Arthritis, Juvenile Idiopathic
Conditions
Keywords
Polyarticular Juvenile Idiopathic Arthritis
Brief summary
This is a multicenter, Phase 3 randomized, placebo-controlled study designed to evaluate adalimumab in children 4 to 17 years old with polyarticular juvenile idiopathic arthritis (JIA) who are either methotrexate (MTX) treated or non-MTX treated.
Detailed description
The study design for this clinical trial was chosen to evaluate adalimumab in subjects who were either methotrexate (MTX)-naive or had been withdrawn from MTX at least 2 weeks prior to study drug administration (non-MTX stratum) or were inadequate responders to MTX and continued MTX treatment (MTX stratum). The study consisted of 4 phases: a 16-week Open-label Lead-in (OL LI), a 32-week Double-blind (DB) phase, an up to 136-week Open-label Extension Body Surface Area (OLE BSA) phase, and an up to 224-week OLE Fixed Dose (FD) phase. All subjects who met entry criteria were enrolled into one of the appropriate strata and received adalimumab (plus concomitant MTX in the MTX stratum) in the 16 week OL LI phase of the study. All subjects who responded to adalimumab during the OL LI phase were to be enrolled in the DB phase of the study and randomized to receive adalimumab (plus concomitant MTX in the MTX stratum) or placebo (plus concomitant MTX in the MTX stratum). Subjects in the DB phase received either adalimumab (24 mg/m2 BSA up to a maximum of 40 mg total body dose) or placebo subcutaneously (SC) administered every other week (eow). Adalimumab or placebo was administered for an additional 32 weeks or until flare of disease (based on PedACR30 response criteria = a worsening of 30% or more in 3 of the 6 response variables (Parent's global assessment of subject's overall well-being by visual analog scale \[VAS\], Physician's global assessment \[PhGA\] of subject's disease severity by VAS, number of active joints \[joints with swelling not due to deformity or joints with limitation of passive motion (LOM)\], pain, tenderness, or both, number of joints with LOM, Childhood Health Assessment Questionnaire \[CHAQ\], and CRP levels), a minimum of 2 active joints, and no more than 1 indicator improving by 30% or more), whichever occurred earlier. For subjects who did not have a disease flare, the DB phase was completed at Week 48. Subjects who experienced disease flare during the DB phase or subjects who completed 48 weeks of the study were given the option to receive adalimumab for up to a minimum of 44 weeks (up to a maximum of 136 weeks) in the OLE BSA phase before being eligible to switch to the OLE FD phase. In this phase, subjects received OL adalimumab (24 mg/m2 BSA up to a maximum of 40 mg total body dose SC eow). All subjects who completed at least 44 weeks of OLE BSA treatment were given the opportunity to continue into the OLE FD phase for up to 224 weeks of additional adalimumab exposure. In this phase, subjects weighing less than 30 kg were treated with a fixed dose of 20 mg of adalimumab SC eow. Subjects weighing 30 kg or more were treated with a fixed dose of 40 mg of adalimumab SC eow.
Interventions
BIOLOGICALDouble-Blind Adalimumab/Placebo + MTX
Subcutaneous injection of 24 mg adalimumab or placebo per square meter of body surface area (BSA) every other week (eow) concomitantly with MTX treatment for 32 weeks during the Double-Blind phase. Total body dose of adalimumab was not to exceed 40 mg.
BIOLOGICALDouble-Blind Adalimumab/Placebo
Subcutaneous injection of 24 mg adalimumab or placebo per square meter of body surface area (BSA) every other week (eow) without MTX treatment for 32 weeks during the Double-Blind Phase. Total body dose of adalimumab was not to exceed 40 mg.
DRUGOLE BSA Adalimumab +/- MTX
Comparison of subcutaneous injection of 24 mg adalimumab per square meter of body surface area (BSA) every other week (eow) either with or without concomitant MTX treatment for a minimum of 44 weeks (up to a maximum of 136 weeks) during the Open-Label Extension BSA Phase.
DRUGOLE FD Adalimumab +/- MTX
Comparison of adalimumab administered subcutaneously every other week (eow) either with or without concomitant MTX treatment for up to 224 weeks during the Open-Label Extension Fixed Dose (FD) Phase.
