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Clinical Trial Results:
A 12-week randomized, double-blind, placebo-controlled, parallel-group, 2-arm study to evaluate the efficacy and safety of tocilizumab in patients with active systemic juvenile idiopathic arthritis (sJIA); with a 92-week single arm open-label extension to examine the long term use of tocilizumab, followed by a 3 year open-label continuation of the study to examine the long term use of tocilizumab

Summary
EudraCT number	2007-000872-18
Trial protocol	BE SE DE NO CZ ES DK NL GR SK IT GB
Global end of trial date	05 Aug 2014

Results information
Results version number	v1(current)
This version publication date	11 May 2016
First version publication date	11 May 2016
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

WA18221

ISRCTN number

US NCT number

NCT00642460

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, CH-4070, Basel, Switzerland,

Public contact

F. Hoffmann-La Roche AG, Roche Trial Information Hotline, +41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche AG, Roche Trial Information Hotline, +41 616878333, global.trial_information@roche.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000309-PIP02-14

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?

Yes

Analysis stage

Final

Date of interim/final analysis

04 Oct 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

05 Aug 2014

Was the trial ended prematurely?

Main objective of the trial

Part I: Primary Objectives: 1. To assess the efficacy of tocilizumab versus placebo in combination with stable ongoing therapy at 12 weeks, with regard to signs and symptoms in sJIA patients with persistent activity and an inadequate response to Non-Steroid Anti-Inflammatory Drugs (NSAIDs) and systemic corticosteroids. Part II: Primary Objectives: 1. To evaluate the safety of tocilizumab in chronic administration and to assess the effect of tocilizumab to enable the reduction or elimination of corticosteroids. Part III: Primary Objective: To assess the long-term safety of 8 mg/kg tocilizumab in children greater than or equal to (≥) 30 kg and 12 mg/kg TCZ in children less than (<) 30 kg with regard to adverse events and laboratory result abnormalities.

Protection of trial subjects

The study was conducted in accordance with the principals or laws of the country in which the study was conducted to ensure maximum protection to the individual. The study fully adhered to the provisions in "Principles of Good Clinical Practice" in the respective countries.

Background therapy

Evidence for comparator

Actual start date of recruitment

09 May 2008

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 12

Country: Number of subjects enrolled

Australia: 5

Country: Number of subjects enrolled

Brazil: 6

Country: Number of subjects enrolled

Canada: 6

Country: Number of subjects enrolled

Mexico: 4

Country: Number of subjects enrolled

United States: 18

Country: Number of subjects enrolled

Netherlands: 3

Country: Number of subjects enrolled

Norway: 2

Country: Number of subjects enrolled

Poland: 3

Country: Number of subjects enrolled

Slovakia: 1

Country: Number of subjects enrolled

Spain: 10

Country: Number of subjects enrolled

United Kingdom: 8

Country: Number of subjects enrolled

Belgium: 8

Country: Number of subjects enrolled

Czech Republic: 3

Country: Number of subjects enrolled

Germany: 6

Country: Number of subjects enrolled

Greece: 4

Country: Number of subjects enrolled

Italy: 13

Worldwide total number of subjects

112

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

Screening details

This study consists of 3 parts. Part I: a 12 week double-blind placebo controlled study followed by Part II: a 92 week single arm open-label extension study followed by Part III: a 3 year open label continuation study.

Period 1 title

Part I: 12 Week Double-Blind

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind ^[1]

Roles blinded

Subject, Carer, Assessor

Are arms mutually exclusive

Yes

Tocilizumab_8 mg/kg

Arm description

Tocilizumab 8 milligrams per kilogram (mg/kg) (for patients greater than or equal to [≥] 30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part I Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.

Arm type

Experimental

Investigational medicinal product name

Tocilizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Patients weighing≥30 kg received 8 mg/kg iv every 2 weeks for 12 weeks in Part I.

Tocilizumab_12 mg/kg

Arm description

Tocilizumab 12 mg/kg (for patients <30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part I and every 2 weeks for 92 weeks in Part II. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable

Arm type

Experimental

Investigational medicinal product name

Tocilizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Patients weighing less than (<) 30 kg received 12 mg/kg iv every 2 weeks for 12 weeks in Part I.

Placebo

Arm description

Placebo iv every 2 weeks for 12 weeks in Part 1. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Patients received placebo infusion iv every 2 weeks for 12 weeks.

Notes
[1] - The roles blinded appear to be inconsistent with a double blind trial.
Justification: Investigator was not blinded in this study.

Number of subjects in period 1	Tocilizumab_8 mg/kg	Tocilizumab_12 mg/kg	Placebo
Started	37	38	37
Completed	36	37	36
Not completed	1	1	1
Adverse event, non-fatal	-	1	1
Refused Treatment	1	-	-

Period 2 title

Part II: Open-Label Up to Week 92

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Tocilizumab_8 mg/kg

Arm description

Tocilizumab 8 mg/kg (for patients ≥30 kg) iv every 2 weeks for 92 weeks. Participants remained on their prescribed standard of care treatment with (NSAIDs, methotrexate and corticosteroids if applicable.

Arm type

Experimental

Investigational medicinal product name

Tocilizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Patients weighing≥30 kg received 8 mg/kg iv every 2 weeks for 12 weeks in Part I and every 2 weeks for 92 weeks in Part II.

Tocilizumab_12 mg/kg

Arm description

Tocilizumab 12 mg/kg (for patients <30 kg) iv every 2 weeks for 92 weeks. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.

Arm type

Experimental

Investigational medicinal product name

Tocilizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Patients weighing < 30 kg received 12 mg/kg iv every 2 weeks for 12 weeks in Part I and every 2 weeks for 92 weeks in Part II.

Tocilizumab Switchers

Arm description

Tocilizumab Switchers includes all participants who changed their dose either Tocilizumab 8 mg/kg or 12 mg/kg iv every 2 weeks in Part II. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.

Arm type

Experimental

Investigational medicinal product name

Tocilizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Patients weighing ≥30 kg received 8 mg/kg and those weighing < 30 kg received 12 mg/kg iv every 2 weeks for 92 weeks.

Number of subjects in period 2	Tocilizumab_8 mg/kg	Tocilizumab_12 mg/kg	Tocilizumab Switchers
Started	52	40	20
Completed	43	32	17
Not completed	9	8	3
Adverse event, serious fatal	-	1	2
Insufficient therapeutic response	2	3	-
Adverse event, non-fatal	4	2	-
Refused Treatment	3	1	-
Administrative reasons	-	-	1
Lost to follow-up	-	1	-

Period 3 title

Part III Open Label Period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Participants ≥30 kg

Arm description

Tocilizumab 8 mg/kg iv every 2 weeks for 12 weeks in Part I, every 2 weeks for 92 weeks in Part II and every 2 weeks up to 260 weeks in Part III based on the body weight (BW) recorded at Baseline. The dose of TCZ could be adjusted for non-transient changes in BW (< 30 kg to ≥ 30 kg) over a minimum of 3 consecutive visits.

Arm type

Experimental

Investigational medicinal product name

Tocilizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

8 mg/kg (for patients ≥30 kg) iv every 2 weeks for 12 weeks in Part I, every 2 weeks for 92 weeks in Part II and every 2 weeks up to 260 weeks in Part III.

Participants <30 kg

Arm description

Tocilizumab 12 mg/kg iv every 2 weeks for 12 weeks in Part I, every 2 weeks for 92 weeks in Part II and every 2 weeks up to 260 weeks in Part III based on the BW recorded at Baseline. The dose of TCZ could be adjusted for non-transient changes in BW ( 30 kg to ≥ 30 kg) over a minimum of 3 consecutive visits.

Arm type

Experimental

Investigational medicinal product name

Tocilizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

12 mg/kg iv every 2 weeks for 12 weeks in Part I, every 2 weeks for 92 weeks in Part II and every 2 weeks up to 260 weeks in Part III.

All Tocilizumab

Arm description

Tocilizumab either 8 mg/kg (participants ≥ 30 kg) or 12 mg/kg (participants <30 kg) iv every 2 weeks for 12 weeks in Part I, every 2 weeks for 92 weeks in Part II and every 2 weeks for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.

Arm type

Experimental

Investigational medicinal product name

Tocilizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

8 mg/kg (for patients ≥30 kg) or 12 mg/kg (participants <30 kg) iv every 2 weeks for 12 weeks in Part I and every 2 weeks for 92 weeks in Part II and every 2 weeks for 156 weeks in Part III.

Number of subjects in period 3	Participants ≥30 kg	Participants <30 kg	All Tocilizumab
Started	53	59	112
Completed on Q2W	28	38	66 ^[2]
Went into Alternative Dosing	23 ^[3]	22 ^[4]	39 ^[5]
Withdrawn from Alternative Dosing	6 ^[6]	2 ^[7]	7 ^[8]
Withdrawn from Q2W	19 ^[9]	19 ^[10]	39 ^[11]
Completed Alternative Dosing	12 ^[12]	20 ^[13]	32 ^[14]
Completed	28	38	73
Not completed	25	21	39
Adverse event, serious fatal	-	3	3
Insufficient therapeutic response	3	4	7
Consent withdrawn by subject	4	1	-
Adverse event, non-fatal	-	6	12
Refused Treatment	8	3	11
Administrative reasons	-	1	-
Adverse event	7	-	-
Unspecified	-	-	4
Lost to follow-up	1	1	2
Unknown reasons	2	2	-

Notes
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
[8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
[9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
[10] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
[11] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
[12] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
[13] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
[14] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.

Baseline characteristics

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Reporting group title

Part I: 12 Week Double-Blind

Reporting group description

Patients received either Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) iv every 2 weeks for 12 weeks or placebo iv every 2 weeks for 12 weeks in Part I of the study. All patients remained on their prescribed standard of care treatment with non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate and corticosteroids if applicable.

Reporting group values	Part I: 12 Week Double-Blind	Total
Number of subjects	112	112
Age categorical
Units: Subjects
2 to 5	27	27
6 to 12	48	48
13 to 17	37	37
Gender categorical
Units: Subjects
Female	56	56
Male	56	56

End points

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Reporting group title

Tocilizumab_8 mg/kg

Reporting group description

Reporting group title

Tocilizumab_12 mg/kg

Reporting group description

Reporting group title

Placebo

Reporting group description

Placebo iv every 2 weeks for 12 weeks in Part 1. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.

Reporting group title

Tocilizumab_8 mg/kg

Reporting group description

Reporting group title

Tocilizumab_12 mg/kg

Reporting group description

Reporting group title

Tocilizumab Switchers

Reporting group description

Reporting group title

Participants ≥30 kg

Reporting group description

Reporting group title

Participants <30 kg

Reporting group description

Reporting group title

All Tocilizumab

Reporting group description

Primary: Part I: Percentage of Participants With ≥30 percent (%) Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever

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End point title

Part I: Percentage of Participants With ≥30 percent (%) Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever ^[1] ^[2]

End point description

Percentage of participants with ≥30% improvement in ACR core set consisting of 6 components: 1) Physician's global assessment of disease activity Visual Analog Scale (VAS), 2) Parent/Patient global assessment of overall well-being VAS, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) consisting of 30 questions in 8 domains. Absence of fever was defined as no diary temperature recording ≥37.5 degrees Celsius in the preceding seven days. Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug.

End point type

Primary

End point timeframe

Baseline, Week 12

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	37	75
Units: percentage of participants
number (not applicable)	24.3	85.3

No statistical analyses for this end point

Primary: Part II: Percentage of Participants With Decreases in Oral Corticosteroid Dose at Week 104

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End point title

Part II: Percentage of Participants With Decreases in Oral Corticosteroid Dose at Week 104 ^[3]

End point description

Percentage of participants with ≥20 percent, ≥50 percent, ≥75 percent and ≥90 percent decreases in oral corticosteroid dose (mg/kg/day) from baseline. Analysis included only participants on oral corticosteroids at baseline.

