Juvenile Idiopathic Arthritis
Conditions
Brief summary
This long-term, open-label extension study will evaluate the safety of RoActemra/Actemra (tocilizumab) in patients with polyarticular-course juvenile idiopathic arthritis who completed the WA19977 core study. Patients will continue to receive RoActemra/Actemra 8 mg/kg intravenously every 4 weeks. Anticipated time on study treatment is 104 weeks.
Interventions
DRUGtocilizumab [RoActemra/Actemra]
8 mg/kg iv every 4 weeks, 104 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who completed visit 33 (week 104) of WA19977 study and who may benefit from study drug treatment according to the investigator's assessment * Patients have to receive the first RoActemra/Actemra infusion in this study at the Week 8 visit at the latest * Females of child-bearing potential and males with female partners of child-bearing potential must agree to use effective contraception as defined by protocol
Exclusion criteria
* Patients with, according to investigator judgment, not satisfactory benefit from RoActemra/Actemra therapy within WA19977 * Treatment with any investigational agent since the last administration of study drug in the core study WA19977 * Patient developed any other autoimmune rheumatic disease or overlap syndrome other than the permitted polyarticular-course Juvenile Idiopathic Arthritis (JIA) subsets: rheumatoid factor positive or negative JIA or extended oligoarticular JIA * Patient is pregnant , lactating, or intending to become pregnant during the study and up to 12 weeks after the last administration of study drug * Any significant concomitant disease or medical or surgical condition * History of significant allergic or infusion reactions to prior biologic therapy * Currently active primary or secondary immunodeficiency * Any infections with contraindications to RoActemra/Actemra therapy according to investigator judgment * Inadequate hepatic, renal or bone marrow function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Adverse Events and Any Serious Adverse Events | Approximately 2 years | An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. |
| Number of Participants With Adverse Events of Special Interest | Approximately 2 years | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. The AEs of special interests included gingival bleeding, tooth abscess, acarodermatitis, ear infection, gastroenteritis, herpes zoster ophthalmic, lice infestation, nasopharyngitis, oral fungal infection, oral herpes, pharyngitis, rhinitis, sinusitis, tonsillitis, tracheitis, tracheobronchitis, urinary tract infection, menorrhagia, asthma, epistaxis, and hematoma. |
| Number of Participants With Adverse Events Related to Tocilizumab | Approximately 2 years | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. Relatedness of any AEs was reported as possibly related, probably related, or remotely related to TCZ. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Abnormal Laboratory Parameters | Approximately 2 years | Clinically significant abnormal parameters included eosinophil count, alanine aminotransferase, total bilirubin, and protein and blood in urine. Number of participants with these abnormal lab parameters was reported. |
| Number of Participants With Abnormality in Physical Examinations | Approximately 2 years | Participants with abnormal physical examinations of ear, nose and throat (asthma); extremities (synovitis, sequelae with flexion of the 5th right proximal interphalangeal joint, hallux valgus, deviations of metatarsophalangeal joints, and callus under metatarsal head); lung (mild bronchospasm); skin (vitiligo and hematoma, fatty subcutaneous infiltration on the neck, cutaneous eruption, and scalp pediculosis); and musculoskeletal system (discomfort in right hip) were reported. |
| Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | Weeks 12, 24, 36, 48, 60, 72, 84, and 108 | The Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) is comprised of six components: Maximum number of joints with active arthritis; Number of joints with limitation of movement; Erythrocyte Sedimentation Rate (ESR) and/or C-reactive Protein (CRP); Childhood Health Assessment Questionnaire-Disease Index (CHAQ-DI) graded on 4-point scales \[0 = without any difficulty and 3 = unable to do\] of 30 items grouped into 8 domains of physical function; Physician's global assessment of disease activity and Participant's global assessment of overall well-being (both assessed on a 0 to 100 mm Visual Analogue Scale \[VAS\], where score 0 = inactive arthritis and 100 = very active arthritis). A JIA ACR50/70 response is defined as improvement in at least three of the six core components by at least 50 percent (%), or 70%, respectively and no more than one of the remaining core components worsening by more than 30%. |
