A Study of Ixekizumab (LY2439821) in Children With Juvenile Idiopathic Arthritis Categories of Enthesitis-related Arthritis (Including Juvenile Onset Ankylosing Spondylitis) and Juvenile Psoriatic Arthritis

JIA ACR, is comprised of 6 variables: number of active joints, number of joints with limited range of motion, Physician's Global Assessment of Disease Activity, Parent's Global Assessment of Well-Being, physical function (measured by the Childhood Health Assessment Questionnaire \[CHAQ\]), and acute-phase reactants (high-sensitivity C-reactive protein \[hsCRP\] and erythrocyte sedimentation rate \[ESR\]). A JIA ACR30 response is defined as at least 30% improvement from baseline in at least 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by more than 30%.

Time frame: Week 16

Population: All randomized participants who received at least one dose of study drug. Non responder Imputation (NRI) is applied for inadequate responders and participants who had missing data at Week 16 for any reason including discontinuation. As per the pre-specified statistical analysis plan, outcomes were analyzed and reported by treatment regimen, as exposure was the same across the different treatment groups.

The LEI was developed specifically for use in psoriatic arthritis (PsA). It measures enthesitis at 6 sites (lateral epicondyle of humerus, right/left (R/L); medial femoral condyle, (R/L); Achilles tendon insertion, (R/L)). Each site is assigned a score of 0 (absent) or 1 (present); the results from each site are then added to produce a total score (range 0 to 6) with the higher scores indicating more severe enthesitis.

Time frame: Baseline, Week 104

The LEI was developed specifically for use in psoriatic arthritis (PsA). It measures enthesitis at 6 sites (lateral epicondyle of humerus, right/left (R/L); medial femoral condyle, (R/L); Achilles tendon insertion, (R/L)). Each site is assigned a score of 0 (absent) or 1 (present); the results from each site are then added to produce a total score (range 0 to 6) with the higher scores indicating more severe enthesitis.

Time frame: Baseline, Week 16

Population: All randomized participants who received at least one dose of study drug and had a baseline enthesitis (LEI \>0). For missing post-baseline values for subjects who discontinued the study drug due to adverse events, imputation was performed using the Modified Baseline Observation Carried Forward (mBOCF) method. As per the pre-specified statistical analysis plan, outcomes were analyzed and reported by treatment regimen, as exposure was the same across the different treatment groups.

The PASI is an index that combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling (S), redness (R), and plaque induration/infiltration thickness (T) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Severity is rated for each index (R, S, T) on a 0 to 4 scale (0 for no involvement up to 4 for severe involvement): 0 = none 1. = slight 2. = moderate 3. = severe 4. = very severe The various body regions are weighted to reflect their respective proportion of BSA.

Time frame: Baseline, Week 104

The PASI is an index that combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling (S), redness (R), and plaque induration/infiltration thickness (T) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Severity is rated for each index (R, S, T) on a 0 to 4 scale (0 for no involvement up to 4 for severe involvement): 0 = none 1. = slight 2. = moderate 3. = severe 4. = very severe The various body regions are weighted to reflect their respective proportion of BSA.

Time frame: Baseline, Week 16

Population: All randomized participants who received at least one dose of study drug with baseline psoriatic lesion(s) involving ≥3% BSA. For missing post-baseline values for subjects who discontinued the study drug due to adverse events, imputation was performed using the Modified Baseline Observation Carried Forward (mBOCF) method. As per the pre-specified statistical analysis plan, outcomes were analyzed and reported by treatment regimen, as exposure was the same across the different treatment groups.

JIA ACR, is comprised of 6 core set variables: number of active joints, number of joints with limited range of motion, Physician's Global Assessment of Disease Activity, Parent's Global Assessment of Well-Being, physical function (measured by the Childhood Health Assessment Questionnaire \[CHAQ\]), and acute-phase reactants (high-sensitivity C-reactive protein \[hsCRP\] and erythrocyte sedimentation rate \[ESR\]). A JIA ACR 30/50/70/90 response is defined as a greater than or equal to (≥) 30/50/70/90/100% improvement from baseline in at least 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by more than 30%.

