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Clinical Trial Results:
A Multicenter, Randomized, Double-blind, Placebo-Controlled Study of the Safety, Efficacy, and Pharmacokinetics of the Human Anti-TNF Monoclonal Antibody Adalimumab in Children With Polyarticular Juvenile Rheumatoid Arthritis

Summary
EudraCT number	2011-001661-40
Trial protocol	Outside EU/EEA
Global end of trial date	02 Jun 2010

Results information
Results version number	v1(current)
This version publication date	20 Apr 2016
First version publication date	07 Jun 2015
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

DE038

ISRCTN number

US NCT number

NCT00048542

WHO universal trial number (UTN)

Sponsor organisation name

AbbVie

Sponsor organisation address

1 North Waukegan Road, North Chicago, IL, United States, 60064

Public contact

Global Medical Information, AbbVie, 001 800-633-9110,

Scientific contact

Aileen L. Pangan MD , AbbVie, aileen.pangan@abbvie.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000036-PIP01-08

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

02 Jun 2010

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

02 Jun 2010

Was the trial ended prematurely?

Main objective of the trial

This is a multicenter, Phase 3 randomized, placebo-controlled study designed to evaluate adalimumab in children 4 to 17 years old with polyarticular juvenile idiopathic arthritis (JIA) who are either methotrexate (MTX) treated or non-MTX treated.

Protection of trial subjects

The subject and/or parent or legal guardian read and understood information provided about the study and signed an informed consent form. Additionally, a written informed assent was obtained from all children in accordance with individual IRB recommendations.

Background therapy

Evidence for comparator

Actual start date of recruitment

19 Sep 2002

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 8

Country: Number of subjects enrolled

Czech Republic: 19

Country: Number of subjects enrolled

France: 11

Country: Number of subjects enrolled

Germany: 25

Country: Number of subjects enrolled

Italy: 10

Country: Number of subjects enrolled

Slovakia: 7

Country: Number of subjects enrolled

Spain: 3

Country: Number of subjects enrolled

United States: 88

Worldwide total number of subjects

171

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Subjects enrolled at 31 sites in Belgium, Czech Republic, France, Germany, Italy,Slovakia, Spain, and the United States. Subjects were methotrexate (MTX)-naive or had been withdrawn from MTX at least 2 weeks prior to study drug administration (non-MTX stratum), or were inadequate responders to MTX and continued MTX treatment (MTX stratum).

Screening details

A total of 171 subjects entered the Open-Label Lead-In (OL-LI) phase and received adalimumab; 160 subjects completed the OL-LI phase; and 133 entered the 32-week Double-Blind Phase (75 in the MTX stratum; 58 in the non-MTX stratum) and were randomized to adalimumab or placebo. For all groups, started indicates when subjects entered the DB Phase.

Period 1 title

Double-blind Phase

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Double-Blind Adalimumab + MTX

Arm description

Subjects in the methotrexate (MTX) stratum, who had an inadequate response to MTX and were adalimumab responders during the Open-Label Lead-In (OL-LI) phase, received adalimumab (24 mg/square meter of body surface area [BSA], up to a maximum of 40 mg total body dose administered subcutaneously every other week) plus concomitant MTX treatment during the Double-Blind Phase of the study. MTX-treated inadequate responders must have had active disease on MTX treatment for at least 3 months prior to screening.

Arm type

Experimental

Investigational medicinal product name

Double-Blind Adalimumab/Placebo + MTX

Investigational medicinal product code

Other name

ABT-D2E7, Humira

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injection of 24 mg adalimumab or placebo per square meter of body surface area (BSA) every other week (eow) concomitantly with MTX treatment for 32 weeks during the Double-Blind phase. Total body dose of adalimumab was not to exceed 40 mg.

Double-Blind Placebo + MTX

Arm description

Subjects in the methotrexate (MTX) stratum, who had an inadequate response to MTX and were adalimumab responders during the Open-Label Lead-In (OL-LI) phase, received placebo (24 mg/square meter of body surface area [BSA], up to a maximum of 40 mg total body dose administered subcutaneously every other week) plus concomitant MTX treatment during the Double-Blind Phase of the study. MTX-treated inadequate responders must have had active disease on MTX treatment for at least 3 months prior to screening.

Arm type

Placebo

Investigational medicinal product name

Double-Blind Adalimumab/Placebo + MTX

Investigational medicinal product code

Other name

ABT-D2E7, Humira

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Double-Blind Adalimumab

Arm description

Subjects in the non-methotrexate (MTX) stratum who were either naïve to MTX or withdrawn from MTX at least 2 weeks prior to study drug administration, and were adalimumab responders during the OL-LI phase, received adalimumab (24 mg/square meter of body surface area [BSA], up to a maximum of 40 mg total body dose administered subcutaneously every other week), but no concomitant MTX treatment, during the Double-Blind Phase of the study.

Arm type

Experimental

Investigational medicinal product name

Double-Blind Adalimumab/Placebo

Investigational medicinal product code

Other name

ABT-D2E7, Humira

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subcutaneous injection of 24 mg adalimumab or placebo per square meter of body surface area (BSA) every other week (eow) without MTX treatment for 32 weeks during the Double-Blind Phase. Total body dose of adalimumab was not to exceed 40 mg.

Double-Blind Placebo

Arm description

Subjects in the non-methotrexate (MTX) stratum who were either naïve to MTX or withdrawn from MTX at least 2 weeks prior to study drug administration, and were adalimumab responders during the OL-LI phase, received placebo (24 mg/square meter of body surface area [BSA], up to a maximum of 40 mg total body dose, administered subcutaneously every other week), but no concomitant MTX treatment, during the Double-Blind Phase of the study.

Arm type

Placebo

Investigational medicinal product name

Double-Blind Adalimumab/Placebo

Investigational medicinal product code

Other name

ABT-D2E7, Humira

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 1 ^[1]	Double-Blind Adalimumab + MTX	Double-Blind Placebo + MTX	Double-Blind Adalimumab	Double-Blind Placebo
Started	38	37	30	28
Completed	35	36	29	28
Not completed	3	1	1	0
Randomized in error	1	-	-	-
Consent withdrawn by subject	-	1	-	-
Sponsor request or decision	2	-	-	-
Protocol deviation	-	-	1	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: For all groups, started indicates when the subjects entered the DB Phase.

Period 2 title

Open-label Extension BSA Phase

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Open-label Extension BSA Adalimumab + MTX

Arm description

Subjects in the methotrexate (MTX) stratum received subcutaneous injections of 24 mg adalimumab per square meter of body surface area (BSA) up to a maximum of 40 mg total body dose every other week (eow) concomitantly with MTX treatment during the Open-Label Extension BSA Phase of the study.

Arm type

Experimental

Investigational medicinal product name

OLE BSA Adalimumab/Placebo +/- MTX

Investigational medicinal product code

Other name

ABT-D2E7, Humira

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Comparison of subcutaneous injection of 24 mg adalimumab per square meter of body surface area (BSA) every other week (eow) either with or without concomitant MTX treatment for a minimum of 44 weeks (up to a maximum of 136 weeks) during the Open-Label Extension BSA Phase.

Open-label Extension BSA Adalimumab

Arm description

Subjects in the non-methotrexate (MTX) stratum received adalimumab (24 mg/square meter of body surface area [BSA], up to a maximum of 40 mg total body dose SC eow) without concomitant MTX treatment during the Open-Label Extension BSA Phase.

Arm type

Experimental

Investigational medicinal product name

OLE BSA Adalimumab/Placebo +/- MTX

Investigational medicinal product code

Other name

ABT-D2E7, Humira

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 2	Open-label Extension BSA Adalimumab + MTX	Open-label Extension BSA Adalimumab
Started	71	57
Completed	59	47
Not completed	12	10
Consent withdrawn by subject	3	6
Sponsor request or decision	5	1
Adverse event	1	1
Lack of efficacy	3	1
Protocol deviation	-	1

Period 3 title

Open-label Extension Fixed Dose Phase

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Open-label Extension FD Adalimumab + MTX

Arm description

Subjects in the methotrexate (MTX) stratum received adalimumab concomitantly with MTX treatment during the Open-Label Extension (OLE) Fixed Dose (FD) Phase of the study in which only body weight (not BSA) determined dosing. Subjects weighing less than 30 kg were dosed with 20 mg of adalimumab SC eow, and subjects weighing 30 kg or more were dosed with 40 mg of adalimumab SC eow.

