A Study of Tocilizumab in Patients With Active Polyarticular Juvenile Idiopathic Arthritis

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT00988221

Collaborator

(none)

188

Enrollment

Locations

Arms

37.9

Actual Duration (Months)

2.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This 3-part study evaluated the efficacy and safety of tocilizumab in patients with active polyarticular-course juvenile idiopathic arthritis who have an inadequate response to, or were intolerant of methotrexate. In Part I of the study, all patients received intravenous (iv) infusions of tocilizumab (8 mg/kg for patients ≥ 30kg, 8 mg/kg or 10 mg/kg for patients < 30kg) every 4 weeks for 16 weeks. In Part II of the study, patients with an adequate response in Part I were randomized to receive either tocilizumab at the same dose as in Part I or placebo every 4 weeks for up to 24 weeks. In Part III of the study, patients received tocilizumab at the same dose as in Part I every 4 weeks for up to another 64 weeks. Standard of care therapy with or without non-steroidal anti-inflammatory drugs (NSAID), corticosteroids, or methotrexate was continued throughout the study.

Condition or Disease	Intervention/Treatment	Phase
Juvenile Idiopathic Arthritis	Drug: Tocilizumab Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

188 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A 24 Week Randomized, Double-blind, Placebo-controlled Withdrawal Trial With a 16 Week Open-label lead-in Phase, and 64 Week Open-label Follow-up, to Evaluate the Effect on Clinical Response and the Safety of Tocilizumab in Patients With Active Polyarticular-course Juvenile Idiopathic Arthritis

Actual Study Start Date :

Nov 30, 2009

Actual Primary Completion Date :

Nov 30, 2011

Actual Study Completion Date :

Jan 28, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tocilizumab 10 mg/kg in patients weighing < 30 kg Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Drug: Tocilizumab Tocilizumab was supplied as a sterile solution in vials. Other Names: RoActemra Actemra
Experimental: Tocilizumab 8 mg/kg in patients weighing < 30 kg Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Drug: Tocilizumab Tocilizumab was supplied as a sterile solution in vials. Other Names: RoActemra Actemra
Experimental: Tocilizumab 8 mg/kg in patients weighing ≥ 30 kg Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Drug: Tocilizumab Tocilizumab was supplied as a sterile solution in vials. Other Names: RoActemra Actemra
Placebo Comparator: Placebo Patients received placebo to tocilizumab intravenously every 4 weeks.	Drug: Placebo Placebo to tocilizumab was supplied as a sterile solution in vials.

Outcome Measures

Primary Outcome Measures

Percent of Patients With a Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) Flare in Part II of the Study (Weeks 16-40) [Week 16 through Week 40]
JIA ACR30 flare is defined as a ≥ 30% worsening of 3 of 6 variables and no more than 1 of the remaining variables improving > 30%. The 6 variables are physician global assessment of disease activity (worsening of 20 units minimum on a 0-100 visual analog scale [VAS]), parent/patient global assessment of overall well-being (worsening of 20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]). Patients who withdrew or who took escape medication are classified as flared. The analysis used the Cochran-Mantel-Haenszel test with the stratification variables background use of methotrexate and oral corticosteroids applied at Week 16.