| Number of Participants With Inactive Disease | Weeks 24, 36, 48, 72, and 108 | Inactive disease was defined as: 1) No joints with active arthritis (no swollen, painful and lack of motion joints), 2) No fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA, 3) No active uveitis, 4) ESR and/or CRP within normal range, and 5) No disease activity according to Physician's global assessment of disease activity (\<= 10 millimeters \[mm\] on a VAS). The participant's treating physician provided a rating of the participant's arthritis disease activity on a 0 to 100 mm horizontal scale where score 0 represented 'arthritis inactive' (i.e., symptom-free and no arthritis symptoms) and score 100 represented 'arthritis very active'. |
| Number of Participants Achieving Clinical Remission | Weeks 24, 36, 48, 72, and 108 | Clinical remission was defined as inactive disease observed for at least 6 continuous months. Clinical remission was defined as per medication uptake as: Level 1 (clinical remission on medication), Level 2 (clinical remission off oral corticosteroid medication \[still on TCZ\]), Level 3 (clinical remission off both oral corticosteroid and methotrexate medication \[still on TCZ\]), and Level 4 (clinical remission off all anti-inflammatory medications \[still on TCZ\]). Number of participants at each clinical remission level was reported. |
| Number of Participants With a Minimally Important Improvement in the Childhood Health Assessment Questionnaire-Disability Index | Weeks 12, 24, 36, 48, 60, 72, 84, and 108 | The CHAQ-DI included questions on dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. The disability index (DI) of the original CHAQ was graded on 4-point categorical scales of 30 items grouped into 8 domains of physical function. The highest scoring item in each domain determined the score for that domain. The score for the disability index was the mean of domain scores ranging from 0 to 3 (0 = without any difficulty and 3 = unable to do) with higher scores meaning higher disability. Minimally important improvement in CHAQ-DI was defined as a change from baseline of WA19977 core study (Day 1/Visit 1) \>=0.13 at each visit. |
| Mean Exposure to Study Treatment | Approximately 2 years | Participants received TCZ for Week 104 or when TCZ was commercially available for pcJIA participants, whichever comes first in France. The mean TCZ exposure (time from first to last administration) was reported. |
| Number of Joints With Active Range of Motion | Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 | The active range of motion joints was counted by physical examination and mean joints was reported. |
| Number of Swollen Joints | Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 | The swollen joints was counted by physical examination and mean swollen joints were reported. |
| Number of Painful Joints | Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 | The painful joints were counted by physical examination and mean painful joints was reported. |
| Physician's Global Assessment of Disease Activity | Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 | The Physician's global assessment of disease activity was recorded on a 0 to 100 mm horizontal VAS where score 0 represented 'arthritis inactive' (i.e., symptom-free and no arthritis symptoms) and score 100 represented 'arthritis very active' (higher score indicate worsening of disease). |
| Parent/Patient's Global Assessment of Disease Activity | Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 | Parent/patient global assessment of disease activity was performed using 0 to 100 mm VAS, and higher the score of VAS, worse the disease status (0= absence of activity or sign or symptom; 100= maximal activity or signs or symptoms). No disease activity was defined as VAS \<=10 mm. |
| Parent/Patient's Discomfort Index (Pain) | Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 | Participants or parents rated participant's pain by placing a horizontal line on a VAS of 0 (no pain) - 100 mm (unbearable pain). To describe the pain, a cut-off at 10 mm was used, and VAS \<10 mm was defined as no pain. |
| Number of Joints With Limitation of Motion | Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 | The most frequent symptom reported by most participants was a limitation of motion (LOM) of joints and it was determined by physical examination. The mean joints with limitation of motion were reported. |
| Mean Duration of Study Follow-Up | Approximately 2 years | The participants were followed-up from Day 1 to last visit date (approximately 2 years). Mean time for which participants were followed up in the study was reported. |
| Number of Participants With AEs Leading to TCZ Modification, AEs Leading to Death, Anaphylaxis or Serious Hypersensitivity and Deaths | Approximately 2 years | Number of participants with AEs leading to TCZ modification, AEs leading to death, anaphylaxis or serious hypersensitivity, and deaths were reported. |
Countries
France
Participant flow
Recruitment details
A total of seven participants who completed the core study WA19977 were enrolled in this extension study conducted from 13 February 2012 to 15 January 2014 at four centers in France.
