A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00642460
• Collaborator: (none)
• Enrollment: 112
• Locations: 54
• Arms: 2
• Duration (Months): 75
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with active systemic juvenile idiopathic arthritis (sJIA) who have an inadequate clinical response to NSAIDs and corticosteroids. In Part I of the study patients will be randomized 2:1 to receive iv infusions of RoActemra/Actemra (8mg/kg iv for patients >=30kg, or 12mg/kg for patients <30kg) or placebo, every 2 weeks. Stable NSAIDs and methotrexate will be continued throughout. After 12 weeks of double-blind treatment, all patients will have the option to enter Part II of the study to receive open-label treatment with RoActemra/Actemra for a further 92 weeks, followed by a 3-year continuation of the study in Part III in which, for patients who meet specific criteria, an optional alternative dosing schedule decreasing the study drug administration frequency will be introduced. Anticipated time on study treatment is up to 5 years.

Condition or Disease	Intervention/Treatment	Phase
Juvenile Idiopathic Arthritis	Drug: tocilizumab [RoActemra/Actemra]; Drug: Placebo; Drug: Non-steroidal anti-inflammatory drugs (NSAIDs); Drug: methotrexate; Drug: corticosteroids	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-controlled Study to Evaluate the Effect of Tocilizumab on Disease Response in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA), With an Open-label Extension to Examine the Long Term Use of Tocilizumab
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: tocilizumab [RoActemra/Actemra]; 8mg/kg (patients>=30kg) or 12mg/kg (patients <30kg) iv every 2 weeks. In Part III, administration frequency may be reduced to every 3 and every 4 weeks, respectively, according to an optional alternative dosing schedule.; Drug: Non-steroidal anti-inflammatory drugs (NSAIDs); as prescribed; Drug: methotrexate; as prescribed; Drug: corticosteroids; orally, as prescribed
Placebo Comparator: 2	Drug: Placebo; iv every 2 weeks for 12 weeks; Drug: Non-steroidal anti-inflammatory drugs (NSAIDs); as prescribed; Drug: methotrexate; as prescribed; Drug: corticosteroids; orally, as prescribed

Outcome Measures

Primary Outcome Measures

1. Part I: Percentage of Participants With ≥30% Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever [Baseline, Week 12]

   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° Celsius in the preceding seven days.

2. Part II: Percentage of Participants With Decreases in Oral Corticosteroid Dose at Week 104 [Baseline, Week 104]

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

Secondary Outcome Measures

1. Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12 [Baseline, Week 12]

   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%.

2. Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity [Baseline, Week 12]

   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.

3. Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being [Baseline, Week 12]

   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.

4. Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis [Baseline, Week 12]

   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.

5. Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement [Baseline, Week 12]

   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'.

6. Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Erythrocyte Sedimentation Rate [Baseline, Week 12]

   Erythrocyte Sedimentation Rate (ESR) is an acute phase reactant measured in mm/hour.

7. Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI) [Baseline, Week 12]

   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).

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

   Fever free was defined as no diary temperature recording ≥37.5° Celsius in the preceding fourteen days.

9. 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 [Baseline, Week 12]

   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.

10. Part I: Percentage of Participants With Concomitant Corticosteroid Reduction [Week 6 or Week 8, Week 12]

    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%.

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

    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.

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

    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).

13. Part I: Percentage of Patients With Rash at Baseline Who Are Free From Rash at Week 12 [Baseline, Week 12]

    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.

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

    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.

15. Part II: Percentage of Participants With JIA ACR70 and JIA ACR90 Responses Week 104 [Baseline, Week 104]

    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%.

16. Part II: Number of Active Joints at Week 104 [Week 104]

    Seventy-one joints were assessed for signs of active arthritis. The mean number of joints with signs of active arthritis is reported.

17. Part II: Percentage of Participants With no Active Joints at Week 104 [Week 104]

    Seventy-one joints were assessed for signs of active arthritis. The percentage of participants with no signs of active arthritis is reported.

18. Part II: Percentage of Participants With Inactive Disease at Week 104 [Week 104]

    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).

19. Part II: Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Week 104 [Baseline, Week 104]

    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).

20. Part II: Percentage of Participants With Oral Corticosteroid Cessation at Week 104 [Baseline, Week 104]

    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.

21. 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 [104 Weeks]

    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.

22. Part III: Percentage of Participants With at Least 30%, 50%, 70%, and 90% Improvement in JIA Core Set According to ACR [Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260]

    Percentage of participants with ≥30%, 50%, 70%, and 90% improvement in ACR core set consisting of 6 components: 1) Physician's global assessment of disease activity 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) CHAQ-DI consisting of 30 questions in 8 domains.

23. Part III: Percentage of Participants Who Maintain JIA ACR30, JIA ACR50, JIA ACR70, JIA ACR90 Response for 6 Months Previous to the Specified Week [Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260]

    JIA ACR core set consisting of 6 components: 1) Physician's global assessment of disease activity 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) CHAQ-DI consisting of 30 questions in 8 domains.

24. Part III: Doses of Oral Corticosteroids [Baseline and Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260]

    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 the visit of withdrawal and all subsequent visits.

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

    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.

26. Part III: Percentage of Participants With a >=20/50/75/90% Decrease From Baseline in Oral Corticosteroid Dose at Visits [Every 2 weeks from Week 104 to Week 260]

    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.

27. Part III: Percentage of Participants With Inactive Disease [Weeks 104, 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260]

    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 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.

28. Part III: Percentage of Participants in Clinical Remission [Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260]

    Patients who previously withdrew are excluded Responders are patients who met all of the following criteria for inactive disease at all visits in the 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. vi. 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.

29. Part III: Percentage of Participants on Corticosteroids at Baseline in Clinical Remission Off All Oral Corticosteroids for 6 Months Prior to Specified Visits [Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260]

    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

30. Part III: Percentage of Participants on Methotrexate At Baseline in Clinical Remission Off Corticosteroids and Methotrexate for 6 Months Prior to Specified Visits [Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260]

    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

31. Part III: Percentage of Participants in Clinical Remission Off All Arthritis Medications Except Tocilizumab for 6 Months Prior to Specified Visits [Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260]

    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

32. Part III: Percentage of Participants Who Developed Antibodies To Tocilizumab During Weeks 104 to 260 [Every 2 weeks from Week 104 to 260]

    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.

33. Part III: Percentage of Participants Who Developed Anti-TCZ Antibodies Associated With The Occurrence of Drug Hypersensitivity Reactions. [Every 2 weeks from Week 104 to 260]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients aged 2-17 years of age

• Systemic juvenile idiopathic arthritis with >= 6 months persistent activity

• Presence of active disease (>=5 active joints, or >=2 active joints + fever + steroids)

• Inadequate clinical response to nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids due to toxicity or lack of efficacy

Exclusion Criteria:

• Wheelchair-bound or bed-ridden

• Any other autoimmune, rheumatic disease or overlap syndrome other than systemic juvenile idiopathic arthritis

• Intravenous long-acting corticosteroids or intra-articular corticosteroids within 4 weeks of baseline, or throughout study

• Disease-modifying antirheumatic drugs (DMARDs), other than methotrexate

• Previous treatment with tocilizumab

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Little Rock	Arkansas	United States	45229-3039
2		Los Angeles	California	United States	90027
3		Hartford	Connecticut	United States	06106
4		Augusta	Georgia	United States	30912
5		Chicago	Illinois	United States
6		Louisville	Kentucky	United States	40202-3906
7		Hackensack	New Jersey	United States	07601
8		Livingston	New Jersey	United States	07039
9		Durham	North Carolina	United States	27710
10		Cincinnati	Ohio	United States	45229
11		Cleveland	Ohio	United States	44195
12		Oklahoma City	Oklahoma	United States	73104
13		Houston	Texas	United States	77030
14		Buenos Aires		Argentina	1270
15		Buenos Aires		Argentina	1425
16		La Plata		Argentina	1900
17		Parkville		Australia	3052
18		Subiaco		Australia	6008
19		Westmead		Australia	2145
20		Gent		Belgium	9000
21		Leuven		Belgium	3000
22		Porto Alegre		Brazil	90035-903
23		Rio de Janeiro		Brazil	20551-030
24		Sao Paulo		Brazil	05403-900
25		Vancouver	British Columbia	Canada	V6H 3V4
26		Halifax	Nova Scotia	Canada	B3J 3G9
27		Ottawa	Ontario	Canada	K1H 8L1
28		Toronto	Ontario	Canada	M5G 1X8
29		Praha		Czech Republic	121-09
30		Copenhagen		Denmark	2100
31		Berlin		Germany	13353
32		Bremen		Germany	28205
33		Sankt Augustin		Germany	53757
34		Athens		Greece	11527
35		Heraklion		Greece	71110
36		Ioannina		Greece	45500
37		Genova		Italy	16147
38		Milano		Italy	20122
39		Padova		Italy	35128
40		Roma		Italy	00165
41		Mexico		Mexico	06720
42		Miexico City		Mexico	06700
43		Utrecht		Netherlands	3584 AE
44		Oslo		Norway	0027
45		Kraków		Poland	31-503
46		Lublin		Poland	20-093
47		Piestany		Slovakia	921 01
48		Barcelona		Spain	08035
49		Esplugas de Llobregat		Spain	08950
50		Madrid		Spain	28046
51		Valencia		Spain	46026
52		Goeteborg		Sweden	41685
53		Liverpool		United Kingdom	L12 2AP
54		London		United Kingdom	WC1N IEH

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00642460
• Other Study ID Numbers: WA18221; 2007-000872-18
• First Posted: Mar 25, 2008
• Last Update Posted: Jul 25, 2016
• Last Verified: Jun 1, 2016