Sponsors
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have a diagnosis of polyarticular juvenile idiopathic arthritis (JIA) age 4 to 17 by the American College of Rheumatology (ACR) criteria. Disease onset may have been systemic, polyarticular, or pauciarticular. If the disease was systemic onset, then the subjects must be free of any systemic JIA manifestations for at least 3 months before the time of qualification. * At the time of study screening, the subject must have continuing active disease defined as \>= 5 swollen joints and \>= 3 joints with limitation of motion (LOM). These joints are not mutually exclusive. * Subjects may be either naïve to MTX, inadequate responders to MTX, or intolerant to MTX. Intolerance to MTX will be defined by the subject's physician. The MTX must be maintained at a dose of at least 10 mg/m2 body surface area/week for a minimum of 3 months, prior to screening. * Duration of disease is not limited, but must have been long enough for a subject to have been given an adequate trial of nonsteroidal anti-inflammatory drugs (NSAIDs). * Have not received other disease-modifying anti-rheumatic drugs (DMARDs) including penicillamine, hydroxychloroquine, sulfasalazine, oral or injectable gold, cyclosporin; or intravenous immunoglobulin (IV Ig); or cytotoxic agents, for at least 4 weeks prior to receiving 1st dose of study drug. Subjects currently on one or more of these DMARDs must demonstrate active disease (defined above) prior to a minimum 4 weeks (28 days) washout of all DMARDs. * Subjects who are refractory to MTX after 3 months of treatment must demonstrate active disease (defined above) prior to enrollment in the open-label part of the trial. * Have not received an intra-articular glucocorticoid injection within 4 weeks (28 days) prior to enrollment into the study. * Have good venous access and stable hematocrit \>= 24%. * All sexually active male and female study participants must be practicing adequate contraception. Post-pubertal females must have a negative serum pregnancy test no greater than 10 days prior to the first dose of study drug. * Parent or guardian has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject's parent or legal guardian has had the opportunity to ask questions.
Exclusion criteria
* Pregnant or nursing female. * Functional class IV by ACR criteria. * Laboratory parameters outside limits established in the protocol. * Medical history, medical condition, or previous treatment not allowed by the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects in the Non-MTX Stratum With Disease Flare During the Double-Blind Phase | Week 16 to Week 48 (32 weeks) | The primary efficacy endpoint was the number of adalimumab-treated subjects in the non-MTX stratum with disease flare during the Double-Blind Phase compared with the number of placebo-treated subjects in the non-MTX stratum with disease flare during the double-blind phase. Subjects met the criteria for disease flare if they had 1) \>= 30% worsening in at least 3 of the 6 Juvenile Rheumatoid Arthritis (JRA) core set criteria and a minimum of 2 active joints, and 2) \>= 30% improvement in not more than 1 of the 6 JRA core set criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Physician's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase | Baseline and Week 48 | A 100 mm horizontal visual analog scale (VAS) was used to assess the Physician Global Assessment of Disease Activity. The left end of the VAS scale (0 mm) signified the absence of symptoms and the right end (100 mm) maximum disease activity. The mean change from open-label baseline to Week 48 was determined. Negative mean changes indicated improvement. |
| Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase | Week 104 | Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria. |
| Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase | Week 48 | Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL-LI baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria. |
| Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase | Week 112 | Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria. |
| Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase | Final Visit (up to 224 weeks of OLE FD phase) | Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. Final Visit = last visit per subject (up to 224 weeks). |
| Number of Subjects Meeting Pediatric American College of Rheumatology 30% (PedACR30) Response Criteria at the End of the Open-Label Lead-In Phase | Week 16 | Responders met the following criteria: \>= 30% improvement in \>= 3 of 6 JRA core set criteria, and \>= 30% worsening in not more than 1 JRA criterion, compared with the open-label baseline. JRA core set criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with limitation of motion \[LOM\] and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. |
| Number of Subjects in the MTX Stratum With Disease Flare During the Double-Blind Phase | Week 16 to Week 48 (32 Weeks) | Subjects met criteria for disease flare if they had \>= 30% worsening in at least 3 of 6 JRA core set criteria and a minimum of 2 active joints, and \>= 30% improvement in not more than 1 JRA criterion. JRA core set criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. |
| Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 16 to Week 48 (32 weeks) | A log rank test was performed and the Kaplan-Meier curve for time to disease flare from double-blind baseline (Week 16) to Week 48 was generated. Disease flare was defined as a \>= 30% worsening in at least 3 of 6 JRA core set criteria and a minimum of 2 active joints, and \>= 30% improvement in not more than 1 JRA criterion. The percentage of subjects without disease flare at each time point is presented. |
| Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 16 to Week 48 (32 weeks) | A log rank test was performed and the Kaplan-Meier curve for time to disease flare from double-blind baseline (Week 16) to Week 48 was generated. Disease flare was defined as a \>= 30% worsening in at least 3 of 6 JRA core set criteria and a minimum of 2 active joints, and \>= 30% improvement in not more than 1 JRA criterion. The percentage of subjects without disease flare at each time point is presented. |
| Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase | Week 48 | Responders met the following criteria: \>= 30% improvement in \>= 3 of 6 JIA core set criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with the OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core criteria are included in PedACR criteria. |
| Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-Blind Phase | Week 48 | Responders met the following criteria: \>= 50% improvement in \>= 3 of 6 JIA core set criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with the OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core variables are included in PedACR criteria. |
| Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-Blind Phase | Week 48 | Responders met the following criteria: \>= 70% improvement in \>= 3 of 6 JIA core set criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with the OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core variables are included in PedACR criteria. |
| Mean Change From Baseline in Parent's/Patient's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase | Baseline and Week 48 | A 100 mm horizontal visual analog scale (VAS) was used to assess the Parent's/Patient's Global Assessment of Disease Activity. The left end of the VAS (0 mm) signified the absence of symptoms and the right end (100 mm) maximum disease activity. The mean change from open-label baseline to Week 48 was determined. Negative mean changes indicated improvement. |
| Mean Change From Baseline in C-Reactive Protein Levels at Week 48 of the Double-Blind Phase | Baseline and Week 48 | Serum levels of C-reactive protein (CRP) were measured at screening (open-label baseline) and at Week 48. Negative mean changes in CRP from open-label baseline to Week 48 indicated improvement. |
| Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase | Open-Label Lead-In Phase Baseline | Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria. |
| Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase | Week 56 | Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria. |
| Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase | Baseline | Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL-LI baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Baseline Measure: Gender, Female/Male - OLE FD Phase | Baseline OLE FD Phase | Gender (female/male) recorded at Baseline of the Open-Label Extension FD phase of the study. This measure was excluded from Baseline Characteristics due to difficulty maintaining correct subject numbers and Baseline value totals in that section while including this phase of the study. |
| Baseline Measure: Age Continuous - OLE FD Phase | Baseline OLE FD Phase | Age continuous (mean +/- SD) recorded at Baseline of the Open-Label Extension FD phase of the study. This measure was excluded from Baseline Characteristics due to difficulty maintaining correct subject numbers and Baseline value totals in that section with this phase included. |
| Baseline Measure: Age Continuous - OLE BSA Phase | Baseline OLE BSA Phase | Age continuous (mean +/- SD) recorded at Baseline of the Open-Label Extension BSA phase of the study. This measure was excluded from Baseline Characteristics due to difficulty maintaining correct subject numbers and Baseline value totals in that section with this phase included. |
| Baseline Measure: Gender, Female/Male - OLE BSA Phase | Baseline OLE BSA Phase | Gender (female/male) recorded at Baseline of the Open-Label Extension BSA phase of the study. This measure was excluded from Baseline Characteristics due to difficulty maintaining correct subject numbers and Baseline value totals in that section while including this phase of the study. |
Countries
Belgium, Czechia, France, Germany, Italy, Slovakia, Spain, United States
Participant flow
Recruitment details
Subjects were enrolled at 31 sites between 19 September 2002 and 13 January 2005.
Pre-assignment details
A total of 171 participants entered the Open-Label Lead-In (OL-LI) phase and received adalimumab. Of these 171 participants, 160 participants completed the OL-LI phase, and 133 participants entered the 32-week Double-Blind Phase (75 in the MTX stratum; 58 in the non-MTX stratum) and were randomized to adalimumab or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Double-Blind Adalimumab + MTX Subjects in the methotrexate (MTX) stratum, who had an inadequate response to MTX and were adalimumab responders during the Open-Label Lead-In (OL-LI) phase, received adalimumab (24 mg/square meter of body surface area \[BSA\], up to a maximum of 40 mg total body dose administered subcutaneously every other week) plus concomitant MTX treatment during the Double-Blind Phase of the study. MTX-treated inadequate responders must have had active disease on MTX treatment for at least 3 months prior to screening. | 38 |
| Double-Blind Placebo + MTX Subjects in the methotrexate (MTX) stratum, who had an inadequate response to MTX and were adalimumab responders during the Open-Label Lead-In (OL-LI) phase, received placebo (24 mg/square meter of body surface area \[BSA\], up to a maximum of 40 mg total body dose administered subcutaneously every other week) plus concomitant MTX treatment during the Double-Blind Phase of the study.