Time frame: Week 104

JIA ACR, is comprised of 6 variables: number of active joints, number of joints with limited range of motion, Physician's Global Assessment of Disease Activity, Parent's Global Assessment of Well-Being, physical function (measured by the Childhood Health Assessment Questionnaire \[CHAQ\]), and acute-phase reactants (high-sensitivity C-reactive protein \[hsCRP\] and erythrocyte sedimentation rate \[ESR\]). A JIA ACR30 response is defined as at least 30% improvement from baseline in at least 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by more than 30%.

Time frame: Week 16

Population: All randomized participants who received at least one dose of study drug. Non responder Imputation (NRI) is applied for inadequate responders and participants who had missing data at Week 16 for any reason including discontinuation. As per the pre-specified statistical analysis plan, outcomes were analyzed and reported by treatment regimen, as exposure was the same across the different treatment groups.

JIA ACR, is comprised of 6 core set variables: number of active joints, number of joints with limited range of motion, Physician's Global Assessment of Disease Activity, Parent's Global Assessment of Well-Being, physical function (measured by the Childhood Health Assessment Questionnaire \[CHAQ\]), and acute-phase reactants (high-sensitivity C-reactive protein \[hsCRP\] and erythrocyte sedimentation rate \[ESR\]). A JIA ACR 50/70/90 response is defined as a greater than or equal to (≥) 50/70/90/100% improvement from baseline in at least 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by more than 30%.

Time frame: Week 16

Population: All randomized participants who received at least one dose of study drug. Non responder Imputation (NRI) is applied for inadequate responders and participants who had missing data at Week 16 for any reason including discontinuation. As per the pre-specified statistical analysis plan, outcomes were analyzed and reported by treatment regimen, as exposure was the same across the different treatment groups.

Disease flare is defined as worsening of ≥30% from baseline in at least 3 of the 6 JIA ACR core set criteria and an improvement of ≥30% in no more than one of the criteria. The JIA ACR, is comprised of 6 core set variables: number of active joints, number of joints with limited range of motion, Physician's Global Assessment of Disease Activity, Parent's Global Assessment of Well-Being, physical function (measured by the Childhood Health Assessment Questionnaire \[CHAQ\]), and acute-phase reactants (high-sensitivity C-reactive protein \[hsCRP\] and erythrocyte sedimentation rate \[ESR\]).

Time frame: Baseline through Week 104

Disease flare is defined as worsening of ≥30% from baseline in at least 3 of the 6 JIA ACR core set criteria and an improvement of ≥30% in no more than one of the criteria. The JIA ACR, is comprised of 6 core set variables: number of active joints, number of joints with limited range of motion, Physician's Global Assessment of Disease Activity, Parent's Global Assessment of Well-Being, physical function (measured by the Childhood Health Assessment Questionnaire \[CHAQ\]), and acute-phase reactants (high-sensitivity C-reactive protein \[hsCRP\] and erythrocyte sedimentation rate \[ESR\]).

Time frame: Week 2 through Week 16

Population: All randomized participants, even if the participant does not take the assigned treatment. As per the pre-specified statistical analysis plan, outcomes were analyzed and reported by treatment regimen, as exposure was the same across the different treatment groups.

Percentage of participants with treatment-emergent positive anti-ixekizumab antibodies was summarized by treatment group. Percentage was calculated based on the number of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-ixekizumab antibodies / number of evaluable participants \* 100%.

Time frame: Baseline through Week 104

Percentage of participants with treatment-emergent positive anti-ixekizumab antibodies was summarized by treatment group. Percentage was calculated based on the number of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-ixekizumab antibodies / number of evaluable participants \* 100%.

Time frame: Baseline through Week 16

Population: All randomized participants who received at least one dose of the study drug and had evaluable data. As per the pre-specified statistical analysis plan, outcomes were analyzed and reported by treatment regimen, as exposure was the same across the different treatment groups.

C-trough were measured at specified time points to assess the minimum concentration of ixekizumab in the blood before the next dose was administered.

Time frame: Week 20, 32, 56, 80 and 104 : Pre-dose

C-trough were measured at specified time points to assess the minimum concentration of ixekizumab in the blood before the next dose was administered.

Time frame: Week 4, 12 and 16 : Pre-dose

Population: All randomized participants who received at least one dose of the study drug and had evaluable C-trough data at the specified time points. As per the pre-specified statistical analysis plan, the PK outcome was analyzed and reported for the ixekizumab treatment arm, categorized by weight.