    55
    13
        I am slightly anxious or depressed
    14
    6
        I am moderately anxious or depressed
    6
    1
        I am severely anxious or depressed
    2
    2
        Missing
    14
    7
    No statistical analyses for this end point

    Secondary: EQ-5D Anxiety/Depression at week 52

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    End point title
    		 EQ-5D Anxiety/Depression at week 52
    End point description
    End point type
    Secondary
    End point timeframe
    EQ-5D Anxiety/Depression at week 52
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        I am not anxious or depressed
    46
    12
        I am slightly anxious or depressed
    10
    2
        I am moderately anxious or depressed
    0
    1
        Missing
    35
    14
    No statistical analyses for this end point

    Secondary: EQ Visual Analogue Scale at week 16

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    End point title
    		 EQ Visual Analogue Scale at week 16
    End point description
    End point type
    Secondary
    End point timeframe
    EQ Visual Analogue Scale at week 16
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    77
    22
    Units: score
        arithmetic mean (standard deviation)
    78.5 ± 19.8
    65.7 ± 26.0
    No statistical analyses for this end point

    Secondary: EQ Visual Analogue Scale at week 52

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    End point title
    		 EQ Visual Analogue Scale at week 52
    End point description
    End point type
    Secondary
    End point timeframe
    EQ Visual Analogue Scale at week 52
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    56
    15
    Units: score
        arithmetic mean (standard deviation)
    83.3 ± 17.6
    82.6 ± 22.2
    No statistical analyses for this end point

    Secondary: PASI 75 Responder Rate at week 52

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    End point title
    		 PASI 75 Responder Rate at week 52
    End point description
    End point type
    Secondary
    End point timeframe
    PASI 75 Responder Rate at week 52
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
    41
    10
    No statistical analyses for this end point

    Secondary: PASI 75 Response Rate at Week 32

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    End point title
    		 PASI 75 Response Rate at Week 32
    End point description
    End point type
    Secondary
    End point timeframe
    PASI 75 Response Rate at Week 32
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
    46
    7
    No statistical analyses for this end point

    Secondary: PASI 50 Responder Rate at Week 52

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    End point title
    		 PASI 50 Responder Rate at Week 52
    End point description
    End point type
    Secondary
    End point timeframe
    PASI 50 Responder Rate at Week 52
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
    53
    10
    No statistical analyses for this end point

    Secondary: PASI 90 Response Rates at week 52

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    End point title
    		 PASI 90 Response Rates at week 52
    End point description
    End point type
    Secondary
    End point timeframe
    PASI 90 Response Rates at week 52
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
    25
    8
    No statistical analyses for this end point

    Secondary: PSAT metex® Benefit at week 16

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    End point title
    		 PSAT metex® Benefit at week 16
    End point description
    The “Patient’s Satisfaction with metex® pre-filled syringe” (PSAT metex®) questionnaire (Benefit, Practicality, Satisfaction) was developed exclusively for this study to assess patient’s overall experience with s.c. self-injection. This questionnaire has not yet been validated. PSAT metex® Benefit Items: 1. The treatment led to a rapid improvement in my skin symptoms. 2. I can easily handle my condition with this treatment. 3. With this treatment my skin no longer itches. 4. My skin is no longer painful with this treatment. 5. The time expenditure for the daily treatment is acceptable. 6. The treatment does not limit my general well-being. 7. As a result of the treatment, I am not worried that my skin condition will get worse. 8. I consider the improvement in the condition of my skin to be acceptable. 9. The treatment has met my expectations. 10. The side effects of the treatment were acceptable. 11. The positive aspects of the treatment outweigh the negative ones.
    End point type
    Secondary
    End point timeframe
    PSAT metex® was assessed at V1, V5 and V0. The PSAT metex® score collected after 16 and 52 weeks of treatment (V5 and V10) was considered as secondary efficacy endpoint.
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        Item 1: 2 – Agree
    21
    4
        Item 1: 3 – Strongly agree
    50
    5
        Item 2: 2 – Agree
    19
    7
        Item 2: 3 – Strongly agree
    50
    5
        Item 3: 2 – Agree
    27
    3
        Item 3: 3 – Strongly agree
    38
    3
        Item 4: 2 – Agree
    16
    4
        Item 4: 3 – Strongly agree
    50
    7
        Item 5: 2 – Agree
    4
    5
        Item 5: 3 – Strongly agree
    71
    12
        Item 6: 2 – Agree
    12
    4
        Item 6: 3 – Strongly agree
    62
    10
        Item 7: 2 – Agree
    19
    7
        Item 7: 3 – Strongly agree
    55
    6
        Item 8: 2 – Agree
    27
    4
        Item 8: 3 – Strongly agree
    31
    1
        Item 9: 2 – Agree
    27
    3
        Item 9: 3 – Strongly agree
    40
    3
        Item 10: 2 – Agree
    18
    4
        Item 10: 3 – Strongly agree
    54
    12
        Item 11: 2 – Agree
    13
    6
        Item 11: 3 – Strongly agree
    61
    7
    No statistical analyses for this end point