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab (8 mg/kg) Eligible participants received TCZ 8 mg/kg intravenously every 4 weeks up to 104 weeks or until TCZ was commercially available for pcJIA in France, whichever came first. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Tocilizumab (8 mg/kg) |
|---|---|
| Age, Customized 12 to 17 years | 2 participants |
| Age, Customized 18 to 64 years | 2 participants |
| Age, Customized 2 to 11 years | 3 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Number of Participants With Adverse Events of Special Interest
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. The AEs of special interests included gingival bleeding, tooth abscess, acarodermatitis, ear infection, gastroenteritis, herpes zoster ophthalmic, lice infestation, nasopharyngitis, oral fungal infection, oral herpes, pharyngitis, rhinitis, sinusitis, tonsillitis, tracheitis, tracheobronchitis, urinary tract infection, menorrhagia, asthma, epistaxis, and hematoma.
Time frame: Approximately 2 years
Population: Safety population included all participants who received at least a single dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Gingival bleeding | 2 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Tooth abscess | 2 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Acarodermatitis | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Ear infection | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Gastroenteritis | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Herpes zoster ophthalmic | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Lice infestation | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Nasopharyngitis | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Oral fungal infection | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Oral herpes | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Pharyngitis | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Rhinitis | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Sinusitis | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Tonsillitis | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Tracheitis | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Tracheobronchitis | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Urinary tract infection | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Menorrhagia | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Asthma | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Epistaxis | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events of Special Interest | Hematoma | 1 participants |
Primary
Number of Participants With Adverse Events Related to Tocilizumab
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. Relatedness of any AEs was reported as possibly related, probably related, or remotely related to TCZ.
Time frame: Approximately 2 years
Population: Safety population included all participants who received at least a single dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events Related to Tocilizumab | AEs possibly related to TCZ | 5 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events Related to Tocilizumab | AEs probably related to TCZ | 2 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Adverse Events Related to Tocilizumab | AEs remotely related to TCZ | 1 participants |
Primary
Number of Participants With Any Adverse Events and Any Serious Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.
Time frame: Approximately 2 years
Population: Safety population included all participants who received at least a single dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Participants With Any Adverse Events and Any Serious Adverse Events | Any AEs | 7 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Any Adverse Events and Any Serious Adverse Events | Any SAEs | 0 participants |
Secondary
Mean Duration of Study Follow-Up
The participants were followed-up from Day 1 to last visit date (approximately 2 years). Mean time for which participants were followed up in the study was reported.
Time frame: Approximately 2 years
Population: Safety population included all participants who received at least a single dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab (8 mg/kg) | Mean Duration of Study Follow-Up | 21.08 Months | Standard Deviation 1.64 |
Secondary
Mean Exposure to Study Treatment
Participants received TCZ for Week 104 or when TCZ was commercially available for pcJIA participants, whichever comes first in France. The mean TCZ exposure (time from first to last administration) was reported.
Time frame: Approximately 2 years
Population: Safety population included all participants who received at least a single dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab (8 mg/kg) | Mean Exposure to Study Treatment | 17.08 Months | Standard Deviation 1.55 |
Secondary
Number of Joints With Active Range of Motion
The active range of motion joints was counted by physical examination and mean joints was reported.