End point type

Primary

End point timeframe

Baseline, Week 104

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	All Tocilizumab
Number of subjects analysed	55
Units: percentage of participants
number (not applicable)
≥20 percent decrease	76
≥50 percent decrease	73
≥75 percent decrease	62
≥90 percent decrease	47

No statistical analyses for this end point

Secondary: Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12

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End point title

Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12 ^[4]

End point description

The six JIA ACR components consist of: 1)Physician's global assessment of disease activity, 2)Parent/Patient global assessment of overall well-being, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) CHAQ-DI. At an assessment visit a JIA ACR30/50/70/90 response in comparison to Baseline is defined as: At least three of the six JIA ACR core components improving by at least 30%/50%/70%/90% and no more than one of the remaining JIA ACR core components worsening by more than 30%. Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	37	75
Units: percentage of participants
number (not applicable)
JIA ACR30 response	24.3	90.7
JIA ACR50 response	10.8	85.3
JIA ACR70 response	8.1	70.7
JIA ACR90 response	5.4	37.3

No statistical analyses for this end point

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity

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End point title

Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity ^[5]

End point description

Physician's Global Assessment of disease activity is a Visual Analog Scale. The scale is 0 to 100 mm horizontal scale, the extreme left end of the line represents ‘arthritis inactive’ (i.e. symptom-free and no arthritis symptoms) and the extreme right end represents ‘arthritis very active’. This item is completed by the treating physician. Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined were excluded. LOCF rule applied to missing JIA ACR core set components at Week 12.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	17	73
Units: percentage change
number (not applicable)	-41.1	-69.6

No statistical analyses for this end point

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being

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End point title

Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being ^[6]

End point description

The Parent/Patient global assessment of overall well-being is a VAS. The scale is a 0 to 100 mm horizontal scale, the extreme left end of the line represents ‘very well’ (i.e. symptom-free and no arthritis disease activity) and the extreme right end represents ‘very poor’ (i.e. maximum arthritis disease activity). This item is completed by the patient or parent/guardian as appropriate.Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined are excluded. LOCF rule applied to missing JIA ACR core set components at Week 12. Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	17	73
Units: percentage change
number (not applicable)	-1.4	-65.8

No statistical analyses for this end point

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis

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End point title

Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis ^[7]

End point description

The maximum number of joints with active arthritis is 71 and these are defined as those in the joint assessment with: swelling present or pain present and limitation of motion. The joint assessment is performed by an independent assessor, who is not the treating physician, blinded to all other aspects of the patient’s efficacy and safety data.Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined are excluded. LOCF rule applied to missing JIA ACR core set components at Week 12. Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	17	73
Units: percentage change
number (not applicable)	-37.2	-70.6

No statistical analyses for this end point

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement

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End point title

Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement ^[8]

End point description

The maximum number of joints with limitation of movement is 67 and these are defined as those in the joint assessment with ‘limitation of motion’. Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug. Patients who withdrew, received escape medication, or for whom the endpoint could not be determined were excluded. LOCF rule applied to missing JIA ACR core set components at Week 12.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	17	72
Units: percentage change
number (not applicable)	-22.5	-51.6

No statistical analyses for this end point

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Erythrocyte Sedimentation Rate

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End point title

Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Erythrocyte Sedimentation Rate ^[9]

End point description

Erythrocyte Sedimentation Rate (ESR) is an acute phase reactant measured in mm/hour. Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug. Patients who withdrew, received escape medication, or for whom the endpoint could not be determined were excluded. LOCF rule applied to missing JIA ACR core set components at Week 12.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	17	73
Units: percentage change
number (not applicable)	33.6	-88.2

No statistical analyses for this end point

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI)

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End point title

Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI) ^[10]

End point description

Functional ability is assessed using the CHAQ-DI. The questionnaire consists of 30 questions referring to eight domains; dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain has at least two component questions and if applicable to the patient there are four possible responses (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do). The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score. This overall score ranges from 0 (best) to 3 (worst). Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug. Patients who withdrew, received escape medication, or for whom the endpoint could not be determined were excluded. LOCF rule applied to missing JIA ACR core set components at Week 12.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	17	72
Units: percentage change
number (not applicable)	-10.3	-45.6

No statistical analyses for this end point

Secondary: Part I: Percentage of Participants With Fever Due to Systemic Juvenile Idiopathic Arthritis (sJIA) at Baseline Who Are Free of Fever at Week 12

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End point title

Part I: Percentage of Participants With Fever Due to Systemic Juvenile Idiopathic Arthritis (sJIA) at Baseline Who Are Free of Fever at Week 12 ^[11]

End point description

Fever free was defined as no diary temperature recording ≥37.5° Celsius in the preceding fourteen days. Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) who had a fever due to Systemic Juvenile Idiopathic Arthritis at baseline were included in analysis.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	24	41
Units: percentage of participants
number (not applicable)	20.8	85.4

No statistical analyses for this end point

Secondary: Part I: Percentage of Participants With Changes in Laboratory Indicators: High-sensitivity C-Reactive Protein (hsCRP), Hemoglobin (Hb), Platelets and Leukocytes From Abnormal at Baseline to Normal at Week 12

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End point title

Part I: Percentage of Participants With Changes in Laboratory Indicators: High-sensitivity C-Reactive Protein (hsCRP), Hemoglobin (Hb), Platelets and Leukocytes From Abnormal at Baseline to Normal at Week 12 ^[12]

End point description

Percentage of participants with a change from an elevated hsCRP value at baseline to a normal hsCRP value at week 12; a change from anemia (low Hemoglobin) at baseline to a normal hemoglobin value at week 12; a change from thrombocytosis (elevated platelets) at baseline to a normal platelet value at week 12; a change from leukocytosis (elevated white blood cell count) at baseline to a normal white blood cell count at week 12.Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug. 'n' in each of the categories is the number of participants with data available at baseline and week 12 for analyses.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	37	75
Units: percentage of participants
number (not applicable)
hsC-Reactive Protein (n=34,72)	5.9	98.6
Hemoglobin (n=29,50)	6.9	80
Platelets (n=26,52)	3.8	90.4
Leukocytes (n=21,28)	9.5	75

No statistical analyses for this end point

Secondary: Part I: Percentage of Participants With Concomitant Corticosteroid Reduction

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End point title

Part I: Percentage of Participants With Concomitant Corticosteroid Reduction ^[13]

End point description

The percentage of participants receiving oral corticosteroids(CS) with a JIA ACR70 response at week 6 or Week 8 who reduced their oral CS dose by at least 20% without subsequent JIA ACR30 flare or occurrence of systemic symptoms at week 12. At an assessment visit a JIA ACR70 response is defined as: At least three of the six JIA ACR core components improving by at least 70% and no more than one of the remaining JIA ACR core components worsening by more than 30%. Analysis was performed on participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) who were taking oral corticosteroids.

End point type

Secondary

End point timeframe

Week 6 or Week 8, Week 12

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	31	70
Units: percentage of participants
number (not applicable)	3.2	24.3

No statistical analyses for this end point

Secondary: Part I: Change From Baseline in the Pain Visual Analog Scale (VAS) at Week 12

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End point title

Part I: Change From Baseline in the Pain Visual Analog Scale (VAS) at Week 12 ^[14]

End point description

Participants rated their pain by placing a horizontal line on a Visual Analog Scale on a scale of 0 (no pain)- 100 mm (severe pain). The score at 12 weeks minus the score at baseline. A negative number indicates improvement. Participants from the Intent-to-treat population who had Pain VAS data available at baseline and week 12. Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined are excluded. LOCF rule applied to missing pain VAS at Week 12.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	17	73
Units: mm
number (not applicable)	-1.1	-41

No statistical analyses for this end point

Secondary: Part I: Percentage of Patients With Minimally Important Improvement in CHAQ-DI Score at Week 12

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End point title

Part I: Percentage of Patients With Minimally Important Improvement in CHAQ-DI Score at Week 12 ^[15]

End point description

Percentage of patients who had at least a 0.13 improvement in CHAQ-DI score from Baseline to Week 12. The CHAQ-DI questionnaire consists of 30 questions referring to eight domains; dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain has at least two component questions and if applicable to the patient there are four possible responses (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do).ntent-to-treat Population. Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined are classified as non-responders. LOCF rule applied to missing CHAQ-DI Scores at Week 12.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	37	75
Units: percentage of participants
number (not applicable)	18.9	77.3

No statistical analyses for this end point

Secondary: Part I: Percentage of Patients With Rash at Baseline Who Are Free From Rash at Week 12

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End point title

Part I: Percentage of Patients With Rash at Baseline Who Are Free From Rash at Week 12 ^[16]

End point description

Percentage of participants who had a rash characteristic of sJIA in the 14 days prior to the baseline visit but no rash characteristic of sJIA in the 14 days preceding the Week 12 visit day. Analysis was performed on participants from the Intent-to-treat population for whom data was available. Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined are classified as non-responders.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	18	22
Units: percentage of participants
number (not applicable)	11.1	63.6

No statistical analyses for this end point

Secondary: Part I: Percentage of Patients With Anemia at Baseline With a ≥10 g/L Increase in Hemoglobin at Week 6 and Week 12

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End point title

Part I: Percentage of Patients With Anemia at Baseline With a ≥10 g/L Increase in Hemoglobin at Week 6 and Week 12 ^[17]

End point description

Part I: Percentage of patients who had anemia (hemoglobin <lower level normal based on sex and age) at Baseline and a ≥10 g/L increase in hemoglobin at Week 6 and at Week 12. Analysis was performed on participants from the Intent-to-treat population for whom hemoglobin data available. Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined are classified as non-responders. LOCF rule applied to missing hemoglobin values at Week 6 and Week 12.

End point type

Secondary

End point timeframe

Baseline, Week 6 and Week 12

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.

End point values	Placebo	All Tocilizumab
Number of subjects analysed	29	50
Units: percentage of participants
number (not applicable)
Week 6	3.4	88
Week 12	3.4	88

No statistical analyses for this end point

Secondary: Part II: Percentage of Participants With JIA ACR70 and JIA ACR90 Responses Week 104

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End point title

Part II: Percentage of Participants With JIA ACR70 and JIA ACR90 Responses Week 104

End point description

The six JIA ACR components consist of: 1)Physician's global assessment of disease activity, 2)Parent/Patient global assessment of overall well-being, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) CHAQ-DI. At an assessment visit a JIA ACR70/90 response in comparison to Baseline is defined as: At least three of the six JIA ACR core components improving by at least 70%/90% and no more than one of the remaining JIA ACR core components worsening by more than 30%. Analysis was performed on participants from the Intent to Treat population who reached the time point plus patients who withdrew because of insufficient therapeutic response and are assumed to have been non-responders.

End point type

Secondary

End point timeframe

Baseline, Week 104

End point values	All Tocilizumab
Number of subjects analysed	75
Units: percentage of participants
number (not applicable)
JIA ACR70 response	76
JIA ACR90 response	61.3

No statistical analyses for this end point

Secondary: Part II: Number of Active Joints at Week 104

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End point title

Part II: Number of Active Joints at Week 104

End point description

Seventy-one joints were assessed for signs of active arthritis. The mean number of joints with signs of active arthritis is reported. Analysis was performed on participants from the Intent to Treat population who reached this time point. No data imputation is applied and patients with missing data are excluded.

End point type

Secondary

End point timeframe

Week 104

End point values	All Tocilizumab
Number of subjects analysed	59
Units: active joints
arithmetic mean (standard deviation)	1.9 ( 3.6 )

No statistical analyses for this end point

Secondary: Part II: Percentage of Participants With no Active Joints at Week 104

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End point title

Part II: Percentage of Participants With no Active Joints at Week 104

End point description

Seventy-one joints were assessed for signs of active arthritis. The percentage of participants with no signs of active arthritis is reported. The Intent to Treat population in Part II includes 112 participants who received at least one dose of study drug. Only those participants who reached this time point are included in the analyses.