• Additional relevant MeSH terms: Arthritis; Arthritis, Juvenile; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Methotrexate

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Tocilizumab_8 mg/kg	Tocilizumab_12 mg/kg	Placebo	Tocilizumab Switchers	Participants ≥30 kg	Participants <30 kg
Arm/Group Description	Tocilizumab 8 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 non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate and corticosteroids if applicable.	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.	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.	Tocilizumab Switchers includes all participants who changed their dose either Tocilizumab 8 mg/kg or 12 mg/kg intravenous (iv) every 2 weeks in Part II. Participants remained on their prescribed standard of care treatment with non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate and corticosteroids if applicable.	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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.	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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
Period Title: Part I: 12 Week Double-Blind
STARTED	37	38	37	0	0	0
Part I : Intent-to-treat	37	38	37	0	0	0
COMPLETED	36	37	36	0	0	0
NOT COMPLETED	1	1	1	0	0	0
Period Title: Part I: 12 Week Double-Blind
STARTED	52	40	0	20	0	0
Part II: Intent-to-treat	52	40	0	20	0	0
COMPLETED	43	32	0	17	0	0
NOT COMPLETED	9	8	0	3	0	0
Period Title: Part I: 12 Week Double-Blind
STARTED	0	0	0	0	53	59
COMPLETED	0	0	0	0	28	38
NOT COMPLETED	0	0	0	0	25	21

Baseline Characteristics

Arm/Group Title	Tocilizumab	Placebo	Total
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part 1. Participants remained on their prescribed standard of care treatment with non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate and corticosteroids if applicable.	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.	Total of all reporting groups
Overall Participants	75	37	112
Age, Customized (years) [Number]
2 to 5	16	11	27
6 to 12	33	15	48
13 to 17	26	11	37
Sex: Female, Male (Count of Participants)
Female	39 52%	17 45.9%	56 50%
Male	36 48%	20 54.1%	56 50%

Outcome Measures

1. Primary Outcome

Title	Part I: Percentage of Participants With ≥30% Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever
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° Celsius in the preceding seven days.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population includes all participants who had at least one dose of study drug.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	75	37
Number [Percentage of participants]	85.3 113.7%	24.3 65.7%

2. Primary Outcome

Title	Part II: Percentage of Participants With Decreases in Oral Corticosteroid Dose at Week 104
Description	Percentage of participants with ≥20 percent, ≥50 percent, ≥75 percent and ≥90 percent decreases in oral corticosteroid dose (mg/kg/day) from baseline.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description

Includes only participants on oral corticosteroids at baseline.

Arm/Group Title	Tocilizumab
Arm/Group Description	Tocilizumab 8 mg/kg (for patients >=30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.
Measure Participants	55
≥20 percent decrease	76 101.3%
≥50 percent decrease	73 97.3%
≥75 percent decrease	62 82.7%
≥90 percent decrease	47 62.7%

3. Secondary Outcome

Title	Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12
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%.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population includes all randomized participants who received at least one dose of study drug.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	75	37
JIA ACR30 response	90.7 120.9%	24.3 65.7%
JIA ACR50 response	85.3 113.7%	10.8 29.2%
JIA ACR70 response	70.7 94.3%	8.1 21.9%
JIA ACR90 response	37.3 49.7%	5.4 14.6%

4. Secondary Outcome

Title	Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity
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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population. Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined are excluded. Last observation carried forward (LOCF) rule applied to missing JIA ACR core set components at Week 12.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	73	17
Number [Percentage change]	-69.6	-41.1

5. Secondary Outcome

Title	Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being
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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population. 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.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	73	17
Number [Percentage change]	-65.8	-1.4

6. Secondary Outcome

Title	Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis
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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population. 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.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	73	17
Number [Percentage change]	-70.6	-37.2

7. Secondary Outcome

Title	Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement
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'.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population. 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.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	72	17
Number [Percentage change]	-51.6	-22.5

8. Secondary Outcome

Title	Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Erythrocyte Sedimentation Rate
Description	Erythrocyte Sedimentation Rate (ESR) is an acute phase reactant measured in mm/hour.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population. 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.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	73	17
Number [Percentage change]	-88.2	33.6

9. Secondary Outcome

Title	Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI)
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).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population. 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.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	72	17
Number [Percentage change]	-45.6	-10.3

10. Secondary Outcome

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
Description	Fever free was defined as no diary temperature recording ≥37.5° Celsius in the preceding fourteen days.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	41	24
Number [Percentage of participants]	85.4 113.9%	20.8 56.2%

11. Secondary Outcome

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
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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population includes all randomized participants who received 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.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	75	37
hsC-Reactive Protein (n=72,34)	98.6 131.5%	5.9 15.9%
Hemoglobin (n=50,29)	80.0 106.7%	6.9 18.6%
Platelets (n=52,26)	90.4 120.5%	3.8 10.3%
Leukocytes (n=28,21)	75.0 100%	9.5 25.7%

12. Secondary Outcome

Title	Part I: Percentage of Participants With Concomitant Corticosteroid Reduction
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%.
Time Frame	Week 6 or Week 8, Week 12

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) who were taking oral corticosteroids.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	70	31
Number [Percentage of participants]	24.3 32.4%	3.2 8.6%

13. Secondary Outcome

Title	Part I: Change From Baseline in the Pain Visual Analog Scale (VAS) at Week 12
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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	73	17
Number [mm]	-41.0	-1.1

14. Secondary Outcome

Title	Part I: Percentage of Patients With Minimally Important Improvement in CHAQ-DI Score at Week 12
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).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-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.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	75	37
Number [Percentage of participants]	77.3 103.1%	18.9 51.1%

15. Secondary Outcome

Title	Part I: Percentage of Patients With Rash at Baseline Who Are Free From Rash at Week 12
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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	22	18
Number [Percentage of participants]	63.6 84.8%	11.1 30%

16. Secondary Outcome

Title	Part I: Percentage of Patients With Anemia at Baseline With a ≥10 g/L Increase in Hemoglobin at Week 6 and Week 12
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.
Time Frame	Baseline, Week 6 and Week 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab	Placebo
Arm/Group Description	Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) intravenous (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.	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.
Measure Participants	50	29
Week 6	88.0 117.3%	3.4 9.2%
Week 12	88.0 117.3%	3.4 9.2%

17. Secondary Outcome

Title	Part II: Percentage of Participants With JIA ACR70 and JIA ACR90 Responses Week 104
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%.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	Tocilizumab 8 mg/kg (for patients >=30 kg) or 12 mg/kg (for patients <30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part 1 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.
Measure Participants	75
JIA ACR70 response	76.0 101.3%
JIA ACR90 response	61.3 81.7%

18. Secondary Outcome

Title	Part II: Number of Active Joints at Week 104
Description	Seventy-one joints were assessed for signs of active arthritis. The mean number of joints with signs of active arthritis is reported.
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description

Participants from the Intent to Treat population who reached this time point. No data imputation is applied and patients with missing data are excluded.

Arm/Group Title	Tocilizumab
Arm/Group Description	Tocilizumab 8 mg/kg (for patients >=30 kg) or 12 mg/kg (for patients <30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part 1 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.
Measure Participants	59
Mean (Standard Deviation) [Active Joints]	1.9 (3.6)

19. Secondary Outcome

Title	Part II: Percentage of Participants With no Active Joints at Week 104
Description	Seventy-one joints were assessed for signs of active arthritis. The percentage of participants with no signs of active arthritis is reported.
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	Tocilizumab 8 mg/kg (for patients >=30 kg) or 12 mg/kg (for patients <30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part 1 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.
Measure Participants	76
Number [Percentage of Participants]	47.4 63.2%

20. Secondary Outcome

Title	Part II: Percentage of Participants With Inactive Disease at Week 104
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).
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	Tocilizumab 8 mg/kg (for patients >=30 kg) or 12 mg/kg (for patients <30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part 1 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.
Measure Participants	75
Number [Percentage of Participants]	26.7 35.6%

21. Secondary Outcome

Title	Part II: Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Week 104
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).
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description

Participants from the Intent to Treat population who withdrew have been excluded at post withdrawal visits.

Arm/Group Title	Tocilizumab
Arm/Group Description	Tocilizumab 8 mg/kg (for patients >=30 kg) or 12 mg/kg (for patients <30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part 1 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.
Measure Participants	112
Baseline (n=112)	1.68 (0.86)
Week 104 (n=57)	0.55 (0.71)

22. Secondary Outcome

Title	Part II: Percentage of Participants With Oral Corticosteroid Cessation at Week 104
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.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description

Participants from the Intent to Treat population who withdrew have been excluded at post withdrawal visits.

