Trial Outcomes & Findings for Extension Study Evaluating Etanercept in 3 Subtypes of Childhood Arthritis (NCT NCT01421069)

This was an extension study in pediatric participants diagnosed with one of three subtypes of juvenile idiopathic arthritis (JIA): extended oligoarticular JIA, enthesitis related arthritis (ERA), or psoriatic arthritis (PsA) and had received at least one dose of Etanercept and completed approximately 96 weeks of participation in study B1801014 (NCT00962741).

Total 127 participants were enrolled and treated in parent study, B1801014 (NCT00962741) and included in analysis of this extension study. Total 109 participants from the Parent study were enrolled in this extension study, B1801023. Out of which 10 participants directly entered into observational phase and did not receive treatment in this extension study. The extension study has 3 periods: active treatment period, withdrawal/re-treatment period and observational period.

Extension Study Evaluating Etanercept in 3 Subtypes of Childhood Arthritis

Number of participants who had adverse event (AE) of malignancy were reported. An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it.

A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it.

Serious infections were defined as any infections those were life threatening or resulted in disability, infections requiring intravenous antibiotic treatment and hospitalization.

Medically important infections were defined as an infection requiring parenteral (intravenous \[IV\], intramuscular \[IM\]) anti-infective agent(s) and/or hospitalization.

Number of participants who had infections as AEs were reported. An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it.

Number of participants who had treatment emergent infections and injection site reactions as adverse events were reported. Treatment emergent infections were infections occurring in a participant who received study medication without regard to possibility of causal relationship to it. An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it.

Number of participants who had treatment emergent infections as AEs were reported. An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it.

Participants withdrew from the study due to AEs were reported. An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it.

Participants withdrew from the study due to AEs were reported. An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it.

Abnormality of laboratory parameters was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.

Growth parameters including weight, height and body-mass index (BMI) were compared to the standard growth data by using Z-Score. Z-Score is a statistical measure to evaluate how a single data point or mean compares to a standard. A Z-Score describes whether a mean is above or below the standard and how unusual the measurement is. Z-scores range from -3 to +3. A Z-score of 0 indicates the same mean, greater than (\>) 0 a greater mean, and less than (\<0) a lesser mean than the standard.

Growth parameters including weight, height and BMI were compared to the standard growth data by using Z-Score. Z-Score is a statistical measure to evaluate how a single data point or mean compares to a standard. A Z-Score describes whether a mean is above or below the standard and how unusual the measurement is. Z-scores range from -3 to +3. A Z-score of 0 indicates the same mean, \>0 a greater mean, and \<0 a lesser mean than the standard.

Growth parameters including weight, height and BMI were compared to the standard growth data by using Z-Score. Z-Score is a statistical measure to evaluate how a single data point or mean compares to a standard. A Z-Score describes whether a mean is above or below the standard and how unusual the measurement is. Z-scores range from -3 to +3. A Z-score of 0 indicates the same mean, \>0 a greater mean, and \<0 a lesser mean than the standard.

Tanner assessment score: used to document the stage of development of secondary sexual characteristics. Female pubertal development staged by pubic hair development and breast size; male pubertal development staged by size of the genitalia and development of pubic hair. Tanner assessment score ranged from 1 (no development) to 5 (adult-like development in quantity and size), higher scores indicated more development.

Tanner assessment score: used to document the stage of development of secondary sexual characteristics. Female pubertal development staged by pubic hair development and breast size; male pubertal development staged by size of the genitalia and development of pubic hair. Tanner assessment score ranged from 1 (no development) to 5 (adult-like development in quantity and size), higher scores indicated more development.

Tanner assessment score: used to document the stage of development of secondary sexual characteristics. Female pubertal development staged by pubic hair development and breast size; male pubertal development staged by size of the genitalia and development of pubic hair. Tanner assessment score ranged from 1 (no development) to 5 (adult-like development in quantity and size), higher scores indicated more development.