Secondary Outcome Measures

Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses in Part I of the Study (Baseline to Week 16) [Baseline to Week 16]
A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening > 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale [VAS]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]).
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at the End of Part I of the Study (Week 16) [Baseline to Week 16]
The patient's treating physician provides a rating of the patient's arthritis disease activity on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'arthritis inactive' (ie, symptom-free and no arthritis symptoms) and the extreme right end represents 'arthritis very active'. A higher score indicates more disease activity. A negative change score indicates improvement.
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at the End of Part I of the Study (Week 16) [Baseline to Week 16]
The patient or parent/guardian, as appropriate, provides a rating of the patient's well-being on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'very well' (ie, symptom-free and no arthritis disease activity) and the extreme right end represents 'very poor' (ie, maximum arthritis disease activity). A higher score indicates poorer well-being. A negative change score indicates improvement.
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at the End of Part I of the Study (Week 16) [Baseline to Week 16]
Joints with active arthritis are defined as joints with swelling present or pain present and limitation of motion. The maximum number of joints with active arthritis is 71. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at the End of Part I of the Study (Week 16) [Baseline to Week 16]
Joints with limitation of movement are defined as joints with limitation of motion. The maximum number of joints with limitation of movement is 67. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at the End of Part I of the Study (Week 16) [Baseline to Week 16]
Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at the End of Part I of the Study (Week 16) [Baseline to Week 16]
Functional ability is assessed with the Childhood Health Assessment Questionnaire (CHAQ-DI) disability index which consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. If aids and devices listed in the questionnaire or assistance from a person are required to perform a task, a domain score of 0 or 1 is increased to 2; if the domain score is 2 or 3, the domain score is not adjusted. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability. A negative change score indicates improvement.
Juvenile Arthritis Disease Activity Score (JADAS-27) at the End of Part I of the Study (Week 16) [Week 16]
The JADAS-27 is derived from the following components: Physician's global assessment of disease activity on a 0-100 mm visual analog scale (VAS)/10, patient/parent's global assessment of overall well-being on a 0-100 mm VAS/10, normalized erythrocyte sedimentation rate (ESR) (if ESR is ≤ 20 then set to 0, if ≥ 120 then set to 10, and if > 20 and < 120 then apply formula [ESR-20]/10), and number of joints (maximum of 27) with active arthritis (cervical spine, left/right elbow, left/right wrist, left/right MCP1-3, left/right PIP1-5, left/right hips, left/right knee and left/right ankle). The scores for the first 3 components range from 0-10; the score for the final component ranges from 0-27. The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity.
Pain Visual Analogue Scale (VAS) Score at the End of Part I of the Study (Week 16) [Week 16]
The patient or parent/guardian, as appropriate, provides a rating of the patient's pain (also called a discomfort index) on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'no pain' and the extreme right end represents 'very extreme pain'. A higher score indicates more pain.
Percent of Patients With Inactive Disease at the End of Part I of the Study (Week 16) [Week 16]
A patient is judged to have inactive disease if all of the following criteria are met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10.
Percent of Patients With an Elevated C-reactive Protein Concentration at Baseline That Had Normalized at the End of Part I of the Study (Week 16) [Baseline to Week 16]
C-reactive protein (CRP), an acute phase protein, was measured in blood samples with a high-sensitivity CRP (hs-CRP) test using laser nephelometry.
Percent of Patients With an Elevated Erythrocyte Sedimentation Rate at Baseline That Had Normalized at the End of Part I of the Study (Week 16) [Baseline to Week 16]
Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory.
Percent of Patients With an Elevated Platelet Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16) [Baseline to Week 16]
Platelets were measured in blood samples taken from the patients.
Percent of Patients With an Elevated White Blood Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16) [Baseline to Week 16]
White blood cells were measured in blood samples taken from the patients.
Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at the End of Part II of the Study (Week 40) [Week 40]
A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening > 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale [VAS]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]). The analysis used the Cochran-Mantel-Haenszel test with the stratification variables background use of methotrexate and oral corticosteroids applied at Week 16.
Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at the End of Part II of the Study (Week 40) [Baseline to Week 40]
The patient's treating physician provides a rating of the patient's arthritis disease activity on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'arthritis inactive' (ie, symptom-free and no arthritis symptoms) and the extreme right end represents 'arthritis very active'. A higher score indicates more disease activity. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.
Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at the End of Part II of the Study (Week 40) [Baseline to Week 40]
The patient or parent/guardian, as appropriate, provides a rating of the patient's well-being on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'very well' (ie, symptom-free and no arthritis disease activity) and the extreme right end represents 'very poor' (ie, maximum arthritis disease activity). A higher score indicates poorer well-being. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.
Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at the End of Part II of the Study (Week 40) [Baseline to Week 40]
Joints with active arthritis are defined as joints with swelling present or pain present and limitation of motion. The maximum number of joints with active arthritis is 71. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.
Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at the End of Part II of the Study (Week 40) [Baseline to Week 40]
Joints with limitation of movement are defined as joints with limitation of motion. The maximum number of joints with limitation of movement is 67. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.
Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at the End of Part II of the Study (Week 40) [Baseline to Week 40]
Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.
Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) at the End of Part II of the Study (Week 40) [Baseline to Week 40]
The Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI), as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.
Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at the End of Part II of the Study (Week 40) [Baseline to Week 40]
The patient or parent/guardian, as appropriate, provides a rating of the patient's pain (also called a discomfort index) on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'no pain' and the extreme right end represents 'very extreme pain'. A higher score indicates more pain. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward (LOCF) imputation for missing values. The analysis was adjusted for the randomization stratification factors background use of methotrexate and background use of oral corticosteroids, and the pain visual analog scale score at Baseline. The adjusted means from the fitted model are presented.
Percent of Patients With Inactive Disease at the End of Part II of the Study (Week 40) [Week 40]
A patient is judged to have inactive disease if all of the following criteria are met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10. The statistical test is not significant due to a break in the hierarchical chain of significance testing.
Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Weeks 2, 52, and 104 [Week 2 to Week 104]
A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening > 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale [VAS]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]).
Percent of Patients With 4 Baseline Disease Characteristics Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Week 104 [Week 104]
A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening > 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]). Results are reported for the subgroups: Previous biologic treatment (yes/no), concomitant methotrexate use (yes/no), rheumatoid factor (positive/negative), concomitant oral corticosteroid use (yes/no). Last observation carried forward was applied to missing components at visits.
Change From Baseline in the Juvenile Arthritis Disease Activity Score-71 (JADAS-71) at Week 104 [Baseline to Week 104]
The JADAS-71 is composed of 4 components: Physician global assessment of disease activity on a visual analog scale (VAS) (range = 0-10, left end of the line = arthritis inactive, ie, symptom-free and no arthritis symptoms; right end = arthritis very active), patient/parent global assessment of overall well-being on a VAS (range = 0-10, left end of the line = very well, ie, symptom-free and no arthritis disease activity; right end = very poor, ie, maximum arthritis disease activity), normalized erythrocyte sedimentation rate (ESR) (range = 0-10, If ESR is ≤ 20 mm/h, set to 0. If ≥ 120 mm/h, set to 10 mm/h. If > 20 mm/h and < 120 mm/h, apply formula: [ESR - 20 mm/h]/10 mm/h), and a count of active arthritis (swelling present or pain present and limitation of motion) in 71 selected joints (range=0-71). The JADAS-71 is the sum of the 4 component scores and ranges from 0-101. A higher score indicates more arthritis disease activity. A positive change score indicates improvement.
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at Week 104 [Baseline to Week 104]
The patient's treating physician provides a rating of the patient's arthritis disease activity on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'arthritis inactive' (ie, symptom-free and no arthritis symptoms) and the extreme right end represents 'arthritis very active'. A negative change score indicates improvement.
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at Week 104 [Baseline to Week 104]
The patient or parent/guardian, as appropriate, provides a rating of the patient's well-being on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'very well' (ie, symptom-free and no arthritis disease activity) and the extreme right end represents 'very poor' (ie, maximum arthritis disease activity). A negative change score indicates improvement.
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at Week 104 [Baseline to Week 104]
Joints with active arthritis are defined as joints with swelling present or pain present and limitation of motion. The maximum number of joints with active arthritis is 71. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at Week 104 [Baseline to Week 104]
Joints with limitation of movement are defined as joints with limitation of motion. The maximum number of joints with limitation of movement is 67. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at Week 104 [Baseline to Week 104]
Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at Week 104 [Baseline to Week 104]
Functional ability is assessed with the Childhood Health Assessment Questionnaire (CHAQ-DI) disability index which consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. If aids and devices listed in the questionnaire or assistance from a person are required to perform a task, a domain score of 0 or 1 is increased to 2; if the domain score is 2 or 3, the domain score is not adjusted. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A negative change score indicates improvement.
Percent of Patients With a Minimally Important Improvement in the Children's Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Weeks 16, 40, 52, 80, and 104 [Baseline to Week 104]
The CHAQ-DI consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. If aids and devices listed in the questionnaire or assistance from a person are required to perform a task, a domain score of 0 or 1 is increased to 2; if the domain score is 2 or 3, the domain score is not adjusted. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A minimally important improvement is an improvement ≥ 0.13 over Baseline. Patients who withdrew due to non-safety reasons are classified as non-responders.
C-reactive Protein Levels From Baseline to Week 104 [Baseline to Week 104]
C-reactive protein (CRP), an acute phase protein, was measured in blood samples with a high-sensitivity CRP (hs-CRP) test using laser nephelometry.
Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at Weeks 2, 40, 52, and 104 [Baseline to Week 104]
The patient or parent/guardian, as appropriate, provides a rating of the patient's pain (also called a discomfort index) on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'no pain' and the extreme right end represents 'very extreme pain'. A higher score indicates more pain. A negative change score indicates improvement.
Percent of Patients With Inactive Disease From Week 16 to Week 104 [Week 16 to Week 104]
A patient is judged to have inactive disease if all of the following criteria are met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10. Patients who withdrew due to non-safety reasons are classified as non-responders.
Percent of Patients in Clinical Remission From Week 40 to 104 [Week 40 to Week 104]
A patient was in clinical remission if they had inactive disease at all visits in the 6 months prior to and including the visit assessment day. A patient was judged to have inactive disease if all of the following criteria were met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10. Patients who withdrew due to non-safety reasons are classified as non-responders.
Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Week 104 by Duration of Disease (< 2 Years, ≥ 2 Years) [Baseline to Week 104]
A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening > 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale [VAS]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]). Patients who withdrew due to non-safety reasons are classified as non-responders.
Oral Corticosteroid Dose at Baseline, Week 52, and Week 104 [Baseline to Week 104]
Due to the different types of corticosteroid medications available, the prednisone equivalent was used in the calculation of the oral corticosteroid dose. Values are based on the average daily dose on the study day and if not available the last observation carried forward is used.
Methotrexate Dose at Baseline, Week 52, and Week 104 [Baseline to Week 104]
Values are based on the average daily dose on the study day and if not available the last observation carried forward is used.
Height Standard Deviation Score at Baseline, Week 52, and Week 104 [Baseline to Week 104]
The height Standard Deviation Score was calculated using the following formula: (Observed height - median of the reference population)/standard deviation of the reference population. The reference population was defined as that of the same sex and age to the nearest completed year and month using the World Health Organization norms. A negative score indicates less height than the reference population.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Children/juveniles, 2-17 years of age.
Polyarticular-course juvenile idiopathic arthritis (pcJIA) ≥ 6 months duration.
Active disease (≥ 5 active joints, ≥ 3 with limitation of motion).
Inadequate response to or inability to tolerate methotrexate.
Methotrexate, oral corticosteroids, and non-steroidal anti-inflammatory drugs (NSAID) at stable dose(at least 8, 4, and 2 weeks,respectively) prior to baseline.
Biologics discontinued, between at least 1 and 20 weeks prior to baseline, depending on biologic.

Exclusion Criteria:

Auto-immune, rheumatic disease or overlap syndrome other than pcJIA.
Wheelchair bound or bedridden.
Intra-articular, intramuscular, intravenous, or long-acting corticosteroids within 4 weeks prior to baseline.
Disease-modifying anti-rheumatic drugs (DMARD) (other than methotrexate) within 4 weeks prior to baseline.
Previous treatment with tocilizumab.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Connecticut Children's Medical Center; 5E Clinical Trials Unit	Hartford	Connecticut	United States	06106
2	Children's National Medical Center; Pediatric Rheumatology	Washington, D.C.	District of Columbia	United States	20010-2970
3	Delray Research Associates	Delray Beach	Florida	United States	33484
4	Miami Children's Hospital	Miami	Florida	United States	33155-3009
5	The University of Chicago;Department of Pediatrics	Chicago	Illinois	United States	60649
6	University of Louisville Research Foundation, Inc; Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky	United States	40202
7	Children's Hospital	New Orleans	Louisiana	United States	70118
8	Hackensack University Medical Center; Pediatric Rheumatology	Hackensack	New Jersey	United States	07601
9	Cincinnati Children'S Hospital Medical Center; Division of Rheumatology	Cincinnati	Ohio	United States	45229-3039
10	Healthcare Research Consultants	Tulsa	Oklahoma	United States	74135
11	Hospital Gral de Niños Pedro Elizalde	Buenos Aires		Argentina	1270
12	Hospital de Niños; Reumatologia	Buenos Aires		Argentina	1425
13	Caici; Rheumatology	Rosario		Argentina	S2000PBJ
14	Centro Medico Privado de Reumatologia; Reumathology	San Miguel		Argentina	T4000AXL
15	Westmead Hospital; Paediatric Rheumatology	Westmead	New South Wales	Australia	2145
16	Royal Children'S Hospital; Paediatric Rheumatology	Parkville	Victoria	Australia	3052
17	Princess Margaret Children'S Hospital; Department of Immunology	Subiaco	Western Australia	Australia	6008
18	UZ Gent	Gent		Belgium	9000
19	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
20	Hospital Universitario Pedro Ernesto; Nucleo de Estudos da Saude do Adolescente	Rio de janeiro	RJ	Brazil	20551030
21	Instituto de Puericultura E Pediatria Martagão Gesteira	Rio de Janeiro	RJ	Brazil	21941-912
22	Hospital das Clinicas - UFRGS	Porto Alegre	RS	Brazil	90035-003
23	Hospital das Clinicas - FMUSP; Instituto da Crianca - Reumatologia	Sao Paulo	SP	Brazil	05403-000
24	Alberta Children'S Hospital	Calgary	Alberta	Canada	T3B 6A8
25	British Columbia Children's Hospital; Rheumatology	Vancouver	British Columbia	Canada	V5Y 2C6
26	Children'S Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
27	Hospital For Sick Children	Toronto	Ontario	Canada	M5G 1X8
28	Hôpital Pellegrin; Urgences Pédiatriques	Bordeaux		France	33076
29	CH de Bicêtre; Pediatrie Generale	Le Kremlin Bicêtre		France	94275
30	Hôpital Lapeyronie; Immuno-Rhumatologie Pr Jorgensen	Montpellier		France	34295
31	Hopital Cochin; Rhumatologie A	Paris		France	75679
32	Hop Necker Enfants Malades;UIH	Paris		France	75743
33	Hopitaux De Brabois; Medecine Infantile II	Vandoeuvre Les Nancy		France	54511
34	Charité Campus; Virchow Klinikum Berlin	Berlin		Germany	13353
35	Klinik Bremen-Mitte; Prof. Hess-Kinderklinik	Bremen		Germany	28177
36	Clementine Hospital; Kinder- und Jugendrheumatologie	Frankfurt/Main		Germany	60316
37	Asklepios Klinik; Zentrum fuer Allgemeine Paediatrie und Neonatologie	Sankt Augustin		Germany	53757
38	Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina	Roma	Lazio	Italy	00165
39	IRCCS G. Gaslini; Pediatria II	Genova	Liguria	Italy	16147
40	ASST CENTRO SPECIALISTICO ORTOPEDICO TRAUMATO-LOGICO GAETANO PINI/CTO; Reumatol. Pediatrica	Milano	Lombardia	Italy	20122
41	Nuovo Ospedale Pediatrico Meyer; Reumatologia - Clinica Pediatrica 1°	Firenze	Toscana	Italy	50139
42	Univ. Di Padova - Dip. Di Pediatria - Unita' Reumatol. Pediatrica	Padova	Veneto	Italy	35128
43	Cif Biotec Medica Sur	Mexico City, Distrito Federal		Mexico	14050
44	Inst. Mexicano de Investigacion Clinica	Mexico City		Mexico	06700
45	Cliditer SA de CV	Miexico City		Mexico	06700
46	Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria	Monterrey		Mexico	64460
47	Clinica San Felipe; Consultorio de Reumatología	Lima		Peru	11
48	Clinica San Borja; Servicio De Reumatologia	Lima		Peru	Lima 41
49	Instituto Nacional De Salud Del Niño	Lima		Peru
50	Wojewodzki Szpital Dzieciecy Im. J. Brudzinskiego	Bydgoszcz		Poland	85-667
51	Wojewodzki Specjalistyczny Szpital Dzieciecy Sw Ludwika; Oddzial Dzieci Starszych	Kraków		Poland	31-503
52	Uniwersytecki Szpital Kliniczny Nr 4 im. M. Konopnickiej; Oddz. Kardiolog. i Reumatolog. dla Dzieci	Lodz		Poland	91-738
53	Dzieciecy Szpital Kliniczny IM. Prof. A. Gebali; Oddzial Pediatrii Chorob Pluc I Reumatologii	Lublin		Poland	20-093
54	Centrum Pediatrii im Jana Pawla II; Oddzial Reumatologiczny	Sosnowiec		Poland	41-218
55	Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Eleonory Reicher	Warszawa		Poland	02-637
56	FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences	Moscow		Russian Federation	115522
57	SI Sceintific children health center RAMS	Moscow		Russian Federation	119991
58	I. M. Sechenov Moscow State Medical University; The Ministry of Health and Social Development of RF	Moscow		Russian Federation	119992
59	Southern District Medical Center of Roszdrav	Rostov-Na-Donu		Russian Federation	344019
60	Saint-Petersburg State; Pediatrics Medical Academy	Saint-Petersburg		Russian Federation	194100
61	Samara Regional Clinical Cardiology Dispensary	Samara		Russian Federation	443070
62	Hospital Universitario Reina Sofia; Servicio de Reumatologia	Cordoba		Spain	14004
63	Hospital General Universitario Gregorio Marañon; Servicio de Reumatología	Madrid		Spain	28007
64	Hospital Ramon y Cajal ; Servicio de Reumatologia	Madrid		Spain	28034
65	Hospital Universitario Virgen Macarena; Servicio de Reumatologia	Sevilla		Spain	41009
66	Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica	Valencia		Spain	46026
67	Bristol Royal Hospital For Children	Bristol		United Kingdom	BS2 8BJ
68	Royal Liverpool Childrens Hospital; Rheumatology	Liverpool		United Kingdom	L12 2AP
69	Great Ormond Street Hospital for Sick Children; Institute of Child Health	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:

NCT00988221

Other Study ID Numbers:

WA19977
2009-011593-15

First Posted:

Oct 2, 2009

Last Update Posted:

Jul 26, 2017

Last Verified:

Jun 1, 2017

Additional relevant MeSH terms:

Arthritis

Arthritis, Juvenile

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	In Part I, patients received either tocilizumab 8 or 10 mg/kg. In Part II, eligible patients were randomized to receive placebo or the same dose of tocilizumab as in Part I of the study. In Part III, patients received the same dose of tocilizumab as in Part I of the study, with adjustments based on weight and change in weight from Baseline.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Placebo
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received placebo to tocilizumab intravenously every 4 weeks.
Period Title: Part I
STARTED	35	34	119	0
COMPLETED	31	24	111	0
NOT COMPLETED	4	10	8	0
Period Title: Part I
STARTED	16	11	55	84
COMPLETED	15	11	52	81
NOT COMPLETED	1	0	3	3
Period Title: Part I
STARTED	30	24	106	0
COMPLETED	29	23	103	0
NOT COMPLETED	1	1	3	0

Baseline Characteristics

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Total
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Total of all reporting groups
Overall Participants	35	34	119	188
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	6.9 (3.02)	7.6 (2.71)	13.1 (2.78)	11.0 (4.01)
Sex: Female, Male (Count of Participants)
Female	30 85.7%	24 70.6%	90 75.6%	144 76.6%
Male	5 14.3%	10 29.4%	29 24.4%	44 23.4%

Outcome Measures

1. Primary Outcome

Title	Percent of Patients With a Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) Flare in Part II of the Study (Weeks 16-40)
Description	JIA ACR30 flare is defined as a ≥ 30% worsening of 3 of 6 variables and no more than 1 of the remaining variables improving > 30%. The 6 variables are physician global assessment of disease activity (worsening of 20 units minimum on a 0-100 visual analog scale [VAS]), parent/patient global assessment of overall well-being (worsening of 20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]). Patients who withdrew or who took escape medication are classified as flared. The analysis used the Cochran-Mantel-Haenszel test with the stratification variables background use of methotrexate and oral corticosteroids applied at Week 16.
Time Frame	Week 16 through Week 40

Outcome Measure Data

Analysis Population Description
Intent-to-treat population-2: All eligible patients completing Part I of the study who were randomized into Part II of the study and received at least 1 dose of tocilizumab in Part II.

Arm/Group Title	Placebo	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received placebo to tocilizumab intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	81	82
Number (95% Confidence Interval) [Percent of patients]	48.1	25.6

2. Secondary Outcome

Title	Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses in Part I of the Study (Baseline to Week 16)
Description	A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening > 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale [VAS]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	35	34	119	188
ACR30 response	88.6	76.5	93.3	89.4
ACR50 response	80.0	70.6	87.4	83.0
ACR70 response	62.9	41.2	68.1	62.2
ACR90 response	31.4	23.5	25.2	26.1

3. Secondary Outcome

Title	Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at the End of Part I of the Study (Week 16)
Description	The patient's treating physician provides a rating of the patient's arthritis disease activity on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'arthritis inactive' (ie, symptom-free and no arthritis symptoms) and the extreme right end represents 'arthritis very active'. A higher score indicates more disease activity. A negative change score indicates improvement.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	35	34	119	188
Mean (Standard Deviation) [Percent change]	-61.48 (48.779)	-65.20 (26.170)	-72.61 (25.977)	-69.19 (31.824)

4. Secondary Outcome

Title	Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at the End of Part I of the Study (Week 16)
Description	The patient or parent/guardian, as appropriate, provides a rating of the patient's well-being on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'very well' (ie, symptom-free and no arthritis disease activity) and the extreme right end represents 'very poor' (ie, maximum arthritis disease activity). A higher score indicates poorer well-being. A negative change score indicates improvement.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	35	34	119	188
Mean (Standard Deviation) [Percent change]	-31.65 (120.268)	-55.56 (42.092)	-53.34 (58.686)	-49.46 (72.920)

5. Secondary Outcome

Title	Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at the End of Part I of the Study (Week 16)
Description	Joints with active arthritis are defined as joints with swelling present or pain present and limitation of motion. The maximum number of joints with active arthritis is 71. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	35	34	119	188
Mean (Standard Deviation) [Percent change]	-63.36 (43.272)	-55.57 (44.876)	-72.96 (33.915)	-68.15 (38.246)

6. Secondary Outcome

Title	Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at the End of Part I of the Study (Week 16)
Description	Joints with limitation of movement are defined as joints with limitation of motion. The maximum number of joints with limitation of movement is 67. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	35	34	119	188
Mean (Standard Deviation) [Percent change]	-61.83 (34.726)	-49.87 (48.091)	-65.96 (30.134)	-62.42 (34.955)