Time frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Population: The ITT population included all the participants who had at least one efficacy assessment. n = number of participants analyzed for the given parameter at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Joints With Active Range of Motion | Day 1 (n=7) | 2.3 joints | Standard Deviation 2.5 |
| Tocilizumab (8 mg/kg) | Number of Joints With Active Range of Motion | Week 12 (n=7) | 1.4 joints | Standard Deviation 2.3 |
| Tocilizumab (8 mg/kg) | Number of Joints With Active Range of Motion | Week 24 (n=6) | 2.2 joints | Standard Deviation 2.2 |
| Tocilizumab (8 mg/kg) | Number of Joints With Active Range of Motion | Week 36 (n=7) | 1.3 joints | Standard Deviation 1.8 |
| Tocilizumab (8 mg/kg) | Number of Joints With Active Range of Motion | Week 48 (n=7) | 2.0 joints | Standard Deviation 1.9 |
| Tocilizumab (8 mg/kg) | Number of Joints With Active Range of Motion | Week 60 (n=7) | 2.0 joints | Standard Deviation 2.2 |
| Tocilizumab (8 mg/kg) | Number of Joints With Active Range of Motion | Week 72 (n=4) | 0.3 joints | Standard Deviation 0.5 |
| Tocilizumab (8 mg/kg) | Number of Joints With Active Range of Motion | Week 84 (n=1) | 0.0 joints | — |
| Tocilizumab (8 mg/kg) | Number of Joints With Active Range of Motion | Week 108 (n=7) | 1.1 joints | Standard Deviation 1.2 |
Secondary
Number of Joints With Limitation of Motion
The most frequent symptom reported by most participants was a limitation of motion (LOM) of joints and it was determined by physical examination. The mean joints with limitation of motion were reported.
Time frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Population: The ITT population included all the participants who had at least one efficacy assessment. n = number of participants analyzed for the given parameter at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Joints With Limitation of Motion | Week 12 (n=7) | 9.4 joints | Standard Deviation 11.9 |
| Tocilizumab (8 mg/kg) | Number of Joints With Limitation of Motion | Week 24 (n=6) | 6.7 joints | Standard Deviation 8.4 |
| Tocilizumab (8 mg/kg) | Number of Joints With Limitation of Motion | Week 36 (n=7) | 8.1 joints | Standard Deviation 9.5 |
| Tocilizumab (8 mg/kg) | Number of Joints With Limitation of Motion | Week 48 (n=7) | 8.6 joints | Standard Deviation 10.5 |
| Tocilizumab (8 mg/kg) | Number of Joints With Limitation of Motion | Week 60 (n=7) | 10.3 joints | Standard Deviation 14.8 |
| Tocilizumab (8 mg/kg) | Number of Joints With Limitation of Motion | Week 72 (n=4) | 8.5 joints | Standard Deviation 16.3 |
| Tocilizumab (8 mg/kg) | Number of Joints With Limitation of Motion | Week 84 (n=1) | 31.0 joints | — |
| Tocilizumab (8 mg/kg) | Number of Joints With Limitation of Motion | Week 108 (n=7) | 10.6 joints | Standard Deviation 13.4 |
| Tocilizumab (8 mg/kg) | Number of Joints With Limitation of Motion | Day 1 (n=7) | 11.4 joints | Standard Deviation 14.3 |
Secondary
Number of Painful Joints
The painful joints were counted by physical examination and mean painful joints was reported.
