Trial Outcomes & Findings for A Study of Decreased Dose Frequency in Participants With Systemic Juvenile Arthritis Who Experience Laboratory Abnormalities During Treatment With RoActemra/Actemra (Tocilizumab) (NCT NCT01734382)

Last Updated: 2020-04-24

Results Overview

JADAS-71 has 4 components: Physician global assessment of disease activity on a visual analog scale (VAS) (range=0-10, left end of line=arthritis inactive, i.e., symptom-free and no arthritis symptoms; right end=arthritis very active), patient/parent global assessment of overall well-being on VAS (range=0-10, left end of line=very well, right end=very poor), 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). JADAS-71 is sum of 4 component scores, range=0-101. A higher score=more arthritis disease activity. Data reported for up to Week 52 was collected in Part 2: Q3W arms: Baseline, Weeks 3,6,9,12,24,36,48 and 51; Q4W arms: Baseline, Weeks 0,4,8,12,24,36 and 40.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

35 participants

Primary outcome timeframe

Part 2: Up to 52 weeks

Results posted on

2020-04-24

Participant Flow

Participants with systemic juvenile idiopathic arthritis (sJIA) were recruited at study sites in 8 countries. The study consisted of two parts: Part 1 was a 24-week Run-in period and Part 2 was a 52-week Main study.

Participants on tocilizumab (TCZ) once every two weeks (Q2W) who had experienced a laboratory abnormality (which resolved) as per protocol criteria either during Part 1 or prior to the study, could enter Part 2. 19 Participants entered Part 1 and 6 continued on to Part 2. 16 participants directly entered Part 2 of the study.

Participant milestones

Participant milestones
Measure	Part 1: Tocilizumab (TCZ) Q2W Participants received tocilizumab intravenous (IV) infusions (12 mg/kg for participants \< 30 kg; 8 mg/kg for participants \>/= 30 kg) once every other week (Q2W) up to 24 weeks or until occurrence of a protocol defined laboratory abnormality in Part 1 of the study.	Part 2: TCZ IV 12 mg/kg Q3W/Q4W Participants with weight \< 30 kg received tocilizumab IV infusions of 12 mg/kg once every three weeks (Q3W) up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg once every four weeks (Q4W) up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q3W/Q4W Participants with weight \>/= 30 kg received tocilizumab IV infusions of 8 mg/kg Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Part 1 STARTED	19	0	0
Part 1 COMPLETED	17	0	0
Part 1 NOT COMPLETED	2	0	0
Part 2 STARTED	0	7	15
Part 2 COMPLETED	0	5	8
Part 2 NOT COMPLETED	0	2	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: Tocilizumab (TCZ) Q2W Participants received tocilizumab intravenous (IV) infusions (12 mg/kg for participants \< 30 kg; 8 mg/kg for participants \>/= 30 kg) once every other week (Q2W) up to 24 weeks or until occurrence of a protocol defined laboratory abnormality in Part 1 of the study.	Part 2: TCZ IV 12 mg/kg Q3W/Q4W Participants with weight \< 30 kg received tocilizumab IV infusions of 12 mg/kg once every three weeks (Q3W) up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg once every four weeks (Q4W) up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q3W/Q4W Participants with weight \>/= 30 kg received tocilizumab IV infusions of 8 mg/kg Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Part 1 Adverse Event	2	0	0
Part 2 Adverse Event	0	0	1
Part 2 Lack of Efficacy	0	1	1
Part 2 Other	0	0	1
Part 2 Physician Decision	0	0	3
Part 2 Protocol Violation	0	1	0
Part 2 Withdrawal by Subject	0	0	1