End point type

Secondary

End point timeframe

Week 104

End point values	All Tocilizumab
Number of subjects analysed	76
Units: percentage of participants
number (not applicable)	47.4

No statistical analyses for this end point

Secondary: Part II: Percentage of Participants With Inactive Disease at Week 104

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End point title

Part II: Percentage of Participants With Inactive Disease at Week 104

End point description

Criteria for Inactive Disease: 1) No joints with active arthritis, 2) No fever, rash, serositis, splenomegaly, hepatomegaly (by physical exam) or generalized lymphadenopathy attributable to systemic juvenile idiopathic arthritis (sJIA), 3) Normal Erythrocyte Sedimentation Rate (<20 mm/hour), 4) Physician’s global assessment of disease activity Visual Analog Scale (VAS) indicates no disease activity (where no disease activity is considered to be a score ≤10 mm on a 100 mm VAS). Participants from the Intent to Treat population who reached time point plus patients who withdrew because of insufficient therapeutic response and are assumed to have been nonresponders.

End point type

Secondary

End point timeframe

Week 104

End point values	All Tocilizumab
Number of subjects analysed	75
Units: percentage of participants
number (not applicable)	26.7

No statistical analyses for this end point

Secondary: Part II: Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Week 104

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End point title

Part II: Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Week 104

End point description

Functional ability is assessed using the CHAQ-DI. The questionnaire consists of 30 questions referring to eight domains; dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain has at least two component questions and if applicable to the patient there are four possible responses (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do). The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score. This overall score ranges from 0 (best) to 3 (worst). Participants from the Intent to Treat population who withdrew have been excluded at post withdrawal visits. n = number of participants analyzed at the specified visit.

End point type

Secondary

End point timeframe

Baseline, Week 104

End point values	All Tocilizumab
Number of subjects analysed	112
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (n=112)	1.68 ( 0.86 )
Week 104 (n=57)	0.55 ( 0.71 )

No statistical analyses for this end point

Secondary: Part II: Percentage of Participants With Oral Corticosteroid Cessation at Week 104

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End point title

Part II: Percentage of Participants With Oral Corticosteroid Cessation at Week 104

End point description

Percentage is based on only those participants who were on oral corticosteroid at baseline and reached a nominal visit day on which dose was calculated. Participants from the Intent to Treat population who withdrew have been excluded at post withdrawal visits.

End point type

Secondary

End point timeframe

Baseline, Week 104

End point values	All Tocilizumab
Number of subjects analysed	42
Units: percentage of participants
number (not applicable)	60

No statistical analyses for this end point

Secondary: Part II: Rate of Serious Adverse Events (SAEs), Serious Infection Adverse Events (AEs), Related SAEs, Macrophage Activation Syndrome, AEs Leading to Withdrawal and Deaths Per 100 Patient Years to Week 104

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End point title

Part II: Rate of Serious Adverse Events (SAEs), Serious Infection Adverse Events (AEs), Related SAEs, Macrophage Activation Syndrome, AEs Leading to Withdrawal and Deaths Per 100 Patient Years to Week 104

End point description

Rate of SAEs, Rate of Serious Infection AEs, Rate of Related SAEs (remotely, possibly, probably) to Tocilizumab (TCZ), Rate of Macrophage Activation Syndrome, Rate of AEs leading to withdrawal and Rate of deaths per 100 patient years (PY) were calculated using the formula: Number of Patient Events / Duration in study (years) * 100. Multiple occurrences of the same AE in one individual are counted. Safety Population- all participants who received at least one dose of study drug and had 1 post-baseline safety assessment. Includes all safety data in the database up to the week 104 infusion based on the date of randomization for each patient. (Last date was 31 May 2011)

End point type

Secondary

End point timeframe

104 Weeks

End point values	All Tocilizumab
Number of subjects analysed	112
Units: events per 100 patient years
number (not applicable)
SAEs	23.3
Serious infection AEs	10.9
SAEs related to TCZ	7.4
Macrophage activation syndrome	1.5
AEs leading to withdrawal	3
Deaths	1.5

No statistical analyses for this end point

Secondary: Part III: Percentage of Participants with at least 30%, 50%, 70%, and 90% improvement in JIA core set according to ACR

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End point title

Part III: Percentage of Participants with at least 30%, 50%, 70%, and 90% improvement in JIA core set according to ACR

End point description

The six JIA ACR components consist of: 1)Physician's global assessment of disease activity, 2)Parent/Patient global assessment of overall well-being, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) CHAQ-DI. At an assessment visit a JIA ACR30/50/70/90 response in comparison to Baseline is defined as: At least three of the six JIA ACR core components improving by at least 30%/50%/70%/90% and no more than one of the remaining JIA ACR core components worsening by more than 30%. n = number of participants analyzed for the given parameter at the specified visit. The Part III intent-to-treat (ITT3) population consists of all participants who entered into Part III of the study and received at least one administration of tocilizumab during Part III.

End point type

Secondary

End point timeframe

Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260

End point values	Participants ≥30 kg	Participants <30 kg
Number of subjects analysed	42	47
Units: percentage of participants
number (not applicable)
Week 104 JIA ACR30 (n=42,47)	100	100
Week 104 JIA ACR50 (n=42,47)	100	100
Week 104 JIA ACR70 (n=42,47)	92.9	95.7
Week 104 JIA ACR90 (n=42,47)	81	72.3
Week 116 JIA ACR30 (n=41,45)	100	100
Week 116 JIA ACR50 (n=41,45)	100	97.8
Week 116 JIA ACR70 (n=41,45)	95.1	97.8
Week 116 JIA ACR90 (n=41,45)	82.9	80
Week 128 JIA ACR30 (n=39,41)	100	100
Week 128 JIA ACR50 (n=39,41)	100	100
Week 128 JIA ACR70 (n=39,41)	97.4	97.6
Week 128 JIA ACR90 (n=39,41)	79.5	82.9
Week 140 JIA ACR30 (n=34,37)	100	100
Week 140 JIA ACR50 (n=34,37)	100	100
Week 140 JIA ACR70 (n=34,37)	100	94.6
Week 140 JIA ACR90 (n=34,37)	73.5	75.7
Week 152 JIA ACR30 (n=27,28)	100	100
Week 152 JIA ACR50 (n=27,28)	100	100
Week 152 JIA ACR70 (n=27,28)	100	96.4
Week 152 JIA ACR90 (n=27,28)	66.7	78.6
Week 164 JIA ACR30 (n=27,24)	100	100
Week 164 JIA ACR50 (n=27,24)	100	100
Week 164 JIA ACR70 (n=27,24)	92.6	95.8
Week 164 JIA ACR90 (n=27,24)	66.7	75
Week 176 JIA ACR30 (n=22,22)	100	100
Week 176 JIA ACR50 (n=22,22)	100	100
Week 176 JIA ACR70 (n=22,22)	100	95.5
Week 176 JIA ACR90 (n=22,22)	63.6	63.6
Week 188 JIA ACR30 (n=20,22)	100	100
Week 188 JIA ACR50 (n=20,22)	100	100
Week 188 JIA ACR70 (n=20,22)	95	95.5
Week 188 JIA ACR90 (n=20,22)	45	72.7
Week 200 JIA ACR30 (n=19,19)	100	100
Week 200 JIA ACR50 (n=19,19)	100	94.7
Week 200 JIA ACR70 (n=19,19)	94.7	89.5
Week 200 JIA ACR90 (n=19,19)	63.2	78.9
Week 212 JIA ACR30 (n=18,18)	100	100
Week 212 JIA ACR50 (n=18,18)	100	94.4
Week 212 JIA ACR70 (n=18,18)	100	94.4
Week 212 JIA ACR90 (n=18,18)	72.2	77.8
Week 224 JIA ACR30 (n=17,18)	100	100
Week 224 JIA ACR50 (n=17,18)	100	88.9
Week 224 JIA ACR70 (n=17,18)	100	88.9
Week 224 JIA ACR90 (n=17,18)	64.7	83.3
Week 236 JIA ACR30 (n=16,17)	100	100
Week 236 JIA ACR50 (n=16,17)	100	100
Week 236 JIA ACR70 (n=16,17)	93.8	100
Week 236 JIA ACR90 (n=16,17)	68.8	88.2
Week 248 JIA ACR30 (n=15,17)	100	100
Week 248 JIA ACR50 (n=15,17)	100	100
Week 248 JIA ACR70 (n=15,17)	86.7	94.1
Week 248 JIA ACR90 (n=15,17)	73.3	70.6
Week 260 JIA ACR30 (n=15,15)	100	93.3
Week 260 JIA ACR50 (n=15,15)	93.3	93.3
Week 260 JIA ACR70 (n=15,15)	86.7	93.3
Week 260 JIA ACR90 (n=15,15)	60	66.7

No statistical analyses for this end point

Secondary: Part III: Percentage of participants who mainitain JIA ACR30, JIA ACR50, JIA ACR70, JIA ACR90 response for 6 months Previous to the specified Week

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End point title

Part III: Percentage of participants who mainitain JIA ACR30, JIA ACR50, JIA ACR70, JIA ACR90 response for 6 months Previous to the specified Week

End point description

The six JIA ACR components consist of: 1)Physician's global assessment of disease activity, 2)Parent/Patient global assessment of overall well-being, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) CHAQ-DI. At an assessment visit a JIA ACR30/50/70/90 response in comparison to Baseline is defined as: At least three of the six JIA ACR core components improving by at least 30%/50%/70%/90% and no more than one of the remaining JIA ACR core components worsening by more than 30%. n = number of participants analyzed for the given parameter at the specified visit. Analysis was performed on The Part III ITT3 population. 99999 = Data not available.

End point type

Secondary

End point timeframe

Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260

End point values	All Tocilizumab
Number of subjects analysed	89
Units: percentage of participants
number (not applicable)
Week 104 JIA ACR30 (n=89)	99999
Week 104 JIA ACR50 (n=89)	99999
Week 104 JIA ACR70 (n=89)	99999
Week 104 JIA ACR90 (n=89)	99999
Week 116 JIA ACR 30 (n=86)	99999
Week 116 JIA ACR 50 (n=86)	99999
Week 116 JIA ACR 70 (n=86)	99999
Week 116 JIA ACR 90 (n=86)	99999
Week 128 JIA ACR 30 (n=80)	100
Week 128 JIA ACR 50 (n=80)	98.8
Week 128 JIA ACR 70 (n=80)	91.3
Week 128 JIA ACR 90 (n=80)	68.8
Week 140 JIA ACR30 (n=71)	100
Week 140 JIA ACR50 (n=71)	98.6
Week 140 JIA ACR70 (n=71)	93
Week 140 JIA ACR90 (n=71)	66.2
Week 152 JIA ACR30 (n=55)	100
Week 152 JIA ACR50 (n=55)	100
Week 152 JIA ACR70 (n=55)	94.5
Week 152 JIA ACR90 (n=55)	60
Week 164 JIA ACR30 (n=51)	100
Week 164 JIA ACR50 (n=51)	100
Week 164 JIA ACR70 (n=51)	92.2
Week 164 JIA ACR90 (n=51)	56.9
Week 176 JIA ACR30 (n=44)	100
Week 176 JIA ACR50 (n=44)	100
Week 176 JIA ACR70 (n=44)	88.6
Week 176 JIA ACR90 (n=44)	52.3
Week 188 JIA ACR30 (n=42)	100
Week 188 JIA ACR50 (n=42)	100
Week 188 JIA ACR70 (n=42)	88.1
Week 188 JIA ACR90 (n=42)	50
Week 200 JIA ACR30 (n=38)	100
Week 200 JIA ACR50 (n=38)	97.4
Week 200 JIA ACR70 (n=38)	86.8
Week 200 JIA ACR90 (n=38)	52.6
Week 212 JIA ACR30 (n=36)	100
Week 212 JIA ACR50 (n=36)	97.2
Week 212 JIA ACR70 (n=36)	88.9
Week 212 JIA ACR90 (n=36)	55.6
Week 224 JIA ACR30 (n=35)	100
Week 224 JIA ACR50 (n=35)	94.3
Week 224 JIA ACR70 (n=35)	91.4
Week 224 JIA ACR90 (n=35)	68.6
Week 236 JIA ACR30 (n=33)	100
Week 236 JIA ACR50 (n=33)	93.9
Week 236 JIA ACR70 (n=33)	90.9
Week 236 JIA ACR90 (n=33)	72.7
Week 248 JIA ACR30 (n=32)	100
Week 248 JIA ACR50 (n=32)	93.8
Week 248 JIA ACR70 (n=32)	87.5
Week 248 JIA ACR90 (n=32)	65.6
Week 260 JIA ACR30 (n=30)	96.7
Week 260 JIA ACR50 (n=30)	93.3
Week 260 JIA ACR70 (n=30)	80
Week 260 JIA ACR90 (n=30)	56.7

No statistical analyses for this end point

Secondary: Part III: Doses of Oral Corticosteroids (CS)

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End point title

Part III: Doses of Oral Corticosteroids (CS)

End point description

Oral corticosteroid values summarized are based on average daily dose on the nominal study day. The prednisone equivalent is used in calculation of oral corticosteroid dose. Participants who withdrew are excluded at the visit of withdrawal and all subsequent visits. n=number of participants contributing to the specific statistic.