Time frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Population: The ITT population included all the participants who had at least one efficacy assessment. n = number of participants analyzed for the given parameter at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Painful Joints | Day 1 (n=7) | 1.9 joints | Standard Deviation 2.3 |
| Tocilizumab (8 mg/kg) | Number of Painful Joints | Week 12 (n=7) | 0.6 joints | Standard Deviation 0.8 |
| Tocilizumab (8 mg/kg) | Number of Painful Joints | Week 24 (n=6) | 2.0 joints | Standard Deviation 2.8 |
| Tocilizumab (8 mg/kg) | Number of Painful Joints | Week 36 (n=7) | 0.7 joints | Standard Deviation 1 |
| Tocilizumab (8 mg/kg) | Number of Painful Joints | Week 48 (n=7) | 0.9 joints | Standard Deviation 1.1 |
| Tocilizumab (8 mg/kg) | Number of Painful Joints | Week 60 (n=7) | 0.7 joints | Standard Deviation 1 |
| Tocilizumab (8 mg/kg) | Number of Painful Joints | Week 72 (n=4) | 0.5 joints | Standard Deviation 1 |
| Tocilizumab (8 mg/kg) | Number of Painful Joints | Week 84 (n=1) | 0.0 joints | — |
| Tocilizumab (8 mg/kg) | Number of Painful Joints | Week 108 (n=7) | 2.0 joints | Standard Deviation 4 |
Secondary
Number of Participants Achieving Clinical Remission
Clinical remission was defined as inactive disease observed for at least 6 continuous months. Clinical remission was defined as per medication uptake as: Level 1 (clinical remission on medication), Level 2 (clinical remission off oral corticosteroid medication \[still on TCZ\]), Level 3 (clinical remission off both oral corticosteroid and methotrexate medication \[still on TCZ\]), and Level 4 (clinical remission off all anti-inflammatory medications \[still on TCZ\]). Number of participants at each clinical remission level was reported.
Time frame: Weeks 24, 36, 48, 72, and 108
Population: The ITT population included all participants who had at least one efficacy assessment. n = number of participants analyzed for the given parameter at the specified visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Participants Achieving Clinical Remission | Week 24, Remission level 1 (n = 7) | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants Achieving Clinical Remission | Week 36, Remission level 1 (n = 6) | 5 participants |
| Tocilizumab (8 mg/kg) | Number of Participants Achieving Clinical Remission | Week 48, Remission level 1 (n = 6) | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants Achieving Clinical Remission | Week 72, Remission level 1 (n = 4) | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants Achieving Clinical Remission | Week 108, Remission level 1 (n = 7) | 1 participants |
Secondary
Number of Participants With Abnormality in Physical Examinations
Participants with abnormal physical examinations of ear, nose and throat (asthma); extremities (synovitis, sequelae with flexion of the 5th right proximal interphalangeal joint, hallux valgus, deviations of metatarsophalangeal joints, and callus under metatarsal head); lung (mild bronchospasm); skin (vitiligo and hematoma, fatty subcutaneous infiltration on the neck, cutaneous eruption, and scalp pediculosis); and musculoskeletal system (discomfort in right hip) were reported.
Time frame: Approximately 2 years
Population: Safety population included all participants who received at least a single dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Participants With Abnormality in Physical Examinations | Ear, nose and throat | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Abnormality in Physical Examinations | Extremities | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Abnormality in Physical Examinations | Lung | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Abnormality in Physical Examinations | Musculoskeletal system | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Abnormality in Physical Examinations | Skin | 3 participants |
Secondary
Number of Participants With AEs Leading to TCZ Modification, AEs Leading to Death, Anaphylaxis or Serious Hypersensitivity and Deaths
Number of participants with AEs leading to TCZ modification, AEs leading to death, anaphylaxis or serious hypersensitivity, and deaths were reported.
Time frame: Approximately 2 years
Population: Safety population included all participants who received at least a single dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Participants With AEs Leading to TCZ Modification, AEs Leading to Death, Anaphylaxis or Serious Hypersensitivity and Deaths | AEs leading to TCZ modification | 2 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With AEs Leading to TCZ Modification, AEs Leading to Death, Anaphylaxis or Serious Hypersensitivity and Deaths | AEs leading to death | 0 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With AEs Leading to TCZ Modification, AEs Leading to Death, Anaphylaxis or Serious Hypersensitivity and Deaths | Anaphylaxis or serious hypersensitivity | 0 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With AEs Leading to TCZ Modification, AEs Leading to Death, Anaphylaxis or Serious Hypersensitivity and Deaths | Death | 0 participants |
Secondary
Number of Participants With a Minimally Important Improvement in the Childhood Health Assessment Questionnaire-Disability Index
The CHAQ-DI included questions on dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. The disability index (DI) of the original CHAQ was graded on 4-point categorical scales of 30 items grouped into 8 domains of physical function. The highest scoring item in each domain determined the score for that domain. The score for the disability index was the mean of domain scores ranging from 0 to 3 (0 = without any difficulty and 3 = unable to do) with higher scores meaning higher disability. Minimally important improvement in CHAQ-DI was defined as a change from baseline of WA19977 core study (Day 1/Visit 1) \>=0.13 at each visit.