Baseline Characteristics

Part 1 of the study had 19 enrolled participants.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Tocilizumab (TCZ) Q2W n=19 Participants Participants received tocilizumab intravenous (IV) infusions (12 mg/kg for participants \< 30 kg; 8 mg/kg for participants \>/= 30 kg) once every other week (Q2W) up to 24 weeks or until occurrence of a protocol defined laboratory abnormality in Part 1 of the study.	Part 2: TCZ IV 12 mg/kg Q3W/Q4W n=7 Participants Participants with weight \< 30 kg received tocilizumab IV infusions of 12 mg/kg once every three weeks (Q3W) up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg once every four weeks (Q4W) up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q3W/Q4W n=15 Participants Participants with weight \>/= 30 kg received tocilizumab IV infusions of 8 mg/kg Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.	Total n=41 Participants Total of all reporting groups
Age, Continuous	8.5 years STANDARD_DEVIATION 3.6 • n=19 Participants • Part 1 of the study had 19 enrolled participants.	6.7 years STANDARD_DEVIATION 1.8 • n=7 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	11.7 years STANDARD_DEVIATION 2.8 • n=15 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	10.1 years STANDARD_DEVIATION 3.4 • n=22 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.
Sex: Female, Male Female	0 Participants Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	4 Participants n=7 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	10 Participants n=15 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	14 Participants n=22 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.
Sex: Female, Male Male	0 Participants Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	3 Participants n=7 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	5 Participants n=15 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	8 Participants n=22 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	2 Participants n=7 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	4 Participants n=15 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	6 Participants n=22 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	5 Participants n=7 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	10 Participants n=15 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	15 Participants n=22 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=7 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	1 Participants n=15 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	1 Participants n=22 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	1 Participants n=7 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	2 Participants n=15 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	3 Participants n=22 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.
Race (NIH/OMB) Asian	0 Participants Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=7 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=15 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=22 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=7 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=15 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=22 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.
Race (NIH/OMB) Black or African American	0 Participants Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=7 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=15 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=22 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.
Race (NIH/OMB) White	0 Participants Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	6 Participants n=7 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	12 Participants n=15 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	18 Participants n=22 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.
Race (NIH/OMB) More than one race	0 Participants Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=7 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=15 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=22 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.
Race (NIH/OMB) Unknown or Not Reported	0 Participants Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	0 Participants n=7 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	1 Participants n=15 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.	1 Participants n=22 Participants • Part 2 of the study had 22 enrolled participants, 6 of whom had completed Part 1 and 16 directly enrolled into Part 2.

PRIMARY outcome

Timeframe: Part 2: Up to 52 weeks

Population: All TCZ population, all participants who have received at least one dose of study drug. Number analyzed is the number of participants with data available at the given timepoint.

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=7 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=15 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=1 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W n=6 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Juvenile Arthritis Disease Activity Score (JADAS-71) Baseline	0.60 score on a scale Standard Deviation 0.839	0.21 score on a scale Standard Deviation 0.247	0.00 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.35 score on a scale Standard Deviation 0.295
Juvenile Arthritis Disease Activity Score (JADAS-71) Week 0	—	—	0.00 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.13 score on a scale Standard Deviation 0.242
Juvenile Arthritis Disease Activity Score (JADAS-71) Week 3	1.60 score on a scale Standard Deviation 2.474	0.61 score on a scale Standard Deviation 0.913	—	—
Juvenile Arthritis Disease Activity Score (JADAS-71) Week 9	2.59 score on a scale Standard Deviation 5.402	0.33 score on a scale Standard Deviation 0.420	—	—
Juvenile Arthritis Disease Activity Score (JADAS-71) Week 4	—	—	0.00 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.17 score on a scale Standard Deviation 0.266
Juvenile Arthritis Disease Activity Score (JADAS-71) Week 6	0.54 score on a scale Standard Deviation 0.812	0.39 score on a scale Standard Deviation 0.498	—	—
Juvenile Arthritis Disease Activity Score (JADAS-71) Week 8	—	—	0.00 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.20 score on a scale Standard Deviation 0.490
Juvenile Arthritis Disease Activity Score (JADAS-71) Week 12	0.30 score on a scale Standard Deviation 0.600	0.84 score on a scale Standard Deviation 2.318	0.00 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.13 score on a scale Standard Deviation 0.327
Juvenile Arthritis Disease Activity Score (JADAS-71) Week 24	0.42 score on a scale Standard Deviation 0.576	0.05 score on a scale Standard Deviation 0.084	0.00 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.20 score on a scale Standard Deviation 0.346
Juvenile Arthritis Disease Activity Score (JADAS-71) Week 36	0.48 score on a scale Standard Deviation 0.950	0.08 score on a scale Standard Deviation 0.150	0.00 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.00 score on a scale Standard Deviation 0.000
Juvenile Arthritis Disease Activity Score (JADAS-71) Week 40	—	—	—	0.00 score on a scale Standard Deviation 0.000
Juvenile Arthritis Disease Activity Score (JADAS-71) Week 48	0.00 score on a scale Standard Deviation 0.000	0.17 score on a scale Standard Deviation 0.289	—	—
Juvenile Arthritis Disease Activity Score (JADAS-71) Week 51	0.00 score on a scale Standard Deviation 0.000	0.17 score on a scale Standard Deviation 0.208	—	—

PRIMARY outcome

Timeframe: Part 2: Up to 52 weeks

Population: All TCZ population, all participants who have received at least one dose of study drug. Number of participants analyzed is the number of participants with data available for analyses.