    Secondary: PSAT metex® Benefit at week 52

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    End point title
    		 PSAT metex® Benefit at week 52
    End point description
    The “Patient’s Satisfaction with metex® pre-filled syringe” (PSAT metex®) questionnaire (Benefit, Practicality, Satisfaction) was developed exclusively for this study to assess patient’s overall experience with s.c. self-injection. This questionnaire has not yet been validated. PSAT metex® Benefit Items: 1. The treatment led to a rapid improvement in my skin symptoms. 2. I can easily handle my condition with this treatment. 3. With this treatment my skin no longer itches. 4. My skin is no longer painful with this treatment. 5. The time expenditure for the daily treatment is acceptable. 6. The treatment does not limit my general well-being. 7. As a result of the treatment, I am not worried that my skin condition will get worse. 8. I consider the improvement in the condition of my skin to be acceptable. 9. The treatment has met my expectations. 10. The side effects of the treatment were acceptable. 11. The positive aspects of the treatment outweigh the negative ones.
    End point type
    Secondary
    End point timeframe
    PSAT metex® was assessed at V1, V5 and V0. The PSAT metex® score collected after 16 and 52 weeks of treatment (V5 and V10) was considered as secondary efficacy endpoint.
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        Item 1: 2 – Agree
    10
    4
        Item 1: 3 – Strongly agree
    40
    11
        Item 2: 2 – Agree
    11
    2
        Item 2: 3 – Strongly agree
    40
    12
        Item 3: 2 – Agree
    24
    3
        Item 3: 3 – Strongly agree
    26
    11
        Item 4: 2 – Agree
    12
    3
        Item 4: 3 – Strongly agree
    37
    11
        Item 5: 2 – Agree
    3
    1
        Item 5: 3 – Strongly agree
    50
    14
        Item 6: 2 – Agree
    9
    2
        Item 6: 3 – Strongly agree
    43
    11
        Item 7: 2 – Agree
    12
    3
        Item 7: 3 – Strongly agree
    41
    11
        Item 8: 2 – Agree
    13
    3
        Item 8: 3 – Strongly agree
    35
    10
        Item 9: 2 – Agree
    9
    4
        Item 9: 3 – Strongly agree
    40
    10
        Item 10: 2 – Agree
    10
    2
        Item 10: 3 – Strongly agree
    39
    11
        Item 11: 2 – Agree
    7
    2
        Item 11: 3 – Strongly agree
    45
    12
    No statistical analyses for this end point

    Secondary: PSAT metex® Practicality at week 16

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    End point title
    		 PSAT metex® Practicality at week 16
    End point description
    The “Patient’s Satisfaction with metex® pre-filled syringe” (PSAT metex®) questionnaire (Benefit, Practicality, Satisfaction) was developed exclusively for this study to assess patient’s overall experience with s.c. self-injection. This questionnaire has not yet been validated. PSAT metex® Practicality Items: 12. I do not feel afraid before being treated with needles or syringes. 13. I am certain that I perform the injection correctly. 14. I am not concerned about the pain when the needle pierces the skin. 15. I am concerned about redenning/swelling at the point of injection. 16. The general handling of the syringe is not difficult for me. 17. The injection can be performed easily when travelling.
    End point type
    Secondary
    End point timeframe
    PSAT metex® was assessed at V1, V5 and V0. The PSAT metex® score collected after 16 and 52 weeks of treatment (V5 and V10) was considered as secondary efficacy endpoint.
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        Item 12: 2 – Agree
    13
    2
        Item 12: 3 – Strongly agree
    58
    17
        Item 13: 2 – Agree
    3
    1
        Item 13: 3 – Strongly agree
    72
    21
        Item 14: 2 – Agree
    9
    2
        Item 14: 3 – Strongly agree
    61
    19
        Item 15: 0 – Strongly disagree
    41
    5
        Item 15: 1 – Disagree
    12
    5
        Item 16: 2 – Agree
    7
    1
        Item 16: 3 – Strongly agree
    67
    15
        Item 17: 2 – Agree
    7
    3
        Item 17: 3 – Strongly agree
    56
    15
    No statistical analyses for this end point