Arm/Group Title	Tocilizumab
Arm/Group Description	Tocilizumab 8 mg/kg (for patients >=30 kg) or 12 mg/kg (for patients <30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part 1 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.
Measure Participants	42
Number [Percentage of Participants]	60 80%

23. Secondary Outcome

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
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.
Time Frame	104 Weeks

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	Tocilizumab
Arm/Group Description	Tocilizumab 8 mg/kg (for patients >=30 kg) or 12 mg/kg (for patients <30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part 1 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.
Measure Participants	112
SAEs	23.3
Serious infection AEs	10.9
SAEs related to TCZ	7.4
Macrophage activation syndrome	1.5
AEs leading to withdrawal	3.0
Deaths	1.5

24. Secondary Outcome

Title	Part III: Percentage of Participants With at Least 30%, 50%, 70%, and 90% Improvement in JIA Core Set According to ACR
Description	Percentage of participants with ≥30%, 50%, 70%, and 90% improvement in ACR core set consisting of 6 components: 1) Physician's global assessment of disease activity 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) CHAQ-DI consisting of 30 questions in 8 domains.
Time Frame	Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Participants ≥30 kg	Participants <30 kg
Arm/Group 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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.	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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
Measure Participants	42	47
Week 104 JIA ACR30 (n=42,47)	100.0 133.3%	100.0 270.3%
Week 104 JIA ACR50 (n=42,47)	100.0 133.3%	100.0 270.3%
Week 104 JIA ACR70 (n=42,47)	92.9 123.9%	95.7 258.6%
Week 104 JIA ACR90 (n=42,47)	81.0 108%	72.3 195.4%
Week 116 JIA ACR30 (n=41,45)	100.0 133.3%	100.0 270.3%
Week 116 JIA ACR50 (n=41,45)	100.0 133.3%	97.8 264.3%
Week 116 JIA ACR70 (n=41,45)	95.1 126.8%	97.8 264.3%
Week 116 JIA ACR90 (n=41,45)	82.9 110.5%	80.0 216.2%
Week 128 JIA ACR30 (n=39,41)	100.0 133.3%	100.0 270.3%
Week 128 JIA ACR50 (n=39,41)	100.0 133.3%	100.0 270.3%
Week 128 JIA ACR70 (n=39,41)	97.4 129.9%	97.6 263.8%
Week 128 JIA ACR90 (n=39,41)	79.5 106%	82.9 224.1%
Week 140 JIA ACR30 (n=34,37)	100.0 133.3%	100.0 270.3%
Week 140 JIA ACR50 (n=34,37)	100.0 133.3%	100.0 270.3%
Week 140 JIA ACR70 (n=34,37)	100.0 133.3%	94.6 255.7%
Week 140 JIA ACR90 (n=34,37)	73.5 98%	75.7 204.6%
Week 152 JIA ACR30 (n=27,28)	100.0 133.3%	100.0 270.3%
Week 152 JIA ACR50 (n=27,28)	100.0 133.3%	100.0 270.3%
Week 152 JIA ACR70 (n=27,28)	100.0 133.3%	96.4 260.5%
Week 152 JIA ACR90 (n=27,28)	66.7 88.9%	78.6 212.4%
Week 164 JIA ACR30 (n=27,24)	100.0 133.3%	100.0 270.3%
Week 164 JIA ACR50 (n=27,24)	100.0 133.3%	100.0 270.3%
Week 164 JIA ACR70 (n=27,24)	92.6 123.5%	95.8 258.9%
Week 164 JIA ACR90 (n=27,24)	66.7 88.9%	75.0 202.7%
Week 176 JIA ACR30 (n=22,22)	100.0 133.3%	100.0 270.3%
Week 176 JIA ACR50 (n=22,22)	100.0 133.3%	100.0 270.3%
Week 176 JIA ACR70 (n=22,22)	100.0 133.3%	95.5 258.1%
Week 176 JIA ACR90 (n=22,22)	63.6 84.8%	63.6 171.9%
Week 188 JIA ACR30 (n=20,22)	100.0 133.3%	100.0 270.3%
Week 188 JIA ACR50 (n=20,22)	100.0 133.3%	100.0 270.3%
Week 188 JIA ACR70 (n=20,22)	95.0 126.7%	95.5 258.1%
Week 188 JIA ACR90 (n=20,22)	45.0 60%	72.7 196.5%
Week 200 JIA ACR30 (n=19,19)	100.0 133.3%	100.0 270.3%
Week 200 JIA ACR50 (n=19,19)	100.0 133.3%	94.7 255.9%
Week 200 JIA ACR70 (n=19,19)	94.7 126.3%	89.5 241.9%
Week 200 JIA ACR90 (n=19,19)	63.2 84.3%	78.9 213.2%
Week 212 JIA ACR30 (n=18,18)	100.0 133.3%	100.0 270.3%
Week 212 JIA ACR50 (n=18,18)	100.0 133.3%	94.4 255.1%
Week 212 JIA ACR70 (n=18,18)	100.0 133.3%	94.4 255.1%
Week 212 JIA ACR90 (n=18,18)	72.2 96.3%	77.8 210.3%
Week 224 JIA ACR30 (n=17,18)	100.0 133.3%	100.0 270.3%
Week 224 JIA ACR50 (n=17,18)	100.0 133.3%	88.9 240.3%
Week 224 JIA ACR70 (n=17,18)	100.0 133.3%	88.9 240.3%
Week 224 JIA ACR90 (n=17,18)	64.7 86.3%	83.3 225.1%
Week 236 JIA ACR30 (n=16,17)	100.0 133.3%	100.0 270.3%
Week 236 JIA ACR50 (n=16,17)	100.0 133.3%	100.0 270.3%
Week 236 JIA ACR70 (n=16,17)	93.8 125.1%	100.0 270.3%
Week 236 JIA ACR90 (n=16,17)	68.8 91.7%	88.2 238.4%
Week 248 JIA ACR30 (n=15,17)	100.0 133.3%	100.0 270.3%
Week 248 JIA ACR50 (n=15,17)	100.0 133.3%	100.0 270.3%
Week 248 JIA ACR70 (n=15,17)	86.7 115.6%	94.1 254.3%
Week 248 JIA ACR90 (n=15,17)	73.3 97.7%	70.6 190.8%
Week 260 JIA ACR30 (n=15,15)	100.0 133.3%	93.3 252.2%
Week 260 JIA ACR50 (n=15,15)	93.3 124.4%	93.3 252.2%
Week 260 JIA ACR70 (n=15,15)	86.7 115.6%	93.3 252.2%
Week 260 JIA ACR90 (n=15,15)	60.0 80%	66.7 180.3%

25. Secondary Outcome

Title	Part III: Percentage of Participants Who Maintain JIA ACR30, JIA ACR50, JIA ACR70, JIA ACR90 Response for 6 Months Previous to the Specified Week
Description	JIA ACR core set consisting of 6 components: 1) Physician's global assessment of disease activity 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) CHAQ-DI consisting of 30 questions in 8 domains.
Time Frame	Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260

Outcome Measure Data

Analysis Population Description

The Part III ITT3 population

Arm/Group Title	All Participants Treated With Tocilizumab
Arm/Group 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.
Measure Participants	89
Week 104 JIA ACR 30 (n=89)	NA NaN
Week 104 JIA ACR 50 (n=89)	NA NaN
Week 104 JIA ACR 70 (n=89)	NA NaN
Week 104 JIA ACR 90 (n=89)	NA NaN
Week 116 JIA ACR 30 (n=86)	NA NaN
Week 116 JIA ACR 50 (n=86)	NA NaN
Week 116 JIA ACR 70 (n=86)	NA NaN
Week 116 JIA ACR 90 (n=86)	NA NaN
Week 128 JIA ACR 30 (n=80)	100.0 133.3%
Week 128 JIA ACR 50 (n=80)	98.8 131.7%
Week 128 JIA ACR 70 (n=80)	91.3 121.7%
Week 128 JIA ACR 90 (n=80)	68.8 91.7%
Week 140 JIA ACR30 (n=71)	100.0 133.3%
Week 140 JIA ACR50 (n=71)	98.6 131.5%
Week 140 JIA ACR70 (n=71)	93.0 124%
Week 140 JIA ACR90 (n=71)	66.2 88.3%
Week 152 JIA ACR30 (n=55)	100.0 133.3%
Week 152 JIA ACR50 (n=55)	100.0 133.3%
Week 152 JIA ACR70 (n=55)	94.5 126%
Week 152 JIA ACR90 (n=55)	60.0 80%
Week 164 JIA ACR30 (n=51)	100.0 133.3%
Week 164 JIA ACR50 (n=51)	100.0 133.3%
Week 164 JIA ACR70 (n=51)	92.2 122.9%
Week 164 JIA ACR90 (n=51)	56.9 75.9%
Week 176 JIA ACR30 (n=44)	100.0 133.3%
Week 176 JIA ACR50 (n=44)	100.0 133.3%
Week 176 JIA ACR70 (n=44)	88.6 118.1%
Week 176 JIA ACR90 (n=44)	52.3 69.7%
Week 188 JIA ACR30 (n=42)	100.0 133.3%
Week 188 JIA ACR50 (n=42)	100.0 133.3%
Week 188 JIA ACR70 (n=42)	88.1 117.5%
Week 188 JIA ACR90 (n=42)	50.0 66.7%
Week 200 JIA ACR30 (n=38)	100.0 133.3%
Week 200 JIA ACR50 (n=38)	97.4 129.9%
Week 200 JIA ACR70 (n=38)	86.8 115.7%
Week 200 JIA ACR90 (n=38)	52.6 70.1%
Week 212 JIA ACR30 (n=36)	100.0 133.3%
Week 212 JIA ACR50 (n=36)	97.2 129.6%
Week 212 JIA ACR70 (n=36)	88.9 118.5%
Week 212 JIA ACR90 (n=36)	55.6 74.1%
Week 224 JIA ACR30 (n=35)	100.0 133.3%
Week 224 JIA ACR50 (n=35)	94.3 125.7%
Week 224 JIA ACR70 (n=35)	91.4 121.9%
Week 224 JIA ACR90 (n=35)	68.6 91.5%
Week 236 JIA ACR30 (n=33)	100.0 133.3%
Week 236 JIA ACR50 (n=33)	93.9 125.2%
Week 236 JIA ACR70 (n=33)	90.9 121.2%
Week 236 JIA ACR90 (n=33)	72.7 96.9%
Week 248 JIA ACR30 (n=32)	100.0 133.3%
Week 248 JIA ACR50 (n=32)	93.8 125.1%
Week 248 JIA ACR70 (n=32)	87.5 116.7%
Week 248 JIA ACR90 (n=32)	65.6 87.5%
Week 260 JIA ACR30 (n=30)	96.7 128.9%
Week 260 JIA ACR50 (n=30)	93.3 124.4%
Week 260 JIA ACR70 (n=30)	80.0 106.7%
Week 260 JIA ACR90 (n=30)	56.7 75.6%