7. Secondary Outcome

Title	Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at the End of Part I of the Study (Week 16)
Description	Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	35	34	119	188
Mean (Standard Deviation) [Percent change]	-70.98 (24.530)	-21.84 (159.592)	-70.87 (33.400)	-62.54 (73.384)

8. Secondary Outcome

Title	Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at the End of Part I of the Study (Week 16)
Description	Functional ability is assessed with the Childhood Health Assessment Questionnaire (CHAQ-DI) disability index which consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. If aids and devices listed in the questionnaire or assistance from a person are required to perform a task, a domain score of 0 or 1 is increased to 2; if the domain score is 2 or 3, the domain score is not adjusted. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability. A negative change score indicates improvement.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	35	34	119	188
Mean (Standard Deviation) [Percent change]	-54.48 (37.214)	-46.16 (50.961)	-49.07 (45.048)	-49.62 (44.573)

9. Secondary Outcome

Title	Juvenile Arthritis Disease Activity Score (JADAS-27) at the End of Part I of the Study (Week 16)
Description	The JADAS-27 is derived from the following components: Physician's global assessment of disease activity on a 0-100 mm visual analog scale (VAS)/10, patient/parent's global assessment of overall well-being on a 0-100 mm VAS/10, normalized erythrocyte sedimentation rate (ESR) (if ESR is ≤ 20 then set to 0, if ≥ 120 then set to 10, and if > 20 and < 120 then apply formula [ESR-20]/10), and number of joints (maximum of 27) with active arthritis (cervical spine, left/right elbow, left/right wrist, left/right MCP1-3, left/right PIP1-5, left/right hips, left/right knee and left/right ankle). The scores for the first 3 components range from 0-10; the score for the final component ranges from 0-27. The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	35	34	119	188
Mean (Standard Deviation) [Units on a scale]	9.08 (8.882)	12.25 (10.277)	7.83 (7.122)	8.82 (8.198)

10. Secondary Outcome

Title	Pain Visual Analogue Scale (VAS) Score at the End of Part I of the Study (Week 16)
Description	The patient or parent/guardian, as appropriate, provides a rating of the patient's pain (also called a discomfort index) on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'no pain' and the extreme right end represents 'very extreme pain'. A higher score indicates more pain.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	35	34	119	188
Mean (Standard Deviation) [Units on a scale]	21.9 (21.66)	24.1 (23.94)	20.3 (21.13)	21.2 (21.65)

11. Secondary Outcome

Title	Percent of Patients With Inactive Disease at the End of Part I of the Study (Week 16)
Description	A patient is judged to have inactive disease if all of the following criteria are met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	35	34	119	188
Number [Percent of patients]	20.0	8.8	18.5	17.0

12. Secondary Outcome

Title	Percent of Patients With an Elevated C-reactive Protein Concentration at Baseline That Had Normalized at the End of Part I of the Study (Week 16)
Description	C-reactive protein (CRP), an acute phase protein, was measured in blood samples with a high-sensitivity CRP (hs-CRP) test using laser nephelometry.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	13	19	46	78
Number [Percent of patients]	76.9	63.2	87.0	79.5

13. Secondary Outcome

Title	Percent of Patients With an Elevated Erythrocyte Sedimentation Rate at Baseline That Had Normalized at the End of Part I of the Study (Week 16)
Description	Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	23	26	73	122
Number [Percent of patients]	82.6	57.7	87.7	80.3

14. Secondary Outcome

Title	Percent of Patients With an Elevated Platelet Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16)
Description	Platelets were measured in blood samples taken from the patients.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	13	18	43	74
Number [Percent of patients]	84.6	55.6	86.0	78.4

15. Secondary Outcome

Title	Percent of Patients With an Elevated White Blood Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16)
Description	White blood cells were measured in blood samples taken from the patients.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description
Intent-to-treat patient population-1: All patients who were randomized into Part I of the study and received at least 1 dose of tocilizumab.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	3	3	2	8
Number [Percent of patients]	66.7	66.7	100.0	75.0

16. Secondary Outcome

Title	Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at the End of Part II of the Study (Week 40)
Description	A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening > 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale [VAS]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]). The analysis used the Cochran-Mantel-Haenszel test with the stratification variables background use of methotrexate and oral corticosteroids applied at Week 16.
Time Frame	Week 40

Outcome Measure Data

Analysis Population Description
Intent-to-treat population-2: All eligible patients completing Part I of the study who were randomized into Part II of the study and received at least 1 dose of tocilizumab in Part II.

Arm/Group Title	Placebo	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received placebo to tocilizumab intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	81	82
ACR30 response	54.3	74.4
ACR50 response	51.9	73.2
ACR70 response	42.0	64.6
ACR90 response	23.5	45.1

17. Secondary Outcome

Title	Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at the End of Part II of the Study (Week 40)
Description	The patient's treating physician provides a rating of the patient's arthritis disease activity on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'arthritis inactive' (ie, symptom-free and no arthritis symptoms) and the extreme right end represents 'arthritis very active'. A higher score indicates more disease activity. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Intent-to-treat population-2: All eligible patients completing Part I of the study who were randomized into Part II of the study and received at least 1 dose of tocilizumab in Part II.

Arm/Group Title	Placebo	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received placebo to tocilizumab intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	81	82
Mean (Standard Deviation) [Units on a scale]	-38.2 (24.77)	-45.6 (21.47)

18. Secondary Outcome

Title	Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at the End of Part II of the Study (Week 40)
Description	The patient or parent/guardian, as appropriate, provides a rating of the patient's well-being on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'very well' (ie, symptom-free and no arthritis disease activity) and the extreme right end represents 'very poor' (ie, maximum arthritis disease activity). A higher score indicates poorer well-being. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Intent-to-treat population-2: All eligible patients completing Part I of the study who were randomized into Part II of the study and received at least 1 dose of tocilizumab in Part II.

Arm/Group Title	Placebo	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received placebo to tocilizumab intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	81	82
Mean (Standard Deviation) [Units on a scale]	-32.4 (28.57)	-31.1 (28.52)

19. Secondary Outcome

Title	Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at the End of Part II of the Study (Week 40)
Description	Joints with active arthritis are defined as joints with swelling present or pain present and limitation of motion. The maximum number of joints with active arthritis is 71. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Intent-to-treat population-2: All eligible patients completing Part I of the study who were randomized into Part II of the study and received at least 1 dose of tocilizumab in Part II.

Arm/Group Title	Placebo	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received placebo to tocilizumab intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	81	82
Mean (Standard Deviation) [Joints]	-11.5 (12.77)	-14.5 (11.14)

20. Secondary Outcome

Title	Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at the End of Part II of the Study (Week 40)
Description	Joints with limitation of movement are defined as joints with limitation of motion. The maximum number of joints with limitation of movement is 67. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Intent-to-treat population-2: All eligible patients completing Part I of the study who were randomized into Part II of the study and received at least 1 dose of tocilizumab in Part II.

Arm/Group Title	Placebo	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received placebo to tocilizumab intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	81	82
Mean (Standard Deviation) [Joints]	-8.1 (9.90)	-10.2 (8.97)

21. Secondary Outcome

Title	Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at the End of Part II of the Study (Week 40)
Description	Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Intent-to-treat population-2: All eligible patients completing Part I of the study who were randomized into Part II of the study and received at least 1 dose of tocilizumab in Part II.

Arm/Group Title	Placebo	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received placebo to tocilizumab intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	81	82
Mean (Standard Deviation) [mm/hour]	-14.0 (28.46)	-25.2 (21.97)

22. Secondary Outcome

Title	Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) at the End of Part II of the Study (Week 40)
Description	The Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI), as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Intent-to-treat population-2: All eligible patients completing Part I of the study who were randomized into Part II of the study and received at least 1 dose of tocilizumab in Part II.

Arm/Group Title	Placebo	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received placebo to tocilizumab intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	81	82
Mean (Standard Deviation) [Units on a scale]	-0.724 (0.6905)	-0.804 (0.6534)

23. Secondary Outcome

Title	Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at the End of Part II of the Study (Week 40)
Description	The patient or parent/guardian, as appropriate, provides a rating of the patient's pain (also called a discomfort index) on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'no pain' and the extreme right end represents 'very extreme pain'. A higher score indicates more pain. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward (LOCF) imputation for missing values. The analysis was adjusted for the randomization stratification factors background use of methotrexate and background use of oral corticosteroids, and the pain visual analog scale score at Baseline. The adjusted means from the fitted model are presented.
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Intent-to-treat population-2: All eligible patients completing Part I of the study who were randomized into Part II of the study and received at least 1 dose of tocilizumab in Part II.