    Secondary: PSAT metex® Practicality at week 52

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    End point title
    		 PSAT metex® Practicality at week 52
    End point description
    The “Patient’s Satisfaction with metex® pre-filled syringe” (PSAT metex®) questionnaire (Benefit, Practicality, Satisfaction) was developed exclusively for this study to assess patient’s overall experience with s.c. self-injection. This questionnaire has not yet been validated. PSAT metex® Practicality Items: 12. I do not feel afraid before being treated with needles or syringes. 13. I am certain that I perform the injection correctly. 14. I am not concerned about the pain when the needle pierces the skin. 15. I am concerned about redenning/swelling at the point of injection. 16. The general handling of the syringe is not difficult for me. 17. The injection can be performed easily when travelling.
    End point type
    Secondary
    End point timeframe
    PSAT metex® was assessed at V1, V5 and V0. The PSAT metex® score collected after 16 and 52 weeks of treatment (V5 and V10) was considered as secondary efficacy endpoint.
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        Item 12: 2 – Agree
    14
    3
        Item 12: 3 – Strongly agree
    35
    9
        Item 13: 2 – Agree
    4
    2
        Item 13: 3 – Strongly agree
    51
    13
        Item 14: 2 – Agree
    13
    4
        Item 14: 3 – Strongly agree
    39
    10
        Item 15: 0 – Strongly disagree
    28
    4
        Item 15: 1 – Disagree
    11
    4
        Item 16: 2 – Agree
    8
    1
        Item 16: 3 – Strongly agree
    45
    13
        Item 17: 2 – Agree
    9
    1
        Item 17: 3 – Strongly agree
    42
    13
    No statistical analyses for this end point

    Secondary: PSAT metex® Satisfaction at week 16

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    End point title
    		 PSAT metex® Satisfaction at week 16
    End point description
    The “Patient’s Satisfaction with metex® pre-filled syringe” (PSAT metex®) questionnaire (Benefit, Practicality, Satisfaction) was developed exclusively for this study to assess patient’s overall experience with s.c. self-injection. This questionnaire has not yet been validated. PSAT metex® Satisfaction Items: 18. I am satisfied with the speed at which the treatment takes effect. 19. I am satisfied with the efficacy of the treatment. 20. I am satisfied with the tolerability of the treatment. 21. I am happy with the way the preparation can be handled, and its storage and application. 22. I would recommend the treatment to other patients. 23. I would repeat/continue with the treatment. 24. I have confidence in the treatment.
    End point type
    Secondary
    End point timeframe
    PSAT metex® was assessed at V1, V5 and V0. The PSAT metex® score collected after 16 and 52 weeks of treatment (V5 and V10) was considered as secondary efficacy endpoint.
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        Item 18: 2 – Agree
    24
    6
        Item 18: 3 – Strongly agree
    47
    3
        Item 19: 2 – Agree
    17
    5
        Item 19: 3 – Strongly agree
    52
    4
        Item 20: 2 – Agree
    19
    3
        Item 20: 3 – Strongly agree
    55
    13
        Item 21: 2 – Agree
    7
    6
        Item 21: 3 – Strongly agree
    69
    16
        Item 22: 2 – Agree
    8
    4
        Item 22: 3 – Strongly agree
    65
    13
        Item 23: 2 – Agree
    7
    2
        Item 23: 3 – Strongly agree
    67
    16
        Item 24: 2 – Agree
    11
    3
        Item 24: 3 – Strongly agree
    64
    16
    No statistical analyses for this end point