Time frame: Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Population: The ITT population included all the participants who had at least one efficacy assessment. n = number of participants analyzed for the given parameter at the specified visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Participants With a Minimally Important Improvement in the Childhood Health Assessment Questionnaire-Disability Index | Week 12 (n=7) | 5 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With a Minimally Important Improvement in the Childhood Health Assessment Questionnaire-Disability Index | Week 24 (n=7) | 5 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With a Minimally Important Improvement in the Childhood Health Assessment Questionnaire-Disability Index | Week 36 (n=7) | 6 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With a Minimally Important Improvement in the Childhood Health Assessment Questionnaire-Disability Index | Week 48 (n=7) | 5 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With a Minimally Important Improvement in the Childhood Health Assessment Questionnaire-Disability Index | Week 60 (n=7) | 6 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With a Minimally Important Improvement in the Childhood Health Assessment Questionnaire-Disability Index | Week 72 (n=3) | 2 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With a Minimally Important Improvement in the Childhood Health Assessment Questionnaire-Disability Index | Week 84 (n=1) | 0 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With a Minimally Important Improvement in the Childhood Health Assessment Questionnaire-Disability Index | Week 108 (n=7) | 6 participants |
Secondary
Number of Participants With Clinically Significant Abnormal Laboratory Parameters
Clinically significant abnormal parameters included eosinophil count, alanine aminotransferase, total bilirubin, and protein and blood in urine. Number of participants with these abnormal lab parameters was reported.
Time frame: Approximately 2 years
Population: Safety population included all participants who received at least a single dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Participants With Clinically Significant Abnormal Laboratory Parameters | Eosinophil count | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Clinically Significant Abnormal Laboratory Parameters | Alanine aminotransferase | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Clinically Significant Abnormal Laboratory Parameters | Total bilirubin | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Clinically Significant Abnormal Laboratory Parameters | Protein and blood in urine | 2 participants |
Secondary
Number of Participants With Inactive Disease
Inactive disease was defined as: 1) No joints with active arthritis (no swollen, painful and lack of motion joints), 2) No fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA, 3) No active uveitis, 4) ESR and/or CRP within normal range, and 5) No disease activity according to Physician's global assessment of disease activity (\<= 10 millimeters \[mm\] on a VAS). The participant's treating physician provided a rating of the participant's arthritis disease activity on a 0 to 100 mm horizontal scale where score 0 represented 'arthritis inactive' (i.e., symptom-free and no arthritis symptoms) and score 100 represented 'arthritis very active'.
Time frame: Weeks 24, 36, 48, 72, and 108
Population: The ITT population included all participants who had at least one efficacy assessment. n = number of participants analyzed for the given parameter at the specified visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Participants With Inactive Disease | Week 72 (n = 4) | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Inactive Disease | Week 108 (n = 7) | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Inactive Disease | Week 24 (n = 6) | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Inactive Disease | Week 36 (n = 7) | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Inactive Disease | Week 48 (n = 6) | 1 participants |
Secondary
Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70
The Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) is comprised of six components: Maximum number of joints with active arthritis; Number of joints with limitation of movement; Erythrocyte Sedimentation Rate (ESR) and/or C-reactive Protein (CRP); Childhood Health Assessment Questionnaire-Disease Index (CHAQ-DI) graded on 4-point scales \[0 = without any difficulty and 3 = unable to do\] of 30 items grouped into 8 domains of physical function; Physician's global assessment of disease activity and Participant's global assessment of overall well-being (both assessed on a 0 to 100 mm Visual Analogue Scale \[VAS\], where score 0 = inactive arthritis and 100 = very active arthritis). A JIA ACR50/70 response is defined as improvement in at least three of the six core components by at least 50 percent (%), or 70%, respectively and no more than one of the remaining core components worsening by more than 30%.