JIA flare was defined as any 3 of the 6 core outcome variables worsening by at least 30% relative to baseline visit of Part 2, with no more than 1 of the remaining variables improving by more than 30%. For the number of joints with active arthritis or the number of joints with limitation of motion a minimum worsening of at least 2 joints had to be present. If the physician global assessment (PGA) or the parent/patient global assessment were used a minimum worsening of at least 2 units on a scale from 0 to 10 had be present. For erythrocyte sedimentation rate (ESR), a worsening of at least 30% was not considered if within normal ranges. The 6 core outcome variables: PGA of disease activity, parent/patient global assessment of overall well-being, number of joints with active arthritis, number of joints with limitation of movement, ESR (measure of acute phase reaction) and functional ability determined by Childhood Health Assessment Questionnaire (CHAQ) Disability Index.

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=7 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=15 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=1 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W n=6 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Number of Participants With Juvenile Idiopathic Arthritis (JIA) Disease Flare as Determined by JIA Core Variables in Part 2 of the Study	1 Participants	3 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Part 2: Up to 52 weeks

Population: All TCZ population, all participants who have received at least one dose of study drug.

Absence of fever at screening visit was defined as a temperature measurement \< 38 degree centigrades (C). Presence of fever at each study visit was defined as a temperature measurement ≥ 38 C.

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=7 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=15 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=1 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W n=6 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Number of Participants With Fever Attributable to Systemic Juvenile Idiopathic Arthritis (sJIA) in Part 2 of the Study	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Part 1 - Baseline up to 24 weeks plus 12 weeks of safety follow up; Part 2 - Baseline up to 52 weeks plus 12 weeks of safety follow up

Population: Safety population, all participants who have received at least one dose of study drug and who have at least one post-baseline assessment of safety.

An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=19 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=7 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=15 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Number of Participants With at Least One Adverse Event	16 Participants	7 Participants	14 Participants	—

SECONDARY outcome

Timeframe: Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40

Population: Pharmacodynamic (PD) population, all participants who have received at least one dose of study drug and who have at least one post-baseline assessment of PD. Number analyzed is the number of participants with data available at the given timepoint.

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=7 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=15 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=1 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W n=6 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study Baseline	36.340 pg/mL Standard Deviation 19.2413	23.453 pg/mL Standard Deviation 12.1440	51.500 pg/mL Standard Deviation NA SD was not estimable for 1 participant.	25.415 pg/mL Standard Deviation 15.0174
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study Week 0	—	—	—	33.000 pg/mL Standard Deviation 23.3195
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study Week 3	61.617 pg/mL Standard Deviation 75.5724	22.727 pg/mL Standard Deviation 7.0321	—	—
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study Week 4	—	—	13.700 pg/mL Standard Deviation NA SD was not estimable for 1 participant.	28.364 pg/mL Standard Deviation 24.8937
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study Week 6	46.698 pg/mL Standard Deviation 50.7148	82.995 pg/mL Standard Deviation 216.2854	—	—
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study Week 8	—	—	14.300 pg/mL Standard Deviation NA SD was not estimable for 1 participant.	30.580 pg/mL Standard Deviation 22.0335
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study Week 9	45.231 pg/mL Standard Deviation 46.2539	47.582 pg/mL Standard Deviation 37.2259	—	—
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study Week 12	84.100 pg/mL Standard Deviation 57.8972	71.867 pg/mL Standard Deviation 156.4710	11.600 pg/mL Standard Deviation NA SD was not estimable for 1 participant.	29.662 pg/mL Standard Deviation 26.0053
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study Week 24	79.200 pg/mL Standard Deviation 44.8853	23.420 pg/mL Standard Deviation 14.5520	45.000 pg/mL Standard Deviation NA SD was not estimable for 1 participant.	29.393 pg/mL Standard Deviation 19.2760
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study Week 36	67.467 pg/mL Standard Deviation 84.7317	30.025 pg/mL Standard Deviation 16.5470	14.100 pg/mL Standard Deviation NA SD was not estimable for 1 participant.	21.500 pg/mL Standard Deviation 15.8392
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study Week 40	—	—	—	22.820 pg/mL Standard Deviation 24.0133
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study Week 48	14.533 pg/mL Standard Deviation 1.4154	15.400 pg/mL Standard Deviation 10.0936	—	—
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study Week 51	17.523 pg/mL Standard Deviation 9.2077	5.060 pg/mL Standard Deviation NA SD was not estimable for 1 participant.	—	—