    Secondary: PSAT metex® Satisfaction at week 52

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    End point title
    		 PSAT metex® Satisfaction at week 52
    End point description
    The “Patient’s Satisfaction with metex® pre-filled syringe” (PSAT metex®) questionnaire (Benefit, Practicality, Satisfaction) was developed exclusively for this study to assess patient’s overall experience with s.c. self-injection. This questionnaire has not yet been validated. PSAT metex® Satisfaction Items: 18. I am satisfied with the speed at which the treatment takes effect. 19. I am satisfied with the efficacy of the treatment. 20. I am satisfied with the tolerability of the treatment. 21. I am happy with the way the preparation can be handled, and its storage and application. 22. I would recommend the treatment to other patients. 23. I would repeat/continue with the treatment. 24. I have confidence in the treatment.
    End point type
    Secondary
    End point timeframe
    PSAT metex® was assessed at V1, V5 and V0. The PSAT metex® score collected after 16 and 52 weeks of treatment (V5 and V10) was considered as secondary efficacy endpoint.
    End point values
    		 Modified intent-to-treat (mITT) set (MTX/MTX) Modified intent-to-treat (mITT) set (Placebo/MTX)
    Number of subjects analysed
    91
    29
    Units: Subjects
        Item 18: 2 – Agree
    13
    3
        Item 18: 3 – Strongly agree
    39
    11
        Item 19: 2 – Agree
    8
    3
        Item 19: 3 – Strongly agree
    42
    12
        Item 20: 2 – Agree
    13
    4
        Item 20: 3 – Strongly agree
    40
    11
        Item 21: 2 – Agree
    8
    3
        Item 21: 3 – Strongly agree
    46
    12
        Item 22: 2 – Agree
    6
    2
        Item 22: 3 – Strongly agree
    48
    13
        Item 23: 2 – Agree
    6
    0
        Item 23: 3 – Strongly agree
    45
    15
        Item 24: 2 – Agree
    10
    0
        Item 24: 3 – Strongly agree
    44
    15
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were monitored throughout the course of the study from 1st injection of IMP (each sign/symptom that occurred between signing informed consent and 1st injection of IMP were recorded as part of the medical history).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    MTX/MTX group (Double-Blind Treatment Phase)
    Reporting group description
    		 From week 0 to week 16: The starting dose and regular maintenance dose was 17.5 mg MTX /0.35 mL NaCl (0.9%) solution (placebo) administered once weekly (every 7 days). However, if PASI 50 was not reached at week 8 the dosage was increased to 22.5 mg MTX per week or 0.45 mL placebo. The primary endpoint was assessed after 16 weeks of treatment. If a patient showed a decrease of leukocytes, lymphocytes, erythrocytes or platelet counts of 30% at Day 5 after the first administration of MTX compared with baseline, the patient was to be withdrawn from treatment.

    Reporting group title
    Placebo/MTX group (Double-Blind Treatment Phase)
    Reporting group description
    		 From week 0 to week 16: The starting dose and regular maintenance dose was 17.5 mg MTX /0.35 mL NaCl (0.9%) solution (placebo) administered once weekly (every 7 days). However, if PASI 50 was not reached at week 8 the dosage was increased to 22.5 mg MTX per week or 0.45 mL placebo. The primary endpoint was assessed after 16 weeks of treatment. If a patient showed a decrease of leukocytes, lymphocytes, erythrocytes or platelet counts of 30% at Day 5 after the first administration of MTX compared with baseline, the patient was to be withdrawn from treatment.

    Reporting group title
    MTX/MTX group (Open-Label Treatment Phase)
    Reporting group description
    		 From week 16 to week 52: MTX/MTX: Patients stayed on their dose in the MTX/MTX. However, if at week 24 patients were receiving 17.5 mg MTX but PASI 75 was not yet reached the dosage was increased to 22.5 mg MTX per week. If patients had already been dosed with 22.5 mg MTX per week at week 24 and PASI 50 was not yet reached, patients were excluded from treatment.

    Reporting group title
    Placebo/MTX group (Open-Label Treatment Phase)
    Reporting group description
    		 From week 16 to week 52: Placebo/MTX: From week 16 to week 52, patients received MTX according to the fixed dose schedule of the MTX/MTX (starting dose 17.5 mg with the possibility of up-titration after 8 weeks, i.e., at week 24). However, patients who reached PASI 75 under placebotreatment after 16 weeks were dosed with neither placebo nor MTX until relapse. After relapse, patients received a starting dose of 17.5 mg MTX as described above.