26. Secondary Outcome

Title	Part III: Doses of Oral Corticosteroids
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 the visit of withdrawal and all subsequent visits.
Time Frame	Baseline and Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260

Outcome Measure Data

Analysis Population Description

ITT3 population; n=number of participants contributing to the specific statistic

Arm/Group Title	Participants ≥30 kg	Participants <30 kg
Arm/Group 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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.	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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
Measure Participants	53	59
Baseline (n=53,59)	0.203 (0.1572)	0.356 (0.1397)
Week 104 (n=45,48)	0.020 (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)	0.060 (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)	0.020 (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)	0.020 (0.0290)	0.076 (0.1429)
Week 260 (n=16,18)	0.019 (0.0282)	0.079 (0.1486)

27. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT3 population; n=number of participants contributing to the specific statistic

Arm/Group Title	Participants ≥30 kg	Participants <30 kg
Arm/Group 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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.	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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
Measure Participants	38	46
Week 104 (n=38,46)	66.0 88%	67.0 181.1%
Week 116 (n=36,44)	67.0 89.3%	68.0 183.8%
Week 128 (n=35,40)	69.0 92%	70.0 189.2%
Week 140 (n=31,36)	68 90.7%	67 181.1%
Week 152 (n=25,30)	64.0 85.3%	57.0 154.1%
Week 164 (n=25,24)	68.0 90.7%	58.0 156.8%
Week 176 (n=22,22)	68.0 90.7%	64.0 173%
Week 188 (n=18,21)	61.0 81.3%	57.0 154.1%
Week 200 (n=17,20)	59.0 78.7%	60.0 162.2%
Week 212 (n=16,19)	56.0 74.7%	63.0 170.3%
Week 224 (n=15,19)	53.0 70.7%	63.0 170.3%
Week 236 (n=14,18)	50.0 66.7%	61.0 164.9%
Week 248 (n=13,18)	46.0 61.3%	61.0 164.9%
Week 260 (n=13,18)	46.0 61.3%	61.0 164.9%

28. Secondary Outcome

Title	Part III: Percentage of Participants With a >=20/50/75/90% Decrease From Baseline in Oral Corticosteroid Dose at Visits
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.
Time Frame	Every 2 weeks from Week 104 to Week 260