Arm type

Experimental

Investigational medicinal product name

OLE FD Adalimumab/Placebo +/- MTX

Investigational medicinal product code

Other name

ABT-D2E7, Humira

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Comparison of adalimumab administered subcutaneously every other week (eow) either with or without concomitant MTX treatment for up to 224 weeks during the Open-Label Extension Fixed Dose (FD) Phase.

Open-label Extension FD Adalimumab

Arm description

Subjects in the non-methotrexate (MTX) stratum received adalimumab without concomitant MTX treatment during the Open-Label Extension (OLE) Fixed Dose (FD) Phase of the study in which body weight (not BSA) determined dosing. Subjects weighing less than 30 kg were dosed with 20 mg of adalimumab SC eow, and subjects weighing 30 kg or more were dosed with 40 mg of adalimumab SC eow.

Arm type

Experimental

Investigational medicinal product name

OLE FD Adalimumab/Placebo +/- MTX

Investigational medicinal product code

Other name

ABT-D2E7, Humira

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Comparison of adalimumab administered subcutaneously every other week (eow) either with or without concomitant MTX treatment for up to 224 weeks during the Open-Label Extension Fixed Dose (FD) Phase.

Number of subjects in period 3	Open-label Extension FD Adalimumab + MTX	Open-label Extension FD Adalimumab
Started	59	47
Completed	37	25
Not completed	22	22
Consent withdrawn by subject	6	3
Sponsor request or decision	6	7
Adverse event	2	2
Lost to follow-up	5	8
Protocol deviation	1	1
Lack of efficacy	2	1

Baseline characteristics

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Reporting group title

Double-Blind Adalimumab + MTX

Reporting group description

Reporting group title

Double-Blind Placebo + MTX

Reporting group description

Reporting group title

Double-Blind Adalimumab

Reporting group description

Reporting group title

Double-Blind Placebo

Reporting group description

Subjects in the non-methotrexate (MTX) stratum who were either naïve to MTX or withdrawn from MTX at least 2 weeks prior to study drug administration, and were adalimumab responders during the OL-LI phase, received placebo (24 mg/square meter of body surface area [BSA], up to a maximum of 40 mg total body dose, administered subcutaneously every other week), but no concomitant MTX treatment, during the Double-Blind Phase of the study.

Reporting group values	Double-Blind Adalimumab + MTX	Double-Blind Placebo + MTX	Double-Blind Adalimumab	Double-Blind Placebo	Total
Number of subjects	38	37	30	28	133
Age categorical
Units: Subjects
Age continuous
Age for subjects in the Double-blind Phase only.
Units: years
arithmetic mean (standard deviation)	11.7 ( 3.29 )	10.8 ( 3.36 )	11.1 ( 4.13 )	11.3 ( 3.77 )	-
Gender categorical
Numbers represent subjects in the Double-blind Phase only.
Units: Subjects
Female	30	30	23	20	103
Male	8	7	7	8	30

End points

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Reporting group title

Double-Blind Adalimumab + MTX

Reporting group description

Reporting group title

Double-Blind Placebo + MTX

Reporting group description

Reporting group title

Double-Blind Adalimumab

Reporting group description

Reporting group title

Double-Blind Placebo

Reporting group description

Subjects in the non-methotrexate (MTX) stratum who were either naïve to MTX or withdrawn from MTX at least 2 weeks prior to study drug administration, and were adalimumab responders during the OL-LI phase, received placebo (24 mg/square meter of body surface area [BSA], up to a maximum of 40 mg total body dose, administered subcutaneously every other week), but no concomitant MTX treatment, during the Double-Blind Phase of the study.

Reporting group title

Open-label Extension BSA Adalimumab + MTX

Reporting group description

Reporting group title

Open-label Extension BSA Adalimumab

Reporting group description

Reporting group title

Open-label Extension FD Adalimumab + MTX

Reporting group description

Reporting group title

Open-label Extension FD Adalimumab

Reporting group description

Subject analysis set title

Open-label Adalimumab + MTX

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received methotrexate (MTX) plus open-label adalimumab (24 mg/square meter up to a maximum of 40 mg total body dose by body surface area [BSA] administered subcutaneously [SC] every other week [eow]) during the Open-Label Lead-In (OL-LI) Phase of the study. The intent-to-treat (ITT) population was defined as all subjects who were randomized and who received at least a single administration of study drug.

Subject analysis set title

Open-label Adalimumab

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received open-label adalimumab (24 mg/square meter up to a maximum of 40 mg total body dose by body surface area [BSA] administered subcutaneously [SC] every other week [eow]), but no methotrexate (MTX), during the Open-Label Lead-In (OL-LI) Phase of the study. The ITT population was defined as all subjects who were randomized and who received at least a single administration of study drug.

Subject analysis set title

Adalimumab

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received adalimumab during the open-label lead-in phase and during the double-blind phase. The ITT population was defined as all subjects who were randomized and who received at least a single administration of study drug.

Subject analysis set title

Placebo

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received adalimumab during the open-label lead-in phase and placebo during the double-blind phase. The ITT population was defined as all subjects who were randomized and who received at least a single administration of study drug.

Subject analysis set title

Adalimumab + MTX

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received adalimumab plus MTX during the open-label lead-in phase and adalimumab plus MTX during the double-blind phase. The ITT population was defined as all subjects who were randomized and who received at least a single administration of study drug.

Subject analysis set title

Placebo + MTX

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received adalimumab plus MTX during the open-label lead-in phase and placebo plus MTX during the double-blind phase. The ITT population was defined as all subjects who were randomized and who received at least a single administration of study drug.

Subject analysis set title

OLE BSA Adalimumab + MTX

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received adalimumab and concomitant MTX during the Open-Label Extension body surface area (BSA) phase. Subjects received OL adalimumab (24 mg/m2 BSA up to a maximum of 40 mg total body dose subcutaneously (SC) every other week (eow). The ITT population was defined as all subjects who were randomized and who received at least a single administration of study drug.

Subject analysis set title

OLE BSA Adalimumab

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received adalimumab, but not concomitant MTX, during the Open-Label Extension body surface area (BSA) phase. Subjects received OL adalimumab (24 mg/m2 BSA up to a maximum of 40 mg total body dose subcutaneously (SC) every other week (eow). The ITT population was defined as all subjects who were randomized and who received at least a single administration of study drug.

Subject analysis set title

OLE FD Adalimumab + MTX

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received adalimumab and concomitant MTX during the Open-Label Extension fixed dose phase. Subjects weighing less than 30 kg were dosed with 20 mg of adalimumab subcutaneously (SC) every other week (eow). Subjects weighing 30 kg or more were dosed with 40 mg of adalimumab SC eow. The ITT population was defined as all subjects who were randomized and who received at least a single administration of study drug.

Subject analysis set title

OLE FD Adalimumab

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received adalimumab, but not concomitant MTX, during the Open-Label Extension Fixed Dose phase. Subjects weighing less than 30 kg were dosed with 20 mg of adalimumab subcutaneously (SC) every other week (eow). Subjects weighing 30 kg or more were dosed with 40 mg of adalimumab SC eow. The ITT population was defined as all subjects who were randomized and who received at least a single administration of study drug.

Subject analysis set title

Double-Blind Adalimumab + MTX

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Double-Blind Placebo + MTX

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Double-Blind Adalimumab

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Double-Blind Placebo

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects in the non-methotrexate (MTX) stratum who were either naïve to MTX or withdrawn from MTX at least 2 weeks prior to study drug administration, and were adalimumab responders during the OL-LI phase, received placebo (24 mg/square meter of body surface area [BSA], up to a maximum of 40 mg total body dose, administered subcutaneously every other week), but no concomitant MTX treatment, during the Double-Blind Phase of the study.