Arm/Group Title	Placebo	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received placebo to tocilizumab intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	81	82
Mean (Standard Deviation) [Units on a scale]	-30.2 (27.12)	-31.5 (31.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tocilizumab 8 or 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Adjusted mean - Placebo
	Estimated Value	-22.3
	Confidence Interval	() % to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tocilizumab 8 or 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Adjusted mean - Tocilizumab
	Estimated Value	-32.4
	Confidence Interval	() % to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tocilizumab 8 or 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0076
	Comments	The analysis was adjusted for the randomization stratification factors background use of methotrexate and background use of oral corticosteroids. The analysis was also adjusted for the pain visual analog scale score at Baseline.
	Method	ANOVA
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.2
	Confidence Interval	(2-Sided) 95% -17.6 to -2.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Percent of Patients With Inactive Disease at the End of Part II of the Study (Week 40)
Description	A patient is judged to have inactive disease if all of the following criteria are met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10. The statistical test is not significant due to a break in the hierarchical chain of significance testing.
Time Frame	Week 40

Outcome Measure Data

Analysis Population Description
Intent-to-treat population-2: All eligible patients completing Part I of the study who were randomized into Part II of the study and received at least 1 dose of tocilizumab in Part II.

Arm/Group Title	Placebo	Tocilizumab 8 or 10 mg/kg
Arm/Group Description	Patients received placebo to tocilizumab intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	81	82
Number (95% Confidence Interval) [Percent of patients]	17.3	36.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tocilizumab 8 or 10 mg/kg
	Comments	The analysis used the Cochran-Mantel-Haenszel test adjusted for the randomization stratification factors background use of methotrexate and background use of oral corticosteroids.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	1.000
	Comments	1.000 is used here as the test was considered as not significant due to the break in the hierarchical testing chain.
	Method	Cochran-Mantel-Haenszel
	Comments	The analysis was adjusted for the randomization stratification factors background use of methotrexate and background use of oral corticosteroids.

Method of Estimation	Estimation Parameter	Weighted difference
	Estimated Value	18
	Confidence Interval	(2-Sided) 95% 5 to 32
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Weeks 2, 52, and 104
Description	A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening > 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale [VAS]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]).
Time Frame	Week 2 to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	9	7	11	55	82
Week 2 - ACR30 Response	55.6	42.9	45.5	54.5	52.4
Week 2 - ACR50 Response	33.3	42.9	18.2	34.5	32.9
Week 2 - ACR70 Response	11.1	0.0	9.1	12.7	11.0
Week 2 - ACR90 Response	0.0	0.0	0.0	0.0	0.0
Week 52 - ACR30 Response	100.0	100.0	100.0	96.4	97.6
Week 52 - ACR50 Response	100.0	100.0	90.9	94.5	95.1
Week 52 - ACR70 Response	100.0	85.7	72.7	87.3	86.6
Week 52 - ACR90 Response	88.9	57.1	54.5	65.5	65.9
Week 104 - ACR30 Response	100.0	100.0	90.9	94.5	95.1
Week 104 - ACR50 Response	100.0	100.0	90.9	87.3	90.2
Week 104 - ACR70 Response	88.9	100.0	90.9	83.6	86.6
Week 104 - ACR90 Response	88.9	71.4	72.7	67.3	70.7

26. Secondary Outcome

Title	Percent of Patients With 4 Baseline Disease Characteristics Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Week 104
Description	A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening > 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]). Results are reported for the subgroups: Previous biologic treatment (yes/no), concomitant methotrexate use (yes/no), rheumatoid factor (positive/negative), concomitant oral corticosteroid use (yes/no). Last observation carried forward was applied to missing components at visits.
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. Patients who withdrew due to non-safety reasons are classified as non-responders. Patients who withdrew due to safety have their last available response prior to withdrawal carried forward.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	9	7	11	55	82
Previous Biologic Use: Yes - ACR30 (n=1,1,0,25,27)	100.0	100.0	0.0	96.0	96.3
Previous Biologic Use: Yes - ACR50 (n=1,1,0,25,27)	100.0	100.0	0.0	80.0	81.5
Previous Biologic Use: Yes - ACR70 (n=1,1,0,25,27)	0.0	100.0	0.0	72.0	70.4
Previous Biologic Use: Yes - ACR90 (n=1,1,0,25,27)	0.0	100.0	0.0	48.0	48.1
Previous Biologic Use: No - ACR30 (n=8 6,11,30,55)	100.0	100.0	90.9	93.3	94.5
Previous Biologic Use: No - ACR50 (n=8,6,11,30,55)	100.0	100.0	90.9	93.3	94.5
Previous Biologic Use: No - ACR70 (n=8,6,11,30,55)	100.0	100.0	90.9	93.3	94.5
Previous Biologic Use: No - ACR90 (n=8,6,11,30,55)	100.0	66.7	72.7	83.3	81.8
Methotrexate Use: Yes - ACR30 (n=7,7,11,42,67)	100.0	100.0	90.9	95.2	95.5
Methotrexate Use: Yes - ACR50 (n=7,7,11,42,67)	100.0	100.0	90.9	88.1	91.0
Methotrexate Use: Yes - ACR70 (n=7,7,11,42,67)	100.0	100.0	90.9	83.3	88.1
Methotrexate Use: Yes - ACR90 (n=7,7,11,42,67)	100.0	71.4	72.7	73.8	76.1
Methotrexate Use: No - ACR30 (n=2,0,0,13,15)	100.0	0.0	0.0	92.3	93.3
Methotrexate Use: No - ACR50 (n=2,0,0,13,15)	100.0	0.0	0.0	84.6	86.7
Methotrexate Use: No - ACR70 (n=2,0,0,13,15)	50.0	0.0	0.0	84.6	80.0
Methotrexate Use: No - ACR90 (n=2,0,0,13,15)	50.0	0.0	0.0	46.2	46.7
Oral Corticosteroid Use:Yes - ACR30(n=2,3,5,23,33)	100.0	100.0	80.0	91.3	90.9
Oral Corticosteroid Use: Yes - ACR50 (2,3,5,23,33)	100.0	100.0	80.0	91.3	90.9
Oral Corticosteroid Use: Yes - ACR70 (2,3,5,23,33)	100.0	100.0	80.0	82.6	84.8
Oral Corticosteroid Use: Yes - ACR90 (2,3,5,23,33)	100.0	66.7	80.0	65.2	69.7
Oral Corticosteroid Use: No - ACR30 (7,4,6,32,49)	100.0	100.0	100.0	96.9	98.0
Oral Corticosteroid Use: No - ACR50 (7,4,6,32,49)	100.0	100.0	100.0	84.4	89.8
Oral Corticosteroid Use: No - ACR70 (7,4,6,32,49)	85.7	100.0	100.0	84.4	87.8
Oral Corticosteroid Use: No - ACR90 (7,4,6,32,49)	85.7	75.0	66.7	68.8	71.4
Rheumatoid Factor: Positive - ACR30 (0,2,2,23,27)	0.0	100.0	100.0	95.7	96.3
Rheumatoid Factor: Positive - ACR50 (0,2,2,23,27)	0.0	100.0	100.0	91.3	92.6
Rheumatoid Factor: Positive - ACR70 (0,2,2,23,27)	0.0	100.0	100.0	91.3	92.6
Rheumatoid Factor: Positive - ACR90 (0,2,2,23,27)	0.0	50.0	100.0	78.3	77.8
Rheumatoid Factor: Negative - ACR30 (9,5,7,29,50)	100.0	100.0	100.0	93.1	96.0
Rheumatoid Factor: Negative - ACR50 (9,5,7,29,50)	100.0	100.0	100.0	82.8	90.0
Rheumatoid Factor: Negative - ACR70 (9,5,7,29,50)	88.9	100.0	100.0	75.9	84.0
Rheumatoid Factor: Negative - ACR90 (9,5,7,29,50)	88.9	80.0	85.7	58.6	70.0

27. Secondary Outcome

Title	Change From Baseline in the Juvenile Arthritis Disease Activity Score-71 (JADAS-71) at Week 104
Description	The JADAS-71 is composed of 4 components: Physician global assessment of disease activity on a visual analog scale (VAS) (range = 0-10, left end of the line = arthritis inactive, ie, symptom-free and no arthritis symptoms; right end = arthritis very active), patient/parent global assessment of overall well-being on a VAS (range = 0-10, left end of the line = very well, ie, symptom-free and no arthritis disease activity; right end = very poor, ie, maximum arthritis disease activity), normalized erythrocyte sedimentation rate (ESR) (range = 0-10, If ESR is ≤ 20 mm/h, set to 0. If ≥ 120 mm/h, set to 10 mm/h. If > 20 mm/h and < 120 mm/h, apply formula: [ESR - 20 mm/h]/10 mm/h), and a count of active arthritis (swelling present or pain present and limitation of motion) in 71 selected joints (range=0-71). The JADAS-71 is the sum of the 4 component scores and ranges from 0-101. A higher score indicates more arthritis disease activity. A positive change score indicates improvement.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. Only patients with non-missing data were included in the analysis.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	7	7	11	51	76
Mean (Standard Deviation) [Units on a scale]	-31.40 (17.471)	-24.17 (14.856)	-25.42 (13.142)	-25.70 (12.200)	-26.05 (12.941)

28. Secondary Outcome

Title	Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at Week 104
Description	The patient's treating physician provides a rating of the patient's arthritis disease activity on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'arthritis inactive' (ie, symptom-free and no arthritis symptoms) and the extreme right end represents 'arthritis very active'. A negative change score indicates improvement.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. The analysis excluded patients without a Baseline assessment or who had withdrawn.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	7	7	11	51	76
Mean (Standard Deviation) [Percent change]	-97.65 (2.689)	-96.01 (9.862)	-90.42 (16.306)	-87.58 (27.588)	-89.70 (23.747)

29. Secondary Outcome

Title	Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at Week 104
Description	The patient or parent/guardian, as appropriate, provides a rating of the patient's well-being on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'very well' (ie, symptom-free and no arthritis disease activity) and the extreme right end represents 'very poor' (ie, maximum arthritis disease activity). A negative change score indicates improvement.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. The analysis excluded patients without a Baseline assessment or who had withdrawn.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	7	7	11	51	76
Mean (Standard Deviation) [Percent change]	-97.01 (5.323)	-38.23 (75.749)	-83.06 (25.986)	-75.81 (42.143)	-75.35 (43.779)

30. Secondary Outcome

Title	Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at Week 104
Description	Joints with active arthritis are defined as joints with swelling present or pain present and limitation of motion. The maximum number of joints with active arthritis is 71. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. The analysis excluded patients without a Baseline assessment or who had withdrawn.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	7	7	11	52	77
Mean (Standard Deviation) [Percent change]	-98.57 (3.780)	-88.22 (24.908)	-76.43 (44.956)	-88.60 (24.043)	-87.73 (27.088)

31. Secondary Outcome

Title	Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at Week 104
Description	Joints with limitation of movement are defined as joints with limitation of motion. The maximum number of joints with limitation of movement is 67. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. Each visit includes patients with a non-missing assessment at the time point. Patients who previously withdrew are excluded. Patients without a Baseline assessment are excluded.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	7	7	11	52	77
Mean (Standard Deviation) [Percent change]	-98.57 (3.780)	-81.81 (32.048)	-76.66 (55.781)	-79.88 (26.831)	-81.30 (31.729)

32. Secondary Outcome

Title	Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at Week 104
Description	Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. Each visit includes patients with a non-missing assessment at the time point. Patients who previously withdrew are excluded. Patients without a Baseline assessment are excluded.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	7	7	11	52	77
Mean (Standard Deviation) [Percent change]	-84.42 (13.141)	-89.21 (4.682)	-74.06 (31.967)	-73.85 (29.073)	-76.24 (27.263)

33. Secondary Outcome

Title	Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at Week 104
Description	Functional ability is assessed with the Childhood Health Assessment Questionnaire (CHAQ-DI) disability index which consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. If aids and devices listed in the questionnaire or assistance from a person are required to perform a task, a domain score of 0 or 1 is increased to 2; if the domain score is 2 or 3, the domain score is not adjusted. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A negative change score indicates improvement.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. Each visit includes patients with a non-missing assessment at the time point. Patients who previously withdrew are excluded. Patients without a Baseline assessment are excluded.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	7	7	11	52	77
Mean (Standard Deviation) [Percent change]	-96.03 (10.499)	-79.50 (18.622)	-78.58 (29.821)	-73.34 (38.745)	-76.71 (34.696)

34. Secondary Outcome

Title	Percent of Patients With a Minimally Important Improvement in the Children's Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Weeks 16, 40, 52, 80, and 104
Description	The CHAQ-DI consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. If aids and devices listed in the questionnaire or assistance from a person are required to perform a task, a domain score of 0 or 1 is increased to 2; if the domain score is 2 or 3, the domain score is not adjusted. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A minimally important improvement is an improvement ≥ 0.13 over Baseline. Patients who withdrew due to non-safety reasons are classified as non-responders.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. Patients who withdrew due to non-safety reasons are classified as non-responders. Patients who withdrew due to safety have their last available response prior to withdrawal carried forward.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	9	7	11	55	82
Week 16	77.8	85.7	81.8	76.4	78.0
Week 40	88.9	100.0	81.8	78.2	81.7
Week 52	88.9	100.0	81.8	80.0	82.9
Week 80	88.9	100.0	90.9	80.0	84.1
Week 104	88.9	100.0	100.0	80.0	85.4

35. Secondary Outcome

Title	C-reactive Protein Levels From Baseline to Week 104
Description	C-reactive protein (CRP), an acute phase protein, was measured in blood samples with a high-sensitivity CRP (hs-CRP) test using laser nephelometry.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. Each visit includes patients with a non-missing assessment at the time point. Patients who previously withdrew are excluded.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	9	7	9	53	78
Week 16 (n=9, 6, 7, 53, 75)	1.726 (2.7395)	0.220 (0.0400)	1.077 (1.1247)	1.137 (3.2472)	1.129 (2.9042)
Week 40 (n=7, 7, 11, 51, 76)	3.709 (9.0383)	2.286 (5.5183)	1.591 (2.6187)	1.451 (5.9168)	1.756 (5.8029)
Week 52 (n=8, 7, 10, 52, 77)	3.405 (8.6491)	0.267 (0.1325)	4.584 (10.4573)	0.882 (2.4335)	1.569 (5.0838)
Week 80 (n=8, 7, 10, 51, 76)	2.329 (5.9286)	0.623 (0.6096)	4.867 (13.0151)	0.718 (1.5474)	1.425 (5.2250)
Week 104 (n=7, 7, 11, 50, 75)	0.249 (0.0949)	0.200 (0.0000)	1.259 (2.8519)	2.032 (6.5732)	1.581 (5.4965)

36. Secondary Outcome

Title	Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at Weeks 2, 40, 52, and 104
Description	The patient or parent/guardian, as appropriate, provides a rating of the patient's pain (also called a discomfort index) on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'no pain' and the extreme right end represents 'very extreme pain'. A higher score indicates more pain. A negative change score indicates improvement.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. Each visit includes patients with a non-missing assessment at the time point. Patients who previously withdrew are excluded. Patients without a Baseline assessment are excluded.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	9	7	11	55	82
Week 2 (n=9, 7, 10, 52, 78)	-11.4 (13.16)	-4.4 (13.13)	-6.1 (20.98)	-10.3 (21.44)	-9.4 (19.80)
Week 40 (n=8, 7, 11, 52, 78)	-44.0 (12.29)	-24.7 (27.76)	-27.9 (35.85)	-33.9 (31.64)	-33.3 (30.44)
Week 52 (n=8, 7, 1, 52, 78)	-47.8 (14.46)	-24.0 (26.59)	-29.6 (28.39)	-35.5 (29.07)	-34.9 (27.76)
Week 104 (n=7, 7, 11, 51, 76)	-48.9 (16.71)	-30.7 (31.63)	-27.1 (39.51)	-34.5 (34.59)	-34.4 (33.72)

37. Secondary Outcome

Title	Percent of Patients With Inactive Disease From Week 16 to Week 104
Description	A patient is judged to have inactive disease if all of the following criteria are met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10. Patients who withdrew due to non-safety reasons are classified as non-responders.
Time Frame	Week 16 to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. Patients who withdrew due to safety have their last available response prior to withdrawal carried forward. Last observation carried forward applied to missing core components at visits.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	9	7	11	55	82
Week 16	11.1	42.9	18.2	20.0	20.7
Week 40	44.4	42.9	45.5	38.2	40.2
Week 52	66.7	57.1	45.5	50.9	52.4
Week 80	66.7	57.1	54.5	56.4	57.3
Week 104	66.7	71.4	54.5	63.6	63.4

38. Secondary Outcome

Title	Percent of Patients in Clinical Remission From Week 40 to 104
Description	A patient was in clinical remission if they had inactive disease at all visits in the 6 months prior to and including the visit assessment day. A patient was judged to have inactive disease if all of the following criteria were met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10. Patients who withdrew due to non-safety reasons are classified as non-responders.
Time Frame	Week 40 to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. Patients who withdrew due to safety have their last available response prior to withdrawal carried forward. Last observation carried forward applied to missing core components at visits.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	9	7	11	55	82
Week 40	0.0	14.3	0.0	7.3	6.1
Week 52	22.2	14.3	18.2	18.2	18.3
Week 80	55.6	42.9	36.4	25.5	31.7
Week 104	55.6	57.1	27.3	34.5	37.8

39. Secondary Outcome

Title	Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Week 104 by Duration of Disease (< 2 Years, ≥ 2 Years)
Description	A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening > 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale [VAS]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]). Patients who withdrew due to non-safety reasons are classified as non-responders.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
Continuous tocilizumab population: Patients randomized to tocilizumab in Part II of the study and who therefore received tocilizumab throughout the study. Patients who withdrew due to safety have their last available response prior to withdrawal carried forward. Last observation carried forward applied to missing core components at visits.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	9	7	11	55	82
Disease Duration < 2 Years - ACR30 (n=4,1,4,17,26)	100.0	100.0	100.0	88.2	92.3
Disease Duration < 2 Years - ACR50 (n=4,1,4,17,26)	100.0	100.0	100.0	82.4	88.5
Disease Duration < 2 Years - ACR70 (n=4,1,4,17,26)	100.0	100.0	100.0	82.4	88.5
Disease Duration < 2 Years - ACR90 (n=4,1,4,17,26)	100.0	100.0	100.0	76.5	84.6
Disease Duration ≥ 2 Years - ACR30 (n=5,6,7,38,56)	100.0	100.0	85.7	97.4	96.4
Disease Duration ≥ 2 Years - ACR50 (n=5,6,7,38,56)	100.0	100.0	85.7	89.5	91.1
Disease Duration ≥ 2 Years - ACR70 (n=5,6,7,38,56)	80.0	100.0	85.7	84.2	85.7
Disease Duration ≥ 2 Years - ACR90 (n=5,6,7,38,56)	80.0	66.7	57.1	63.2	64.3