Outcome Measure Data

Analysis Population Description

ITT3 population; n=number of participants contributing to the specific statistic

Arm/Group Title	Participants ≥30 kg	Participants <30 kg
Arm/Group 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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.	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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
Measure Participants	38	46
Week 104 >20% decrease (n=38,46)	100.0 133.3%	97.8 264.3%
Week 104 >50% decrease (n=38,46)	94.7 126.3%	91.3 246.8%
Week 104 >75% decrease (n=38,46)	84.2 112.3%	82.6 223.2%
Week 104 >90% decrease (n=38,46)	71.1 94.8%	71.7 193.8%
Week 106 >20% decrease (n=37,46)	100.0 133.3%	97.8 264.3%
Week 106 >50% decrease (n=37,46)	91.9 122.5%	91.3 246.8%
Week 106 >75% decrease (n=37,46)	83.8 111.7%	82.6 223.2%
Week 106 >90% decrease (n=37,46)	70.3 93.7%	71.7 193.8%
Week 108 >20% decrease (n=37,45)	100.0 133.3%	100.0 270.3%
Week 108 >50% decrease (n=37,45)	89.2 118.9%	91.1 246.2%
Week 108 >75% decrease (n=37,45)	81.1 108.1%	84.4 228.1%
Week 108 >90% decrease (n=37,45)	70.3 93.7%	73.3 198.1%
Week 110 >20% decrease (n=36,44)	100.0 133.3%	100.0 270.3%
Week 110 >50% decrease (n=36,44)	88.9 118.5%	93.2 251.9%
Week 110 >75% decrease (n=36,44)	80.6 107.5%	84.1 227.3%
Week 110 >90% decrease (n=36,44)	72.2 96.3%	75.0 202.7%
Week 112 >20% decrease (n=36,44)	100.0 133.3%	100.0 270.3%
Week 112 >50% decrease (n=36,44)	88.9 118.5%	95.5 258.1%
Week 112 >75% decrease (n=36,44)	80.6 107.5%	81.8 221.1%
Week 112 >90% decrease (n=36,44)	72.2 96.3%	75.0 202.7%
Week 114 >20% decrease (n=36,44)	100.0 133.3%	100.0 270.3%
Week 114 >50% decrease (n=36,44)	88.9 118.5%	95.5 258.1%
Week 114 >75% decrease (n=36,44)	80.6 107.5%	79.5 214.9%
Week 114 >90% decrease (n=36,44)	72.2 96.3%	72.7 196.5%
Week 116 >20% decrease (n=35,44)	100.0 133.3%	100.0 270.3%
Week 116 >50% decrease (n=35,44)	91.4 121.9%	93.2 251.9%
Week 116 >75% decrease (n=35,44)	80.0 106.7%	79.5 214.9%
Week 116 >90% decrease (n=35,44)	71.4 95.2%	72.7 196.5%
Week 118 >20% decrease (n=35,43)	100.0 133.3%	100.0 270.3%
Week 118 >50% decrease (n=35,43)	88.6 118.1%	93.0 251.4%
Week 118 >75% decrease (n=35,43)	80.0 106.7%	81.4 220%
Week 118 >90% decrease (n=35,43)	71.4 95.2%	74.4 201.1%
Week 120 >20% decrease (n=35,43)	100.0 133.3%	100.0 270.3%
Week 120 >50% decrease (n=35,43)	88.6 118.1%	93.0 251.4%
Week 120 >75% decrease (n=35,43)	80.0 106.7%	83.7 226.2%
Week 120 >90% decrease (n=35,43)	74.3 99.1%	76.7 207.3%
Week 122 >20% decrease (n=35,43)	97.1 129.5%	100.0 270.3%
Week 122 >50% decrease (n=35,43)	88.6 118.1%	93.0 251.4%
Week 122>75% decrease (n=35,43)	77.1 102.8%	81.4 220%
Week 122 >90% decrease (n=35,43)	74.3 99.1%	74.4 201.1%
Week 124 >20% decrease (n=35,43)	100.0 133.3%	100.0 270.3%
Week 124 >50% decrease (n=35,43)	94.3 125.7%	93.0 251.4%
Week 124 >75% decrease (n=35,43)	80.0 106.7%	83.7 226.2%
Week 124 >90% decrease (n=35,43)	77.1 102.8%	74.4 201.1%
Week 126 >20% decrease (n=35,43)	100.0 133.3%	100.0 270.3%
Week 126 >50% decrease (n=35,43)	94.3 125.7%	90.7 245.1%
Week 126 >75% decrease (n=35,43)	80.0 106.7%	81.4 220%
Week 126 >90% decrease (n=35,43)	77.1 102.8%	74.4 201.1%
Week 128 >20% decrease (n=35,39)	100.0 133.3%	97.4 263.2%
Week 128 >50% decrease (n=35,39)	91.4 121.9%	89.7 242.4%
Week 128 >75% decrease (n=35,39)	80.0 106.7%	82.1 221.9%
Week 128 >90% decrease (n=35,39)	77.1 102.8%	71.8 194.1%
Week 130 >20% decrease (n=35,39)	100.0 133.3%	97.4 263.2%
Week 130 >50% decrease (n=35,39)	91.4 121.9%	89.7 242.4%
Week 130 >75% decrease (n=35,39)	80.0 106.7%	87.2 235.7%
Week 130 >90% decrease (n=35,39)	80.0 106.7%	74.4 201.1%
Week 132 >20% decrease (n=35,39)	100.0 133.3%	97.4 263.2%
Week 132 >50% decrease (n=35,39)	91.4 121.9%	87.2 235.7%
Week 132 >75% decrease (n=35,39)	80.0 106.7%	84.6 228.6%
Week 132 >90% decrease (n=35,39)	80.0 106.7%	71.8 194.1%
Week 134 >20% decrease (n=35,39)	94.3 125.7%	97.4 263.2%
Week 134 >50% decrease (n=35,39)	88.6 118.1%	87.2 235.7%
Week 134 >75% decrease (n=35,39)	77.1 102.8%	84.6 228.6%
Week 134 >90% decrease (n=35,39)	77.1 102.8%	71.8 194.1%
Week 136 >20% decrease (n=34,39)	97.1 129.5%	97.4 263.2%
Week 136 >50% decrease (n=34,39)	91.2 121.6%	89.7 242.4%
Week 136 >75% decrease (n=34,39)	76.5 102%	84.6 228.6%
Week 136 >90% decrease (n=34,39)	76.5 102%	71.8 194.1%
Week 138 >20% decrease (n=34,39)	94.1 125.5%	97.4 263.2%
Week 138 >50% decrease (n=34,39)	88.2 117.6%	89.7 242.4%
Week 138 >75% decrease (n=34,39)	76.5 102%	84.6 228.6%
Week 138 >90% decrease (n=34,39)	76.5 102%	71.8 194.1%
Week 140 >20% decrease (n=29,36)	93.1 124.1%	97.2 262.7%
Week 140 >50% decrease (n=29,36)	86.2 114.9%	88.9 240.3%
Week 140 >75% decrease (n=29,36)	72.4 96.5%	83.3 225.1%
Week 140 >90% decrease (n=29,36)	72.4 96.5%	72.2 195.1%
Week 142 >20% decrease (n=29,36)	93.1 124.1%	97.2 262.7%
Week 142 >50% decrease (n=29,36)	86.2 114.9%	88.9 240.3%
Week 142 >75% decrease (n=29,36)	72.4 96.5%	83.3 225.1%
Week 142 >90% decrease (n=29,36)	69.0 92%	72.2 195.1%
Week 144 >20% decrease (n=28,36)	92.9 123.9%	97.2 262.7%
Week 144 >50% decrease (n=28,36)	89.3 119.1%	88.9 240.3%
Week 144 >75% decrease (n=28,36)	71.4 95.2%	83.3 225.1%
Week 144 >90% decrease (n=28,36)	67.9 90.5%	72.2 195.1%
Week 146 >20% decrease (n=28,36)	96.4 128.5%	97.2 262.7%
Week 146 >50% decrease (n=28,36)	92.9 123.9%	86.1 232.7%
Week 146 >75% decrease (n=28,36)	75.0 100%	80.6 217.8%
Week 146 >90% decrease (n=28,36)	71.4 95.2%	66.7 180.3%
Week 148 >20% decrease (n=27,35)	100.0 133.3%	97.1 262.4%
Week 148 >50% decrease (n=27,35)	96.3 128.4%	85.7 231.6%
Week 148 >75% decrease (n=27,35)	77.8 103.7%	80.0 216.2%
Week 148 >90% decrease (n=27,35)	74.1 98.8%	65.7 177.6%
Week 150 >20% decrease (n=25,35)	100.0 133.3%	97.1 262.4%
Week 150 >50% decrease (n=25,35)	96.0 128%	88.6 239.5%
Week 150 >75% decrease (n=25,35)	76.0 101.3%	80.0 216.2%
Week 150 >90% decrease (n=25,35)	76.0 101.3%	68.6 185.4%
Week 152 >20% decrease (n=25,27)	100.0 133.3%	96.3 260.3%
Week 152 >50% decrease (n=25,27)	96.0 128%	85.2 230.3%
Week 152 >75% decrease (n=25,27)	76.0 101.3%	77.8 210.3%
Week 152 >90% decrease (n=25,27)	76.0 101.3%	63.0 170.3%
Week 154 >20% decrease (n=25,27)	100.0 133.3%	96.3 260.3%
Week 154 >50% decrease (n=25,27)	96.0 128%	88.9 240.3%
Week 154 >75% decrease (n=25,27)	76.0 101.3%	77.8 210.3%
Week 154 >90% decrease (n=25,27)	76.0 101.3%	70.4 190.3%
Week 156 >20% decrease (n=25,27)	100.0 133.3%	96.3 260.3%
Week 156 >50% decrease (n=25,27)	96.0 128%	85.2 230.3%
Week 156 >75% decrease (n=25,27)	76.0 101.3%	77.8 210.3%
Week 156 >90% decrease (n=25,27)	76.0 101.3%	70.4 190.3%
Week 158 >20% decrease (n=25,27)	100.0 133.3%	96.3 260.3%
Week 158 >50% decrease (n=25,27)	96.0 128%	88.9 240.3%
Week 158 >75% decrease (n=25,27)	76.0 101.3%	77.8 210.3%
Week 158 >90% decrease (n=25,27)	76.0 101.3%	70.4 190.3%
Week 160 >20% decrease (n=25,27)	100.0 133.3%	96.3 260.3%
Week 160 >50% decrease (n=25,27)	96.0 128%	85.2 230.3%
Week 160 >75% decrease (n=25,27)	76.0 101.3%	77.8 210.3%
Week 160 >90% decrease (n=25,27)	76.0 101.3%	70.4 190.3%
Week 162 >20% decrease (n=25,27)	100.0 133.3%	96.3 260.3%
Week 162 >50% decrease (n=25,27)	96.0 128%	81.5 220.3%
Week 162 >75% decrease (n=25,27)	76.0 101.3%	77.8 210.3%
Week 162 >90% decrease (n=25,27)	76.0 101.3%	70.4 190.3%
Week 164 >20% decrease (n=24,24)	100.0 133.3%	95.8 258.9%
Week 164 >50% decrease (n=24,24)	95.8 127.7%	83.3 225.1%
Week 164 >75% decrease (n=24,24)	75.0 100%	75.0 202.7%
Week 164 >90% decrease (n=24,24)	75.0 100%	70.8 191.4%
Week 166 >20% decrease (n=24,22)	100.0 133.3%	95.5 258.1%
Week 166 >50% decrease (n=24,22)	95.8 127.7%	81.8 221.1%
Week 166 >75% decrease (n=24,22)	75.0 100%	72.7 196.5%
Week 166 >90% decrease (n=24,22)	75.0 100%	68.2 184.3%
Week 168 >20% decrease (n=24,22)	100.0 133.3%	95.5 258.1%
Week 168 >50% decrease (n=24,22)	95.8 127.7%	81.8 221.1%
Week 168 >75% decrease (n=24,22)	75.0 100%	72.7 196.5%
Week 168 >90% decrease (n=24,22)	75.0 100%	68.2 184.3%
Week 170 >20% decrease (n=22,22)	100.0 133.3%	90.9 245.7%
Week 170 >50% decrease (n=22,22)	95.5 127.3%	81.8 221.1%
Week 170 >75% decrease (n=22,22)	77.3 103.1%	72.7 196.5%
Week 170 >90% decrease (n=22,22)	77.3 103.1%	68.2 184.3%
Week 172 >20% decrease (n=22,22)	100.0 133.3%	90.9 245.7%
Week 172 >50% decrease (n=22,22)	95.5 127.3%	90.9 245.7%
Week 172 >75% decrease (n=22,22)	77.3 103.1%	72.7 196.5%
Week 172 >90% decrease (n=22,22)	77.3 103.1%	68.2 184.3%
Week 174 >20% decrease (n=22,22)	100.0 133.3%	90.9 245.7%
Week 174 >50% decrease (n=22,22)	95.5 127.3%	90.9 245.7%
Week 174 >75% decrease (n=22,22)	77.3 103.1%	72.7 196.5%
Week 174 >90% decrease (n=22,22)	77.3 103.1%	68.2 184.3%
Week 176 >20% decrease (n=19,22)	100.0 133.3%	90.9 245.7%
Week 176 >50% decrease (n=19,22)	94.7 126.3%	90.9 245.7%
Week 176 >75% decrease (n=19,22)	73.7 98.3%	72.7 196.5%
Week 176 >90% decrease (n=19,22)	73.7 98.3%	68.2 184.3%
Week 178 >20% decrease (n=19,22)	100.0 133.3%	90.9 245.7%
Week 178 >50% decrease (n=19,22)	94.7 126.3%	90.9 245.7%
Week 178 >75% decrease (n=19,22)	73.7 98.3%	72.7 196.5%
Week 178 >90% decrease (n=19,22)	73.7 98.3%	68.2 184.3%
Week 180 >20% decrease (n=19,22)	100.0 133.3%	90.9 245.7%
Week 180 >50% decrease (n=19,22)	94.7 126.3%	90.9 245.7%