End point type

Secondary

End point timeframe

Baseline and Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260

End point values	Participants ≥30 kg	Participants <30 kg
Number of subjects analysed	53	59
Units: mg/kg/day
arithmetic mean (standard deviation)
Baseline (n=53,59)	0.203 ( 0.1572 )	0.356 ( 0.1397 )
Week 104 (n=45,48)	0.02 ( 0.0455 )	0.047 ( 0.0869 )
Week 116 (n=42,46)	0.022 ( 0.0464 )	0.046 ( 0.0831 )
Week 128 (n=41,42)	0.022 ( 0.0449 )	0.058 ( 0.1635 )
Week 140 (n=34,38)	0.031 ( 0.0625 )	0.051 ( 0.1112 )
Week 152 (n=28,31)	0.021 ( 0.0388 )	0.06 ( 0.1125 )
Week 164 (n=28,25)	0.018 ( 0.0349 )	0.068 ( 0.1179 )
Week 176 (n=25,23)	0.019 ( 0.0383 )	0.073 ( 0.1327 )
Week 188 (n=21,22)	0.02 ( 0.0366 )	0.075 ( 0.1275 )
Week 200 (n=20,20)	0.017 ( 0.0284 )	0.083 ( 0.1397 )
Week 212 (n=19,19)	0.016 ( 0.0274 )	0.077 ( 0.1449 )
Week 224 (n=18,19)	0.017 ( 0.0279 )	0.075 ( 0.1399 )
Week 236 (n=17,18)	0.018 ( 0.0283 )	0.077 ( 0.1436 )
Week 248 (n=16,18)	0.02 ( 0.029 )	0.076 ( 0.1429 )
Week 260 (n=16,18)	0.019 ( 0.0282 )	0.079 ( 0.1486 )

No statistical analyses for this end point

Secondary: Part III: Percentage of Participants on Corticosteroids at Baseline Able to Discontinue Corticosteroids by Weeks 104,116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260

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End point title

Part III: Percentage of Participants on Corticosteroids at Baseline Able to Discontinue Corticosteroids by Weeks 104,116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260

End point description

Values summarized are based on average daily dose on the nominal study day. The prednisone equivalent is used in calculation of oral corticosteroid dose. Participants who withdrew are excluded at the timepoint of this event and at all subsequent visits. Baseline considered first dose of study treatment. Data presented up to entry into the Alternative Dosing Schedule. ITT3 population; n=number of participants contributing to the specific statistic.

End point type

Secondary

End point timeframe

Weeks 104,116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260

End point values	Participants ≥30 kg	Participants <30 kg
Number of subjects analysed	38	46
Units: percentage of participants
number (not applicable)
Week 104 (n=38,46)	66	67
Week 116 (n=36,44)	67	68
Week 128 (n=35,40)	69	70
Week 140 (n=31,36)	68	67
Week 152 (n=25,30)	64	57
Week 164 (n=25,24)	68	58
Week 176 (n=22,22)	68	64
Week 188 (n=18,21)	61	57
Week 200 (n=17,20)	59	60
Week 212 (n=16,19)	56	63
Week 224 (n=15,19)	53	63
Week 236 (n=14,18)	50	61
Week 248 (n=13,18)	46	61
Week 260 (n=13,18)	46	61

No statistical analyses for this end point

Secondary: Part III: Percentage of Participants with a ≥20/50/75/90% Decrease from Baseline in Oral Corticosteroid Dose at Visits

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End point title

Part III: Percentage of Participants with a ≥20/50/75/90% Decrease from Baseline in Oral Corticosteroid Dose at Visits

End point description

Values summarized are based on average daily dose on the nominal study day. The prednisone equivalent is used in calculation of oral corticosteroid dose. Participants who withdrew are excluded at the timepoint of this event and at all subsequent visits. Baseline considered first dose of study treatment. ITT3 population; n=number of participants contributing to the specific statistic.