MTX-treated inadequate responders must have had active disease on MTX treatment for at least 3 months prior to screening. | 37 |
| Double-Blind Adalimumab Subjects in the non-methotrexate (MTX) stratum who were either naïve to MTX or withdrawn from MTX at least 2 weeks prior to study drug administration, and were adalimumab responders during the OL-LI phase, received adalimumab (24 mg/square meter of body surface area \[BSA\], up to a maximum of 40 mg total body dose administered subcutaneously every other week), but no concomitant MTX treatment, during the Double-Blind Phase of the study. | 30 |
| Double-Blind Placebo Subjects in the non-methotrexate (MTX) stratum who were either naïve to MTX or withdrawn from MTX at least 2 weeks prior to study drug administration, and were adalimumab responders during the OL-LI phase, received placebo (24 mg/square meter of body surface area \[BSA\], up to a maximum of 40 mg total body dose, administered subcutaneously every other week), but no concomitant MTX treatment, during the Double-Blind Phase of the study. | 28 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Double-Blind Phase | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind Phase | Randomized in error | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind Phase | Sponsor request or decision | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind Phase | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Open-Label Extension BSA Phase | Adverse Event | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| Open-Label Extension BSA Phase | Lack of Efficacy | 0 | 0 | 0 | 0 | 3 | 1 | 0 | 0 |
| Open-Label Extension BSA Phase | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Open-Label Extension BSA Phase | Sponsor request or decision | 0 | 0 | 0 | 0 | 5 | 1 | 0 | 0 |
| Open-Label Extension BSA Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 3 | 6 | 0 | 0 |
| Open-Label Extension Fixed Dose Phase | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 |
| Open-Label Extension Fixed Dose Phase | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
| Open-Label Extension Fixed Dose Phase | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 8 |
| Open-Label Extension Fixed Dose Phase | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Open-Label Extension Fixed Dose Phase | Sponsor request or decision | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 7 |
| Open-Label Extension Fixed Dose Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 3 |
Baseline characteristics
| Characteristic | Double-Blind Adalimumab + MTX | Double-Blind Placebo + MTX | Double-Blind Adalimumab | Double-Blind Placebo | Total |
|---|---|---|---|---|---|
| Age Continuous | 11.7 years STANDARD_DEVIATION 3.29 | 10.8 years STANDARD_DEVIATION 3.36 | 11.1 years STANDARD_DEVIATION 4.13 | 11.3 years STANDARD_DEVIATION 3.77 | 11.2 years STANDARD_DEVIATION 3.64 |
| Sex: Female, Male Female | 30 Participants | 30 Participants | 23 Participants | 20 Participants | 103 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 7 Participants | 8 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 27 / 38 | 19 / 37 | 20 / 30 | 20 / 28 | 62 / 71 | 46 / 57 | 54 / 59 | 37 / 47 |
| serious Total, serious adverse events | 3 / 38 | 2 / 37 | 1 / 30 | 0 / 28 | 13 / 71 | 9 / 57 | 7 / 59 | 10 / 47 |
Outcome results
Primary
Number of Subjects in the Non-MTX Stratum With Disease Flare During the Double-Blind Phase
The primary efficacy endpoint was the number of adalimumab-treated subjects in the non-MTX stratum with disease flare during the Double-Blind Phase compared with the number of placebo-treated subjects in the non-MTX stratum with disease flare during the double-blind phase. Subjects met the criteria for disease flare if they had 1) \>= 30% worsening in at least 3 of the 6 Juvenile Rheumatoid Arthritis (JRA) core set criteria and a minimum of 2 active joints, and 2) \>= 30% improvement in not more than 1 of the 6 JRA core set criteria.