Week 180 >75% decrease (n=19,22)	73.7 98.3%	68.2 184.3%
Week 180 >90% decrease (n=19,22)	73.7 98.3%	63.6 171.9%
Week 182 >20% decrease (n=18,22)	100.0 133.3%	90.9 245.7%
Week 182 >50% decrease (n=18,22)	94.4 125.9%	90.9 245.7%
Week 182 >75% decrease (n=18,22)	72.2 96.3%	68.2 184.3%
Week 182 >90% decrease (n=18,22)	72.2 96.3%	63.6 171.9%
Week 184 >20% decrease (n=18,22)	100.0 133.3%	90.9 245.7%
Week 184 >50% decrease (n=18,22)	94.4 125.9%	86.4 233.5%
Week 184 >75% decrease (n=18,22)	72.2 96.3%	68.2 184.3%
Week 184 >90% decrease (n=18,22)	72.2 96.3%	63.6 171.9%
Week 186 >20% decrease (n=18,22)	100.0 133.3%	90.0 243.2%
Week 186 >50% decrease (n=18,22)	94.4 125.9%	90.9 245.7%
Week 186 >75% decrease (n=18,22)	72.2 96.3%	68.2 184.3%
Week 186 >90% decrease (n=18,22)	72.2 96.3%	63.6 171.9%
Week 188 >20% decrease (n=18,21)	100.0 133.3%	90.5 244.6%
Week 188 >50% decrease (n=18,21)	94.4 125.9%	90.5 244.6%
Week 188 >75% decrease (n=18,21)	72.2 96.3%	71.4 193%
Week 188 >90% decrease (n=18,21)	72.2 96.3%	61.9 167.3%
Week 190 >20% decrease (n=18,21)	100.0 133.3%	95.2 257.3%
Week 190 >50% decrease (n=18,21)	94.4 125.9%	85.7 231.6%
Week 190 >75% decrease (n=18,21)	72.2 96.3%	66.7 180.3%
Week 190 >90% decrease (n=18,21)	72.2 96.3%	61.9 167.3%
Week 192 >20% decrease (n=18,21)	100.0 133.3%	95.2 257.3%
Week 192 >50% decrease (n=18,21)	94.4 125.9%	81.0 218.9%
Week 192 >75% decrease (n=18,21)	72.2 96.3%	66.7 180.3%
Week 192 >90% decrease (n=18,21)	72.2 96.3%	61.9 167.3%
Week 194 >20% decrease (n=18,20)	100.0 133.3%	95.0 256.8%
Week 194 >50% decrease (n=18,20)	94.4 125.9%	80.0 216.2%
Week 194 >75% decrease (n=18,20)	72.2 96.3%	70.0 189.2%
Week 194 >90% decrease (n=18,20)	72.2 96.3%	65.0 175.7%
Week 196 >20% decrease (n=18,20)	100.0 133.3%	90.0 243.2%
Week 196 >50% decrease (n=18,20)	94.4 125.9%	80.0 216.2%
Week 196 >75% decrease (n=18,20)	72.2 96.3%	70.0 189.2%
Week 196 >90% decrease (n=18,20)	72.2 96.3%	65.0 175.7%
Week 198 >20% decrease (n=18,20)	100.0 133.3%	90.0 243.2%
Week 198 >50% decrease (n=18,20)	94.4 125.9%	80.0 216.2%
Week 198 >75% decrease (n=18,20)	72.2 96.3%	70.0 189.2%
Week 198 >90% decrease (n=18,20)	72.2 96.3%	65.0 175.7%
Week 200 >20% decrease (n=17,20)	100.0 133.3%	90.0 243.2%
Week 200 >50% decrease (n=17,20)	94.1 125.5%	85.0 229.7%
Week 200 >75% decrease (n=17,20)	76.5 102%	75.0 202.7%
Week 200 >90% decrease (n=17,20)	70.6 94.1%	65.0 175.7%
Week 202 >20% decrease (n=17,20)	100.0 133.3%	90.0 243.2%
Week 202 >50% decrease (n=17,20)	94.1 125.5%	85.0 229.7%
Week 202 >75% decrease (n=17,20)	76.5 102%	75.0 202.7%
Week 202 >90% decrease (n=17,20)	70.6 94.1%	65.0 175.7%
Week 204 >20% decrease (n=17,20)	100.0 133.3%	90.0 243.2%
Week 204 >50% decrease (n=17,20)	94.1 125.5%	85.0 229.7%
Week 204 >70% decrease (n=17,20)	76.5 102%	75.0 202.7%
Week 204 >90% decrease (n=17,20)	70.6 94.1%	65.0 175.7%
Week 206 >20% decrease (n=16,20)	100.0 133.3%	85.0 229.7%
Week 206 >50% decrease (n=16,20)	93.8 125.1%	75.0 202.7%
Week 206 >75% decrease (n=16,20)	75.0 100%	75.0 202.7%
Week 206 >90% decrease (n=16,20)	68.8 91.7%	70.0 189.2%
Week 208 >20% decrease (n=16,20)	100.0 133.3%	90.0 243.2%
Week 208 >50% decrease (n=16,20)	93.8 125.1%	80.0 216.2%
Week 208 >75% decrease (n=16,20)	75.0 100%	75.0 202.7%
Week 208 >90% decrease (n=16,20)	68.8 91.7%	70.0 189.2%
Week 210 >20% decrease (n=16,19)	100.0 133.3%	89.5 241.9%
Week 210 >50% decrease (n=16,19)	93.8 125.1%	84.2 227.6%
Week 210 >75% decrease (n=16,19)	81.3 108.4%	78.9 213.2%
Week 210 >90% decrease (n=16,19)	75.0 100%	73.7 199.2%
Week 212 >20% decrease (n=15,19)	100.0 133.3%	89.5 241.9%
Week 212 >50% decrease (n=15,19)	93.3 124.4%	84.2 227.6%
Week 212 >75% decrease (n=15,19)	73.3 97.7%	78.9 213.2%
Week 212 >90% decrease (n=15,19)	73.3 97.7%	73.7 199.2%
Week 214 >20% decrease (n=15,19)	100.0 133.3%	89.5 241.9%
Week 214 >50% decrease (n=15,19)	93.3 124.4%	84.2 227.6%
Week 214 >75% decrease (n=15,19)	73.3 97.7%	78.9 213.2%
Week 214 >90% decrease (n=15,19)	73.3 97.7%	73.7 199.2%
Week 216 >20% decrease (n=15,19)	100.0 133.3%	94.7 255.9%
Week 216 >50% decrease (n=15,19)	93.3 124.4%	84.2 227.6%
Week 216 >75% decrease (n=15,19)	73.3 97.7%	78.9 213.2%
Week 216 >90% decrease (n=15,19)	73.3 97.7%	73.7 199.2%
Week 218 >20% decrease (n=15,19)	100.0 133.3%	89.5 241.9%
Week 218 >50% decrease (n=15,19)	93.3 124.4%	84.2 227.6%
Week 218 >75% decrease (n=15,19)	80.0 106.7%	78.9 213.2%
Week 218 >90% decrease (n=15,19)	73.3 97.7%	73.7 199.2%
Week 220 >20% decrease (n=15,19)	100.0 133.3%	89.5 241.9%
Week 220 >50% decrease (n=15,19)	93.3 124.4%	84.2 227.6%
Week 220 >75% decrease (n=15,19)	80.0 106.7%	78.9 213.2%
Week 220 >90% decrease (n=15,19)	73.3 97.7%	73.7 199.2%
Week 222 >20% decrease (n=15,19)	100.0 133.3%	89.5 241.9%
Week 222 >50% decrease (n=15,19)	93.3 124.4%	84.2 227.6%
Week 222 >75% decrease (n=15,19)	80.0 106.7%	78.9 213.2%
Week 222 >90% decrease (n=15,19)	73.3 97.7%	73.7 199.2%
Week 224 >20% decrease (n=15,19)	100.0 133.3%	89.5 241.9%
Week 224 >50% decrease (n=15,19)	93.3 124.4%	84.2 227.6%
Week 224 >75% decrease (n=15,19)	80.0 106.7%	78.9 213.2%
Week 224 >90% decrease (n=15,19)	73.3 97.7%	73.7 199.2%
Week 226 >20% decrease (n=14,19)	100.0 133.3%	89.5 241.9%
Week 226 >50% decrease (n=14,19)	92.9 123.9%	84.2 227.6%
Week 226 >75% decrease (n=14,19)	78.6 104.8%	78.9 213.2%
Week 226 >90% decrease (n=14,19)	71.4 95.2%	73.7 199.2%
Week 228 >20% decrease (n=14,19)	100.0 133.3%	89.5 241.9%
Week 228 >50% decrease (n=14,19)	92.9 123.9%	89.5 241.9%
Week 228 >75% decrease (n=14,19)	78.6 104.8%	78.9 213.2%
Week 228 >90% decrease (n=14,19)	71.4 95.2%	73.7 199.2%
Week 230 >20% decrease (n=14,19)	100.0 133.3%	89.5 241.9%
Week 230 >50% decrease (n=14,19)	92.9 123.9%	89.5 241.9%
Week 230 >75% decrease (n=14,19)	78.6 104.8%	78.9 213.2%
Week 230 >90% decrease (n=14,19)	71.4 95.2%	73.7 199.2%
Week 232 >20% decrease (n=14,18)	100.0 133.3%	88.9 240.3%
Week 232 >50% decrease (n=14,18)	92.9 123.9%	88.9 240.3%
Week 232 >75% decrease (n=14,18)	78.6 104.8%	77.8 210.3%
Week 232 >90% decrease (n=14,18)	71.4 95.2%	72.2 195.1%
Week 234 >20% decrease (n=14,18)	100.0 133.3%	88.9 240.3%
Week 234 >50% decrease (n=14,18)	92.9 123.9%	88.9 240.3%
Week 234 >75% decrease (n=14,18)	78.6 104.8%	77.8 210.3%
Week 234 >90% decrease (n=14,18)	71.4 95.2%	72.2 195.1%
Week 236 >20% decrease (n=14,18)	100.0 133.3%	94.4 255.1%
Week 236 >50% decrease (n=14,18)	92.9 123.9%	88.9 240.3%
Week 236 >75% decrease (n=14,18)	78.6 104.8%	77.8 210.3%
Week 236 >90% decrease (n=14,18)	71.4 95.2%	72.2 195.1%
Week 238 >20% decrease (n=14,18)	100.0 133.3%	94.4 255.1%
Week 238 >50% decrease (n=14,18)	92.9 123.9%	88.9 240.3%
Week 238 >75% decrease (n=14,18)	78.6 104.8%	77.8 210.3%
Week 238 >90% decrease (n=14,18)	71.4 95.2%	72.2 195.1%
Week 240 >20% decrease (n=13,18)	100.0 133.3%	94.4 255.1%
Week 240 >50% decrease (n=13,18)	92.3 123.1%	88.9 240.3%
Week 240 >75% decrease (n=13,18)	76.9 102.5%	77.8 210.3%
Week 240 >90% decrease (n=13,18)	69.2 92.3%	72.2 195.1%
Week 242 >20% decrease (n=13,18)	100.0 133.3%	94.4 255.1%
Week 242 >50% decrease (n=13,18)	92.3 123.1%	88.9 240.3%
Week 242 >75% decrease (n=13,18)	76.9 102.5%	77.8 210.3%
Week 242 >90% decrease (n=13,18)	69.2 92.3%	72.2 195.1%
Week 244 >20% decrease (n=13,18)	100.0 133.3%	94.4 255.1%
Week 244 >50% decrease (n=13,18)	92.3 123.1%	88.9 240.3%
Week 244 >75% decrease (n=13,18)	76.9 102.5%	77.8 210.3%
Week 244 >90% decrease (n=13,18)	69.2 92.3%	72.2 195.1%
Week 246 >20% decrease (n=13,18)	100.0 133.3%	94.4 255.1%
Week 246 >50% decrease (n=13,18)	92.3 123.1%	88.9 240.3%
Week 246 >75% decrease (n=13,18)	76.9 102.5%	77.8 210.3%
Week 246 >90% decrease (n=13,18)	69.2 92.3%	72.2 195.1%
Week 248 >20% decrease (n=13,18)	100.0 133.3%	94.4 255.1%
Week 248 >50% decrease (n=13,18)	92.3 123.1%	88.9 240.3%
Week 248 >75% decrease (n=13,18)	76.9 102.5%	77.8 210.3%
Week 248 >90% decrease (n=13,18)	69.2 92.3%	72.2 195.1%
Week 250 >20% decrease (n=13,18)	100.0 133.3%	94.4 255.1%
Week 250 >50% decrease (n=13,18)	92.3 123.1%	83.3 225.1%
Week 250 >75% decrease (n=13,18)	76.9 102.5%	77.8 210.3%
Week 250 >90% decrease (n=13,18)	69.2 92.3%	72.2 195.1%
Week 252 >20% decrease (n=13,18)	100.0 133.3%	94.4 255.1%
Week 252 >50% decrease (n=13,18)	92.3 123.1%	83.3 225.1%
Week 252 >75% decrease (n=13,18)	76.9 102.5%	77.8 210.3%
Week 252 >90% decrease (n=13,18)	69.2 92.3%	72.2 195.1%
Week 254 >20% decrease (n=13,18)	100.0 133.3%	94.4 255.1%
Week 254 >50% decrease (n=13,18)	92.3 123.1%	83.3 225.1%
Week 254 >75% decrease (n=13,18)	76.9 102.5%	77.8 210.3%
Week 254 >90% decrease (n=13,18)	69.2 92.3%	72.2 195.1%
Week 256 >20% decrease (n=13,18)	100.0 133.3%	94.4 255.1%
Week 256 >50% decrease (n=13,18)	92.3 123.1%	83.3 225.1%
Week 256 >75% decrease (n=13,18)	76.9 102.5%	77.8 210.3%
Week 256 >90% decrease (n=13,18)	69.2 92.3%	72.2 195.1%
Week 258 >20% decrease (n=13,18)	100.0 133.3%	94.4 255.1%
Week 258 >50% decrease (n=13,18)	92.3 123.1%	83.3 225.1%
Week 258 >75% decrease (n=13,18)	76.9 102.5%	77.8 210.3%
Week 258 >90% decrease (n=13,18)	69.2 92.3%	72.2 195.1%
Week 260 >20% decrease (n=13,18)	100.0 133.3%	94.4 255.1%
Week 260 >50% decrease (n=13,18)	92.3 123.1%	88.9 240.3%
Week 260 >75% decrease (n=13,18)	76.9 102.5%	77.8 210.3%
Week 260 >90% decrease (n=13,18)	69.2 92.3%	72.2 195.1%