40. Secondary Outcome

Title	Oral Corticosteroid Dose at Baseline, Week 52, and Week 104
Description	Due to the different types of corticosteroid medications available, the prednisone equivalent was used in the calculation of the oral corticosteroid dose. Values are based on the average daily dose on the study day and if not available the last observation carried forward is used.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
All exposure safety population: All patients randomized into Part I of the study who received at least 1 infusion of tocilizumab and had at least 1 post-baseline safety assessment or event. Each visit includes patients with a non-missing assessment at the time point. Patients who previously withdrew are excluded.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	22	13	34	119	188
Baseline (n=22, 13, 34, 119, 188)	0.041 (0.0704)	0.095 (0.0836)	0.079 (0.0802)	0.055 (0.0708)	0.061 (0.0743)
Week 52 (n=17, 13, 24, 105, 159)	0.021 (0.0474)	0.064 (0.0599)	0.037 (0.0591)	0.032 (0.0490)	0.034 (0.0518)
Week 104 (n=16, 13, 23, 103, 155)	0.014 (0.0418)	0.028 (0.0497)	0.019 (0.0412)	0.020 (0.0558)	0.020 (0.0518)

41. Secondary Outcome

Title	Methotrexate Dose at Baseline, Week 52, and Week 104
Description	Values are based on the average daily dose on the study day and if not available the last observation carried forward is used.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
All exposure safety population: All participants randomized into Part I of the study who received at least 1 infusion of tocilizumab and had at least 1 post-baseline safety assessment or event. Each visit includes patients with a non-missing assessment at the time point. Patients who previously withdrew are excluded.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg	Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing < 30 kg	Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg	All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.	Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	22	13	34	119	188
Baseline (n=22, 13, 34, 118, 187)	11.304 (6.7521)	17.562 (17.0864)	12.146 (5.2822)	8.768 (5.5387)	10.292 (7.3586)
Week 52 (n=17, 13, 24, 105, 159)	9.247 (5.6513)	15.568 (15.2521)	11.216 (4.6890)	8.326 (4.9825)	9.453 (6.6963)
Week 104 (n=16, 13, 23, 103, 155)	8.342 (5.2618)	11.858 (14.3458)	10.050 (4.6316)	6.855 (5.0401)	7.902 (6.4332)

42. Secondary Outcome

Title	Height Standard Deviation Score at Baseline, Week 52, and Week 104
Description	The height Standard Deviation Score was calculated using the following formula: (Observed height - median of the reference population)/standard deviation of the reference population. The reference population was defined as that of the same sex and age to the nearest completed year and month using the World Health Organization norms. A negative score indicates less height than the reference population.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
Growth population: All participants who received at least 1 dose of tocilizumab but who did not take the growth hormone somatotropin.

Arm/Group Title	Placebo to Tocilizumab	Tocilizumab 8 or 10 mg/kg	All Tocilizumab Patients
Arm/Group Description	Patients received placebo to tocilizumab intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.	Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
Measure Participants	84	82	187
Baseline	-0.57 (1.005)	-0.33 (1.290)	-0.51 (1.219)
Week 52	-0.51 (1.004)	-0.15 (1.216)	-0.33 (1.125)
Week 104	-0.34 (0.954)	-0.01 (1.150)	-0.18 (1.066)

Adverse Events

	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg		Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg		Tocilizumab 8 mg/kg in Patients Weighing < 30 kg		Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg		All Tocilizumab Patients
Time Frame	All exposure safety population: All participants randomized into Part I of the study who received at least 1 infusion of tocilizumab and had at least 1 post-baseline safety assessment or event.
Adverse Event Reporting Description	The patients were exposed to weight-adjusted doses for the 104 week duration of the study with the exception of those patients randomized in Part II (Weeks 16-40) to receive placebo. Adverse events (AE) are reported for all participants and by the various weight-based dose groups. AEs which occurred in the placebo group in Part II are not included.