ACR30PR: \>=30% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

ACR30PR: \>=30% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

ACR30PR: \>=30% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

ACR50PR: \>=50% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

ACR50PR: \>=50% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

ACR50PR:\>=50% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria:1)PGA of disease activity(DA),2)PtGA of arthritis pain,3) CHAQ 4)number(no.) of active joints5)no. of joints with limited range of motion 6)C-reactive protein.PGA of DA: 21-circle VAS ranging 0-10, with 0=\&10=maximumDA,higher score=more severe disease.PGA:21-circle VAS ranging 0-10,0=very well,10=very poor,higher scores=worsening condition.CHAQ: assessment of functional disability,discomfort. Ability to perform activities:dressing,arising,eating,walking,hygiene,reach,grip, common activities distributed in total of 30 items. Ranging 0=no difficulty;1=some difficulty;2=much difficulty;3=unable to do.Highest score for each domain:score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered.Ranged 0=no difficulty to 3=extreme difficulty;higher scores indicated more functional disability and discomfort. Participants \>18 years assessed using CHAQ.

ACR70PR: \>=70% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

ACR70PR: \>=70% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

ACR70PR: \>=70% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

ACR90PR: \>=90% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

ACR90PR: \>=90% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

ACR90PR: \>=90% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

ACR100PR: 100% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

ACR100PR: 100% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

ACR100PR: 100% improvement from baseline in 3 of 6 criteria with worsening \>30% in no more than 1 of 6 criteria: physician's global assessment (on 21-circle VAS ranging 0 \[no disease activity\] to 10 \[maximum disease activity\],higher score=more severe disease), patient global assessment (on 21-circle VAS ranging 0 \[very well\] to 10 \[very poor\],higher score=higher pain), childhood health assessment questionnaire (\[CHAQ\] Participants \>18 years assessed for functional disability, discomfort. Ability to dressing, arising, eat, walk, hygiene, reach, grip, common activities were distributed in 30 items. Each item scored from 0 \[no difficulty\] to 3 \[unable to do\]. Highest score for each domain was score for that domain. Overall CHAQ score=sum of domain scores/number of domains answered and ranged from 0 \[no difficulty\] to 3 \[extreme difficulty\], where higher scores=more functional disability and discomfort), number of active joints and joints with limited range of motion, C-reactive protein.

PGA of disease activity was measured on a 21-circle Visual Analog Scale (VAS) ranging from 0 to 10, with 0 = no disease activity and 10= maximum disease activity, where higher score indicated more severe disease.

PGA of disease activity was measured on a 21-circle VAS ranging from 0 to 10, with 0 = no disease activity and 10= maximum disease activity, where higher score indicated more severe disease.

PGA of disease activity was measured on a 21-circle VAS ranging from 0 to 10, with 0 = no disease activity and 10= maximum disease activity, where higher score indicated more severe disease.

Patient/Parent Global Assessment was assessed by the participant's parent using a 21-circle VAS ranging from 0 to 10, with 0 = very well and 10 = very poor, where higher scores indicated worsening of condition.

Patient/Parent Global Assessment was assessed by the participant's parent using a 21-circle VAS ranging from 0 to 10, with 0 = very well and 10 = very poor, where higher scores indicated worsening of condition.

Patient/Parent Global Assessment was assessed by the participant's parent using a 21-circle VAS ranging from 0 to 10, with 0 = very well and 10 = very poor, where higher scores indicated worsening of condition.

CHAQ: parent-administered, valid assessment of functional disability, discomfort in pediatrics with rheumatic diseases. Parents report participant's ability to perform activities in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, common activities distributed in total of 30 items. Each item is scored on 4-point Likert scale: 0=no difficulty;1=some difficulty;2=much difficulty;3=unable to do. Highest score reported for each domain is score for that domain. Overall CHAQ score was calculated as sum of domain scores divided by number of domains answered and ranged from 0=no difficulty to 3=extreme difficulty, where higher scores indicated more functional disability and discomfort in pediatrics with rheumatic disease. Participants below 18 years of age were assessed using CHAQ.