29. Secondary Outcome

Title	Part III: Percentage of Participants With Inactive Disease
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 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.
Time Frame	Weeks 104, 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260

Outcome Measure Data

Analysis Population Description

ITT3 population; n=number of participants contributing to the specific statistic

Arm/Group Title	Participants ≥30 kg	Participants <30 kg
Arm/Group 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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.	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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
Measure Participants	42	47
Week 104 (n=42,47)	45.2 60.3%	46.8 126.5%
Week 116 (n=41,46)	48.8 65.1%	43.5 117.6%
Week 128 (n=40,43)	55.0 73.3%	48.8 131.9%
Week 140 (n=38,40)	55.3 73.7%	45.0 121.6%
Week 152 (n=27,35)	33.3 44.4%	54.3 146.8%
Week 164 (n=27,25)	37.0 49.3%	28.0 75.7%
Week 176 (n=24,22)	41.7 55.6%	36.4 98.4%
Week 188 (n=21,22)	23.8 31.7%	31.8 85.9%
Week 200 (n=19,21)	42.1 56.1%	14.3 38.6%
Week 212 (n=18,18	55.6 74.1%	44.4 120%
Week 224 (n=17,18)	47.1 62.8%	44.4 120%
Week 236 (n=16,17)	43.8 58.4%	29.4 79.5%
Week 248 (n=15,17)	26.7 35.6%	41.2 111.4%
Week 260 (n=15,15)	46.7 62.3%	6.7 18.1%

30. Secondary Outcome

Title	Part III: Percentage of Participants in Clinical Remission
Description	Patients who previously withdrew are excluded Responders are patients who met all of the following criteria for inactive disease at all visits in the 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. vi. 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.
Time Frame	Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260

Outcome Measure Data

Analysis Population Description

ITT3 population; n=number of participants contributing to the specific statistic

Arm/Group Title	Participants ≥30 kg	Participants <30 kg
Arm/Group 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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.	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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
Measure Participants	41	47
Week 116 (n=41,47)	14.6 19.5%	17.4 47%
Week 128 (n=40,43)	32.5 43.3%	23.3 63%
Week 140 (n=38,40)	34.2 45.6%	25.0 67.6%
Week 152 (n=27,35)	25.9 34.5%	25.7 69.5%
Week 164 (n=27,25)	22.2 29.6%	16.0 43.2%
Week 176 (n=24,22)	16.7 22.3%	13.6 36.8%
Week 188 (n=21,22)	14.3 19.1%	9.1 24.6%
Week 200 (n=19,21)	15.8 21.1%	4.8 13%
Week 212 (n=18,18)	16.7 22.3%	5.6 15.1%
Week 224 (n=17,18)	29.4 39.2%	11.1 30%
Week 236 (n=16,17)	25.0 33.3%	29.4 79.5%
Week 248 (n=15,17)	13.3 17.7%	23.5 63.5%
Week 260 (n=15,15)	13.3 17.7%	6.7 18.1%

31. Secondary Outcome

Title	Part III: Percentage of Participants on Corticosteroids at Baseline in Clinical Remission Off All Oral Corticosteroids for 6 Months Prior to Specified Visits
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
Time Frame	Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260

Outcome Measure Data

Analysis Population Description

ITT3 population; n=number of participants contributing to the specific statistic

Arm/Group Title	Participants ≥30 kg	Participants <30 kg
Arm/Group 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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.	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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
Measure Participants	41	46
Week 116 (n=41,46)	12.2 16.3%	17.4 47%
Week 128 (n=40,43)	32.5 43.3%	20.9 56.5%
Week 140 (n=38,40)	28.9 38.5%	20.0 54.1%
Week 152 (n=27,35)	18.5 24.7%	20.0 54.1%
Week 164 (n=27,25)	18.5 24.7%	12.0 32.4%
Week 176 (n=24,22)	16.7 22.3%	9.1 24.6%
Week 188 (n=21,22)	14.3 19.1%	4.5 12.2%
Week 200 (n=19,21)	10.5 14%	4.8 13%
Week 212 (n=18,18)	11.1 14.8%	5.6 15.1%
Week 224 (n=17,18)	23.5 31.3%	11.1 30%
Week 236 (n=16,17)	25.0 33.3%	23.5 63.5%
Week 248 (n=15,17)	6.7 8.9%	17.6 47.6%
Week 260 (n=15,15)	6.7 8.9%	6.7 18.1%

32. Secondary Outcome

Title	Part III: Percentage of Participants on Methotrexate At Baseline in Clinical Remission Off Corticosteroids and Methotrexate for 6 Months Prior to Specified Visits
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
Time Frame	Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260

Outcome Measure Data

Analysis Population Description

ITT3 population; n=number of participants contributing to the specific statistic

Arm/Group Title	Participants ≥30 kg	Participants <30 kg
Arm/Group 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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.	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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
Measure Participants	41	46
Week 116 (n=41,46)	7.3 9.7%	8.7 23.5%
Week 128 (n=40,43)	20.0 26.7%	11.6 31.4%
Week 140 (n=38,40)	18.4 24.5%	5.0 13.5%
Week 152 (n=27,35)	3.7 4.9%	2.9 7.8%
Week 164 (n=27,25)	3.7 4.9%	4.0 10.8%
Week 176 (n=24,22)	4.2 5.6%	0.0 0%
Week 188 (n=21,22)	4.8 6.4%	0.0 0%
Week 200 (n=19,21)	5.3 7.1%	4.8 13%
Week 212 (n=18,18)	5.6 7.5%	5.6 15.1%
Week 224 (n=17,18)	5.9 7.9%	5.6 15.1%
Week 236 (n=16,17)	12.5 16.7%	5.9 15.9%
Week 248 (n=15,17)	0.0 0%	5.9 15.9%
Week 260 (n=15,15)	0.0 0%	0.0 0%

33. Secondary Outcome

Title	Part III: Percentage of Participants in Clinical Remission Off All Arthritis Medications Except Tocilizumab for 6 Months Prior to Specified Visits
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
Time Frame	Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260

Outcome Measure Data

Analysis Population Description

ITT3 population; n=number of participants contributing to the specific statistic

Arm/Group Title	Participants ≥30 kg	Participants <30 kg
Arm/Group 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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.	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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
Measure Participants	41	46
Week 116 (n=41,46)	4.9 6.5%	8.7 23.5%
Week 128 (n=40,43)	15.0 20%	9.3 25.1%
Week 140 (n=38,40)	15.8 21.1%	5.0 13.5%
Week 152 (n=27,35)	0.0 0%	2.9 7.8%
Week 164 (n=27,25)	0.0 0%	0.0 0%
Week 176 (n=24,22)	4.2 5.6%	0.0 0%
Week 188 (n=21,22)	4.8 6.4%	0.0 0%
Week 200 (n=19,21)	5.3 7.1%	0.0 0%
Week 212 (n=18,18)	5.6 7.5%	0.0 0%
Week 224 (n=17,18)	5.9 7.9%	0.0 0%
Week 236 (n=16,17)	12.5 16.7%	0.0 0%
Week 248 (n=15,17)	0.0 0%	0.0 0%
Week 260 (n=15,15)	0.0 0%	0.0 0%