Primary: Number of Subjects in the Non-MTX Stratum With Disease Flare During the Double-Blind Phase

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End point title

Number of Subjects in the Non-MTX Stratum With Disease Flare During the Double-Blind Phase

End point description

The primary efficacy endpoint was the number of adalimumab-treated subjects in the non-MTX stratum with disease flare during the Double-Blind Phase compared with the number of placebo-treated subjects in the non-MTX stratum with disease flare during the double-blind phase. Subjects met the criteria for disease flare if they had 1) >= 30% worsening in at least 3 of the 6 Juvenile Rheumatoid Arthritis (JRA) core set criteria and a minimum of 2 active joints, and 2) >= 30% improvement in not more than 1 of the 6 JRA core set criteria. Missing values were treated as disease flare.

End point type

Primary

End point timeframe

Week 16 to Week 48 (32 weeks)

End point values	Double-Blind Adalimumab	Double-Blind Placebo
Number of subjects analysed	30 ^[1]	28 ^[2]
Units: subjects	13	20

Notes
[1] - All subjects in the ITT population in the non-MTX stratum.
[2] - All subjects in the ITT population in the non-MTX stratum.

Statistical Analysis 1

Statistical analysis description

The study was sized to detect a difference in the proportion of subjects (40%) between placebo and the active adalimumab dose group who would experience disease flare assuming a placebo rate of 70% vs. a rate of 30% in the active group. Assuming a binomial distribution, an alpha of 0.05, 80% power, two-sided test, and an initial monotherapy responder rate of 70%, a minimum of 29 subjects were needed per treatment group within the appropriate strata.

Comparison groups

Double-Blind Adalimumab v Double-Blind Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.031

Method

Chi-squared

Confidence interval

Secondary: Number of Subjects Meeting Pediatric American College of Rheumatology 30% (PedACR30) Response Criteria at the End of the Open-Label Lead-In Phase

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End point title

Number of Subjects Meeting Pediatric American College of Rheumatology 30% (PedACR30) Response Criteria at the End of the Open-Label Lead-In Phase

End point description

Responders met the following criteria: >= 30% improvement in >= 3 of 6 JRA core set criteria, and >= 30% worsening in not more than 1 JRA criterion, compared with the open-label baseline. JRA core set criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with limitation of motion [LOM] and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. Missing values were treated as non-responders.

End point type

Secondary

End point timeframe

Week 16

End point values	Open-label Adalimumab + MTX	Open-label Adalimumab
Number of subjects analysed	85 ^[3]	86 ^[4]
Units: subjects	80	64

Notes
[3] - All subjects in the ITT population.
[4] - All subjects in the ITT population.

No statistical analyses for this end point

Secondary: Number of Subjects in the MTX Stratum With Disease Flare During the Double-Blind Phase

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End point title

Number of Subjects in the MTX Stratum With Disease Flare During the Double-Blind Phase

End point description

Subjects met criteria for disease flare if they had >= 30% worsening in at least 3 of 6 JRA core set criteria and a minimum of 2 active joints, and >= 30% improvement in not more than 1 JRA criterion. JRA core set criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. Missing values were treated as disease flares.

End point type

Secondary

End point timeframe

Week 16 to Week 48 (32 Weeks)

End point values	Double-Blind Adalimumab + MTX	Double-Blind Placebo + MTX
Number of subjects analysed	38 ^[5]	37 ^[6]
Units: subjects	14	24

Notes
[5] - All subjects in the ITT population in the MTX stratum.
[6] - All subjects in the ITT population in the MTX stratum.

Statistical Analysis 1

Comparison groups

Double-Blind Adalimumab + MTX v Double-Blind Placebo + MTX

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.015

Method

Chi-squared

Confidence interval

Secondary: Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum

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End point title

Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum

End point description

A log rank test was performed and the Kaplan-Meier curve for time to disease flare from double-blind baseline (Week 16) to Week 48 was generated. Disease flare was defined as a >= 30% worsening in at least 3 of 6 JRA core set criteria and a minimum of 2 active joints, and >= 30% improvement in not more than 1 JRA criterion. The percentage of subjects without disease flare at each time point is presented.

End point type

Secondary

End point timeframe

Week 16 to Week 48 (32 weeks)

End point values	Double-Blind Adalimumab	Double-Blind Placebo
Number of subjects analysed	30 ^[7]	28 ^[8]
Units: percent subjects w/o disease flare
number (not applicable)
Week 20	90	78.6
Week 24	83.3	64.3
Week 28	80	60.7
Week 32	70	46.4
Week 36	66.7	46.4
Week 40	60	39.3
Week 44	60	32.1
Week 48	56.7	28.6

Notes
[7] - All subjects in the ITT population in the non-MTX stratum.
[8] - All subjects in the ITT population in the non-MTX stratum.

Statistical Analysis 1

Comparison groups

Double-Blind Adalimumab v Double-Blind Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.029

Method

Logrank

Confidence interval

Secondary: Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum

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End point title

Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum

End point description

End point type

Secondary

End point timeframe

Week 16 to Week 48 (32 weeks)

End point values	Double-Blind Adalimumab + MTX	Double-Blind Placebo + MTX
Number of subjects analysed	38	37
Units: percent subjects w/o disease flare
number (not applicable)
Week 20	86.8	83.8
Week 24	78.9	70.3
Week 28	68.4	59.5
Week 32	68.4	56.8
Week 36	63.2	48.6
Week 40	63.2	45.9
Week 44	63.2	43.2
Week 48	63.2	35.1

Statistical Analysis 1

Comparison groups

Double-Blind Adalimumab + MTX v Double-Blind Placebo + MTX

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.031

Method

Logrank

Confidence interval

Secondary: Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase

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End point title

Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase

End point description

Responders met the following criteria: >= 30% improvement in >= 3 of 6 JIA core set criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with the OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core criteria are included in PedACR criteria. Missing values were treated as non-responders.

End point type

Secondary

End point timeframe

Week 48

End point values	Adalimumab	Placebo	Adalimumab + MTX	Placebo + MTX
Number of subjects analysed	30 ^[9]	28 ^[10]	38 ^[11]	37 ^[12]
Units: subjects	17	9	24	14

Notes
[9] - All subjects in the ITT population.
[10] - All subjects in the ITT population.
[11] - All subjects in the ITT population.
[12] - All subjects in the ITT population.

Statistical Analysis 1

Comparison groups

Adalimumab v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.061

Method

Pearson's Chi-square test

Confidence interval

Statistical Analysis 2

Comparison groups

Adalimumab + MTX v Placebo + MTX

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.028

Method

Pearson's Chi-square test

Confidence interval

Secondary: Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-Blind Phase

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End point title

Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-Blind Phase

End point description

Responders met the following criteria: >= 50% improvement in >= 3 of 6 JIA core set criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with the OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core variables are included in PedACR criteria. Missing values were treated as non-responders.

End point type

Secondary

End point timeframe

Week 48

End point values	Adalimumab	Placebo	Adalimumab + MTX	Placebo + MTX
Number of subjects analysed	30 ^[13]	28 ^[14]	38 ^[15]	37 ^[16]
Units: subjects	16	9	24	14

Notes
[13] - All subjects in the ITT population.
[14] - All subjects in the ITT population.
[15] - All subjects in the ITT population.
[16] - All subjects in the ITT population.

Statistical Analysis 1

Comparison groups

Placebo v Adalimumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.103

Method

Pearson's Chi-square test

Confidence interval

Statistical Analysis 2

Comparison groups

Adalimumab + MTX v Placebo + MTX

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.028

Method

Pearson's Chi-square test

Confidence interval

Secondary: Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-Blind Phase

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End point title

Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-Blind Phase

End point description

Responders met the following criteria: >= 70% improvement in >= 3 of 6 JIA core set criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with the OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core variables are included in PedACR criteria. Missing values were treated as non-responders.

End point type

Secondary

End point timeframe

Week 48

End point values	Adalimumab	Placebo	Adalimumab + MTX	Placebo + MTX
Number of subjects analysed	30 ^[17]	28 ^[18]	38 ^[19]	37 ^[20]
Units: subjects	14	8	24	10

Notes
[17] - All subjects in the ITT population.
[18] - All subjects in the ITT population.
[19] - All subjects in the ITT population.
[20] - All subjects in the ITT population.