SECONDARY outcome

Timeframe: Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=7 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=15 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=1 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W n=6 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study Baseline	621.04 ngEq/mL Standard Deviation 443.779	735.16 ngEq/mL Standard Deviation 310.983	447.00 ngEq/mL Standard Deviation NA SD was not estimable for 1 participant.	855.00 ngEq/mL Standard Deviation 325.572
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study Week 0	—	—	72.50 ngEq/mL Standard Deviation NA SD was not estimable for 1 participant.	722.83 ngEq/mL Standard Deviation 229.530
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study Week 3	632.43 ngEq/mL Standard Deviation 261.172	707.73 ngEq/mL Standard Deviation 291.228	—	—
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study Week 4	—	—	379.00 ngEq/mL Standard Deviation NA SD was not estimable for 1 participant.	653.00 ngEq/mL Standard Deviation 143.386
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study Week 6	518.67 ngEq/mL Standard Deviation 272.217	721.73 ngEq/mL Standard Deviation 253.114	—	—
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study Week 8	—	—	434.00 ngEq/mL Standard Deviation NA SD was not estimable for 1 participant.	628.50 ngEq/mL Standard Deviation 145.891
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study Week 9	596.58 ngEq/mL Standard Deviation 318.685	646.92 ngEq/mL Standard Deviation 174.932	—	—
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study Week 12	656.80 ngEq/mL Standard Deviation 123.611	666.75 ngEq/mL Standard Deviation 144.510	411.00 ngEq/mL Standard Deviation NA SD was not estimable for 1 participant.	645.33 ngEq/mL Standard Deviation 106.952
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study Week 24	574.54 ngEq/mL Standard Deviation 347.127	554.33 ngEq/mL Standard Deviation 124.498	519.00 ngEq/mL Standard Deviation NA SD was not estimable for 1 participant.	546.25 ngEq/mL Standard Deviation 330.265
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study Week 36	492.50 ngEq/mL Standard Deviation 258.445	646.00 ngEq/mL Standard Deviation 198.499	439.00 ngEq/mL Standard Deviation NA SD was not estimable for 1 participant.	599.75 ngEq/mL Standard Deviation 122.200
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study Week 40	—	—	—	609.50 ngEq/mL Standard Deviation 115.613
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study Week 48	551.00 ngEq/mL Standard Deviation 91.000	391.00 ngEq/mL Standard Deviation 220.293	—	—
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study Week 51	651.00 ngEq/mL Standard Deviation 135.765	517.00 ngEq/mL Standard Deviation 140.007	—	—

SECONDARY outcome

Timeframe: Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=7 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=15 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=1 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W n=6 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
C-reactive Protein (CRP) Concentration in Part 2 of the Study Week 6	0.291 mg/L Standard Deviation 0.1499	0.526 mg/L Standard Deviation 1.0163	—	—
C-reactive Protein (CRP) Concentration in Part 2 of the Study Week 8	—	—	0.200 mg/L Standard Deviation NA SD was not estimable for 1 participant.	0.200 mg/L Standard Deviation 0.0000
C-reactive Protein (CRP) Concentration in Part 2 of the Study Week 9	0.208 mg/L Standard Deviation 0.0179	0.255 mg/L Standard Deviation 0.1250	0.200 mg/L Standard Deviation NA SD was not estimable for 1 participant.	0.200 mg/L Standard Deviation 0.0000
C-reactive Protein (CRP) Concentration in Part 2 of the Study Baseline	4.844 mg/L Standard Deviation 12.2832	2.309 mg/L Standard Deviation 6.9847	0.200 mg/L Standard Deviation NA SD was not estimable for 1 participant.	0.958 mg/L Standard Deviation 1.8575
C-reactive Protein (CRP) Concentration in Part 2 of the Study Week 0	—	—	0.610 mg/L Standard Deviation NA SD was not estimable for 1 participant.	0.200 mg/L Standard Deviation 0.0000
C-reactive Protein (CRP) Concentration in Part 2 of the Study Week 3	0.223 mg/L Standard Deviation 0.0427	0.216 mg/L Standard Deviation 0.0407	0.200 mg/L Standard Deviation NA SD was not estimable for 1 participant.	0.200 mg/L Standard Deviation 0.0000
C-reactive Protein (CRP) Concentration in Part 2 of the Study Week 4	—	—	0.200 mg/L Standard Deviation NA SD was not estimable for 1 participant.	0.200 mg/L Standard Deviation 0.0000
C-reactive Protein (CRP) Concentration in Part 2 of the Study Week 12	0.200 mg/L Standard Deviation 0.0000	0.238 mg/L Standard Deviation 0.1201	0.200 mg/L Standard Deviation NA SD was not estimable for 1 participant.	0.203 mg/L Standard Deviation 0.0082
C-reactive Protein (CRP) Concentration in Part 2 of the Study Week 24	0.280 mg/L Standard Deviation 0.1789	0.254 mg/L Standard Deviation 0.1207	0.200 mg/L Standard Deviation NA SD was not estimable for 1 participant.	4.040 mg/L Standard Deviation 8.5865
C-reactive Protein (CRP) Concentration in Part 2 of the Study Week 36	0.225 mg/L Standard Deviation 0.0500	0.200 mg/L Standard Deviation 0.0000	0.200 mg/L Standard Deviation NA SD was not estimable for 1 participant.	0.200 mg/L Standard Deviation 0.0000
C-reactive Protein (CRP) Concentration in Part 2 of the Study Week 40	—	—	—	0.200 mg/L Standard Deviation 0.0000
C-reactive Protein (CRP) Concentration in Part 2 of the Study Week 48	0.200 mg/L Standard Deviation 0.0000	0.820 mg/L Standard Deviation 1.0739	—	—
C-reactive Protein (CRP) Concentration in Part 2 of the Study Week 51	0.318 mg/L Standard Deviation 0.2350	0.200 mg/L Standard Deviation 0.0000	—	—