Time frame: Week 16 to Week 48 (32 weeks)
Population: All subjects in the intent-to-treat population, defined as all subjects who were randomized and who received at least a single administration of study drug, in the non-MTX stratum. Missing values were treated as disease flare.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind Adalimumab | Number of Subjects in the Non-MTX Stratum With Disease Flare During the Double-Blind Phase | 13 Participants |
| Double-Blind Placebo | Number of Subjects in the Non-MTX Stratum With Disease Flare During the Double-Blind Phase | 20 Participants |
Comparison: The study was sized to detect a difference in the proportion of subjects (40%) between placebo and the active adalimumab dose group who would experience disease flare assuming a placebo rate of 70% vs. a rate of 30% in the active group. Assuming a binomial distribution, an alpha of 0.05, 80% power, two-sided test, and an initial monotherapy responder rate of 70%, a minimum of 29 subjects were needed per treatment group within the appropriate strata.p-value: 0.031Chi-square test
Secondary
Mean Change From Baseline in C-Reactive Protein Levels at Week 48 of the Double-Blind Phase
Serum levels of C-reactive protein (CRP) were measured at screening (open-label baseline) and at Week 48. Negative mean changes in CRP from open-label baseline to Week 48 indicated improvement.
Time frame: Baseline and Week 48
Population: All subjects in the intent-to-treat population, defined as all subjects who were randomized and who received at least a single administration of study drug, who completed Week 48. Observed data of subjects who remained in the study at Week 48 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Adalimumab | Mean Change From Baseline in C-Reactive Protein Levels at Week 48 of the Double-Blind Phase | -1.79 mg/dL | Standard Error 0.803 |
| Double-Blind Placebo | Mean Change From Baseline in C-Reactive Protein Levels at Week 48 of the Double-Blind Phase | -3.91 mg/dL | Standard Error 2 |
| Adalimumab + MTX | Mean Change From Baseline in C-Reactive Protein Levels at Week 48 of the Double-Blind Phase | -1.71 mg/dL | Standard Error 0.529 |
| Placebo + MTX | Mean Change From Baseline in C-Reactive Protein Levels at Week 48 of the Double-Blind Phase | -0.10 mg/dL | Standard Error 0.333 |
Secondary
Mean Change From Baseline in Parent's/Patient's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase
A 100 mm horizontal visual analog scale (VAS) was used to assess the Parent's/Patient's Global Assessment of Disease Activity. The left end of the VAS (0 mm) signified the absence of symptoms and the right end (100 mm) maximum disease activity. The mean change from open-label baseline to Week 48 was determined. Negative mean changes indicated improvement.
Time frame: Baseline and Week 48
Population: All subjects in the intent-to-treat population, defined as all subjects who were randomized and who received at least a single administration of study drug, who completed Week 48. Observed data of subjects who remained in the study at Week 48 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Adalimumab | Mean Change From Baseline in Parent's/Patient's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase | -41.53 Units on a scale | Standard Error 5.562 |
| Double-Blind Placebo | Mean Change From Baseline in Parent's/Patient's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase | -50.56 Units on a scale | Standard Error 6.129 |
| Adalimumab + MTX | Mean Change From Baseline in Parent's/Patient's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase | -36.42 Units on a scale | Standard Error 5.177 |
| Placebo + MTX | Mean Change From Baseline in Parent's/Patient's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase | -26.87 Units on a scale | Standard Error 5.644 |
Secondary
Mean Change From Baseline in Physician's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase
A 100 mm horizontal visual analog scale (VAS) was used to assess the Physician Global Assessment of Disease Activity. The left end of the VAS scale (0 mm) signified the absence of symptoms and the right end (100 mm) maximum disease activity. The mean change from open-label baseline to Week 48 was determined. Negative mean changes indicated improvement.
Time frame: Baseline and Week 48
Population: All subjects in the intent-to-treat population, defined as all subjects who were randomized and who received at least a single administration of study drug, who completed Week 48. Observed data of subjects who remained in the study at Week 48 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Adalimumab | Mean Change From Baseline in Physician's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase | -52.06 Units on a scale | Standard Error 3.713 |
| Double-Blind Placebo | Mean Change From Baseline in Physician's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase | -38.73 Units on a scale | Standard Error 6.554 |
| Adalimumab + MTX | Mean Change From Baseline in Physician's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase | -48.50 Units on a scale | Standard Error 3.89 |
| Placebo + MTX | Mean Change From Baseline in Physician's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase | -38.73 Units on a scale | Standard Error 6.554 |
Secondary
Number of Subjects in the MTX Stratum With Disease Flare During the Double-Blind Phase
Subjects met criteria for disease flare if they had \>= 30% worsening in at least 3 of 6 JRA core set criteria and a minimum of 2 active joints, and \>= 30% improvement in not more than 1 JRA criterion. JRA core set criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein.
