Apremilast Pediatric Study in Children With Active Juvenile Psoriatic Arthritis

The ACR Pedi 30 is defined as a minimum of 30 percent improvement from baseline in a minimum of 3 out of 6 components, with no more than 1 component worsening by >30 percent.

The ACR Pedi consists of 6 core criteria:

• physician global assessment (PGA) of disease activity (visual analog scale [VAS]) where 0 represents no disease activity and 100 represents the most disease activity
• assessment of overall well-being (VAS) where 0 represents very well and 100 represents very poor for overall well-being
• functional ability (assessed using the Childhood Health Assessment Questionnaire [CHAQ]);
• number of joints with active arthritis (defined as joints with swelling not caused by deformity or joints, in the absence of swelling, with limitation of passive motion accompanied by pain, tenderness, or both)
• number of joints with limited range of motion
• laboratory marker of inflammation (C-reactive protein [CRP]).

The participants assessment of pain will be assessed using a visual analogue scale (VAS). Participants will be asked to place a vertical line on a 100-mm VAS where the left-hand boundary represents "no pain" and the right-hand boundary represents "worst possible pain".

The ACR Pedi 20, 50, 70 and 90 is defined as a minimum of either 20 percent, 50 percent. 70 percent or 90 percent improvement respectively from baseline in a minimum of 3 out of 6 components, with no more than 1 component worsening by >20 percent, >50 percent, >70 percent or >90 percent respectively.

The ACR Pedi consists of 6 core criteria:

• PGA of disease activity (VAS) where 0 represents no disease activity and 100 represents the most disease activity
• assessment of overall well-being (VAS) where 0 represents very well and 100 represents very poor for overall well-being
• functional ability (assessed using the CHAQ)
• number of joints with active arthritis (defined as joints with swelling not caused by deformity or joints, in the absence of swelling, with limitation of passive motion accompanied by pain, tenderness, or both) 5. number of joints with limited range of motion

• laboratory marker of inflammation (CRP).

PGA of disease activity is assessed using a visual analog scale (VAS), where 0 represents no disease activity and 100 represents the most disease activity.

Assessment of overall well-being is assessed using a visual analog scale (VAS), where 0 represents very well and 100 represents very poor for overall well-being. This assessment can be completed by either the participant or the parent/caregiver.

Active arthritis is defined as joints with swelling not caused by deformity of joints, in the absence of swelling, with limitation of passive motion accompanied by pain, tenderness, or both.

The CHAQ will be used to assess physical ability and functional status of participants as well as their quality of life.

The CHAQ consists of 20 items concerning difficulty in performing the following 8 activities of daily living: dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping, and activities. Subjects will choose from 4 responses ranging from 0 (without any difficulty) to 3 (unable to do). A lower score indicates a better outcome. The subject's/parent's/caregiver's assessment of arthritis-related pain will also be assessed on a VAS that is part of the CHAQ.

JADAS is a composite score of participant well-being visual analog scale (VAS) score, physician global assessment (PGA) VAS score, active joint count, and laboratory marker of inflammation (C-reactive protein [CRP]).

There are 4 components of the JADAS:

• Active joint count (71 joints)
• PGA (0 to 100) measured on a VAS
• Patient/parent global assessment of well-being (0 to 100) measured on a VAS
• CRP (normalized to a 0 to 10 scale)

The active joint count is taken from 71 joints: Temporomandibular joints, cervical spine, glenohumeral joints, acromioclavicular joints, sternoclavicular joints, elbows, wrists, metacarpophalangeal joints, interphalangeal joints, proximal interphalangeal joints, distal interphalangeal joints, hips, subtalar joints, midfoot joints, knees and ankles .

The total score is calculated by adding all 4 components of the JADAS. The score for the JADAS ranges from 0 to 101 where a lower score indicates a better outcome.

PsA flares are defined as more than or equal to 30 percent worsening in at least 3 of 6 American College of Rheumatology Pediatric (ACR Pedi) core set variables with a more than or equal to 30 percent improvement in not more than 1 of 6 ACR Pedi core set variables.

PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.

The PASI score is determined only for subjects whose BSA involved by psoriasis is

≥3 percent. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on the 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90 percent < 100 percent involvement). The sum of scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region, and then multiplied by a constant corresponding to the region's percentage of BSA. The resultant values for each anatomic region are then summed to yield the PASI score.

The C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. Number of participants with suicidal ideation or behavior is defined as the number of participants who answer "yes" at any time during the study (up to end of safety follow-up, Week 56) to one of the 10 categories:

Category 1: Wish to be dead Category 2: Non-specific active suicidal thoughts Category 3: Active suicidal ideation with any methods (not plan) without intent to act Category 4: Active suicidal ideation with some intent to act, without specific plan Category 5: Active suicidal ideation with specific plan and intent Category 6: Preparatory acts or behavior Category 7: Aborted attempt Category 8: Interrupted attempt Category 9: Actual attempt (non-fatal) Category 10: Completed suicide

Tanner Staging of sexual development assessment will be used to assess sexual maturity. Tanner Staging assessment consists of 3 domains (pubic hair, breast development, and other changes) for girls and 4 domains (pubic hair, penis development, testes development, and other changes) for boys. Stages range from 1-5, with 1 indicating preadolescent and 5 adult.

Taste and acceptability will be assessed using a questionnaire with a 7-point faces Likert Scale, with 1 ranging from "super bad" to 7 "super good" and questions to determine whether the participants are able to take the treatment medication.