End point type

Secondary

End point timeframe

Every 2 weeks from Week 104 to 260

End point values	Participants ≥30 kg	Participants <30 kg
Number of subjects analysed	38	46
Units: percentage of participants
number (not applicable)
Week 104 ≥20% decrease (n=38,46)	100	97.8
Week 104 ≥50% decrease (n=38,46)	94.7	91.3
Week 104 ≥75% decrease (n=38,46)	84.2	82.6
Week 104 ≥90% decrease (n=38,46)	71.1	71.7
Week 106 ≥20% decrease (n=37,46)	100	97.8
Week 106 ≥50% decrease (n=37,46)	91.9	91.3
Week 106 ≥75% decrease (n=37,46)	83.8	82.6
Week 106 ≥90% decrease (n=37,46)	70.3	71.7
Week 108 ≥20% decrease (n=37,45)	100	100
Week 108 ≥50% decrease (n=37,45)	89.2	91.1
Week 108 ≥75% decrease (n=37,45)	81.1	84.4
Week 108 ≥90% decrease (n=37,45)	70.3	73.3
Week 110 ≥20% decrease (n=36,44)	100	100
Week 110 ≥50% decrease (n=36,44)	88.9	93.2
Week 110 ≥75% decrease (n=36,44)	80.6	84.1
Week 110 ≥90% decrease (n=36,44)	72.2	75
Week 112 ≥20% decrease (n=36,44)	100	100
Week 112 ≥50% decrease (n=36,44)	88.9	95.5
Week 112 ≥75% decrease (n=36,44)	80.6	81.8
Week 112 ≥90% decrease (n=36,44)	72.2	75
Week 114 ≥20% decrease (n=36,44)	100	100
Week 114 ≥50% decrease (n=36,44)	88.9	95.5
Week 114 ≥75% decrease (n=36,44)	80.6	79.5
Week 114 ≥90% decrease (n=36,44)	72.2	72.7
Week 116 ≥20% decrease (n=35,44)	100	100
Week 116 ≥50% decrease (n=35,44)	91.4	93.2
Week 116 ≥75% decrease (n=35,44)	80	79.5
Week 116 ≥90% decrease (n=35,44)	71.4	72.7
Week 118 ≥20% decrease (n=35,43)	100	100
Week 118 ≥50% decrease (n=35,43)	88.6	93
Week 118 ≥75% decrease (n=35,43)	80	81.4
Week 118 ≥90% decrease (n=35,43)	71.4	74.4
Week 120 ≥20% decrease (n=35,43)	100	100
Week 120 ≥50% decrease (n=35,43)	88.6	93
Week 120 ≥75% decrease (n=35,43)	80	83.7
Week 120 ≥90% decrease (n=35,43)	74.3	76.7
Week 122 ≥20% decrease (n=35,43)	97.1	100
Week 122 ≥50% decrease (n=35,43)	88.6	93
Week 122 ≥75% decrease (n=35,43)	77.1	81.4
Week 122 ≥90% decrease (n=35,43)	74.3	74.4
Week 124 ≥20% decrease (n=35,43)	100	100
Week 124 ≥50% decrease (n=35,43)	94.3	93
Week 124 ≥75% decrease (n=35,43)	80	83.7
Week 124 ≥90% decrease (n=35,43)	77.1	74.4
Week 126 ≥20% decrease (n=35,43)	100	100
Week 126 ≥50% decrease (n=35,43)	94.3	90.7
Week 126 ≥75% decrease (n=35,43)	80	81.4
Week 126 ≥90% decrease (n=35,43)	77.1	74.4
Week 128 ≥20% decrease (n=35,39)	100	97.4
Week 128 ≥50% decrease (n=35,39)	91.4	89.7
Week 128 ≥75% decrease (n=35,39)	80	82.1
Week 128 ≥90% decrease (n=35,39)	77.1	71.8
Week 130 ≥20% decrease (n=35,39)	100	97.4
Week 130 ≥50% decrease (n=35,39)	91.4	89.7
Week 130 ≥75% decrease (n=35,39)	80	87.2
Week 130 ≥90% decrease (n=35,39)	80	74.4
Week 132 ≥20% decrease (n=35,39)	100	97.4
Week 132 ≥50% decrease (n=35,39)	91.4	87.2
Week 132 ≥75% decrease (n=35,39)	80	84.6
Week 132 ≥90% decrease (n=35,39)	80	71.8
Week 134 ≥20% decrease (n=35,39)	94.3	97.4
Week 134 ≥50% decrease (n=35,39)	88.6	87.2
Week 134 ≥75% decrease (n=35,39)	77.1	84.6
Week 134 ≥90% decrease (n=35,39)	77.1	71.8
Week 136 ≥20% decrease (n=34,39)	97.1	97.4
Week 136 ≥50% decrease (n=34,39)	91.2	89.7
Week 136 ≥75% decrease (n=34,39)	76.5	84.6
Week 136 ≥90% decrease (n=34,39)	76.5	71.8
Week 138 ≥20% decrease (n=34,39)	94.1	97.4
Week 138 ≥50% decrease (n=34,39)	88.2	89.7
Week 138 ≥75% decrease (n=34,39)	76.5	84.6
Week 138 ≥90% decrease (n=34,39)	76.5	71.8
Week 140 ≥20% decrease (n=29,36)	93.1	97.2
Week 140 ≥50% decrease (n=29,36)	86.2	88.9
Week 140 ≥75% decrease (n=29,36)	72.4	83.3
Week 140 ≥90% decrease (n=29,36)	72.4	72.2
Week 142 ≥20% decrease (n=29,36)	93.1	97.2
Week 142 ≥50% decrease (n=29,36)	86.2	88.9
Week 142 ≥75% decrease (n=29,36)	72.4	83.3
Week 142 ≥90% decrease (n=29,36)	69	72.2
Week 144 ≥20% decrease (n=28,36)	92.9	97.2
Week 144 ≥50% decrease (n=28,36)	89.3	88.9
Week 144 ≥75% decrease (n=28,36)	71.4	83.3
Week 144 ≥90% decrease (n=28,36)	67.9	72.2
Week 146 ≥20% decrease (n=28,36)	96.4	97.2
Week 146 ≥50% decrease (n=28,36)	92.9	86.1
Week 146 ≥75% decrease (n=28,36)	75	80.6
Week 146 ≥90% decrease (n=28,36)	71.4	66.7
Week 148 ≥20% decrease (n=27,35)	100	97.1
Week 148 ≥50% decrease (n=27,35)	96.3	85.7
Week 148 ≥75% decrease (n=27,35)	77.8	80
Week 148 ≥90% decrease (n=27,35)	74.1	65.7
Week 150 ≥20% decrease (n=25,35)	100	97.1
Week 150 ≥50% decrease (n=25,35)	96	88.6
Week 150 ≥75% decrease (n=25,35)	76	80
Week 150 ≥90% decrease (n=25,35)	76	68.6
Week 152 ≥20% decrease (n=25,27)	100	96.3
Week 152 ≥50% decrease (n=25,27)	96	85.2
Week 152 ≥75% decrease (n=25,27)	76	77.8
Week 152 ≥90% decrease (n=25,27)	76	63
Week 154 ≥20% decrease (n=25,27)	100	96.3
Week 154 ≥50% decrease (n=25,27)	96	88.9
Week 154 ≥75% decrease (n=25,27)	76	77.8
Week 154 ≥90% decrease (n=25,27)	76	70.4
Week 156 ≥20% decrease (n=25,27)	100	96.3
Week 156 ≥50% decrease (n=25,27)	96	85.2
Week 156 ≥75% decrease (n=25,27)	76	77.8
Week 156 ≥90% decrease (n=25,27)	76	70.4
Week 158 ≥20% decrease (n=25,27)	100	96.3
Week 158 ≥50% decrease (n=25,27)	96	88.9
Week 158 ≥75% decrease (n=25,27)	76	77.8
Week 158 ≥90% decrease (n=25,27)	76	70.4
Week 160 ≥20% decrease (n=25,27)	100	96.3
Week 160 ≥50% decrease (n=25,27)	96	85.2
Week 160 ≥75% decrease (n=25,27)	76	77.8
Week 160 ≥90% decrease (n=25,27)	76	70.4
Week 162 ≥20% decrease (n=25,27)	100	96.3
Week 162 ≥50% decrease (n=25,27)	96	81.5
Week 162 ≥75% decrease (n=25,27)	76	77.8
Week 162 ≥90% decrease (n=25,27)	76	70.4
Week 164 ≥20% decrease (n=24,24)	100	95.8
Week 164 ≥50% decrease (n=24,24)	95.8	83.3
Week 164 ≥75% decrease (n=24,24)	75	75
Week 164 ≥90% decrease (n=24,24)	75	70.8
Week 166 ≥20% decrease (n=24,22)	100	95.5
Week 166 ≥50% decrease (n=24,22)	95.8	81.8
Week 166 ≥75% decrease (n=24,22)	75	72.7
Week 166 ≥90% decrease (n=24,22)	75	68.2
Week 168 ≥20% decrease (n=24,22)	100	95.5
Week 168 ≥50% decrease (n=24,22)	95.8	81.8
Week 168 ≥75% decrease (n=24,22)	75	72.7
Week 168 ≥90% decrease (n=24,22)	75	68.2
Week 170 ≥20% decrease (n=22,22)	100	90.9
Week 170 ≥50% decrease (n=22,22)	95.5	81.8
Week 170 ≥75% decrease (n=22,22)	77.3	72.7
Week 170 ≥90% decrease (n=22,22)	77.3	68.2
Week 172 ≥20% decrease (n=22,22)	100	90.9
Week 172 ≥50% decrease (n=22,22)	95.5	90.9
Week 172 ≥75% decrease (n=22,22)	77.3	72.7
Week 172 ≥90% decrease (n=22,22)	77.3	68.2
Week 174 ≥20% decrease (n=22,22)	100	90.9
Week 174 ≥50% decrease (n=22,22)	95.5	90.9
Week 174 ≥75% decrease (n=22,22)	77.3	72.7
Week 174 ≥90% decrease (n=22,22)	77.3	68.2
Week 176 ≥20% decrease (n=19,22)	100	90.9
Week 176 ≥50% decrease (n=19,22)	94.7	90.9
Week 176 ≥75% decrease (n=19,22)	73.7	72.7
Week 176 ≥90% decrease (n=19,22)	73.7	68.2
Week 178 ≥20% decrease (n=19,22)	100	90.9
Week 178 ≥50% decrease (n=19,22)	94.7	90.9
Week 178 ≥75% decrease (n=19,22)	73.7	72.7
Week 178 ≥90% decrease (n=19,22)	73.7	68.2
Week 180 ≥20% decrease (n=19,22)	100	90.9
Week 180 ≥50% decrease (n=19,22)	94.7	90.9
Week 180 ≥75% decrease (n=19,22)	73.7	68.2
Week 180 ≥90% decrease (n=19,22)	73.7	63.6
Week 182 ≥20% decrease (n=18,22)	100	90.9
Week 182 ≥50% decrease (n=18,22)	94.4	90.9
Week 182 ≥75% decrease (n=18,22)	72.2	68.2
Week 182 ≥90% decrease (n=18,22)	72.2	63.6
Week 184 ≥20% decrease (n=18,22)	100	90.9
Week 184 ≥50% decrease (n=18,22)	94.4	86.4
Week 184 ≥75% decrease (n=18,22)	72.2	68.2
Week 184 ≥90% decrease (n=18,22)	72.2	63.6
Week 186 ≥20% decrease (n=18,22)	100	90.9
Week 186 ≥50% decrease (n=18,22)	94.4	90.9
Week 186 ≥75% decrease (n=18,22)	72.2	68.2
Week 186 ≥90% decrease (n=18,22)	72.2	63.6
Week 188 ≥20% decrease (n=18,21)	100	90.5
Week 188 ≥50% decrease (n=18,21)	94.4	90.5
Week 188 ≥75% decrease (n=18,21)	72.2	71.4
Week 188 ≥90% decrease (n=18,21)	72.2	61.9
Week 190 ≥20% decrease (n=18,21)	100	95.2
Week 190 ≥50% decrease (n=18,21)	94.4	85.7
Week 190 ≥75% decrease (n=18,21)	72.2	66.7
Week 190 ≥90% decrease (n=18,21)	72.2	61.9
Week 192 ≥20% decrease (n=18,21)	100	95.2
Week 192 ≥50% decrease (n=18,21)	94.4	81
Week 192 ≥75% decrease (n=18,21)	72.2	66.7
Week 192 ≥90% decrease (n=18,21)	72.2	61.9
Week 194 ≥20% decrease (n=18,20)	100	95
Week 194 ≥50% decrease (n=18,20)	94.4	80
Week 194 ≥75% decrease (n=18,20)	72.2	70
Week 194 ≥90% decrease (n=18,20)	72.2	65
Week 196 ≥20% decrease (n=18,20)	100	90
Week 196 ≥50% decrease (n=18,20)	94.4	80
Week 196 ≥75% decrease (n=18,20)	72.2	70
Week 196 ≥90% decrease (n=18,20)	72.2	65
Week 198 ≥20% decrease (n=18,20)	100	90
Week 198 ≥50% decrease (n=18,20)	94.4	80
Week 198 >75% decrease (n=18,20)	72.2	75
Week 198 ≥90% decrease (n=18,20)	72.2	65
Week 200 ≥20% decrease (n=17,20)	100	90
Week 200 ≥50% decrease (n=17,20)	94.1	85
Week 200 ≥75% decrease (n=17,20)	76.5	75
Week 200 ≥90% decrease (n=17,20)	70.6	65
Week 202 ≥20% decrease (n=17,20)	100	90
Week 202 ≥50% decrease (n=17,20)	94.1	85
Week 202 ≥75% decrease (n=17,20)	76.5	75
Week 202 ≥90% decrease (n=17,20)	70.6	65
Week 204 ≥20% decrease (n=17,20)	100	90
Week 204 ≥50% decrease (n=17,20)	94.1	85
Week 204 ≥70% decrease (n=17,20)	76.5	75
Week 204 ≥90% decrease (n=17,20)	70.6	65
Week 206 ≥20% decrease (n=16,20)	100	85
Week 206 ≥50% decrease (n=16,20)	93.8	75
Week 206 ≥75% decrease (n=16,20)	75	75
Week 206 ≥90% decrease (n=16,20)	68.8	70
Week 208 ≥20% decrease (n=16,20)	100	90
Week 208 ≥50% decrease (n=16,20)	93.8	80
Week 208 ≥75% decrease (n=16,20	75	75
Week 208 ≥90% decrease (n=16,20)	68.8	70
Week 210 ≥20% decrease (n=16,19)	100	89.5
Week 210 ≥50% decrease (n=16,19)	93.8	84.2
Week 210 ≥75% decrease (n=16,19)	81.3	78.9
Week 210 ≥90% decrease (n=16,19)	75	73.7
Week 212 ≥20% decrease (n=15,19)	100	89.5
Week 212 ≥50% decrease (n=15,19)	93.3	84.2
Week 212 ≥75% decrease (n=15,19)	73.3	78.9
Week 212 ≥90% decrease (n=15,19)	73.3	73.7
Week 214 ≥20% decrease (n=15,19)	100	89.5
Week 214 ≥50% decrease (n=15,19)	93.3	84.2
Week 214 ≥75% decrease (n=15,19)	73.3	78.9
Week 214 ≥90% decrease (n=15,19)	73.3	73.7
Week 216 ≥20% decrease (n=15,19)	100	94.7
Week 216 ≥50% decrease (n=15,19)	93.3	84.2
Week 216 ≥75% decrease (n=15,19)	73.3	78.9
Week 216 ≥90% decrease (n=15,19)	73.3	73.7
Week 218 ≥20% decrease (n=15,19)	100	89.5
Week 218 ≥50% decrease (n=15,19)	93.3	84.2
Week 218 ≥75% decrease (n=15,19)	80	78.9
Week 218 ≥90% decrease (n=15,19)	73.3	73.7
Week 220 ≥20% decrease (n=15,19)	100	89.5
Week 220 ≥50% decrease (n=15,19)	93.3	84.2
Week 220 ≥75% decrease (n=15,19)	80	78.9
Week 220 ≥90% decrease (n=15,19)	73.3	73.7
Week 222 ≥20% decrease (n=15,19)	100	89.5
Week 222 ≥50% decrease (n=15,19)	93.3	84.2
Week 222 ≥75% decrease (n=15,19)	80	78.9
Week 222 ≥90% decrease (n=15,19)	73.3	73.7
Week 224 ≥20% decrease (n=15,19)	100	89.5
Week 224 ≥50% decrease (n=15,19)	93.3	84.2
Week 224 ≥75% decrease (n=15,19)	80	78.9
Week 224 ≥90% decrease (n=15,19)	73.3	73.7
Week 226 ≥20% decrease (n=14,19)	100	89.5
Week 226 ≥50% decrease (n=14,19)	92.9	84.2
Week 226 ≥75% decrease (n=14,19)	78.6	78.9
Week 226 ≥90% decrease (n=14,19)	71.4	73.7
Week 228 ≥20% decrease (n=14,19)	100	89.5
Week 228 ≥50% decrease (n=14,19)	92.9	89.5
Week 228 ≥75% decrease (n=14,19)	78.6	78.9
Week 228 ≥90% decrease (n=14,19)	71.4	73.7
Week 230 ≥20% decrease (n=14,19)	100	89.5
Week 230 ≥50% decrease (n=14,19)	92.9	89.5
Week 230 ≥75% decrease (n=14,19)	78.6	78.9
Week 230 ≥90% decrease (n=14,19)	71.4	73.7
Week 232 ≥20% decrease (n=14,18)	100	88.9
Week 232 ≥50% decrease (n=14,18)	92.9	88.9
Week 232 ≥75% decrease (n=14,18)	78.6	77.8
Week 232 ≥90% decrease (n=14,18)	71.4	72.2
Week 234 ≥20% decrease (n=14,18)	100	88.9
Week 234 ≥50% decrease (n=14,18)	92.9	88.9
Week 234 ≥75% decrease (n=14,18)	78.6	77.8
Week 234 ≥90% decrease (n=14,18)	71.4	72.2
Week 236 ≥20% decrease (n=14,18)	100	94.4
Week 236 ≥50% decrease (n=14,18)	92.9	88.9
Week 236 ≥75% decrease (n=14,18)	78.6	77.8
Week 236 ≥90% decrease (n=14,18)	71.4	72.2
Week 238 ≥20% decrease (n=14,18)	100	94.4
Week 238 ≥50% decrease (n=14,18)	92.9	88.9
Week 238 ≥75% decrease (n=14,18)	78.6	77.8
Week 238 ≥90% decrease (n=14,18)	71.4	72.2
Week 240 ≥20% decrease (n=13,18)	100	94.4
Week 240 ≥50% decrease (n=13,18)	92.3	88.9
Week 240 ≥75% decrease (n=13,18)	76.9	77.8
Week 240 ≥90% decrease (n=13,18)	69.2	72.2
Week 242 ≥20% decrease (n=13,18)	100	94.4
Week 242 ≥50% decrease (n=13,18)	92.3	88.9
Week 242 ≥75% decrease (n=13,18)	76.9	77.8
Week 242 ≥90% decrease (n=13,18)	69.2	72.2
Week 244 ≥20% decrease (n=13,18)	100	94.4
Week 244 ≥50% decrease (n=13,18)	92.3	88.9
Week 244 ≥75% decrease (n=13,18)	76.9	77.8
Week 244 ≥90% decrease (n=13,18)	69.2	72.2
Week 246 ≥20% decrease (n=13,18)	100	94.4
Week 246 ≥50% decrease (n=13,18)	92.3	88.9
Week 246 ≥75% decrease (n=13,18)	76.9	77.8
Week 246 ≥90% decrease (n=13,18)	69.2	72.2
Week 248 ≥20% decrease (n=13,18)	100	94.4
Week 248 ≥50% decrease (n=13,18)	92.3	88.9
Week 248 ≥75% decrease (n=13,18)	76.9	77.8
Week 248 ≥90% decrease (n=13,18)	69.2	72.2
Week 250 ≥20% decrease (n=13,18)	100	94.4
Week 250 ≥50% decrease (n=13,18)	92.3	83.3
Week 250 ≥75% decrease (n=13,18)	76.9	77.8
Week 250 ≥90% decrease (n=13,18)	69.2	72.2
Week 252 ≥20% decrease (n=13,18)	100	94.4
Week 252 ≥50% decrease (n=13,18)	92.3	83.3
Week 252 ≥75% decrease (n=13,18)	76.9	77.8
Week 252 ≥90% decrease (n=13,18)	69.2	72.2
Week 254 ≥20% decrease (n=13,18)	100	94.4
Week 254 ≥50% decrease (n=13,18)	92.3	83.3
Week 254 ≥75% decrease (n=13,18)	76.9	77.8
Week 254 ≥90% decrease (n=13,18)	69.2	72.2
Week 256 ≥20% decrease (n=13,18)	100	94.4
Week 256 ≥50% decrease (n=13,18)	92.3	83.3
Week 256 ≥75% decrease (n=13,18)	76.9	77.8
Week 256 ≥90% decrease (n=13,18)	69.2	72.2
Week 258 ≥20% decrease (n=13,18)	100	94.4
Week 258 ≥50% decrease (n=13,18)	92.3	83.3
Week 258 ≥75% decrease (n=13,18)	76.9	77.8
Week 258 ≥90% decrease (n=13,18)	69.2	72.2
Week 260 ≥20% decrease (n=13,18)	100	94.4
Week 260 ≥50% decrease (n=13,18)	92.3	88.9
Week 260 ≥75% decrease (n=13,18)	76.9	77.8
Week 260 ≥90% decrease (n=13,18)	69.2	72.2