SECONDARY outcome

Timeframe: Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40

Population: PD population, all participants who have received at least one dose of study drug and who have at least one post-baseline assessment of PD. Number analyzed is the number of participants with data available at the given timepoint.

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=7 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=15 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=1 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W n=6 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study Baseline	3.43 mm/h Standard Deviation 5.192	3.00 mm/h Standard Deviation 1.852	1.00 mm/h Standard Deviation NA SD was not estimable for 1 participant.	3.17 mm/h Standard Deviation 1.602
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study Week 0	—	—	4.00 mm/h Standard Deviation NA SD was not estimable for 1 participant.	2.67 mm/h Standard Deviation 1.633
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study Week 3	2.86 mm/h Standard Deviation 2.035	3.57 mm/h Standard Deviation 2.709	2.00 mm/h Standard Deviation NA SD was not estimable for 1 participant.	2.75 mm/h Standard Deviation 0.957
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study Week 4	—	—	1.00 mm/h Standard Deviation NA SD was not estimable for 1 participant.	3.17 mm/h Standard Deviation 1.722
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study Week 6	4.14 mm/h Standard Deviation 4.598	4.13 mm/h Standard Deviation 3.681	—	—
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study Week 8	—	—	1.00 mm/h Standard Deviation NA SD was not estimable for 1 participant.	3.33 mm/h Standard Deviation 2.160
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study Week 9	2.50 mm/h Standard Deviation 2.510	3.23 mm/h Standard Deviation 2.204	3.00 mm/h Standard Deviation NA SD was not estimable for 1 participant.	2.25 mm/h Standard Deviation 0.957
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study Week 12	2.20 mm/h Standard Deviation 1.789	3.92 mm/h Standard Deviation 3.315	1.00 mm/h Standard Deviation NA SD was not estimable for 1 participant.	4.50 mm/h Standard Deviation 3.209
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study Week 24	2.80 mm/h Standard Deviation 1.304	3.17 mm/h Standard Deviation 2.137	1.00 mm/h Standard Deviation NA SD was not estimable for 1 participant.	2.80 mm/h Standard Deviation 1.789
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study Week 36	2.25 mm/h Standard Deviation 2.217	4.50 mm/h Standard Deviation 2.646	1.00 mm/h Standard Deviation NA SD was not estimable for 1 participant.	2.25 mm/h Standard Deviation 1.893
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study Week 40	—	—	—	2.25 mm/h Standard Deviation 1.893
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study Week 48	3.00 mm/h Standard Deviation 0.816	4.67 mm/h Standard Deviation 1.528	—	—
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study Week 51	1.75 mm/h Standard Deviation 1.708	6.00 mm/h Standard Deviation 3.000	—	—

SECONDARY outcome

Timeframe: Part 2: Up to Week 52

Population: Safety population, all participants who have received at least one dose of study drug and who have at least one post-baseline assessment of safety.

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=7 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=15 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=1 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W n=6 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Number of Participants With Anti-TCZ Antibodies in Part 2 of the Study	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40