Arm/Group Title	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg		Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg		Tocilizumab 8 mg/kg in Patients Weighing < 30 kg		Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg		All Tocilizumab Patients
Arm/Group Description	Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.		Patients weighing < 30 kg at baseline receiving tocilizumab 10 mg/kg whose body weight increased to ≥ 30 kg and ≥ 5 kg over baseline body weight for 3 consecutive visits had the tocilizumab dose reduced to 8 mg/kg.		Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.		Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.		Patients received tocilizumab 8 or 10 mg/kg intravenously every 4 weeks.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg		Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg		Tocilizumab 8 mg/kg in Patients Weighing < 30 kg		Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg		All Tocilizumab Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/22 (18.2%)		1/13 (7.7%)		4/34 (11.8%)		17/119 (14.3%)		26/188 (13.8%)
Congenital, familial and genetic disorders
Familial mediterranean fever	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Eye disorders
Uveitis	0/22 (0%)		0/13 (0%)		2/34 (5.9%)		0/119 (0%)		2/188 (1.1%)
Gastrointestinal disorders
Constipation	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Hepatobiliary disorders
Cholangitis sclerosing	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Hypertransaminasaemia	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Infections and infestations
Pneumonia	1/22 (4.5%)		0/13 (0%)		0/34 (0%)		3/119 (2.5%)		4/188 (2.1%)
Bronchitis	2/22 (9.1%)		0/13 (0%)		0/34 (0%)		0/119 (0%)		2/188 (1.1%)
Cellulitis	0/22 (0%)		0/13 (0%)		0/34 (0%)		2/119 (1.7%)		2/188 (1.1%)
Varicella	1/22 (4.5%)		0/13 (0%)		1/34 (2.9%)		0/119 (0%)		2/188 (1.1%)
Appendicitis	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Epstein-Barr Virus Infection	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Paronychia	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Pyelonephritis	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		0/119 (0%)		1/188 (0.5%)
Tonsillitis	0/22 (0%)		0/13 (0%)		1/34 (2.9%)		0/119 (0%)		1/188 (0.5%)
Viral infection	0/22 (0%)		0/13 (0%)		1/34 (2.9%)		0/119 (0%)		1/188 (0.5%)
Injury, poisoning and procedural complications
Neck injury	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Synovial rupture	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Upper limb fracture	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Musculoskeletal and connective tissue disorders
Back pain	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Osteoporosis	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Scleroderma	1/22 (4.5%)		0/13 (0%)		0/34 (0%)		0/119 (0%)		1/188 (0.5%)
Nervous system disorders
Benign intracranial hypertension	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Psychiatric disorders
Psychosomatic disease	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Renal and urinary disorders
Calculus urinary	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Respiratory, thoracic and mediastinal disorders
Asthmatic crisis	0/22 (0%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		1/188 (0.5%)
Other (Not Including Serious) Adverse Events
	Tocilizumab 10 mg/kg in Patients Weighing < 30 kg		Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg		Tocilizumab 8 mg/kg in Patients Weighing < 30 kg		Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg		All Tocilizumab Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/22 (86.4%)		11/13 (84.6%)		25/34 (73.5%)		102/119 (85.7%)		157/188 (83.5%)
Blood and lymphatic system disorders
Thrombocytopenia	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		1/119 (0.8%)		2/188 (1.1%)
Eosinophilia	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		0/119 (0%)		1/188 (0.5%)
Hypochromic anaemia	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		0/119 (0%)		1/188 (0.5%)
Ear and labyrinth disorders
Ear pain	0/22 (0%)		0/13 (0%)		2/34 (5.9%)		6/119 (5%)		8/188 (4.3%)
Eye disorders
Conjunctivitis	2/22 (9.1%)		0/13 (0%)		1/34 (2.9%)		6/119 (5%)		9/188 (4.8%)
Iridocyclitis	0/22 (0%)		0/13 (0%)		2/34 (5.9%)		0/119 (0%)		2/188 (1.1%)
Gastrointestinal disorders
Nausea	0/22 (0%)		0/13 (0%)		2/34 (5.9%)		15/119 (12.6%)		17/188 (9%)
Diarrhoea	1/22 (4.5%)		0/13 (0%)		2/34 (5.9%)		14/119 (11.8%)		17/188 (9%)
Vomiting	1/22 (4.5%)		1/13 (7.7%)		3/34 (8.8%)		12/119 (10.1%)		17/188 (9%)
Abdominal pain	1/22 (4.5%)		1/13 (7.7%)		2/34 (5.9%)		12/119 (10.1%)		16/188 (8.5%)
Abdominal pain upper	0/22 (0%)		0/13 (0%)		2/34 (5.9%)		8/119 (6.7%)		10/188 (5.3%)
Mouth ulceration	0/22 (0%)		0/13 (0%)		1/34 (2.9%)		6/119 (5%)		7/188 (3.7%)
Aphthous stomatitis	0/22 (0%)		1/13 (7.7%)		1/34 (2.9%)		3/119 (2.5%)		5/188 (2.7%)
Dental caries	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		3/119 (2.5%)		4/188 (2.1%)
General disorders
Pyrexia	0/22 (0%)		1/13 (7.7%)		2/34 (5.9%)		4/119 (3.4%)		7/188 (3.7%)
Infections and infestations
Nasopharyngitis	7/22 (31.8%)		1/13 (7.7%)		5/34 (14.7%)		32/119 (26.9%)		45/188 (23.9%)
Upper respiratory tract infection	2/22 (9.1%)		0/13 (0%)		4/34 (11.8%)		17/119 (14.3%)		23/188 (12.2%)
Pharyngitis	4/22 (18.2%)		1/13 (7.7%)		3/34 (8.8%)		18/119 (15.1%)		26/188 (13.8%)
Rhinitis	1/22 (4.5%)		2/13 (15.4%)		5/34 (14.7%)		7/119 (5.9%)		15/188 (8%)
Ear infection	1/22 (4.5%)		2/13 (15.4%)		2/34 (5.9%)		10/119 (8.4%)		15/188 (8%)
Gastroenteritis	1/22 (4.5%)		0/13 (0%)		3/34 (8.8%)		7/119 (5.9%)		11/188 (5.9%)
Influenza	2/22 (9.1%)		1/13 (7.7%)		1/34 (2.9%)		7/119 (5.9%)		11/188 (5.9%)
Sinusitis	1/22 (4.5%)		2/13 (15.4%)		2/34 (5.9%)		5/119 (4.2%)		10/188 (5.3%)
Bronchitis	1/22 (4.5%)		0/13 (0%)		1/34 (2.9%)		6/119 (5%)		8/188 (4.3%)
Urinary tract infection	1/22 (4.5%)		0/13 (0%)		1/34 (2.9%)		6/119 (5%)		8/188 (4.3%)
Oral herpes	2/22 (9.1%)		1/13 (7.7%)		1/34 (2.9%)		3/119 (2.5%)		7/188 (3.7%)
Pharyngotonsillitis	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		6/119 (5%)		7/188 (3.7%)
Otitis media	0/22 (0%)		0/13 (0%)		2/34 (5.9%)		3/119 (2.5%)		5/188 (2.7%)
Pneumonia	2/22 (9.1%)		0/13 (0%)		0/34 (0%)		3/119 (2.5%)		5/188 (2.7%)
Respiratory tract infection viral	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		4/119 (3.4%)		5/188 (2.7%)
Respiratory tract infection	0/22 (0%)		1/13 (7.7%)		1/34 (2.9%)		2/119 (1.7%)		4/188 (2.1%)
Viral infection	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		3/119 (2.5%)		4/188 (2.1%)
Laryngitis	2/22 (9.1%)		0/13 (0%)		0/34 (0%)		1/119 (0.8%)		3/188 (1.6%)
Varicella	1/22 (4.5%)		2/13 (15.4%)		0/34 (0%)		0/119 (0%)		3/188 (1.6%)
Infection parasitic	0/22 (0%)		1/13 (7.7%)		1/34 (2.9%)		0/119 (0%)		2/188 (1.1%)
Mumps	0/22 (0%)		0/13 (0%)		2/34 (5.9%)		0/119 (0%)		2/188 (1.1%)
Abscess	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		0/119 (0%)		1/188 (0.5%)
Abscess limb	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		0/119 (0%)		1/188 (0.5%)
Muscle abscess	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		0/119 (0%)		1/188 (0.5%)
Skin bacterial infection	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		0/119 (0%)		1/188 (0.5%)
Injury, poisoning and procedural complications
Ligament sprain	2/22 (9.1%)		1/13 (7.7%)		1/34 (2.9%)		3/119 (2.5%)		7/188 (3.7%)
Arthropod bite	2/22 (9.1%)		1/13 (7.7%)		1/34 (2.9%)		2/119 (1.7%)		6/188 (3.2%)
Contusion	2/22 (9.1%)		0/13 (0%)		0/34 (0%)		2/119 (1.7%)		4/188 (2.1%)
Thermal burn	1/22 (4.5%)		1/13 (7.7%)		2/34 (5.9%)		0/119 (0%)		4/188 (2.1%)
Fall	0/22 (0%)		1/13 (7.7%)		1/34 (2.9%)		1/119 (0.8%)		3/188 (1.6%)
Tibia fracture	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		2/119 (1.7%)		3/188 (1.6%)
Foot fracture	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		1/119 (0.8%)		2/188 (1.1%)
Investigations
Transaminases increased	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		4/119 (3.4%)		5/188 (2.7%)
Musculoskeletal and connective tissue disorders
Juvenile arthritis	6/22 (27.3%)		3/13 (23.1%)		6/34 (17.6%)		37/119 (31.1%)		52/188 (27.7%)
Arthralgia	3/22 (13.6%)		2/13 (15.4%)		0/34 (0%)		5/119 (4.2%)		10/188 (5.3%)
Muscle disorder	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		0/119 (0%)		1/188 (0.5%)
Polyarthritis	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		0/119 (0%)		1/188 (0.5%)
Nervous system disorders
Headache	1/22 (4.5%)		3/13 (23.1%)		5/34 (14.7%)		22/119 (18.5%)		31/188 (16.5%)
Dizziness	1/22 (4.5%)		0/13 (0%)		0/34 (0%)		7/119 (5.9%)		8/188 (4.3%)
Renal and urinary disorders
Rhinorrhoea	1/22 (4.5%)		1/13 (7.7%)		0/34 (0%)		4/119 (3.4%)		6/188 (3.2%)
Reproductive system and breast disorders
Vaginal haemorrhage	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		0/119 (0%)		1/188 (0.5%)
Respiratory, thoracic and mediastinal disorders
Cough	4/22 (18.2%)		2/13 (15.4%)		6/34 (17.6%)		13/119 (10.9%)		25/188 (13.3%)
Oropharyngeal pain	1/22 (4.5%)		0/13 (0%)		3/34 (8.8%)		15/119 (12.6%)		19/188 (10.1%)
Epistaxis	2/22 (9.1%)		0/13 (0%)		1/34 (2.9%)		5/119 (4.2%)		8/188 (4.3%)
Pneumonitis	0/22 (0%)		0/13 (0%)		2/34 (5.9%)		1/119 (0.8%)		3/188 (1.6%)
Nasal obstruction	0/22 (0%)		1/13 (7.7%)		1/34 (2.9%)		0/119 (0%)		2/188 (1.1%)
Productive cough	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		1/119 (0.8%)		2/188 (1.1%)
Rhinitis allergic	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		0/119 (0%)		1/188 (0.5%)
Sneezing	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		0/119 (0%)		1/188 (0.5%)
Skin and subcutaneous tissue disorders
Rash	1/22 (4.5%)		0/13 (0%)		3/34 (8.8%)		7/119 (5.9%)		11/188 (5.9%)
Ingrowing nail	0/22 (0%)		0/13 (0%)		0/34 (0%)		6/119 (5%)		6/188 (3.2%)
Urticaria	0/22 (0%)		1/13 (7.7%)		0/34 (0%)		5/119 (4.2%)		6/188 (3.2%)
Eczema	0/22 (0%)		0/13 (0%)		2/34 (5.9%)		3/119 (2.5%)		5/188 (2.7%)
Alopecia	0/22 (0%)		0/13 (0%)		2/34 (5.9%)		1/119 (0.8%)		3/188 (1.6%)
Erythema	0/22 (0%)		1/13 (7.7%)		1/34 (2.9%)		1/119 (0.8%)		3/188 (1.6%)
Prurigo	0/22 (0%)		0/13 (0%)		2/34 (5.9%)		0/119 (0%)		2/188 (1.1%)
Vascular disorders
Hypotension	0/22 (0%)		1/13 (7.7%)		1/34 (2.9%)		2/119 (1.7%)		4/188 (2.1%)

Limitations/Caveats

[Not Specified]

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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.

Results Point of Contact

Name/Title	Medical Communications
Organization	Hoffman-La Roche
Phone	800 821-8590
Email

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT00988221

Other Study ID Numbers:

WA19977
2009-011593-15

First Posted:

Oct 2, 2009

Last Update Posted:

Jul 26, 2017

Last Verified:

Jun 1, 2017

A Study of Tocilizumab in Patients With Active Polyarticular Juvenile Idiopathic Arthritis

Study Details

Study Description

Brief Summary

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Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

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Exclusion Criteria:

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Study Results

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Baseline Characteristics

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Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

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Adverse Events

All Cause Mortality

Serious Adverse Events

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