No statistical analyses for this end point

Secondary: Part III: Percentage of Participants with Inactive Disease

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End point title

Part III: Percentage of Participants with Inactive Disease

End point description

Participants who previously withdrew are excluded. Responders are participants who met all of the following criteria for inactive disease at the visit assessment day: i. Number of active joints = 0. ii. Absence of lymphadenopathy, hepatomegaly or splenomegaly in the nearest non-missing physical examination prior to or after the week assessment day. This could include results outside of the time window. iii. Absence of symptomatic serositis adverse event. iv. In the 14 days preceding the week assessment day no fever (temperature >=37.5 degrees C) or rash characteristic of sJIA. v. Normal ESR as defined by an ESR <20 mm/hr regardless of age and sex. vi. Physician global assessment VAS <=10. LOCF rule applied to missing number of active joints, ESR and Physician global assessment VAS. Data presented up to the point of entry into the Alternative Dosing Schedule. ITT3 population; n=number of participants contributing to the specific statistic.

End point type

Secondary

End point timeframe

Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260

End point values	Participants ≥30 kg	Participants <30 kg
Number of subjects analysed	42	47
Units: percentage of participants
number (not applicable)
Week 104 (n=42,47)	45.2	46.8
Week 116 (n=41,46)	48.8	43.5
Week 128 (n=40,43)	55	48.8
Week 140 (n=38,40)	55.3	45
Week 152 (n=27,35)	33.3	54.3
Week 164 (n=27,25)	37	28
Week 176 (n=24,22)	41.7	36.4
Week 188 (n=21,22)	23.8	31.8
Week 200 (n=19,21)	42.1	14.3
Week 212 (n=18,18 )	55.6	44.4
Week 224 (n=17,18)	47.1	44.4
Week 236 (n=16,17)	43.8	29.4
Week 248 (n=15,17)	26.7	41.2
Week 260 (n=15,15)	46.7	6.7

No statistical analyses for this end point

Secondary: Part III: Percentage of Participants in Clinical Remission

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End point title

Part III: Percentage of Participants in Clinical Remission

End point description

Patients who previously withdrew are excluded. Responders are patients who met all of the following criteria for inactive disease at all visits in 6 months (180 days) prior to and including the visit assessment day: i. Number of active joints = 0. ii. Absence of lymphadenopathy, hepatomegaly or splenomegaly in the nearest non-missing physical examination prior to or after the week assessment day. This could include results outside of the time window. iii. Absence of symptomatic serositis adverse event. iv. In the 14 days preceding the week assessment day no fever (temperature >=37.5 C) or rash characteristic of sJIA. v. Normal ESR as defined by an ESR <20 mm/hr regardless of age and sex. iv. Physician global assessment VAS <=10. LOCF rule applied to missing number of active joints, ESR and Physician global assessment VAS. ESR = Erythrocyte Sedimentation Rate. VAS = Visual Analogue Scale. Data presented up to the point of entry into the Alternative Dosing Schedule. ITT3 population.

End point type

Secondary

End point timeframe

Weeks 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260

End point values	Participants ≥30 kg	Participants <30 kg
Number of subjects analysed	41	47
Units: percentage of participants
number (not applicable)
Week 116 (n=41,46)	14.6	17.4
Week 128 (n=40,43)	32.5	23.3
Week 140 (n=38,40)	34.2	25
Week 152 (n=27,35)	25.9	25.7
Week 164 (n=27,25)	22.2	16
Week 176 (n=24,22)	16.7	13.6
Week 188 (n=21,22)	14.3	9.1
Week 200 (n=19,21)	15.8	4.8
Week 212 (n=18,18)	16.7	5.6
Week 224 (n=17,18)	29.4	11.1
Week 236 (n=16,17)	25	29.4
Week 248 (n=15,17)	13.3	23.5
Week 260 (n=15,15)	13.3	6.7

No statistical analyses for this end point

Secondary: Part III: Percentage of Participants on CSs at Baseline in Clinical Remission off all Oral CSs for 6 Months Prior to Specific Weeks

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End point title

Part III: Percentage of Participants on CSs at Baseline in Clinical Remission off all Oral CSs for 6 Months Prior to Specific Weeks

End point description

There were 4 levels of clinical remission defined while the patient remained on tocilizumab as defined below.. After level 1, each successive level required that all the previous level criteria be met: Level 1: inactive disease criteria have been met at all assessments in the last 6 months (180 days) preceding the timepoint assessment day Level 2: level 1 criteria and no oral corticosteroids received in the last 6 months (180 days) preceding the timepoint assessment day. Level 3: level 2 criteria and no methotrexate received in the last 6 months (180 days) preceding the timepoint assessment day Level 4: level 3 criteria and no NSAIDs received for sJIA in the last 6 months (180 days) preceding the timepoint assessment day. ITT3 population; n=number of participants contributing to the specific statistic.

End point type

Secondary

End point timeframe

Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260

End point values	Participants ≥30 kg	Participants <30 kg
Number of subjects analysed	41	46
Units: percentage of participants
number (not applicable)
Week 116 (n=41,46)	12.2	17.4
Week 128 (n=40,43)	32.5	20.9
Week 140 (n=38,40)	28.9	20
Week 152 (n=27,35)	18.5	20
Week 164 (n=27,25)	18.5	12
Week 176 (n=24,22)	16.7	9.1
Week 188 (n=21,22)	14.3	4.5
Week 200 (n=19,21)	10.5	4.8
Week 212 (n=18,18)	11.1	5.6
Week 224 (n=17,18)	23.5	11.1
Week 236 (n=16,17)	25	23.5
Week 248 (n=15,17)	6.7	17.6
Week 260 (n=15,15)	6.7	6.7

No statistical analyses for this end point

Secondary: Part III: Percentage of Participants on Methotrexate (MTX) at Baseline in Clinical Remission off Corticosteroids and MTX for 6 Months Prior to Specified Weeks

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End point title

Part III: Percentage of Participants on Methotrexate (MTX) at Baseline in Clinical Remission off Corticosteroids and MTX for 6 Months Prior to Specified Weeks

End point description

There were 4 levels of clinical remission defined while the patient remained on tocilizumab as defined below.. After level 1, each successive level required that all the previous level criteria be met: Level 1: inactive disease criteria have been met at all assessments in the last 6 months (180 days) preceding the timepoint assessment day Level 2: level 1 criteria and no oral corticosteroids received in the last 6 months (180 days) preceding the timepoint assessment day Level 3: level 2 criteria and no methotrexate received in the last 6 months (180 days) preceding the timepoint assessment day Level 4: level 3 criteria and no NSAIDs received for sJIA in the last 6 months (180 days) preceding the timepoint assessment day. ITT3 population; n=number of participants contributing to the specific statistic

End point type

Secondary

End point timeframe

Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260

End point values	Participants ≥30 kg	Participants <30 kg
Number of subjects analysed	41	46
Units: percentage of participants
number (not applicable)
Week 116 (n=41,46)	7.3	8.7
Week 128 (n=40,43)	20	11.6
Week 140 (n=38,40)	18.4	5
Week 152 (n=27,35)	3.7	2.9
Week 164 (n=27,25)	3.7	4
Week 176 (n=24,22)	4.2	0
Week 188 (n=21,22)	4.8	0
Week 200 (n=19,21)	5.3	4.8
Week 212 (n=18,18)	5.6	5.6
Week 224 (n=17,18)	5.9	5.6
Week 236 (n=16,17)	12.5	5.9
Week 248 (n=15,17)	0	5.9
Week 260 (n=15,15)	0	0

No statistical analyses for this end point

Secondary: Part III: Percentage of Participants in Clinical Remission off all Arthritis Medications except TCZ for 6 months Prior to Specified Weeks

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End point title

Part III: Percentage of Participants in Clinical Remission off all Arthritis Medications except TCZ for 6 months Prior to Specified Weeks

End point description

There were 4 levels of clinical remission defined while the patient remained on tocilizumab as defined below.. After level 1, each successive level required that all the previous level criteria be met: Level 1: inactive disease criteria have been met at all assessments in the last 6 months (180 days) preceding the timepoint assessment day Level 2: level 1 criteria and no oral corticosteroids received in the last 6 months (180 days) preceding the timepoint assessment day Level 3: level 2 criteria and no methotrexate received in the last 6 months (180 days) preceding the timepoint assessment day Level 4: level 3 criteria and no NSAIDs received for sJIA in the last 6 months (180 days) preceding the timepoint assessment day. ITT3 population; n=number of participants contributing to the specific statistic.

End point type

Secondary

End point timeframe

Weeks 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260

End point values	Participants ≥30 kg	Participants <30 kg
Number of subjects analysed	41	46
Units: percentage of participants
number (not applicable)
Week 116 (n=41,46)	4.9	8.7
Week 128 (n=40,43)	15	9.3
Week 140 (n=38,40)	15.8	5
Week 152 (n=27,35)	0	2.9
Week 164 (n=27,25)	0	0
Week 176 (n=24,22)	4.2	0
Week 188 (n=21,22)	4.8	0
Week 200 (n=19,21)	5.3	0
Week 212 (n=18,18)	5.6	0
Week 224 (n=17,18)	5.9	0
Week 236 (n=16,17)	12.5	0
Week 248 (n=15,17)	0	0
Week 260 (n=15,15)	0	0

No statistical analyses for this end point

Secondary: Part III: Percentage of Participants Who Develop Anti-TCZ Antibodies

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End point title

Part III: Percentage of Participants Who Develop Anti-TCZ Antibodies

End point description

Human antibodies against human antibodies (HAHA), anti-tocilizumab antibodies were assessed by immunogenicity techniques from blood samples drawn every two weeks during Part III of the study. ITT3 population; n=number of participants contributing to the specific statistic.

End point type

Secondary

End point timeframe

Every 2 weeks from Week 104 to 260

End point values	Participants ≥30 kg	Participants <30 kg
Number of subjects analysed	45	47
Units: percentage of participants
number (not applicable)	0	0

No statistical analyses for this end point

Secondary: Part III: Percentage of Participants who Develop Anti-TCZ Antibodies Associated With Drug Hypersensitivity Reactions

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End point title

Part III: Percentage of Participants who Develop Anti-TCZ Antibodies Associated With Drug Hypersensitivity Reactions

End point description

HAHA, anti-tocilizumab antibodies were assessed by immunogenicity techniques from blood samples drawn every two weeks during Part III of the study. ITT3 population; n=number of participants contributing to the specific statistic.

End point type

Secondary

End point timeframe

Every 2 weeks from Week 104 to 260

End point values	Participants ≥30 kg	Participants <30 kg
Number of subjects analysed	45	47
Units: percentage of participants
number (not applicable)	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AE onset between time of very first drug intake and date of last contact or 30 days after very last drug intake. 30 days after 12 weeks of treatment in Part I, 30 days after up to Week 104 in Part II and 30 days after up to Week 260 in Part III .

Adverse event reporting additional description

Adverse Events (AEs) reported in the All Tocilizumab (Part I, Part II and Part III) arm are cumulative to Week 260 and include AEs previously reported in the Tocilizumab_8 mg/kg (Part I) and Tocilizumab_12 mg/kg (Part I) arms that occurred in the 12 week treatment period.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

All Tocilizumab (Part I, II and III)

Reporting group description

Serious adverse events	All Tocilizumab (Part I, II and III)
Total subjects affected by serious adverse events
subjects affected / exposed	48 / 112 (42.86%)
number of deaths (all causes)	4
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Pregnancy, puerperium and perinatal conditions
Pregnancy
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
General disorders and administration site conditions
Drug intolerance
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Influenza like illness
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Reproductive system and breast disorders
Testicular torsion
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Respiratory, thoracic and mediastinal disorders
Pneumothorax
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 1
Pulmonary veno-occlusive disease
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Psychiatric disorders
Abnormal behaviour
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Self injurious behaviour
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Investigations
Liver function test abnormal
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Injury, poisoning and procedural complications
Joint dislocation
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Femur fracture
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Forearm fracture
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Fracture
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Road traffic accident
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Spinal fracture
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Tendon rupture
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Ulna fracture
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Cardiac disorders
Cardiac failure
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Blood and lymphatic system disorders
Histiocytosis haematophagic
subjects affected / exposed	5 / 112 (4.46%)
occurrences causally related to treatment / all	3 / 5
deaths causally related to treatment / all	0 / 0
Lymphadenitis
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Constipation
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Diarrhoea
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Gastritis
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Vomiting
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Hepatobiliary disorders
Hypertransaminasaemia
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Skin and subcutaneous tissue disorders
Angioedema
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Panniculitis
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Urticaria
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Arthritis
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Juvenile idiopathic arthritis
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Pain in extremity
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Infections and infestations
Gastroenteritis
subjects affected / exposed	5 / 112 (4.46%)
occurrences causally related to treatment / all	2 / 7
deaths causally related to treatment / all	0 / 0
Pneumonia
subjects affected / exposed	5 / 112 (4.46%)
occurrences causally related to treatment / all	0 / 5
deaths causally related to treatment / all	0 / 0
Varicella
subjects affected / exposed	5 / 112 (4.46%)
occurrences causally related to treatment / all	1 / 5
deaths causally related to treatment / all	0 / 0
Herpes zoster
subjects affected / exposed	3 / 112 (2.68%)
occurrences causally related to treatment / all	1 / 3
deaths causally related to treatment / all	0 / 0
Sepsis
subjects affected / exposed	2 / 112 (1.79%)
occurrences causally related to treatment / all	1 / 3
deaths causally related to treatment / all	1 / 1
Lower respiratory tract infection
subjects affected / exposed	2 / 112 (1.79%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Arthritis bacterial
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Bronchopneumonia
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Device related sepsis
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Gastroenteritis viral
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Kidney infection
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Otitis media
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Pharyngitis
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Pharyngotonsillitis
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Tonsillitis
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Upper respiratory tract infection
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Cellulitis
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 1
Hyperkalaemia
subjects affected / exposed	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0

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

Non-serious adverse events	All Tocilizumab (Part I, II and III)
Total subjects affected by non serious adverse events
subjects affected / exposed	112 / 112 (100.00%)
Vascular disorders
Haematoma
subjects affected / exposed	7 / 112 (6.25%)
occurrences all number	11
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	11 / 112 (9.82%)
occurrences all number	19
Influenza like illness
subjects affected / exposed	10 / 112 (8.93%)
occurrences all number	14
Fatigue
subjects affected / exposed	6 / 112 (5.36%)
occurrences all number	6
Local swelling
subjects affected / exposed	5 / 112 (4.46%)
occurrences all number	6
Pain
subjects affected / exposed	4 / 112 (3.57%)
occurrences all number	4
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	3 / 112 (2.68%)
occurrences all number	13
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	45 / 112 (40.18%)
occurrences all number	70
Oropharyngeal pain
subjects affected / exposed	24 / 112 (21.43%)
occurrences all number	40
Nasal congestion
subjects affected / exposed	10 / 112 (8.93%)
occurrences all number	16
Epistaxis
subjects affected / exposed	9 / 112 (8.04%)
occurrences all number	10
Rhinorrhoea
subjects affected / exposed	7 / 112 (6.25%)
occurrences all number	8
Investigations
Transaminases increased
subjects affected / exposed	11 / 112 (9.82%)
occurrences all number	12
Neutrophil count decreased
subjects affected / exposed	5 / 112 (4.46%)
occurrences all number	13
Platelet count decreased
subjects affected / exposed	5 / 112 (4.46%)
occurrences all number	36
Alanine aminotransferase increased
subjects affected / exposed	4 / 112 (3.57%)
occurrences all number	5
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	17 / 112 (15.18%)
occurrences all number	24
Ligament sprain
subjects affected / exposed	13 / 112 (11.61%)
occurrences all number	16
Contusion
subjects affected / exposed	10 / 112 (8.93%)
occurrences all number	18
Excoriation
subjects affected / exposed	8 / 112 (7.14%)
occurrences all number	8
Limb injury
subjects affected / exposed	8 / 112 (7.14%)
occurrences all number	15
Fall
subjects affected / exposed	7 / 112 (6.25%)
occurrences all number	7
Joint injury
subjects affected / exposed	7 / 112 (6.25%)
occurrences all number	8
Traumatic haematoma
subjects affected / exposed	7 / 112 (6.25%)
occurrences all number	10
Wound
subjects affected / exposed	6 / 112 (5.36%)
occurrences all number	8
Hand fracture
subjects affected / exposed	5 / 112 (4.46%)
occurrences all number	5
Laceration
subjects affected / exposed	5 / 112 (4.46%)
occurrences all number	5
Infusion related reaction
subjects affected / exposed	4 / 112 (3.57%)
occurrences all number	5
Muscle strain
subjects affected / exposed	4 / 112 (3.57%)
occurrences all number	4
Thermal burn
subjects affected / exposed	4 / 112 (3.57%)
occurrences all number	4
Nervous system disorders
Headache
subjects affected / exposed	25 / 112 (22.32%)
occurrences all number	53
Dizziness
subjects affected / exposed	6 / 112 (5.36%)
occurrences all number	11
Migraine
subjects affected / exposed	3 / 112 (2.68%)
occurrences all number	6
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	25 / 112 (22.32%)
occurrences all number	143
Leukopenia
subjects affected / exposed	11 / 112 (9.82%)
occurrences all number	34
Lymphadenopathy
subjects affected / exposed	6 / 112 (5.36%)
occurrences all number	12
Lymphadenitis
subjects affected / exposed	4 / 112 (3.57%)
occurrences all number	5
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	11 / 112 (9.82%)
occurrences all number	14
Middle ear effusion
subjects affected / exposed	4 / 112 (3.57%)
occurrences all number	4
Eye disorders
Cataract
subjects affected / exposed	4 / 112 (3.57%)
occurrences all number	4
Chalazion
subjects affected / exposed	3 / 112 (2.68%)
occurrences all number	6
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	29 / 112 (25.89%)
occurrences all number	44
Vomiting
subjects affected / exposed	29 / 112 (25.89%)
occurrences all number	34
Nausea
subjects affected / exposed	26 / 112 (23.21%)
occurrences all number	37
Abdominal pain
subjects affected / exposed	16 / 112 (14.29%)
occurrences all number	22
Abdominal pain upper
subjects affected / exposed	15 / 112 (13.39%)
occurrences all number	21
Dental caries
subjects affected / exposed	6 / 112 (5.36%)
occurrences all number	6
Gastrointestinal disorder
subjects affected / exposed	6 / 112 (5.36%)
occurrences all number	7
Abdominal discomfort
subjects affected / exposed	3 / 112 (2.68%)
occurrences all number	4
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	22 / 112 (19.64%)
occurrences all number	31
Eczema
subjects affected / exposed	10 / 112 (8.93%)
occurrences all number	18
Prurigo
subjects affected / exposed	8 / 112 (7.14%)
occurrences all number	10
Urticaria
subjects affected / exposed	8 / 112 (7.14%)
occurrences all number	14
Dry skin
subjects affected / exposed	5 / 112 (4.46%)
occurrences all number	6
Pruritus
subjects affected / exposed	4 / 112 (3.57%)
occurrences all number	9
Dermatitis atopic
subjects affected / exposed	3 / 112 (2.68%)
occurrences all number	3
Dermatitis contact
subjects affected / exposed	3 / 112 (2.68%)
occurrences all number	5
Erythema
subjects affected / exposed	3 / 112 (2.68%)
occurrences all number	4
Renal and urinary disorders
Haematuria
subjects affected / exposed	5 / 112 (4.46%)
occurrences all number	5
Musculoskeletal and connective tissue disorders
Juvenile idiopathic arthritis
subjects affected / exposed	31 / 112 (27.68%)
occurrences all number	72
Arthralgia
subjects affected / exposed	25 / 112 (22.32%)
occurrences all number	48
Back pain
subjects affected / exposed	12 / 112 (10.71%)
occurrences all number	19
Pain in extremity
subjects affected / exposed	12 / 112 (10.71%)
occurrences all number	24
Musculoskeletal pain
subjects affected / exposed	11 / 112 (9.82%)
occurrences all number	23
Neck pain
subjects affected / exposed	9 / 112 (8.04%)
occurrences all number	16
Joint swelling
subjects affected / exposed	7 / 112 (6.25%)
occurrences all number	10
Arthritis
subjects affected / exposed	5 / 112 (4.46%)
occurrences all number	9
Musculoskeletal stiffness
subjects affected / exposed	4 / 112 (3.57%)
occurrences all number	6
Osteoporosis
subjects affected / exposed	3 / 112 (2.68%)
occurrences all number	3
Infections and infestations
Nasopharyngitis
subjects affected / exposed	53 / 112 (47.32%)
occurrences all number	168
Upper respiratory tract infection
subjects affected / exposed	49 / 112 (43.75%)
occurrences all number	156
Gastroenteritis
subjects affected / exposed	28 / 112 (25.00%)
occurrences all number	43
Pharyngitis
subjects affected / exposed	20 / 112 (17.86%)
occurrences all number	26
Rhinitis
subjects affected / exposed	19 / 112 (16.96%)
occurrences all number	40
Ear infection
subjects affected / exposed	18 / 112 (16.07%)
occurrences all number	34
Viral infection
subjects affected / exposed	16 / 112 (14.29%)
occurrences all number	17
Impetigo
subjects affected / exposed	14 / 112 (12.50%)
occurrences all number	22
Otitis media
subjects affected / exposed	14 / 112 (12.50%)
occurrences all number	15
Conjunctivitis
subjects affected / exposed	12 / 112 (10.71%)
occurrences all number	14
Viral upper respiratory tract infection
subjects affected / exposed	12 / 112 (10.71%)
occurrences all number	14
Bronchitis
subjects affected / exposed	11 / 112 (9.82%)
occurrences all number	15
Sinusitis
subjects affected / exposed	10 / 112 (8.93%)
occurrences all number	11
Urinary tract infection
subjects affected / exposed	10 / 112 (8.93%)
occurrences all number	30
Gastroenteritis viral
subjects affected / exposed	9 / 112 (8.04%)
occurrences all number	9
Influenza
subjects affected / exposed	9 / 112 (8.04%)
occurrences all number	12
Tonsillitis
subjects affected / exposed	9 / 112 (8.04%)
occurrences all number	11
Otitis externa
subjects affected / exposed	8 / 112 (7.14%)
occurrences all number	15
Paronychia
subjects affected / exposed	7 / 112 (6.25%)
occurrences all number	10
Herpes zoster
subjects affected / exposed	6 / 112 (5.36%)
occurrences all number	6
Laryngitis
subjects affected / exposed	6 / 112 (5.36%)
occurrences all number	9
Cellulitis
subjects affected / exposed	5 / 112 (4.46%)
occurrences all number	5
Skin infection
subjects affected / exposed	5 / 112 (4.46%)
occurrences all number	5
Tinea pedis
subjects affected / exposed	5 / 112 (4.46%)
occurrences all number	8
Varicella
subjects affected / exposed	4 / 112 (3.57%)
occurrences all number	4
Otitis media acute
subjects affected / exposed	3 / 112 (2.68%)
occurrences all number	4
Pneumonia
subjects affected / exposed	3 / 112 (2.68%)
occurrences all number	3