CHAQ: parent-administered, valid assessment of functional disability, discomfort in pediatrics with rheumatic diseases. Parents report participant's ability to perform activities in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, common activities distributed in total of 30 items. Each item is scored on 4-point Likert scale: 0=no difficulty;1=some difficulty;2=much difficulty;3=unable to do. Highest score reported for each domain is score for that domain. Overall CHAQ score was calculated as sum of domain scores divided by number of domains answered and ranged from 0=no difficulty to 3=extreme difficulty, where higher scores indicated more functional disability and discomfort in pediatrics with rheumatic disease. Participants below 18 years of age were assessed using CHAQ.

CHAQ: parent-administered, valid assessment of functional disability, discomfort in pediatrics with rheumatic diseases. Parents report participant's ability to perform activities in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, common activities distributed in total of 30 items. Each item is scored on 4-point Likert scale: 0=no difficulty;1=some difficulty;2=much difficulty;3=unable to do. Highest score reported for each domain is score for that domain. Overall CHAQ score was calculated as sum of domain scores divided by number of domains answered and ranged from 0=no difficulty to 3=extreme difficulty, where higher scores indicated more functional disability and discomfort in pediatrics with rheumatic disease. Participants below 18 years of age were assessed using CHAQ.

HAQ is a self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ total score range from 0 to 3, where 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; \> 1=significant functional limitation. Participants aged 18 years or above were assessed using HAQ scores.

HAQ is a self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ total score range from 0 to 3, where 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; \> 1=significant functional limitation. Participants aged 18 years or above were assessed using HAQ scores.

HAQ is a self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ total score range from 0 to 3, where 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; \> 1=significant functional limitation. Participants aged 18 years or above were assessed using HAQ scores.

Joints with active arthritis were defined as joints that were swollen or, in the absence of swelling, joints with limited range of motion accompanied by pain and/or tenderness.

Joints with active arthritis were defined as joints that were swollen or, in the absence of swelling, joints with limited range of motion accompanied by pain and/or tenderness.

Joints with active arthritis were defined as joints that were swollen or, in the absence of swelling, joints with limited range of motion accompanied by pain and/or tenderness.

Total number of joints with limited range of motion was the number of joints with limited range of motion. It was defined as 69\*(total number of joints with score of limited range of motion greater than zero)/number of non-missing limited range of motions. Joint replacement (JR) and not evaluable (NE) were treated as missing. If more than 34 scores of limited range of motion were missing, then the total number of joints with limited range of motion was defined as missing.

Total number of joints with limited range of motion was the number of joints with limited range of motion. It was defined as 69\*(total number of joints with score of limited range of motion greater than zero)/number of non-missing limited range of motions. JR and NE were treated as missing. If more than 34 scores of limited range of motion were missing, then the total number of joints with limited range of motion was defined as missing.

Total number of joints with limited range of motion was the number of joints with limited range of motion. It was defined as 69\*(total number of joints with score of limited range of motion greater than zero)/number of non-missing limited range of motions. JR and NE were treated as missing. If more than 34 scores of limited range of motion were missing, then the total number of joints with limited range of motion was defined as missing.

The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

VAS: 10-point pain intensity ordinal rating system: 0 = no pain, 1-3 = mild pain, 4-6 = moderate pain, 7-9 = severe pain, 10 = worst possible pain. A higher score indicates greater pain intensity.

VAS: 10-point pain intensity ordinal rating system: 0 = no pain, 1-3 = mild pain, 4-6 = moderate pain, 7-9 = severe pain, 10 = worst possible pain. A higher score indicates greater pain intensity.

VAS: 10-point pain intensity ordinal rating system: 0 = no pain, 1-3 = mild pain, 4-6 = moderate pain, 7-9 = severe pain, 10 = worst possible pain. A higher score indicates greater pain intensity.

Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes (if none was present = 0; if stiffness persisted the entire day = 1440 minutes was recorded; if morning stiffness was continuing at the time of assessment or was unusual compared to the recent past, average of duration of stiffness over the past 3 days was reported).

Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes (if none was present = 0; if stiffness persisted the entire day, 1440 minutes was recorded; if morning stiffness was continuing at the time of assessment or was unusual compared to the recent past, average of duration of stiffness over the past 3 days was reported).

Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes (if none was present = 0; if stiffness persisted the entire day, 1440 minutes was recorded; if morning stiffness was continuing at the time of assessment or was unusual compared to the recent past, average of duration of stiffness over the past 3 days was reported).

Clinically inactive disease was defined as no joints with active arthritis; no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA; no active uveitis; normal range of CRP; PGA of disease activity of 0 on a 21-circle VAS and duration of morning stiffness of less than or equal to (\<=) 15 minutes.

Clinically inactive disease was defined as no joints with active arthritis; no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA; no active uveitis; normal range of CRP; PGA of disease activity of 0 on a 21-circle VAS and duration of morning stiffness of \<=15 minutes.

Clinically inactive disease was defined as no joints with active arthritis; no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA; no active uveitis; normal range of CRP; PGA of disease activity of 0 on a 21-circle VAS and duration of morning stiffness of \<=15 minutes.

JADAS-73 is a validated composite disease activity measure for JIA. It was derived from four components; 1) Physician global assessment of disease activity (assessed on 10 cm VAS, where 0= no activity and 10=maximum activity, higher scores indicated more disease activity). 2) Parent/participant global assessment of overall well-being (assessed on a VAS, where 0= very well and 10=very poor, higher scores indicated worse condition). 3) Number of joints with active disease (defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness). 4) An inflammatory marker, CRP that was measured in mg/L and its value normalized to 0 to 10 scale, where higher scores indicated more disease activity. JADAS total score was calculated as the sum of its four components and ranged from 0-103. A higher score indicates more disease activity.

JADAS-73 is a validated composite disease activity measure for JIA. It was derived from four components; 1) Physician global assessment of disease activity (assessed on 10 cm VAS, where 0= no activity and 10=maximum activity, higher scores indicated more disease activity). 2) Parent/participant global assessment of overall well-being (assessed on a VAS, where 0= very well and 10=very poor, higher scores indicated worse condition). 3) Number of joints with active disease (defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness). 4) An inflammatory marker, CRP that was measured in mg/L and its value normalized to 0 to 10 scale, where higher scores indicated more disease activity. JADAS total score was calculated as the sum of its four components and ranged from 0-103. A higher score indicates more disease activity.

JADAS-73 is a validated composite disease activity measure for JIA. It was derived from four components; 1) Physician global assessment of disease activity (assessed on 10 cm VAS, where 0= no activity and 10=maximum activity, higher scores indicated more disease activity). 2) Parent/participant global assessment of overall well-being (assessed on a VAS, where 0= very well and 10=very poor, higher scores indicated worse condition). 3) Number of joints with active disease (defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness). 4) An inflammatory marker, CRP that was measured in mg/L and its value normalized to 0 to 10 scale, where higher scores indicated more disease activity. JADAS total score was calculated as the sum of its four components and ranged from 0-103. A higher score indicates more disease activity.

Overall back pain assessed by participant's parent using a 100 millimeter (mm) VAS with 0 mm= no pain and 100 mm= most severe pain, higher scores indicated more pain.

Overall back pain assessed by participant's parent using a 100 millimeter (mm) VAS with 0 mm= no pain and 100 mm= most severe pain, higher scores indicated more pain.

Overall back pain assessed by participant's parent using a 100 mm VAS with 0 mm= no pain and 100 mm= most severe pain, higher scores indicated more pain.