34. Secondary Outcome

Title	Part III: Percentage of Participants Who Developed Antibodies To Tocilizumab During Weeks 104 to 260
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.
Time Frame	Every 2 weeks from Week 104 to 260

Outcome Measure Data

Analysis Population Description

ITT3 population; n=number of participants contributing to the specific statistic

Arm/Group Title	Participants ≥30 kg	Participants <30 kg
Arm/Group 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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.	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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
Measure Participants	45	47
Number [percentage of participants]	0.0 0%	0.0 0%

35. Secondary Outcome

Title	Part III: Percentage of Participants Who Developed Anti-TCZ Antibodies Associated With The Occurrence of Drug Hypersensitivity Reactions.
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.
Time Frame	Every 2 weeks from Week 104 to 260

Outcome Measure Data

Analysis Population Description

ITT3 population; n=number of participants contributing to the specific statistic

Arm/Group Title	Participants ≥30 kg	Participants <30 kg
Arm/Group 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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.	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 for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
Measure Participants	45	47
Number [percentage of participants]	0.0 0%	0.0 0%

Adverse Events

Time Frame	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 Description	Note: 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.
Arm/Group Title	All Tocilizumab (Part I, Part II and Part III)
Arm/Group 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.
All Cause Mortality
	All Tocilizumab (Part I, Part II and Part III)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Tocilizumab (Part I, Part II and Part III)
	Affected / at Risk (%)	# Events
Total	48/112 (42.9%)
Blood and lymphatic system disorders
Histiocytosis haematophagic	5/112 (4.5%)
Lymphadenitis	1/112 (0.9%)
Cardiac disorders
Cardiac failure	1/112 (0.9%)
Gastrointestinal disorders
Abdominal pain	1/112 (0.9%)
Constipation	1/112 (0.9%)
Diarrhoea	1/112 (0.9%)
Gastritis	1/112 (0.9%)
Vomiting	1/112 (0.9%)
General disorders
Drug intolerance	1/112 (0.9%)
Influenza like illness	1/112 (0.9%)
Hepatobiliary disorders
Hypertransaminasaemia	1/112 (0.9%)
Immune system disorders
Anaphylactic reaction	1/112 (0.9%)
Infections and infestations
Arthritis bacterial	1/112 (0.9%)
Bronchopneumonia	1/112 (0.9%)
Cellulitis	1/112 (0.9%)
Device related sepsis	1/112 (0.9%)
Gastroenteritis	5/112 (4.5%)
Gastroenteritis viral	1/112 (0.9%)
Herpes zoster	3/112 (2.7%)
Kidney infection	1/112 (0.9%)
Lower respiratory tract infection	2/112 (1.8%)
Otitis media	1/112 (0.9%)
Pharyngitis	1/112 (0.9%)
Pharyngotonsillitis	1/112 (0.9%)
Pneumonia	5/112 (4.5%)
Pulmonary tuberculosis	1/112 (0.9%)
Sepsis	2/112 (1.8%)
Tonsillitis	1/112 (0.9%)
Upper respiratory tract infection	1/112 (0.9%)
Varicella	5/112 (4.5%)
Injury, poisoning and procedural complications
Femur fracture	1/112 (0.9%)
Forearm fracture	1/112 (0.9%)
Fracture	1/112 (0.9%)
Joint dislocation	1/112 (0.9%)
Road traffic accident	1/112 (0.9%)
Spinal fracture	1/112 (0.9%)
Tendon rupture	1/112 (0.9%)
Ulna fracture	1/112 (0.9%)
Investigations
Liver function test abnormal	1/112 (0.9%)
Metabolism and nutrition disorders
Dehydration	1/112 (0.9%)
Hyperkalaemia	1/112 (0.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/112 (0.9%)
Arthritis	1/112 (0.9%)
Juvenile idiopathic arthritis	1/112 (0.9%)
Pain in extremity	1/112 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Lymphocytic leukaemia	1/112 (0.9%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	1/112 (0.9%)
Psychiatric disorders
Abnormal behaviour	1/112 (0.9%)
Self injurious behavior	1/112 (0.9%)
Reproductive system and breast disorders
Testicular torsion	1/112 (0.9%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/112 (0.9%)
Pulmonary veno-occlusive disease	1/112 (0.9%)
Skin and subcutaneous tissue disorders
Angioedema	1/112 (0.9%)
Panniculitis	1/112 (0.9%)
Urticaria	1/112 (0.9%)
Other (Not Including Serious) Adverse Events
	All Tocilizumab (Part I, Part II and Part III)
	Affected / at Risk (%)	# Events
Total	112/112 (100%)
Blood and lymphatic system disorders
Neutropenia	25/112 (22.3%)
Leukopenia	11/112 (9.8%)
Lymphadenopathy	6/112 (5.4%)
Lymphadenitis	4/112 (3.6%)
Ear and labyrinth disorders
Ear pain	11/112 (9.8%)
Middle ear effusion	4/112 (3.6%)
Eye disorders
Cataract	4/112 (3.6%)
Chalazion	3/112 (2.7%)
Gastrointestinal disorders
Diarrhoea	29/112 (25.9%)
Vomiting	29/112 (25.9%)
Abdominal pain	16/112 (14.3%)
Gastrointestinal disorder	6/112 (5.4%)
Nausea	26/112 (23.2%)
Abdominal pain upper	15/112 (13.4%)
Dental Caries	6/112 (5.4%)
Abdominal discomfort	3/112 (2.7%)
General disorders
Pyrexia	11/112 (9.8%)
Influenza like illness	10/112 (8.9%)
Fatigue	6/112 (5.4%)
Local swelling	5/112 (4.5%)
Pain	4/112 (3.6%)
Infections and infestations
Upper Respiratory Tract Infection	49/112 (43.8%)
Nasopharyngitis	53/112 (47.3%)
Gastroenteritis viral	9/112 (8%)
Pharyngitis	20/112 (17.9%)
Gastroenteritis	28/112 (25%)
Ear infection	18/112 (16.1%)
Rhinitis	19/112 (17%)
Impetigo	14/112 (12.5%)
Viral infection	16/112 (14.3%)
Otitis media	14/112 (12.5%)
Viral upper respiratory tract infection	12/112 (10.7%)
Bronchitis	11/112 (9.8%)
Otitis externa	8/112 (7.1%)
Tonsillitis	9/112 (8%)
Urinary tract infection	10/112 (8.9%)
Conjunctivitis	12/112 (10.7%)
Sinusitis	10/112 (8.9%)
Influenza	9/112 (8%)
Paronychia	7/112 (6.3%)
Herpes Zoster	6/112 (5.4%)
Laryngitis	6/112 (5.4%)
Cellulitis	5/112 (4.5%)
Skin infection	5/112 (4.5%)
Tinea pedis	5/112 (4.5%)
Varicella	4/112 (3.6%)
Otitis media acute	3/112 (2.7%)
Pneumonia	3/112 (2.7%)
Injury, poisoning and procedural complications
Contusion	10/112 (8.9%)
Excoriation	8/112 (7.1%)
Joint injury	7/112 (6.3%)
Traumatic haematoma	7/112 (6.3%)
Ligament Sprain	13/112 (11.6%)
Limb Injury	8/112 (7.1%)
Fall	7/112 (6.3%)
Wound	6/112 (5.4%)
Arthropod bite	17/112 (15.2%)
Hand fracture	5/112 (4.5%)
Laceration	5/112 (4.5%)
Infusion related reaction	4/112 (3.6%)
Muscle strain	4/112 (3.6%)
Thermal burn	4/112 (3.6%)
Investigations
Transaminases increased	11/112 (9.8%)
Neutrophil count decreased	5/112 (4.5%)
Platelet count decreased	5/112 (4.5%)
Alanine aminotransferase increased	4/112 (3.6%)
Musculoskeletal and connective tissue disorders
Juvenile idiopathic arthritis	31/112 (27.7%)
Back pain	12/112 (10.7%)
Arthralgia	25/112 (22.3%)
Musculoskeletal pain	11/112 (9.8%)
Pain in extremity	12/112 (10.7%)
Neck pain	9/112 (8%)
Joint Swelling	7/112 (6.3%)
Arthritis	5/112 (4.5%)
Musculoskeletal stiffness	4/112 (3.6%)
Osteoporosis	3/112 (2.7%)
Nervous system disorders
Headache	25/112 (22.3%)
Dizziness	6/112 (5.4%)
Migraine	3/112 (2.7%)
Renal and urinary disorders
Haematuria	5/112 (4.5%)
Reproductive system and breast disorders
Dysmenorrhoea	3/112 (2.7%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	24/112 (21.4%)
Cough	45/112 (40.2%)
Epistaxis	9/112 (8%)
Nasal congestion	10/112 (8.9%)
Rhinorrhoea	7/112 (6.3%)
Skin and subcutaneous tissue disorders
Urticaria	8/112 (7.1%)
Rash	22/112 (19.6%)
Eczema	10/112 (8.9%)
Prurigo	8/112 (7.1%)
Dry skin	5/112 (4.5%)
Pruritus	4/112 (3.6%)
Dermatitis atopic	3/112 (2.7%)
Dermatitis contact	3/112 (2.7%)
Erythema	3/112 (2.7%)
Vascular disorders
Haematoma	7/112 (6.3%)

Limitations/Caveats

This study consists of 3 parts: Part I: a 12 week double-blind placebo controlled study is complete. Part II: a 92 week single arm open-label extension study- CSR completed Dec. 2011. Part III: a 3 year open label continuation study is ongoing.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.