Time frame: Week 16 to Week 48 (32 Weeks)
Population: All subjects in the intent-to-treat population, defined as all subjects who were randomized and who received at least a single administration of study drug, in the MTX stratum. Missing values were treated as disease flare.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind Adalimumab | Number of Subjects in the MTX Stratum With Disease Flare During the Double-Blind Phase | 14 Participants |
| Double-Blind Placebo | Number of Subjects in the MTX Stratum With Disease Flare During the Double-Blind Phase | 24 Participants |
p-value: 0.015Chi-square test
Secondary
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase
Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.
Time frame: Open-Label Lead-In Phase Baseline
Population: The ITT population was used for analysis in the Open-Label Extension Body Surface Area phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase | PedACR30 Baseline | 55 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase | PedACR50 Baseline | 47 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase | PedACR70 Baseline | 35 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase | PedACR30 Baseline | 46 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase | PedACR50 Baseline | 41 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase | PedACR70 Baseline | 30 Participants |
Secondary
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase
Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL-LI baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.
Time frame: Baseline
Population: The ITT population was used for analysis in the Open-Label Extension Fixed Dose phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase | PedACR30 OLE FD Baseline | 53 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase | PedACR50 OLE FD Baseline | 50 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase | PedACR70 OLE FD Baseline | 46 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase | PedACR30 OLE FD Baseline | 44 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase | PedACR50 OLE FD Baseline | 43 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase | PedACR70 OLE FD Baseline | 40 Participants |
Secondary
Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase
Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. Final Visit = last visit per subject (up to 224 weeks).
Time frame: Final Visit (up to 224 weeks of OLE FD phase)
Population: The ITT population was used for analysis in the Open-Label Extension Fixed Dose phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase | PedACR30 Final Visit | 48 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase | PedACR50 Final Visit | 45 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase | PedACR70 Final Visit | 43 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase | PedACR50 Final Visit | 43 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase | PedACR30 Final Visit | 44 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase | PedACR70 Final Visit | 40 Participants |
Secondary
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase
Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.
Time frame: Week 104
Population: The ITT population was used for analysis in the Open-Label Extension Body Surface Area phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase | PedACR30 Week 104 | 18 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase | PedACR50 Week 104 | 16 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase | PedACR70 Week 104 | 14 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase | PedACR30 Week 104 | 16 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase | PedACR50 Week 104 | 16 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase | PedACR70 Week 104 | 14 Participants |
Secondary
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase
Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.
Time frame: Week 112
Population: The ITT population was used for analysis in the Open-Label Extension Fixed Dose phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase | PedACR30 Week 112 | 39 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase | PedACR50 Week 112 | 39 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase | PedACR70 Week 112 | 34 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase | PedACR30 Week 112 | 31 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase | PedACR50 Week 112 | 30 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase | PedACR70 Week 112 | 29 Participants |
Secondary
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase
Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL-LI baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.
Time frame: Week 48
Population: The ITT population was used for analysis in the Open-Label Extension Fixed Dose phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase | PedACR30 Week 48 | 47 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase | PedACR50 Week 48 | 47 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase | PedACR70 Week 48 | 44 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase | PedACR30 Week 48 | 40 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase | PedACR50 Week 48 | 39 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase | PedACR70 Week 48 | 38 Participants |
Secondary
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase
Responders met the following criteria: \>= 30%/50%/70% improvement in \>= 3 of 6 JIA core criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.