Statistical Analysis 1

Comparison groups

Adalimumab v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.156

Method

Pearson's Chi-square test

Confidence interval

Statistical Analysis 2

Comparison groups

Adalimumab + MTX v Placebo + MTX

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.002

Method

Pearson's Chi-square test

Confidence interval

Secondary: Mean Change From Baseline in Physician's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase

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End point title

Mean Change From Baseline in Physician's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase

End point description

A 100 mm horizontal visual analog scale (VAS) was used to assess the Physician Global Assessment of Disease Activity. The left end of the VAS scale (0 mm) signified the absence of symptoms and the right end (100 mm) maximum disease activity. The mean change from open-label baseline to Week 48 was determined. Negative mean changes indicated improvement. Observed data were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 48

End point values	Adalimumab	Placebo	Adalimumab + MTX	Placebo + MTX
Number of subjects analysed	17 ^[21]	9 ^[22]	24 ^[23]	15 ^[24]
Units: units on a scale
arithmetic mean (standard error)	-52.06 ( 3.713 )	-38.73 ( 6.554 )	-48.5 ( 3.89 )	-38.73 ( 6.554 )

Notes
[21] - All subjects in the ITT population who remained in the study at Week 48.
[22] - All subjects in the ITT population who remained in the study at Week 48.
[23] - All subjects in the ITT population who remained in the study at Week 48.
[24] - All subjects in the ITT population who remained in the study at Week 48.

No statistical analyses for this end point

Secondary: Mean Change From Baseline in Parent's/Patient's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase

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End point title

Mean Change From Baseline in Parent's/Patient's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase

End point description

A 100 mm horizontal visual analog scale (VAS) was used to assess the Parent's/Patient's Global Assessment of Disease Activity. The left end of the VAS (0 mm) signified the absence of symptoms and the right end (100 mm) maximum disease activity. The mean change from open-label baseline to Week 48 was determined. Negative mean changes indicated improvement. Observed data were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 48

End point values	Adalimumab	Placebo	Adalimumab + MTX	Placebo + MTX
Number of subjects analysed	17 ^[25]	9 ^[26]	24 ^[27]	15 ^[28]
Units: units on a scale
arithmetic mean (standard error)	-41.53 ( 5.562 )	-50.56 ( 6.129 )	-36.42 ( 5.177 )	-26.87 ( 5.644 )

Notes
[25] - All subjects in the ITT population who completed Week 48.
[26] - All subjects in the ITT population who completed Week 48.
[27] - All subjects in the ITT population who completed Week 48.
[28] - All subjects in the ITT population who completed Week 48.

No statistical analyses for this end point

Secondary: Mean Change From Baseline in C-Reactive Protein Levels at Week 48 of the Double-Blind Phase

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End point title

Mean Change From Baseline in C-Reactive Protein Levels at Week 48 of the Double-Blind Phase

End point description

Serum levels of C-reactive protein (CRP) were measured at screening (open-label baseline) and at Week 48. Negative mean changes in CRP from open-label baseline to Week 48 indicated improvement. Observed data were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 48

End point values	Adalimumab	Placebo	Adalimumab + MTX	Placebo + MTX
Number of subjects analysed	17 ^[29]	9 ^[30]	24 ^[31]	15 ^[32]
Units: mg/dL
arithmetic mean (standard error)	-1.79 ( 0.803 )	-3.91 ( 2 )	-1.71 ( 0.529 )	-0.1 ( 0.333 )

Notes
[29] - All subjects in the ITT population who remained in the study at Week 48.
[30] - All subjects in the ITT population who remained in the study at Week 48.
[31] - All subjects in the ITT population who remained in the study at Week 48.
[32] - All subjects in the ITT population who remained in the study at Week 48.

No statistical analyses for this end point

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase

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End point title

Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase

End point description

Responders met the following criteria: >= 30%/50%/70% improvement in >= 3 of 6 JIA core criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.

End point type

Secondary

End point timeframe

Open-Label Lead-In Phase Baseline

End point values	OLE BSA Adalimumab + MTX	OLE BSA Adalimumab
Number of subjects analysed	67 ^[33]	53 ^[34]
Units: subjects
PedACR30 Baseline	55	46
PedACR50 Baseline	47	41
PedACR70 Baseline	35	30

Notes
[33] - The ITT population was used for analysis in the Open-Label Extension Body Surface Area phase.
[34] - The ITT population was used for analysis in the Open-Label Extension Body Surface Area phase.

No statistical analyses for this end point

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase

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End point title

Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase

End point description

End point type

Secondary

End point timeframe

Week 56

End point values	OLE BSA Adalimumab + MTX	OLE BSA Adalimumab
Number of subjects analysed	55 ^[35]	41 ^[36]
Units: subjects
PedACR30 Week 56	50	40
PedACR50 Week 56	49	40
PedACR70 Week 56	43	35

Notes
[35] - The ITT population was used for analysis in the Open-Label Extension Body Surface Area phase.
[36] - The ITT population was used for analysis in the Open-Label Extension Body Surface Area phase.

No statistical analyses for this end point

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase

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End point title

Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase

End point description

End point type

Secondary

End point timeframe

Week 104

End point values	OLE BSA Adalimumab + MTX	OLE BSA Adalimumab
Number of subjects analysed	19 ^[37]	17 ^[38]
Units: subjects
PedACR30 Week 104	18	16
PedACR50 Week 104	16	16
PedACR70 Week 104	14	14

Notes
[37] - The ITT population was used for analysis in the Open-Label Extension Body Surface Area phase.
[38] - The ITT population was used for analysis in the Open-Label Extension Body Surface Area phase.

No statistical analyses for this end point

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase

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End point title

Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase

End point description

Responders met the following criteria: >= 30%/50%/70% improvement in >= 3 of 6 JIA core criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with OL-LI baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.

End point type

Secondary

End point timeframe

Baseline

End point values	OLE FD Adalimumab + MTX	OLE FD Adalimumab
Number of subjects analysed	53 ^[39]	45 ^[40]
Units: subjects
PedACR30 OLE FD Baseline	53	44
PedACR50 OLE FD Baseline	50	43
PedACR70 OLE FD Baseline	46	40

Notes
[39] - The ITT population was used for analysis in the Open-Label Extension Fixed Dose phase.
[40] - The ITT population was used for analysis in the Open-Label Extension Fixed Dose phase.

No statistical analyses for this end point

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase

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End point title

Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase

End point description

End point type

Secondary

End point timeframe

Week 48

End point values	OLE FD Adalimumab + MTX	OLE FD Adalimumab
Number of subjects analysed	51 ^[41]	40 ^[42]
Units: subjects
PedACR30 Week 48	47	40
PedACR50 Week 48	47	39
PedACR70 Week 48	44	38

Notes
[41] - The ITT population was used for analysis in the Open-Label Extension Fixed Dose phase.
[42] - The ITT population was used for analysis in the Open-Label Extension Fixed Dose phase.

No statistical analyses for this end point

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase

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End point title

Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase

End point description

End point type

Secondary

End point timeframe

Week 112

End point values	OLE FD Adalimumab + MTX	OLE FD Adalimumab
Number of subjects analysed	41 ^[43]	31 ^[44]
Units: subjects
PedACR30 Week 112	39	31
PedACR50 Week 112	39	30
PedACR70 Week 112	34	29

Notes
[43] - The ITT population was used for analysis in the Open-Label Extension Fixed Dose phase.
[44] - The ITT population was used for analysis in the Open-Label Extension Fixed Dose phase.

No statistical analyses for this end point

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase

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End point title

Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase

End point description

Responders met the following criteria: >= 30%/50%/70% improvement in >= 3 of 6 JIA core criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. Final Visit = last visit per subject (up to 224 weeks).

End point type

Secondary

End point timeframe

Final Visit (up to 224 weeks of OLE FD phase)

End point values	OLE FD Adalimumab + MTX	OLE FD Adalimumab
Number of subjects analysed	55 ^[45]	46 ^[46]
Units: subjects
PedACR30 Final Visit	48	44
PedACR50 Final Visit	45	43
PedACR70 Final Visit	43	40

Notes
[45] - The ITT population was used for analysis in the Open-Label Extension Fixed Dose phase.
[46] - The ITT population was used for analysis in the Open-Label Extension Fixed Dose phase.