Population: All TCZ population in Part 2, all participants who have received at least one dose of study drug in Part 2. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=7 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=15 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=1 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W n=6 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Serum TCZ Concentration in Part 2 of the Study Baseline	29.916 ug/mL Standard Deviation 35.8002	44.210 ug/mL Standard Deviation 33.2547	9.520 ug/mL Standard Deviation NA SD was not estimable for 1 participant.	53.622 ug/mL Standard Deviation 48.5163
Serum TCZ Concentration in Part 2 of the Study Week 0	—	—	—	24.212 ug/mL Standard Deviation 13.1659
Serum TCZ Concentration in Part 2 of the Study Week 3	26.420 ug/mL Standard Deviation 21.1844	37.239 ug/mL Standard Deviation 21.8192	—	—
Serum TCZ Concentration in Part 2 of the Study Week 4	—	—	11.100 ug/mL Standard Deviation NA SD was not estimable for 1 participant.	17.718 ug/mL Standard Deviation 11.1580
Serum TCZ Concentration in Part 2 of the Study Week 6	28.636 ug/mL Standard Deviation 13.5744	30.482 ug/mL Standard Deviation 19.2402	—	—
Serum TCZ Concentration in Part 2 of the Study Week 8	—	—	22.800 ug/mL Standard Deviation NA SD was not estimable for 1 participant.	17.578 ug/mL Standard Deviation 13.0611
Serum TCZ Concentration in Part 2 of the Study Week 9	32.020 ug/mL Standard Deviation 6.3739	26.962 ug/mL Standard Deviation 17.9122	—	—
Serum TCZ Concentration in Part 2 of the Study Week 12	37.600 ug/mL Standard Deviation 20.5254	44.763 ug/mL Standard Deviation 77.1798	23.800 ug/mL Standard Deviation NA SD was not estimable for 1 participant.	15.442 ug/mL Standard Deviation 11.0714
Serum TCZ Concentration in Part 2 of the Study Week 24	24.363 ug/mL Standard Deviation 20.3686	20.842 ug/mL Standard Deviation 25.9417	30.300 ug/mL Standard Deviation NA SD was not estimable for 1 participant.	16.030 ug/mL Standard Deviation 14.2124
Serum TCZ Concentration in Part 2 of the Study Week 36	30.517 ug/mL Standard Deviation 18.6058	19.733 ug/mL Standard Deviation 8.2218	19.800 ug/mL Standard Deviation NA SD was not estimable for 1 participant.	12.903 ug/mL Standard Deviation 11.1808
Serum TCZ Concentration in Part 2 of the Study Week 40	—	—	—	28.778 ug/mL Standard Deviation 16.0031
Serum TCZ Concentration in Part 2 of the Study Week 48	25.433 ug/mL Standard Deviation 34.3053	22.950 ug/mL Standard Deviation 0.9192	—	—
Serum TCZ Concentration in Part 2 of the Study Week 51	12.207 ug/mL Standard Deviation 8.5862	10.945 ug/mL Standard Deviation 14.6449	—	—

SECONDARY outcome

Timeframe: Baseline of Part 2

Population: All TCZ population, all participants who have received at least one dose of study drug.

CHAQ- Disability Index consists of 30 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed, among a total of 30 items. Each question was rated on 4-point scale with range 0=no difficulty to 3=unable to do. To calculate overall score, participant must have a domain score in at least 6 of 8 domains. Scores were averaged to calculate CHAQ disability index, range is 0=no/minimal physical dysfunction)-3=very severe physical dysfunction, higher score indicates more disability.

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=7 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=15 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=1 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W n=6 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Baseline Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study	0.0000 score on a scale Standard Deviation 0.00000	0.0417 score on a scale Standard Deviation 0.09047	0.0000 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.0000 score on a scale Standard Deviation 0.00000

SECONDARY outcome

Timeframe: Baseline; Part 2: Q3W arm groups - Weeks 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 51; Q4W arm groups - Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36 and 40

Population: All TCZ population, all participants who have received at least one dose of study drug. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=7 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=15 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=1 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W n=6 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 3	0.2500 score on a scale Standard Deviation 0.66144	0.0167 score on a scale Standard Deviation 0.25384	—	—
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 6	0.1071 score on a scale Standard Deviation 0.28347	-0.0083 score on a scale Standard Deviation 0.07420	—	—
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 18	0.1000 score on a scale Standard Deviation 0.22361	0.2500 score on a scale Standard Deviation 0.85009	—	—
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 0	—	—	0.0000 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.0000 score on a scale Standard Deviation 0.00000
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 4	—	—	0.0000 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.0000 score on a scale Standard Deviation 0.00000
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 8	—	—	0.0000 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.0000 score on a scale Standard Deviation 0.00000
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 9	0.2500 score on a scale Standard Deviation 0.51539	-0.0268 score on a scale Standard Deviation 0.10022	—	—
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 12	0.1250 score on a scale Standard Deviation 0.27951	-0.0481 score on a scale Standard Deviation 0.09599	0.0000 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.0000 score on a scale Standard Deviation 0.00000
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 15	0.1458 score on a scale Standard Deviation 0.35722	0.1771 score on a scale Standard Deviation 0.54994	—	—
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 16	—	—	0.0000 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.0000 score on a scale Standard Deviation 0.00000
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 20	—	—	0.0000 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.0000 score on a scale Standard Deviation 0.00000
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 21	0.0000 score on a scale Standard Deviation 0.00000	0.2656 score on a scale Standard Deviation 0.90740	—	—
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 24	0.1250 score on a scale Standard Deviation 0.27951	-0.0750 score on a scale Standard Deviation 0.11180	0.0000 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.0000 score on a scale Standard Deviation 0.00000
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 27	0.0000 score on a scale Standard Deviation 0.00000	0.0000 score on a scale Standard Deviation 0.10206	—	—
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 28	—	—	0.0000 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.0000 score on a scale Standard Deviation 0.00000
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 30	0.0000 score on a scale Standard Deviation 0.00000	0.0000 score on a scale Standard Deviation 0.00000	—	—
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 32	—	—	0.0000 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.0000 score on a scale Standard Deviation 0.00000
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 33	0.0000 score on a scale Standard Deviation 0.00000	-0.0417 score on a scale Standard Deviation 0.07217	—	—
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 36	0.0000 score on a scale Standard Deviation 0.00000	0.0417 score on a scale Standard Deviation 0.07217	0.0000 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	0.0000 score on a scale Standard Deviation 0.00000
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 39	0.0000 score on a scale Standard Deviation 0.00000	-0.0417 score on a scale Standard Deviation 0.07217	—	—
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 40	—	—	—	0.0000 score on a scale Standard Deviation 0.00000
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 42	0.0000 score on a scale Standard Deviation 0.00000	-0.0417 score on a scale Standard Deviation 0.07217	—	—
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 45	0.0000 score on a scale Standard Deviation 0.00000	-0.0417 score on a scale Standard Deviation 0.07217	—	—
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 48	0.0000 score on a scale Standard Deviation 0.00000	-0.0417 score on a scale Standard Deviation 0.07217	—	—
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study Change from Baseline at Week 51	0.0000 score on a scale Standard Deviation 0.00000	-0.0417 score on a scale Standard Deviation 0.07217	—	—