More information

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Were there any global substantial amendments to the protocol? Yes

01 Jun 2009

Updated disease definitions including sJIA disease and MAS; Clarified section 4.1.1.2 title to indicate that first open label treatment dose was administered at Week 12 for Part II; Clarified the inclusion and exclusion criteria; Updated treatments allowed and prohibited for sJIA; Updated the withdrawal requirements for patients and discontinuation criteria if patients did not achieve a JIA ACR30 response; Extended the length of the study design from a two-part, 3 year study to a three-part, 5 year study; Clarified the visits and weeks of Part I – the double-blind portion of the study to evaluate efficacy and safety; Changed the day of the Baseline score taken as the pre-dose assessment at Visit 1 (the day of the first infusion of study drug) to Day 1 from Day 0; Updated the timing of reporting to Roche with local serum ferritin results ≥ 3,000 nanograms/milliliter (ng/mL); Clarified the definition of improvement in JIA and Tanner Stage; If at least two consecutive TCZ infusions were missed for safety reasons, quantitative immunoglobulin (Ig) and PK/PD assessments (IL-6, TCZ, sIL-6R and anti-TCZ antibodies) were performed pre-dose at the next scheduled visit and pre-dose 2 weeks later; Clarified responsibility of collaborative groups and the guidance for steroid tapering during and after escape therapy; Added the escape option to allow children with more severe disease at Baseline an opportunity to escape and receive active open-label study drug; To allow varicella zoster immunoglobulin upon exposure to chicken pox in children who had not had chicken pox; Clarified safety parameters and thus improved safety monitoring and reporting.

07 Jan 2011

The primary goal of this amendment was to introduce an optional, less frequent, dosing schedule in Part III for patients who had achieved inactive disease while off oral CSs and met specific response criteria. Other changes were made to correct ambiguous or incorrect wording and to improve clarity and included the following: Updated secondary and exploratory endpoints for Part II of the study; Updated the sample size of the study; Changes to add clarity to safety parameters, address safety issues seen with TCZ, and modified risk mitigation rules, particularly related to an infusion related reaction; Protocol additions based on the information which was gathered from the current conduct of the protocol. Clarification of the timing of the interim analyses of efficacy and safety data: at study week 12, when the 50th patient completed the 1 year on TCZ in study Part II, at week 104 (end of study Part II), and at week 260 (end of study Part III).

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part I: Percentage of Participants With ≥30 percent (%) Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever

Primary: Part I: Percentage of Participants With ≥30 percent (%) Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever

Primary: Part II: Percentage of Participants With Decreases in Oral Corticosteroid Dose at Week 104

Primary: Part II: Percentage of Participants With Decreases in Oral Corticosteroid Dose at Week 104

Secondary: Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12

Secondary: Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Erythrocyte Sedimentation Rate

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Erythrocyte Sedimentation Rate

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI)

Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI)

Secondary: Part I: Percentage of Participants With Fever Due to Systemic Juvenile Idiopathic Arthritis (sJIA) at Baseline Who Are Free of Fever at Week 12

Secondary: Part I: Percentage of Participants With Fever Due to Systemic Juvenile Idiopathic Arthritis (sJIA) at Baseline Who Are Free of Fever at Week 12

Secondary: Part I: Percentage of Participants With Changes in Laboratory Indicators: High-sensitivity C-Reactive Protein (hsCRP), Hemoglobin (Hb), Platelets and Leukocytes From Abnormal at Baseline to Normal at Week 12

Secondary: Part I: Percentage of Participants With Changes in Laboratory Indicators: High-sensitivity C-Reactive Protein (hsCRP), Hemoglobin (Hb), Platelets and Leukocytes From Abnormal at Baseline to Normal at Week 12

Secondary: Part I: Percentage of Participants With Concomitant Corticosteroid Reduction

Secondary: Part I: Percentage of Participants With Concomitant Corticosteroid Reduction

Secondary: Part I: Change From Baseline in the Pain Visual Analog Scale (VAS) at Week 12

Secondary: Part I: Change From Baseline in the Pain Visual Analog Scale (VAS) at Week 12

Secondary: Part I: Percentage of Patients With Minimally Important Improvement in CHAQ-DI Score at Week 12

Secondary: Part I: Percentage of Patients With Minimally Important Improvement in CHAQ-DI Score at Week 12

Secondary: Part I: Percentage of Patients With Rash at Baseline Who Are Free From Rash at Week 12

Secondary: Part I: Percentage of Patients With Rash at Baseline Who Are Free From Rash at Week 12

Secondary: Part I: Percentage of Patients With Anemia at Baseline With a ≥10 g/L Increase in Hemoglobin at Week 6 and Week 12

Secondary: Part I: Percentage of Patients With Anemia at Baseline With a ≥10 g/L Increase in Hemoglobin at Week 6 and Week 12

Secondary: Part II: Percentage of Participants With JIA ACR70 and JIA ACR90 Responses Week 104

Secondary: Part II: Percentage of Participants With JIA ACR70 and JIA ACR90 Responses Week 104

Secondary: Part II: Number of Active Joints at Week 104

Secondary: Part II: Number of Active Joints at Week 104

Secondary: Part II: Percentage of Participants With no Active Joints at Week 104

Secondary: Part II: Percentage of Participants With no Active Joints at Week 104

Secondary: Part II: Percentage of Participants With Inactive Disease at Week 104

Secondary: Part II: Percentage of Participants With Inactive Disease at Week 104

Secondary: Part II: Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Week 104

Secondary: Part II: Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Week 104

Secondary: Part II: Percentage of Participants With Oral Corticosteroid Cessation at Week 104

Secondary: Part II: Percentage of Participants With Oral Corticosteroid Cessation at Week 104

Secondary: Part II: Rate of Serious Adverse Events (SAEs), Serious Infection Adverse Events (AEs), Related SAEs, Macrophage Activation Syndrome, AEs Leading to Withdrawal and Deaths Per 100 Patient Years to Week 104

Secondary: Part II: Rate of Serious Adverse Events (SAEs), Serious Infection Adverse Events (AEs), Related SAEs, Macrophage Activation Syndrome, AEs Leading to Withdrawal and Deaths Per 100 Patient Years to Week 104

Secondary: Part III: Percentage of Participants with at least 30%, 50%, 70%, and 90% improvement in JIA core set according to ACR

Secondary: Part III: Percentage of Participants with at least 30%, 50%, 70%, and 90% improvement in JIA core set according to ACR

Secondary: Part III: Percentage of participants who mainitain JIA ACR30, JIA ACR50, JIA ACR70, JIA ACR90 response for 6 months Previous to the specified Week

Secondary: Part III: Percentage of participants who mainitain JIA ACR30, JIA ACR50, JIA ACR70, JIA ACR90 response for 6 months Previous to the specified Week

Secondary: Part III: Doses of Oral Corticosteroids (CS)

Secondary: Part III: Doses of Oral Corticosteroids (CS)

Secondary: Part III: Percentage of Participants on Corticosteroids at Baseline Able to Discontinue Corticosteroids by Weeks 104,116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260

Secondary: Part III: Percentage of Participants on Corticosteroids at Baseline Able to Discontinue Corticosteroids by Weeks 104,116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260

Secondary: Part III: Percentage of Participants with a ≥20/50/75/90% Decrease from Baseline in Oral Corticosteroid Dose at Visits

Secondary: Part III: Percentage of Participants with a ≥20/50/75/90% Decrease from Baseline in Oral Corticosteroid Dose at Visits

Secondary: Part III: Percentage of Participants with Inactive Disease

Secondary: Part III: Percentage of Participants with Inactive Disease

Secondary: Part III: Percentage of Participants in Clinical Remission

Secondary: Part III: Percentage of Participants in Clinical Remission

Secondary: Part III: Percentage of Participants on CSs at Baseline in Clinical Remission off all Oral CSs for 6 Months Prior to Specific Weeks

Secondary: Part III: Percentage of Participants on CSs at Baseline in Clinical Remission off all Oral CSs for 6 Months Prior to Specific Weeks

Secondary: Part III: Percentage of Participants on Methotrexate (MTX) at Baseline in Clinical Remission off Corticosteroids and MTX for 6 Months Prior to Specified Weeks

Secondary: Part III: Percentage of Participants on Methotrexate (MTX) at Baseline in Clinical Remission off Corticosteroids and MTX for 6 Months Prior to Specified Weeks

Secondary: Part III: Percentage of Participants in Clinical Remission off all Arthritis Medications except TCZ for 6 months Prior to Specified Weeks

Secondary: Part III: Percentage of Participants in Clinical Remission off all Arthritis Medications except TCZ for 6 months Prior to Specified Weeks

Secondary: Part III: Percentage of Participants Who Develop Anti-TCZ Antibodies

Secondary: Part III: Percentage of Participants Who Develop Anti-TCZ Antibodies

Secondary: Part III: Percentage of Participants who Develop Anti-TCZ Antibodies Associated With Drug Hypersensitivity Reactions

Secondary: Part III: Percentage of Participants who Develop Anti-TCZ Antibodies Associated With Drug Hypersensitivity Reactions

Adverse events