Time frame: Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Population: The ITT population included all participants who had at least one efficacy assessment. Number (n) = number of participants analyzed for the given parameter at the specified visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR50, Week 12 (n = 5) | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR50, Week 24 (n = 5) | 2 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR50, Week 36 (n = 6) | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR50, Week 48 (n = 5) | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR50, Week 60 (n = 5) | 0 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR50, Week 72 (n = 2) | 0 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR50, Week 84 (n = 1) | 1 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR50, Week 108 (n = 6) | 2 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR70, Week 12 (n = 5) | 4 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR70, Week 24 (n = 5) | 3 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR70, Week 60 (n = 5) | 5 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR70, Week 36 (n = 6) | 5 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR70, Week 48 (n = 5) | 4 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR70, Week 72 (n = 2) | 2 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR70, Week 84 (n = 1) | 0 participants |
| Tocilizumab (8 mg/kg) | Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70 | JIA ACR70, Week 108 (n = 6) | 4 participants |
Secondary
Number of Swollen Joints
The swollen joints was counted by physical examination and mean swollen joints were reported.
Time frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Population: The ITT population included all the participants who had at least one efficacy assessment. n = number of participants analyzed for the given parameter at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab (8 mg/kg) | Number of Swollen Joints | Day 1 (n=7) | 1.6 joints | Standard Deviation 2.1 |
| Tocilizumab (8 mg/kg) | Number of Swollen Joints | Week 12 (n=7) | 1.0 joints | Standard Deviation 2.2 |
| Tocilizumab (8 mg/kg) | Number of Swollen Joints | Week 24 (n=6) | 1.0 joints | Standard Deviation 1.7 |
| Tocilizumab (8 mg/kg) | Number of Swollen Joints | Week 36 (n=7) | 0.9 joints | Standard Deviation 1.5 |
| Tocilizumab (8 mg/kg) | Number of Swollen Joints | Week 48 (n=7) | 1.9 joints | Standard Deviation 1.8 |
| Tocilizumab (8 mg/kg) | Number of Swollen Joints | Week 60 (n=7) | 1.7 joints | Standard Deviation 2.2 |
| Tocilizumab (8 mg/kg) | Number of Swollen Joints | Week 72 (n=4) | 0.3 joints | Standard Deviation 0.5 |
| Tocilizumab (8 mg/kg) | Number of Swollen Joints | Week 84 (n=1) | 0.0 joints | — |
| Tocilizumab (8 mg/kg) | Number of Swollen Joints | Week 108 (n=7) | 0.7 joints | Standard Deviation 1.3 |
Secondary
Parent/Patient's Discomfort Index (Pain)
Participants or parents rated participant's pain by placing a horizontal line on a VAS of 0 (no pain) - 100 mm (unbearable pain). To describe the pain, a cut-off at 10 mm was used, and VAS \<10 mm was defined as no pain.
Time frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Population: The ITT population included all the participants who had at least one efficacy assessment. n = number of participants analyzed for the given parameter at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab (8 mg/kg) | Parent/Patient's Discomfort Index (Pain) | Day 1 (n=7) | 15.0 mm | Standard Deviation 27.2 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Discomfort Index (Pain) | Week 12 (n=7) | 5.6 mm | Standard Deviation 7.7 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Discomfort Index (Pain) | Week 24 (n=7) | 7.7 mm | Standard Deviation 11.1 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Discomfort Index (Pain) | Week 36 (n=7) | 3.0 mm | Standard Deviation 3.1 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Discomfort Index (Pain) | Week 48 (n=7) | 12.9 mm | Standard Deviation 18.5 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Discomfort Index (Pain) | Week 60 (n=7) | 6.4 mm | Standard Deviation 7.3 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Discomfort Index (Pain) | Week 72 (n=3) | 0.7 mm | Standard Deviation 0.6 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Discomfort Index (Pain) | Week 84 (n=1) | 51.0 mm | — |
| Tocilizumab (8 mg/kg) | Parent/Patient's Discomfort Index (Pain) | Week 108 (n=7) | 5.1 mm | Standard Deviation 9 |
Secondary
Parent/Patient's Global Assessment of Disease Activity
Parent/patient global assessment of disease activity was performed using 0 to 100 mm VAS, and higher the score of VAS, worse the disease status (0= absence of activity or sign or symptom; 100= maximal activity or signs or symptoms). No disease activity was defined as VAS \<=10 mm.