Time frame: Week 56
Population: The ITT population was used for analysis in the Open-Label Extension Body Surface Area phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase | PedACR30 Week 56 | 50 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase | PedACR50 Week 56 | 49 Participants |
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase | PedACR70 Week 56 | 43 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase | PedACR30 Week 56 | 40 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase | PedACR50 Week 56 | 40 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase | PedACR70 Week 56 | 35 Participants |
Secondary
Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase
Responders met the following criteria: \>= 30% improvement in \>= 3 of 6 JIA core set criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with the OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core criteria are included in PedACR criteria.
Time frame: Week 48
Population: All subjects in the intent-to-treat population, defined as all subjects who were randomized and who received at least a single administration of study drug. Missing values were treated as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase | 17 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase | 9 Participants |
| Adalimumab + MTX | Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase | 24 Participants |
| Placebo + MTX | Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase | 14 Participants |
p-value: 0.061Pearson's Chi-square test
p-value: 0.028Pearson's Chi-square test
Secondary
Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-Blind Phase
Responders met the following criteria: \>= 50% improvement in \>= 3 of 6 JIA core set criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with the OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core variables are included in PedACR criteria.
Time frame: Week 48
Population: All subjects in the intent-to-treat population, defined as all subjects who were randomized and who received at least a single administration of study drug. Missing values were treated as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-Blind Phase | 16 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-Blind Phase | 9 Participants |
| Adalimumab + MTX | Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-Blind Phase | 24 Participants |
| Placebo + MTX | Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-Blind Phase | 14 Participants |
p-value: 0.103Pearson's Chi-square test
p-value: 0.028Pearson's Chi-square test
Secondary
Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-Blind Phase
Responders met the following criteria: \>= 70% improvement in \>= 3 of 6 JIA core set criteria, and \>= 30% worsening in not more than 1 JIA criterion, compared with the OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core variables are included in PedACR criteria.
Time frame: Week 48
Population: All subjects in the intent-to-treat population, defined as all subjects who were randomized and who received at least a single administration of study drug. Missing values were treated as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind Adalimumab | Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-Blind Phase | 14 Participants |
| Double-Blind Placebo | Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-Blind Phase | 8 Participants |
| Adalimumab + MTX | Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-Blind Phase | 24 Participants |
| Placebo + MTX | Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-Blind Phase | 10 Participants |
p-value: 0.156Pearson's Chi-square test
p-value: 0.002Pearson's Chi-square test
Secondary
Number of Subjects Meeting Pediatric American College of Rheumatology 30% (PedACR30) Response Criteria at the End of the Open-Label Lead-In Phase
Responders met the following criteria: \>= 30% improvement in \>= 3 of 6 JRA core set criteria, and \>= 30% worsening in not more than 1 JRA criterion, compared with the open-label baseline. JRA core set criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with limitation of motion \[LOM\] and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein.
Time frame: Week 16
Population: All subjects in the intent-to-treat population, defined as all subjects who were randomized and who received at least a single administration of study drug. Missing values were treated as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind Adalimumab | Number of Subjects Meeting Pediatric American College of Rheumatology 30% (PedACR30) Response Criteria at the End of the Open-Label Lead-In Phase | 80 Participants |
| Double-Blind Placebo | Number of Subjects Meeting Pediatric American College of Rheumatology 30% (PedACR30) Response Criteria at the End of the Open-Label Lead-In Phase | 64 Participants |
Secondary
Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum
A log rank test was performed and the Kaplan-Meier curve for time to disease flare from double-blind baseline (Week 16) to Week 48 was generated. Disease flare was defined as a \>= 30% worsening in at least 3 of 6 JRA core set criteria and a minimum of 2 active joints, and \>= 30% improvement in not more than 1 JRA criterion. The percentage of subjects without disease flare at each time point is presented.
Time frame: Week 16 to Week 48 (32 weeks)
Population: All subjects in the intent-to-treat population, defined as all subjects who were randomized and who received at least a single administration of study drug, in the MTX stratum.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 32 | 68.4 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 24 | 78.9 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 36 | 63.2 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 20 | 86.8 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 40 | 63.2 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 28 | 68.4 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 44 | 63.2 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 48 | 63.2 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 48 | 35.1 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 20 | 83.8 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 24 | 70.3 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 28 | 59.5 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 32 | 56.8 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 36 | 48.6 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 40 | 45.9 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum | Week 44 | 43.2 Percent participants w/o disease flare |
p-value: 0.031Log Rank
Secondary
Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum
A log rank test was performed and the Kaplan-Meier curve for time to disease flare from double-blind baseline (Week 16) to Week 48 was generated. Disease flare was defined as a \>= 30% worsening in at least 3 of 6 JRA core set criteria and a minimum of 2 active joints, and \>= 30% improvement in not more than 1 JRA criterion. The percentage of subjects without disease flare at each time point is presented.