No statistical analyses for this end point

Other pre-specified: Baseline Measure: Gender, Female/Male - OLE BSA Phase

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End point title

Baseline Measure: Gender, Female/Male - OLE BSA Phase

End point description

Gender (female/male) recorded at Baseline of the Open-Label Extension BSA phase of the study. This measure was excluded from Baseline Characteristics due to difficulty maintaining correct subject numbers and Baseline value totals in that section while including this phase of the study.

End point type

Other pre-specified

End point timeframe

Baseline OLE BSA Phase

End point values	OLE BSA Adalimumab + MTX	OLE BSA Adalimumab
Number of subjects analysed	71	57
Units: subjects
OLE BSA Phase - Female	56	42
OLE BSA Phase - Male	15	15

No statistical analyses for this end point

Other pre-specified: Baseline Measure: Age Continuous - OLE BSA Phase

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End point title

Baseline Measure: Age Continuous - OLE BSA Phase

End point description

Age continuous (mean +/- SD) recorded at Baseline of the Open-Label Extension BSA phase of the study. This measure was excluded from Baseline Characteristics due to difficulty maintaining correct subject numbers and Baseline value totals in that section with this phase included.

End point type

Other pre-specified

End point timeframe

Baseline OLE BSA Phase

End point values	OLE BSA Adalimumab + MTX	OLE BSA Adalimumab
Number of subjects analysed	71	57
Units: years
arithmetic mean (standard deviation)	11.3 ( 3.32 )	11.2 ( 3.96 )

No statistical analyses for this end point

Other pre-specified: Baseline Measure: Gender, Female/Male - OLE FD Phase

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End point title

Baseline Measure: Gender, Female/Male - OLE FD Phase

End point description

Gender (female/male) recorded at Baseline of the Open-Label Extension FD phase of the study. This measure was excluded from Baseline Characteristics due to difficulty maintaining correct subject numbers and Baseline value totals in that section while including this phase of the study.

End point type

Other pre-specified

End point timeframe

Baseline OLE FD Phase

End point values	OLE FD Adalimumab + MTX	OLE FD Adalimumab
Number of subjects analysed	59	47
Units: subjects
OLE FD Phase - Female	45	33
OLE FD Phase - Male	14	14

No statistical analyses for this end point

Other pre-specified: Baseline Measure: Age Continuous - OLE FD Phase

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End point title

Baseline Measure: Age Continuous - OLE FD Phase

End point description

Age continuous (mean +/- SD) recorded at Baseline of the Open-Label Extension FD phase of the study. This measure was excluded from Baseline Characteristics due to difficulty maintaining correct subject numbers and Baseline value totals in that section with this phase included.

End point type

Other pre-specified

End point timeframe

Baseline OLE FD Phase

End point values	OLE FD Adalimumab + MTX	OLE FD Adalimumab
Number of subjects analysed	59	47
Units: years
arithmetic mean (standard deviation)	11.1 ( 3.36 )	11 ( 4.12 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

DB Phase - Week 16 to 48 (32 Weeks), Open-Label Extension BSA Phase - OLE BSA Baseline to Week 136 (136 weeks), Open-Label Extension FD Phase - OLE FD Baseline to Final Visit (up to 224 weeks)* *Last observation of each subject in FD population.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

12.1

Reporting group title

Double-Blind Adalimumab + MTX

Reporting group description

Reporting group title

Double-Blind Placebo + MTX

Reporting group description

Reporting group title

Double-Blind Adalimumab

Reporting group description

Reporting group title

Double-Blind Placebo

Reporting group description

Subjects in the non-methotrexate (MTX) stratum who were either naïve to MTX or withdrawn from MTX at least 2 weeks prior to study drug administration, and were adalimumab responders during the OL-LI phase, received placebo (24 mg/square meter of body surface area [BSA], up to a maximum of 40 mg total body dose, administered subcutaneously every other week), but no concomitant MTX treatment, during the Double-Blind Phase of the study.

Reporting group title

Open-Label Extension BSA Adalimumab + MTX

Reporting group description

Reporting group title

Open-Label Extension BSA Adalimumab

Reporting group description

Reporting group title

Open-Label Extension FD Adalimumab + MTX

Reporting group description

Subjects in the methotrexate (MTX) stratum received adalimumab concomitantly with MTX treatment during the Open-Label Extension (OLE) Fixed Dose (FD) Phase of the study, in which subjects were dosed based on body weight (not BSA). Subjects were separated into 2 body weight categories; subjects weighing less than 30 kg were dosed with 20 mg of adalimumab SC eow, and subjects weighing 30 kg or more were dosed with 40 mg of adalimumab SC eow.

Reporting group title

Open-Label Extension FD Adalimumab

Reporting group description

Subjects in the methotrexate (MTX) stratum received adalimumab without concomitant MTX treatment during the Open-Label Extension (OLE) Fixed Dose (FD) Phase of the study, in which subjects were dosed based on body weight (not BSA). Subjects were separated into 2 body weight categories; subjects weighing less than 30 kg were dosed with 20 mg of adalimumab SC eow, and subjects weighing 30 kg or more were dosed with 40 mg of adalimumab SC eow.