SECONDARY outcome

Timeframe: Baseline of Part 2

Population: All TCZ population, all participants who have received at least one dose of study drug.

Participant's/parent's global assessment of overall well-being was determined on a VAS (range = 0-100, left end of the line = very well, i.e., symptom-free and no arthritis disease activity; right end = very poor, i.e., maximum arthritis disease activity).

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=7 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=15 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=1 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W n=6 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Baseline Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study	2.3 score on a scale Standard Deviation 3.95	1.6 score on a scale Standard Deviation 2.29	0.0 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	2.5 score on a scale Standard Deviation 3.21

SECONDARY outcome

Timeframe: Baseline; Part 2: Q3W arm groups - Weeks 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 51; Q4W arm groups - Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36 and 40

Participant's/Parent's global assessment of overall well-being was determined on a VAS (range = 0-100, left end of the line = very well, i.e., symptom-free and no arthritis disease activity; right end = very poor, i.e., maximum arthritis disease activity). Reported is the change from baseline in VAS score with a negative change from baseline indicating an improvement.

Outcome measures

Outcome measures
Measure	Part 2: TCZ IV 12 mg/kg Q3W n=7 Participants Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 8 mg/kg Q3W n=15 Participants Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria.	Part 2: TCZ IV 12 mg/kg Q4W n=1 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q4W n=6 Participants Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 0	—	—	0.0000 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	-1.2 score on a scale Standard Deviation 1.60
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 3	-0.3 score on a scale Standard Deviation 2.36	2.0 score on a scale Standard Deviation 6.12	—	—
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 4	—	—	0.0000 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	-1.2 score on a scale Standard Deviation 1.26
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 6	-1.6 score on a scale Standard Deviation 3.51	2.2 score on a scale Standard Deviation 4.55	—	—
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 8	—	—	0.0 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	-0.5 score on a scale Standard Deviation 3.56
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 9	8.4 score on a scale Standard Deviation 26.48	0.1 score on a scale Standard Deviation 2.62	—	—
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 12	-1.6 score on a scale Standard Deviation 3.58	-0.7 score on a scale Standard Deviation 2.32	0.0 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	-1.2 score on a scale Standard Deviation 2.56
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 15	-1.5 score on a scale Standard Deviation 3.67	7.1 score on a scale Standard Deviation 29.34	—	—
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 16	—	—	0.0 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	-1.5 score on a scale Standard Deviation 1.97
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 18	-1.4 score on a scale Standard Deviation 3.71	6.9 score on a scale Standard Deviation 23.26	—	—
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 20	—	—	0.0 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	-1.6 score on a scale Standard Deviation 2.61
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 21	0.0 score on a scale Standard Deviation 0.00	9.9 score on a scale Standard Deviation 30.02	—	—
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 24	-1.8 score on a scale Standard Deviation 4.02	-0.8 score on a scale Standard Deviation 2.17	0.0 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	-1.0 score on a scale Standard Deviation 2.00
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 27	0.0 score on a scale Standard Deviation 0.00	0.3 score on a scale Standard Deviation 2.87	—	—
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 28	—	—	0.0 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	-1.2 score on a scale Standard Deviation 2.39
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 30	0.0 score on a scale Standard Deviation 0.00	-0.3 score on a scale Standard Deviation 2.52	—	—
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 32	—	—	0.0 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	5.4 score on a scale Standard Deviation 14.35
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 33	25.0 score on a scale Standard Deviation 50.00	0.0 score on a scale Standard Deviation 3.00	—	—
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 36	0.3 score on a scale Standard Deviation 0.50	0.0 score on a scale Standard Deviation 3.00	0.0 score on a scale Standard Deviation NA SD was not estimable for 1 participant.	-2.0 score on a scale Standard Deviation 2.83
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 39	0.3 score on a scale Standard Deviation 0.50	-1.0 score on a scale Standard Deviation 1.73	—	—
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 40	—	—	—	-2.7 score on a scale Standard Deviation 3.06
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 42	0.0 score on a scale Standard Deviation 0.00	-0.7 score on a scale Standard Deviation 2.08	—	—
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 45	0.0 score on a scale Standard Deviation 0.00	0.3 score on a scale Standard Deviation 3.51	—	—
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 48	0.0 score on a scale Standard Deviation 0.00	0.7 score on a scale Standard Deviation 4.04	—	—
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study Change from Baseline at Week 51	0.0 score on a scale Standard Deviation 0.00	0.3 score on a scale Standard Deviation 3.51	—	—