Time frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Population: The ITT population included all the participants who had at least one efficacy assessment. n = number of participants analyzed for the given parameter at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab (8 mg/kg) | Parent/Patient's Global Assessment of Disease Activity | Day 1 (n=7) | 14.9 mm | Standard Deviation 27.5 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Global Assessment of Disease Activity | Week 12 (n=7) | 8.0 mm | Standard Deviation 12.2 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Global Assessment of Disease Activity | Week 24 (n=7) | 12.7 mm | Standard Deviation 23.3 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Global Assessment of Disease Activity | Week 36 (n=7) | 3.9 mm | Standard Deviation 6.8 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Global Assessment of Disease Activity | Week 48 (n=7) | 10.1 mm | Standard Deviation 17.4 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Global Assessment of Disease Activity | Week 60 (n=7) | 7.4 mm | Standard Deviation 8.3 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Global Assessment of Disease Activity | Week 72 (n=3) | 0.3 mm | Standard Deviation 0.6 |
| Tocilizumab (8 mg/kg) | Parent/Patient's Global Assessment of Disease Activity | Week 84 (n=1) | 73.0 mm | — |
| Tocilizumab (8 mg/kg) | Parent/Patient's Global Assessment of Disease Activity | Week 108 (n=7) | 12.1 mm | Standard Deviation 17.8 |
Secondary
Physician's Global Assessment of Disease Activity
The Physician's global assessment of disease activity was recorded on a 0 to 100 mm horizontal VAS where score 0 represented 'arthritis inactive' (i.e., symptom-free and no arthritis symptoms) and score 100 represented 'arthritis very active' (higher score indicate worsening of disease).
Time frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Population: The ITT population included all the participants who had at least one efficacy assessment. n = number of participants analyzed for the given parameter at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab (8 mg/kg) | Physician's Global Assessment of Disease Activity | Day 1 (n=7) | 8.6 millimeter (mm) | Standard Deviation 7.7 |
| Tocilizumab (8 mg/kg) | Physician's Global Assessment of Disease Activity | Week 12 (n=6) | 4.2 millimeter (mm) | Standard Deviation 6.4 |
| Tocilizumab (8 mg/kg) | Physician's Global Assessment of Disease Activity | Week 24 (n=7) | 9.3 millimeter (mm) | Standard Deviation 12.2 |
| Tocilizumab (8 mg/kg) | Physician's Global Assessment of Disease Activity | Week 36 (n=7) | 6.7 millimeter (mm) | Standard Deviation 6.9 |
| Tocilizumab (8 mg/kg) | Physician's Global Assessment of Disease Activity | Week 48 (n=7) | 3.7 millimeter (mm) | Standard Deviation 3.6 |
| Tocilizumab (8 mg/kg) | Physician's Global Assessment of Disease Activity | Week 60 (n=7) | 4.0 millimeter (mm) | Standard Deviation 3.4 |
| Tocilizumab (8 mg/kg) | Physician's Global Assessment of Disease Activity | Week 72 (n=4) | 2.8 millimeter (mm) | Standard Deviation 4.3 |
| Tocilizumab (8 mg/kg) | Physician's Global Assessment of Disease Activity | Week 84 (n=1) | 4.0 millimeter (mm) | — |
| Tocilizumab (8 mg/kg) | Physician's Global Assessment of Disease Activity | Week 108 (n=7) | 6.6 millimeter (mm) | Standard Deviation 7.1 |