Serious adverse events	Double-Blind Adalimumab + MTX	Double-Blind Placebo + MTX	Double-Blind Adalimumab	Double-Blind Placebo	Open-Label Extension BSA Adalimumab + MTX	Open-Label Extension BSA Adalimumab	Open-Label Extension FD Adalimumab + MTX	Open-Label Extension FD Adalimumab
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 38 (7.89%)	2 / 37 (5.41%)	1 / 30 (3.33%)	0 / 28 (0.00%)	13 / 71 (18.31%)	9 / 57 (15.79%)	7 / 59 (11.86%)	10 / 47 (21.28%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events
Surgical and medical procedures
Abortion induced
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	1 / 59 (1.69%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	1 / 57 (1.75%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Abortion spontaneous
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Breast enlargement
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	1 / 71 (1.41%)	2 / 57 (3.51%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	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	0 / 0
Nasal septum deviation
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	1 / 57 (1.75%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Tonsillar hypertrophy
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	1 / 71 (1.41%)	2 / 57 (3.51%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	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	0 / 0
Psychiatric disorders
Bipolar disorder
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Psychotic disorder
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Investigations
Laboratory test abnormal
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	1 / 59 (1.69%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Injury, poisoning and procedural complications
Injury
subjects affected / exposed	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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	0 / 0
Joint dislocation
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	1 / 57 (1.75%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Cardiac disorders
Pericarditis
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Nervous system disorders
Hydrocephalus
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	1 / 71 (1.41%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Speech disorder
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	1 / 57 (1.75%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Eye disorders
Retinal detachment
subjects affected / exposed	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	1 / 71 (1.41%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroduodenitis
subjects affected / exposed	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Haematochezia
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	1 / 71 (1.41%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malabsorption
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	1 / 57 (1.75%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Vomiting
subjects affected / exposed	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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	0 / 0
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Musculoskeletal and connective tissue disorders
Arthritis
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	2 / 71 (2.82%)	0 / 57 (0.00%)	1 / 59 (1.69%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	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	0 / 0
Joint contracture
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	1 / 57 (1.75%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Juvenile arthritis
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	5 / 71 (7.04%)	1 / 57 (1.75%)	1 / 59 (1.69%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 9	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Knee deformity
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	1 / 59 (1.69%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	1 / 71 (1.41%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Osteochondrosis
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Rheumatoid arthritis
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	1 / 59 (1.69%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Spondylolisthesis
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Tendon disorder
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Tendonitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	1 / 59 (1.69%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	1 / 71 (1.41%)	0 / 57 (0.00%)	0 / 59 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	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	0 / 0
Bronchopneumonia
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	1 / 57 (1.75%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 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	0 / 0
Cervicitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	1 / 59 (1.69%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Herpes zoster
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	1 / 71 (1.41%)	1 / 57 (1.75%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 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	0 / 0
Pharyngitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	1 / 71 (1.41%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 30 (3.33%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Viral infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	1 / 71 (1.41%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Diabetic ketoacidosis
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	1 / 59 (1.69%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Double-Blind Adalimumab + MTX	Double-Blind Placebo + MTX	Double-Blind Adalimumab	Double-Blind Placebo	Open-Label Extension BSA Adalimumab + MTX	Open-Label Extension BSA Adalimumab	Open-Label Extension FD Adalimumab + MTX	Open-Label Extension FD Adalimumab
Total subjects affected by non serious adverse events
subjects affected / exposed	28 / 38 (73.68%)	22 / 37 (59.46%)	21 / 30 (70.00%)	20 / 28 (71.43%)	63 / 71 (88.73%)	48 / 57 (84.21%)	54 / 59 (91.53%)	38 / 47 (80.85%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	1 / 38 (2.63%)	0 / 37 (0.00%)	1 / 30 (3.33%)	2 / 28 (7.14%)	2 / 71 (2.82%)	3 / 57 (5.26%)	2 / 59 (3.39%)	3 / 47 (6.38%)
occurrences all number	2	0	3	2	3	3	4	5
General disorders and administration site conditions
Fatigue
subjects affected / exposed	1 / 38 (2.63%)	0 / 37 (0.00%)	1 / 30 (3.33%)	1 / 28 (3.57%)	2 / 71 (2.82%)	2 / 57 (3.51%)	3 / 59 (5.08%)	0 / 47 (0.00%)
occurrences all number	2	0	1	1	2	2	3	0
Influenza like illness
subjects affected / exposed	0 / 38 (0.00%)	4 / 37 (10.81%)	0 / 30 (0.00%)	0 / 28 (0.00%)	4 / 71 (5.63%)	1 / 57 (1.75%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	6	0	0	5	1	0	0
Injection site erythema
subjects affected / exposed	2 / 38 (5.26%)	1 / 37 (2.70%)	1 / 30 (3.33%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences all number	2	1	10	0	0	0	0	0
Injection site pain
subjects affected / exposed	7 / 38 (18.42%)	7 / 37 (18.92%)	9 / 30 (30.00%)	3 / 28 (10.71%)	14 / 71 (19.72%)	10 / 57 (17.54%)	4 / 59 (6.78%)	4 / 47 (8.51%)
occurrences all number	48	49	45	16	172	108	8	6
Injection site reaction
subjects affected / exposed	7 / 38 (18.42%)	1 / 37 (2.70%)	3 / 30 (10.00%)	1 / 28 (3.57%)	8 / 71 (11.27%)	9 / 57 (15.79%)	2 / 59 (3.39%)	1 / 47 (2.13%)
occurrences all number	19	1	11	1	35	30	2	2
Pain
subjects affected / exposed	1 / 38 (2.63%)	1 / 37 (2.70%)	3 / 30 (10.00%)	3 / 28 (10.71%)	0 / 71 (0.00%)	3 / 57 (5.26%)	0 / 59 (0.00%)	3 / 47 (6.38%)
occurrences all number	13	1	9	23	0	10	0	3
Pyrexia
subjects affected / exposed	2 / 38 (5.26%)	0 / 37 (0.00%)	1 / 30 (3.33%)	1 / 28 (3.57%)	4 / 71 (5.63%)	6 / 57 (10.53%)	2 / 59 (3.39%)	5 / 47 (10.64%)
occurrences all number	3	0	1	1	6	6	3	5
Immune system disorders
Hypersensitivity
subjects affected / exposed	2 / 38 (5.26%)	1 / 37 (2.70%)	2 / 30 (6.67%)	0 / 28 (0.00%)	2 / 71 (2.82%)	2 / 57 (3.51%)	2 / 59 (3.39%)	3 / 47 (6.38%)
occurrences all number	3	1	3	0	2	3	2	4
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 30 (0.00%)	1 / 28 (3.57%)	2 / 71 (2.82%)	3 / 57 (5.26%)	3 / 59 (5.08%)	0 / 47 (0.00%)
occurrences all number	2	0	0	1	6	3	5	0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	2 / 38 (5.26%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	2 / 57 (3.51%)	1 / 59 (1.69%)	1 / 47 (2.13%)
occurrences all number	3	0	0	0	0	3	1	1
Cough
subjects affected / exposed	2 / 38 (5.26%)	0 / 37 (0.00%)	1 / 30 (3.33%)	1 / 28 (3.57%)	6 / 71 (8.45%)	5 / 57 (8.77%)	2 / 59 (3.39%)	2 / 47 (4.26%)
occurrences all number	2	0	1	1	6	6	2	2
Oropharyngeal pain
subjects affected / exposed	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 30 (0.00%)	1 / 28 (3.57%)	6 / 71 (8.45%)	0 / 57 (0.00%)	4 / 59 (6.78%)	0 / 47 (0.00%)
occurrences all number	0	2	0	1	6	0	4	0
Rhinitis allergic
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 30 (3.33%)	0 / 28 (0.00%)	0 / 71 (0.00%)	2 / 57 (3.51%)	3 / 59 (5.08%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0	0	2	5	0
Investigations
Blood triglycerides increased
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	1 / 57 (1.75%)	3 / 59 (5.08%)	2 / 47 (4.26%)
occurrences all number	0	0	0	0	0	1	4	2
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 30 (0.00%)	2 / 28 (7.14%)	4 / 71 (5.63%)	2 / 57 (3.51%)	0 / 59 (0.00%)	2 / 47 (4.26%)
occurrences all number	1	0	0	3	4	2	0	3
Contusion
subjects affected / exposed	7 / 38 (18.42%)	5 / 37 (13.51%)	2 / 30 (6.67%)	2 / 28 (7.14%)	4 / 71 (5.63%)	3 / 57 (5.26%)	1 / 59 (1.69%)	4 / 47 (8.51%)
occurrences all number	12	7	2	5	4	5	1	6
Excoriation