    Serious adverse events
    		 MTX/MTX group (Double-Blind Treatment Phase) Placebo/MTX group (Double-Blind Treatment Phase) MTX/MTX group (Open-Label Treatment Phase) Placebo/MTX group (Open-Label Treatment Phase)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 91 (1.10%)
    4 / 29 (13.79%)
    2 / 76 (2.63%)
    1 / 22 (4.55%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign salivary gland neoplasm
         subjects affected / exposed
    0 / 91 (0.00%)
    0 / 29 (0.00%)
    1 / 76 (1.32%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Inguinal hernia repair
         subjects affected / exposed
    1 / 91 (1.10%)
    0 / 29 (0.00%)
    0 / 76 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arterial stent insertion
         subjects affected / exposed
    0 / 91 (0.00%)
    1 / 29 (3.45%)
    0 / 76 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroidectomy
         subjects affected / exposed
    0 / 91 (0.00%)
    0 / 29 (0.00%)
    1 / 76 (1.32%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Coronary artery stenosis
         subjects affected / exposed
    0 / 91 (0.00%)
    0 / 29 (0.00%)
    0 / 76 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Multiple sclerosis
         subjects affected / exposed
    0 / 91 (0.00%)
    1 / 29 (3.45%)
    0 / 76 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastric ulcer
         subjects affected / exposed
    0 / 91 (0.00%)
    1 / 29 (3.45%)
    0 / 76 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Psoriasis
         subjects affected / exposed
    0 / 91 (0.00%)
    1 / 29 (3.45%)
    0 / 76 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 MTX/MTX group (Double-Blind Treatment Phase) Placebo/MTX group (Double-Blind Treatment Phase) MTX/MTX group (Open-Label Treatment Phase) Placebo/MTX group (Open-Label Treatment Phase)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    75 / 91 (82.42%)
    27 / 29 (93.10%)
    59 / 76 (77.63%)
    17 / 22 (77.27%)
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    7 / 91 (7.69%)
    2 / 29 (6.90%)
    7 / 76 (9.21%)
    4 / 22 (18.18%)
         occurrences all number
    7
    2
    7
    4
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 91 (4.40%)
    0 / 29 (0.00%)
    2 / 76 (2.63%)
    2 / 22 (9.09%)
         occurrences all number
    4
    0
    3
    2
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 91 (0.00%)
    0 / 29 (0.00%)
    2 / 76 (2.63%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    3
    1
    Mean cell volume increased
         subjects affected / exposed
    2 / 91 (2.20%)
    0 / 29 (0.00%)
    4 / 76 (5.26%)
    1 / 22 (4.55%)
         occurrences all number
    2
    0
    5
    2
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 91 (3.30%)
    0 / 29 (0.00%)
    3 / 76 (3.95%)
    2 / 22 (9.09%)
         occurrences all number
    3
    0
    4
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    12 / 91 (13.19%)
    5 / 29 (17.24%)
    5 / 76 (6.58%)
    1 / 22 (4.55%)
         occurrences all number
    15
    6
    6
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    8 / 91 (8.79%)
    1 / 29 (3.45%)
    0 / 76 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    11
    1
    0
    2
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    2 / 91 (2.20%)
    0 / 29 (0.00%)
    3 / 76 (3.95%)
    1 / 22 (4.55%)
         occurrences all number
    2
    0
    3
    1
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    12 / 91 (13.19%)
    0 / 29 (0.00%)
    7 / 76 (9.21%)
    3 / 22 (13.64%)
         occurrences all number
    17
    0
    7
    3
    Diarrhoea
         subjects affected / exposed
    3 / 91 (3.30%)
    1 / 29 (3.45%)
    4 / 76 (5.26%)
    3 / 22 (13.64%)
         occurrences all number
    4
    1
    4
    3
    Gastric ulcer
         subjects affected / exposed
    0 / 91 (0.00%)
    1 / 29 (3.45%)
    0 / 76 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    5 / 91 (5.49%)
    1 / 29 (3.45%)
    2 / 76 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    5
    1
    2
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 91 (1.10%)
    2 / 29 (6.90%)
    0 / 76 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    1
    2
    0
    1
    Skin and subcutaneous tissue disorders
    Psoriasis
         subjects affected / exposed
    1 / 91 (1.10%)
    4 / 29 (13.79%)
    0 / 76 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    4
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    6 / 91 (6.59%)
    3 / 29 (10.34%)
    7 / 76 (9.21%)
    1 / 22 (4.55%)
         occurrences all number
    7
    3
    11
    1
    Arthralgia
         subjects affected / exposed
    2 / 91 (2.20%)
    0 / 29 (0.00%)
    3 / 76 (3.95%)
    1 / 22 (4.55%)
         occurrences all number
    3
    0
    5
    1
    Osteoarthritis
         subjects affected / exposed
    0 / 91 (0.00%)
    0 / 29 (0.00%)
    2 / 76 (2.63%)
    3 / 22 (13.64%)
         occurrences all number
    0
    0
    2
    3
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    24 / 91 (26.37%)
    7 / 29 (24.14%)
    18 / 76 (23.68%)
    5 / 22 (22.73%)
         occurrences all number
    28
    7
    24
    5
    Bronchitis
         subjects affected / exposed
    3 / 91 (3.30%)
    0 / 29 (0.00%)
    3 / 76 (3.95%)
    0 / 22 (0.00%)
         occurrences all number
    3
    0
    4
    0
    Influenza
         subjects affected / exposed
    1 / 91 (1.10%)
    1 / 29 (3.45%)
    4 / 76 (5.26%)
    5 / 22 (22.73%)
         occurrences all number
    1
    1
    5
    5

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/28012564
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