An Extension Study to WA19977 in Patients With Active Polyarticular-Course Juvenile Idiopathic Arthritis

AE: unfavorable and unintended sign, symptom, or disease associated with use of treatment, regardless of treatment relation. Pre-existing conditions that worsened and laboratory or clinical tests that resulted in change in treatment or discontinuation from treatment were reported as AEs. Serious AE: resulted in death, life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was medically significant. Severe AE: AE that caused inability to work or perform normal daily activity. AEs of special interest: Serious infections (including opportunistic infections), Myocardial infarction/Acute coronary syndrome, Gastrointestinal perforations and related AE, Malignant neoplasms, Anaphylaxis event, Demyelination-related events, Stroke, Spontaneous or serious bleeding, Serious/medically significant hepatic events. Any AE included serious and non-serious AE.

JIA ACR30 response was defined as 3 of any 6 core outcome variables improved by at least 30% of the baseline assessments, with no more than 1 of the remaining variables worsened by more than 30%. Six core variables were: Physician global assessment (PGA) of disease activity using Visual Analog Scale (VAS) from left end of line 0 (inactive arthritis) to right end of line 100 (very active arthritis); Patient/parent global assessment (PtGA) of overall well-being using a VAS from left end of line 0 (very well) to right end of line 100 (very poor); Number of joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); Number of joints with limitation of movement; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and Erythrocyte Sedimentation Rate (ESR).

JIA ACR50 response was defined as 3 of any 6 core outcome variables improved by at least 50% of the baseline assessments, with no more than 1 of the remaining variables worsened by more than 30%. Six core variables were: PGA of disease activity using VAS from left end of line 0 (inactive arthritis) to right end of line 100 (very active arthritis); PtGA of overall well-being using a VAS from left end of line 0 (very well) to right end of line 100 (very poor); Number of joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); Number of joints with limitation of movement; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and ESR.

JIA ACR70 response was defined as 3 of any 6 core outcome variables improved by at least 70% of the baseline assessments, with no more than 1 of the remaining variables worsened by more than 30%. Six core variables were: PGA of disease activity using VAS from left end of line 0 (inactive arthritis) to right end of line 100 (very active arthritis); PtGA of overall well-being using a VAS from left end of line 0 (very well) to right end of line 100 (very poor); Number of joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); Number of joints with limitation of movement; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and ESR

JIA ACR90 response was defined as 3 of any 6 core outcome variables improved by at least 90% of the baseline assessments, with no more than 1 of the remaining variables worsened by more than 30%. Six core variables were: PGA of disease activity using VAS from left end of line 0 (inactive arthritis) to right end of line 100 (very active arthritis); PtGA of overall well-being using a VAS from left end of line 0 (very well) to right end of line 100 (very poor); Number of joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); Number of joints with limitation of movement; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and ESR.

Criteria for Inactive Disease: 1) No joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both), 2) No fever, rash, serositis, splenomegaly, hepatomegaly (by physical exam) or generalized lymphadenopathy attributable to systemic juvenile idiopathic arthritis (sJIA), 3) Normal ESR (less than [<] 20 millimeters per hour [mm/hour]), and 4) PGA of disease activity using VAS indicated no disease activity (where no disease activity is considered to be a score less than or equal to [≤]10 mm on a 100 mm VAS where left end of line 0 [inactive arthritis] to right end of line 100 [very active arthritis]).

Clinical remission: inactive disease for minimum of 6 continuous months while on medication (Level 1); off oral corticosteroid medications but still on tocilizumab (Level 2); off both methotrexate and oral corticosteroids but still on tocilizumab (Level 3); or off all anti-arthritis medications-oral corticosteroids, methotrexate, non-steroidal anti-inflammatory drugs but still on tocilizumab (Level 4). Inactive disease: No joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); No fever, rash, serositis, splenomegaly, hepatomegaly (by physical exam) or generalized lymphadenopathy attributable to sJIA; Normal ESR (<20 mm/hour); PGA of disease activity indicated no disease activity (score ≤10 mm on a 100 mm VAS where 0 [inactive arthritis] and 100 [very active arthritis]). Overall percentage of participants with clinical remission (any level) are reported.

Joint with active arthritis was defined as a joint with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both.

The maximum number of joints with limitation of movement is 67 and these were defined as those with 'limitation of motion'.

The physician provides a rating of the participant's arthritis disease activity on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'arthritis inactive' (ie, symptom-free and no arthritis symptoms) and the extreme right end represents 'arthritis very active'. A higher score indicates more disease activity. A negative change score indicates improvement.

The participant or parent/guardian, as appropriate, provides a rating of the participant's well-being on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'very well' (ie, symptom-free and no arthritis disease activity) and the extreme right end represents 'very poor' (ie, maximum arthritis disease activity). A higher score indicates poorer well-being. A negative change score indicates improvement.

The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. To calculate the overall score, the participant must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability.

The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. To calculate the overall score, the participant must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability. A minimally important improvement was defined as at least a 0.13 improvement in CHAQ-DI score from baseline.

The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Activity component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Arising component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Dressing and Grooming component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Eating component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Grip component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Hygiene component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Reach component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Walking component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).