Time frame: Week 16 to Week 48 (32 weeks)
Population: All subjects in the intent-to-treat population, defined as all subjects who were randomized and who received at least a single administration of study drug, in the non-MTX stratum.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 20 | 90.0 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 24 | 83.3 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 28 | 80.0 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 32 | 70.0 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 36 | 66.7 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 40 | 60.0 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 44 | 60.0 Percent participants w/o disease flare |
| Double-Blind Adalimumab | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 48 | 56.7 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 48 | 28.6 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 20 | 78.6 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 36 | 46.4 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 24 | 64.3 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 44 | 32.1 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 28 | 60.7 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 40 | 39.3 Percent participants w/o disease flare |
| Double-Blind Placebo | Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum | Week 32 | 46.4 Percent participants w/o disease flare |
p-value: 0.029Log Rank
Other Pre-specified
Baseline Measure: Age Continuous - OLE BSA Phase
Age continuous (mean +/- SD) recorded at Baseline of the Open-Label Extension BSA phase of the study. This measure was excluded from Baseline Characteristics due to difficulty maintaining correct subject numbers and Baseline value totals in that section with this phase included.
Time frame: Baseline OLE BSA Phase
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Adalimumab | Baseline Measure: Age Continuous - OLE BSA Phase | 11.3 Years | Standard Deviation 3.32 |
| Double-Blind Placebo | Baseline Measure: Age Continuous - OLE BSA Phase | 11.2 Years | Standard Deviation 3.96 |
Other Pre-specified
Baseline Measure: Age Continuous - OLE FD Phase
Age continuous (mean +/- SD) recorded at Baseline of the Open-Label Extension FD phase of the study. This measure was excluded from Baseline Characteristics due to difficulty maintaining correct subject numbers and Baseline value totals in that section with this phase included.
Time frame: Baseline OLE FD Phase
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Adalimumab | Baseline Measure: Age Continuous - OLE FD Phase | 11.1 Years | Standard Deviation 3.36 |
| Double-Blind Placebo | Baseline Measure: Age Continuous - OLE FD Phase | 11.0 Years | Standard Deviation 4.12 |
Other Pre-specified
Baseline Measure: Gender, Female/Male - OLE BSA Phase
Gender (female/male) recorded at Baseline of the Open-Label Extension BSA phase of the study. This measure was excluded from Baseline Characteristics due to difficulty maintaining correct subject numbers and Baseline value totals in that section while including this phase of the study.
Time frame: Baseline OLE BSA Phase
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Adalimumab | Baseline Measure: Gender, Female/Male - OLE BSA Phase | OLE BSA Phase - Female | 56 Participants |
| Double-Blind Adalimumab | Baseline Measure: Gender, Female/Male - OLE BSA Phase | OLE BSA Phase - Male | 15 Participants |
| Double-Blind Placebo | Baseline Measure: Gender, Female/Male - OLE BSA Phase | OLE BSA Phase - Female | 42 Participants |
| Double-Blind Placebo | Baseline Measure: Gender, Female/Male - OLE BSA Phase | OLE BSA Phase - Male | 15 Participants |
Other Pre-specified
Baseline Measure: Gender, Female/Male - OLE FD Phase
Gender (female/male) recorded at Baseline of the Open-Label Extension FD phase of the study. This measure was excluded from Baseline Characteristics due to difficulty maintaining correct subject numbers and Baseline value totals in that section while including this phase of the study.
Time frame: Baseline OLE FD Phase
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Adalimumab | Baseline Measure: Gender, Female/Male - OLE FD Phase | OLE FD Phase - Female | 45 Participants |
| Double-Blind Adalimumab | Baseline Measure: Gender, Female/Male - OLE FD Phase | OLE FD Phase - Male | 14 Participants |
| Double-Blind Placebo | Baseline Measure: Gender, Female/Male - OLE FD Phase | OLE FD Phase - Female | 33 Participants |
| Double-Blind Placebo | Baseline Measure: Gender, Female/Male - OLE FD Phase | OLE FD Phase - Male | 14 Participants |