subjects affected / exposed	4 / 38 (10.53%)	1 / 37 (2.70%)	3 / 30 (10.00%)	1 / 28 (3.57%)	7 / 71 (9.86%)	4 / 57 (7.02%)	2 / 59 (3.39%)	4 / 47 (8.51%)
occurrences all number	10	1	6	1	12	4	2	7
Injury
subjects affected / exposed	2 / 38 (5.26%)	1 / 37 (2.70%)	0 / 30 (0.00%)	4 / 28 (14.29%)	3 / 71 (4.23%)	1 / 57 (1.75%)	1 / 59 (1.69%)	4 / 47 (8.51%)
occurrences all number	2	1	0	4	4	1	1	6
Joint sprain
subjects affected / exposed	2 / 38 (5.26%)	0 / 37 (0.00%)	0 / 30 (0.00%)	3 / 28 (10.71%)	1 / 71 (1.41%)	4 / 57 (7.02%)	1 / 59 (1.69%)	2 / 47 (4.26%)
occurrences all number	2	0	0	3	1	6	1	2
Muscle strain
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	2 / 30 (6.67%)	1 / 28 (3.57%)	1 / 71 (1.41%)	4 / 57 (7.02%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	0	3	1	1	4	0	0
Skin laceration
subjects affected / exposed	2 / 38 (5.26%)	0 / 37 (0.00%)	1 / 30 (3.33%)	0 / 28 (0.00%)	2 / 71 (2.82%)	0 / 57 (0.00%)	0 / 59 (0.00%)	1 / 47 (2.13%)
occurrences all number	3	0	1	0	4	0	0	1
Thermal burn
subjects affected / exposed	1 / 38 (2.63%)	3 / 37 (8.11%)	0 / 30 (0.00%)	1 / 28 (3.57%)	1 / 71 (1.41%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences all number	1	3	0	1	1	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	2 / 38 (5.26%)	4 / 37 (10.81%)	2 / 30 (6.67%)	4 / 28 (14.29%)	9 / 71 (12.68%)	8 / 57 (14.04%)	4 / 59 (6.78%)	11 / 47 (23.40%)
occurrences all number	3	5	2	10	13	11	4	21
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	3 / 30 (10.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	2 / 57 (3.51%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	0	3	0	0	2	0	0
Eye disorders
Conjunctivitis
subjects affected / exposed	2 / 38 (5.26%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	4 / 57 (7.02%)	2 / 59 (3.39%)	2 / 47 (4.26%)
occurrences all number	2	0	0	0	0	4	2	2
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 30 (0.00%)	2 / 28 (7.14%)	3 / 71 (4.23%)	1 / 57 (1.75%)	5 / 59 (8.47%)	4 / 47 (8.51%)
occurrences all number	0	1	0	3	3	1	5	6
Abdominal pain upper
subjects affected / exposed	1 / 38 (2.63%)	1 / 37 (2.70%)	0 / 30 (0.00%)	1 / 28 (3.57%)	0 / 71 (0.00%)	1 / 57 (1.75%)	1 / 59 (1.69%)	4 / 47 (8.51%)
occurrences all number	1	1	0	1	0	1	1	4
Nausea
subjects affected / exposed	1 / 38 (2.63%)	1 / 37 (2.70%)	0 / 30 (0.00%)	1 / 28 (3.57%)	9 / 71 (12.68%)	3 / 57 (5.26%)	2 / 59 (3.39%)	6 / 47 (12.77%)
occurrences all number	1	1	0	1	15	6	4	8
Vomiting
subjects affected / exposed	3 / 38 (7.89%)	2 / 37 (5.41%)	0 / 30 (0.00%)	1 / 28 (3.57%)	5 / 71 (7.04%)	3 / 57 (5.26%)	2 / 59 (3.39%)	3 / 47 (6.38%)
occurrences all number	3	2	0	1	5	4	2	4
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	1 / 38 (2.63%)	0 / 37 (0.00%)	2 / 30 (6.67%)	1 / 28 (3.57%)	3 / 71 (4.23%)	2 / 57 (3.51%)	3 / 59 (5.08%)	2 / 47 (4.26%)
occurrences all number	1	0	2	1	3	2	4	2
Blister
subjects affected / exposed	2 / 38 (5.26%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	1 / 71 (1.41%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences all number	2	0	0	0	1	0	0	0
Dermatitis contact
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 30 (3.33%)	0 / 28 (0.00%)	5 / 71 (7.04%)	0 / 57 (0.00%)	3 / 59 (5.08%)	4 / 47 (8.51%)
occurrences all number	0	0	1	0	5	0	3	4
Ecchymosis
subjects affected / exposed	2 / 38 (5.26%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	2 / 71 (2.82%)	1 / 57 (1.75%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences all number	2	0	0	0	2	1	0	0
Eczema
subjects affected / exposed	0 / 38 (0.00%)	2 / 37 (5.41%)	0 / 30 (0.00%)	1 / 28 (3.57%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	2	0	1	0	0	0	0
Pruritus
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	2 / 28 (7.14%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0
Rash
subjects affected / exposed	1 / 38 (2.63%)	0 / 37 (0.00%)	2 / 30 (6.67%)	0 / 28 (0.00%)	5 / 71 (7.04%)	4 / 57 (7.02%)	2 / 59 (3.39%)	6 / 47 (12.77%)
occurrences all number	1	0	2	0	5	4	2	7
Erythema
subjects affected / exposed	0 / 38 (0.00%)	1 / 37 (2.70%)	1 / 30 (3.33%)	2 / 28 (7.14%)	1 / 71 (1.41%)	0 / 57 (0.00%)	1 / 59 (1.69%)	1 / 47 (2.13%)
occurrences all number	0	1	1	3	1	0	1	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 38 (5.26%)	0 / 37 (0.00%)	2 / 30 (6.67%)	1 / 28 (3.57%)	5 / 71 (7.04%)	6 / 57 (10.53%)	4 / 59 (6.78%)	7 / 47 (14.89%)
occurrences all number	4	0	2	1	7	9	7	12
Arthritis
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	1 / 28 (3.57%)	3 / 71 (4.23%)	1 / 57 (1.75%)	4 / 59 (6.78%)	7 / 47 (14.89%)
occurrences all number	0	0	0	1	3	1	5	10
Juvenile arthritis
subjects affected / exposed	2 / 38 (5.26%)	1 / 37 (2.70%)	1 / 30 (3.33%)	1 / 28 (3.57%)	2 / 71 (2.82%)	3 / 57 (5.26%)	4 / 59 (6.78%)	4 / 47 (8.51%)
occurrences all number	2	1	1	1	3	3	5	5
Muscle spasms
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	1 / 71 (1.41%)	3 / 57 (5.26%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	0	0	0	1	3	0	0
Pain in extremity
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	2 / 28 (7.14%)	4 / 71 (5.63%)	0 / 57 (0.00%)	1 / 59 (1.69%)	1 / 47 (2.13%)
occurrences all number	0	0	0	2	4	0	1	1
Rheumatoid arthritis
subjects affected / exposed	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 30 (0.00%)	0 / 28 (0.00%)	7 / 71 (9.86%)	7 / 57 (12.28%)	7 / 59 (11.86%)	6 / 47 (12.77%)
occurrences all number	0	1	0	0	11	8	11	10
Synovitis
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	0 / 57 (0.00%)	0 / 59 (0.00%)	3 / 47 (6.38%)
occurrences all number	0	0	0	0	0	0	0	4
Infections and infestations
Acute tonsillitis
subjects affected / exposed	1 / 38 (2.63%)	2 / 37 (5.41%)	0 / 30 (0.00%)	0 / 28 (0.00%)	4 / 71 (5.63%)	0 / 57 (0.00%)	6 / 59 (10.17%)	0 / 47 (0.00%)
occurrences all number	1	3	0	0	6	0	10	0
Bronchitis
subjects affected / exposed	0 / 38 (0.00%)	1 / 37 (2.70%)	1 / 30 (3.33%)	1 / 28 (3.57%)	4 / 71 (5.63%)	2 / 57 (3.51%)	1 / 59 (1.69%)	2 / 47 (4.26%)
occurrences all number	0	1	1	1	5	2	1	2
Ear infection
subjects affected / exposed	1 / 38 (2.63%)	0 / 37 (0.00%)	1 / 30 (3.33%)	1 / 28 (3.57%)	4 / 71 (5.63%)	0 / 57 (0.00%)	7 / 59 (11.86%)	3 / 47 (6.38%)
occurrences all number	1	0	1	1	4	0	7	3
Gastroenteritis viral
subjects affected / exposed	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 30 (0.00%)	1 / 28 (3.57%)	1 / 71 (1.41%)	2 / 57 (3.51%)	3 / 59 (5.08%)	1 / 47 (2.13%)
occurrences all number	0	1	0	1	1	2	3	1
Herpes virus infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	2 / 30 (6.67%)	0 / 28 (0.00%)	1 / 71 (1.41%)	0 / 57 (0.00%)	0 / 59 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	0	3	0	1	0	0	0
Impetigo
subjects affected / exposed	2 / 38 (5.26%)	0 / 37 (0.00%)	1 / 30 (3.33%)	0 / 28 (0.00%)	2 / 71 (2.82%)	5 / 57 (8.77%)	0 / 59 (0.00%)	2 / 47 (4.26%)
occurrences all number	3	0	2	0	3	5	0	2
Influenza
subjects affected / exposed	1 / 38 (2.63%)	1 / 37 (2.70%)	1 / 30 (3.33%)	2 / 28 (7.14%)	2 / 71 (2.82%)	4 / 57 (7.02%)	3 / 59 (5.08%)	5 / 47 (10.64%)
occurrences all number	1	1	1	2	2	4	3	5
Nasopharyngitis
subjects affected / exposed	4 / 38 (10.53%)	4 / 37 (10.81%)	0 / 30 (0.00%)	3 / 28 (10.71%)	8 / 71 (11.27%)	4 / 57 (7.02%)	7 / 59 (11.86%)	3 / 47 (6.38%)
occurrences all number	4	6	0	4	9	6	7	3
Oral herpes
subjects affected / exposed	1 / 38 (2.63%)	2 / 37 (5.41%)	0 / 30 (0.00%)	0 / 28 (0.00%)	2 / 71 (2.82%)	2 / 57 (3.51%)	3 / 59 (5.08%)	0 / 47 (0.00%)
occurrences all number	1	5	0	0	3	3	3	0
Otitis media
subjects affected / exposed	1 / 38 (2.63%)	1 / 37 (2.70%)	0 / 30 (0.00%)	0 / 28 (0.00%)	2 / 71 (2.82%)	5 / 57 (8.77%)	3 / 59 (5.08%)	1 / 47 (2.13%)
occurrences all number	3	1	0	0	2	6	3	2
Paronychia
subjects affected / exposed	1 / 38 (2.63%)	0 / 37 (0.00%)	2 / 30 (6.67%)	1 / 28 (3.57%)	3 / 71 (4.23%)	1 / 57 (1.75%)	0 / 59 (0.00%)	1 / 47 (2.13%)
occurrences all number	1	0	2	1	3	1	0	2
Pharyngitis
subjects affected / exposed	1 / 38 (2.63%)	2 / 37 (5.41%)	0 / 30 (0.00%)	1 / 28 (3.57%)	9 / 71 (12.68%)	4 / 57 (7.02%)	6 / 59 (10.17%)	1 / 47 (2.13%)
occurrences all number	2	2	0	1	12	4	9	1
Pharyngitis streptococcal
subjects affected / exposed	0 / 38 (0.00%)	1 / 37 (2.70%)	1 / 30 (3.33%)	1 / 28 (3.57%)	3 / 71 (4.23%)	6 / 57 (10.53%)	1 / 59 (1.69%)	3 / 47 (6.38%)
occurrences all number	0	1	1	1	3	8	1	3
Rhinitis
subjects affected / exposed	3 / 38 (7.89%)	0 / 37 (0.00%)	2 / 30 (6.67%)	0 / 28 (0.00%)	4 / 71 (5.63%)	2 / 57 (3.51%)	3 / 59 (5.08%)	4 / 47 (8.51%)
occurrences all number	3	0	3	0	4	3	6	5
Sinusitis
subjects affected / exposed	2 / 38 (5.26%)	0 / 37 (0.00%)	0 / 30 (0.00%)	1 / 28 (3.57%)	7 / 71 (9.86%)	7 / 57 (12.28%)	7 / 59 (11.86%)	3 / 47 (6.38%)
occurrences all number	3	0	0	2	8	10	7	4
Tonsillitis
subjects affected / exposed	1 / 38 (2.63%)	1 / 37 (2.70%)	0 / 30 (0.00%)	0 / 28 (0.00%)	0 / 71 (0.00%)	2 / 57 (3.51%)	3 / 59 (5.08%)	2 / 47 (4.26%)
occurrences all number	1	1	0	0	0	2	3	5
Upper respiratory tract infection
subjects affected / exposed	6 / 38 (15.79%)	4 / 37 (10.81%)	6 / 30 (20.00%)	5 / 28 (17.86%)	21 / 71 (29.58%)	19 / 57 (33.33%)	15 / 59 (25.42%)	13 / 47 (27.66%)
occurrences all number	7	5	6	6	34	40	23	27
Urinary tract infection
subjects affected / exposed	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 30 (0.00%)	1 / 28 (3.57%)	5 / 71 (7.04%)	4 / 57 (7.02%)	5 / 59 (8.47%)	2 / 47 (4.26%)
occurrences all number	2	0	0	1	6	4	10	2
Viral infection
subjects affected / exposed	6 / 38 (15.79%)	2 / 37 (5.41%)	6 / 30 (20.00%)	3 / 28 (10.71%)	13 / 71 (18.31%)	9 / 57 (15.79%)	15 / 59 (25.42%)	8 / 47 (17.02%)
occurrences all number	7	3	7	3	22	12	17	11
Viral upper respiratory tract infection
subjects affected / exposed	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 30 (3.33%)	1 / 28 (3.57%)	3 / 71 (4.23%)	4 / 57 (7.02%)	2 / 59 (3.39%)	2 / 47 (4.26%)
occurrences all number	0	0	1	1	3	6	2	3

More information

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Were there any global substantial amendments to the protocol? Yes

24 Jun 2002

To clarify that subjects who respond to treatment with adalimumab will be randomized at Week 16; all sites will develop their institution-specific informed consent form.

26 Sep 2002

To add an additional pharmacokinetic blood sample to be taken between Day 2 and Day 10 after the first dose of adalimumab; to incorporate the open-label extension study (subjects who complete 48 weeks of treatment or are withdrawn from the double-blind phase due to disease flare were eligible).

03 Jul 2003

To expand the safety assessments to include a serum pregnancy on all females aged 10 years and older at all visits, and clarify the visit schedule for the OL extension portion.

05 Feb 2004

To extend the OL extension portion of study to up to 5 years or 60 days post marketing approval in each country; clarify which study visits require a blinded joint assessor, clarify the requirements for chest X-rays and/or PPD skin tests in Europe; clarify the study visit window schedule.

26 Aug 2005

To switch subjects from a dose of study medication based on BSA to a fixed dose of study drug (20 or 40 mg eow based on weight); remove Post Study Visit (Follow-Up); update the schedule for drug administration at the study site; amend study visit schedule to allow for pharmacokinetic sampling and validate safety and efficacy of new fixed dosing regimen; clarify that the DSMB will not participate in the OL portion of the trial; change the evaluation time period for joints injected with intra-articular and/or soft-tissue corticosteroids from non-evaluable for the duration of the study to evaluable after 3 months;

01 Apr 2009

To extend the fixed dose portion of the study to 244 weeks to accommodate patients in Europe who are not yet able to receive drug commercially because of their age; and add 4 additional visits to the OL Fixed Dose.

24 Sep 2009

To update the protocol to reflect the renaming and reclassification of juvenile rheumatoid arthritis (JRA) to juvenile idiopathic arthritis (JIA); clarify study visits and procedures for subjects in the EU who will be continuing in the study past Fixed Dose Week 176; update conditions in which a subject should be withdrawn for safety reasons; update introduction, CTC Grading Severity of Adverse Events version, excluded medications.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Multicenter, Randomized, Double-blind, Placebo-Controlled Study of the Safety, Efficacy, and Pharmacokinetics of the Human Anti-TNF Monoclonal Antibody Adalimumab in Children With Polyarticular Juvenile Rheumatoid Arthritis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Subjects in the Non-MTX Stratum With Disease Flare During the Double-Blind Phase

Primary: Number of Subjects in the Non-MTX Stratum With Disease Flare During the Double-Blind Phase

Secondary: Number of Subjects Meeting Pediatric American College of Rheumatology 30% (PedACR30) Response Criteria at the End of the Open-Label Lead-In Phase

Secondary: Number of Subjects Meeting Pediatric American College of Rheumatology 30% (PedACR30) Response Criteria at the End of the Open-Label Lead-In Phase

Secondary: Number of Subjects in the MTX Stratum With Disease Flare During the Double-Blind Phase

Secondary: Number of Subjects in the MTX Stratum With Disease Flare During the Double-Blind Phase

Secondary: Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum

Secondary: Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum

Secondary: Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum

Secondary: Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum

Secondary: Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase

Secondary: Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase

Secondary: Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-Blind Phase

Secondary: Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-Blind Phase

Secondary: Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-Blind Phase

Secondary: Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-Blind Phase

Secondary: Mean Change From Baseline in Physician's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase

Secondary: Mean Change From Baseline in Physician's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase

Secondary: Mean Change From Baseline in Parent's/Patient's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase

Secondary: Mean Change From Baseline in Parent's/Patient's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase

Secondary: Mean Change From Baseline in C-Reactive Protein Levels at Week 48 of the Double-Blind Phase

Secondary: Mean Change From Baseline in C-Reactive Protein Levels at Week 48 of the Double-Blind Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase

Secondary: Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase

Other pre-specified: Baseline Measure: Gender, Female/Male - OLE BSA Phase

Other pre-specified: Baseline Measure: Gender, Female/Male - OLE BSA Phase

Other pre-specified: Baseline Measure: Age Continuous - OLE BSA Phase

Other pre-specified: Baseline Measure: Age Continuous - OLE BSA Phase

Other pre-specified: Baseline Measure: Gender, Female/Male - OLE FD Phase

Other pre-specified: Baseline Measure: Gender, Female/Male - OLE FD Phase

Other pre-specified: Baseline Measure: Age Continuous - OLE FD Phase

Other pre-specified: Baseline Measure: Age Continuous - OLE FD Phase

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Multicenter, Randomized, Double-blind, Placebo-Controlled Study of the Safety, Efficacy, and Pharmacokinetics of the Human Anti-TNF Monoclonal Antibody Adalimumab in Children With Polyarticular Juvenile Rheumatoid Arthritis