Adverse Events

Part 1: Tocilizumab (TCZ) Q2W

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Part 2: TCZ IV 12 mg/kg Q3W/Q4W

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Part 2: TCZ IV 8 mg/kg Q3W/Q4W

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part 1: Tocilizumab (TCZ) Q2W n=19 participants at risk Participants received tocilizumab intravenous (IV) infusions (12 mg/kg for participants \< 30 kg; 8 mg/kg for participants \>/= 30 kg) once every other week (Q2W) up to 24 weeks or until occurrence of a protocol defined laboratory abnormality in Part 1 of the study.	Part 2: TCZ IV 12 mg/kg Q3W/Q4W n=7 participants at risk Participants with weight \< 30 kg received tocilizumab IV infusions of 12 mg/kg once every three weeks (Q3W) up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg once every four weeks (Q4W) up to Week 52 in Part 2 of the study.	Part 2: TCZ IV 8 mg/kg Q3W/Q4W n=15 participants at risk Participants with weight \>/= 30 kg received tocilizumab IV infusions of 8 mg/kg Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Hepatobiliary disorders HYPERTRANSAMINASAEMIA	0.00% 0/19 • Part 1 - Up to 24 weeks plus 12 weeks safety follow up; Part 2 - Up to 52 weeks plus 12 weeks safety follow up Safety population, all participants who received at least one dose of study drug and who had at least one post-baseline assessment of safety.	0.00% 0/7 • Part 1 - Up to 24 weeks plus 12 weeks safety follow up; Part 2 - Up to 52 weeks plus 12 weeks safety follow up Safety population, all participants who received at least one dose of study drug and who had at least one post-baseline assessment of safety.	6.7% 1/15 • Number of events 1 • Part 1 - Up to 24 weeks plus 12 weeks safety follow up; Part 2 - Up to 52 weeks plus 12 weeks safety follow up Safety population, all participants who received at least one dose of study drug and who had at least one post-baseline assessment of safety.
Infections and infestations PNEUMONIA	0.00% 0/19 • Part 1 - Up to 24 weeks plus 12 weeks safety follow up; Part 2 - Up to 52 weeks plus 12 weeks safety follow up Safety population, all participants who received at least one dose of study drug and who had at least one post-baseline assessment of safety.	14.3% 1/7 • Number of events 1 • Part 1 - Up to 24 weeks plus 12 weeks safety follow up; Part 2 - Up to 52 weeks plus 12 weeks safety follow up Safety population, all participants who received at least one dose of study drug and who had at least one post-baseline assessment of safety.	0.00% 0/15 • Part 1 - Up to 24 weeks plus 12 weeks safety follow up; Part 2 - Up to 52 weeks plus 12 weeks safety follow up Safety population, all participants who received at least one dose of study drug and who had at least one post-baseline assessment of safety.
Immune system disorders HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS	5.3% 1/19 • Number of events 1 • Part 1 - Up to 24 weeks plus 12 weeks safety follow up; Part 2 - Up to 52 weeks plus 12 weeks safety follow up Safety population, all participants who received at least one dose of study drug and who had at least one post-baseline assessment of safety.	0.00% 0/7 • Part 1 - Up to 24 weeks plus 12 weeks safety follow up; Part 2 - Up to 52 weeks plus 12 weeks safety follow up Safety population, all participants who received at least one dose of study drug and who had at least one post-baseline assessment of safety.	0.00% 0/15 • Part 1 - Up to 24 weeks plus 12 weeks safety follow up; Part 2 - Up to 52 weeks plus 12 weeks safety follow up Safety population, all participants who received at least one dose of study drug and who had at least one post-baseline assessment of safety.

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER