A Study in Participants With Moderate to Severe Psoriasis

The sPGA of psoriasis is scored on a 6-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 6 point severity scale (0 [clear] to 5 [severe]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the sPGA score and category (0=clear; 1=minimal; 2=mild; 3=moderate; 4=marked; 5 = severe). As defined by protocol, a responder is a participant who has a post-baseline sPGA score of '0' or a post-baseline score of '1' with at least a 2 point improvement from baseline.

Treatment-emergent adverse events (TEAEs) are events which were not present at baseline or pre-existing conditions at baseline that worsened in severity following the start of treatment. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.

The HADS is a 14-item, participant self-reported scale that consists of an anxiety scale and a depression scale, each with 7 items. Items are rated on a 4-point Likert-type scale ranging from 0 (low level of anxiety or depression) to 3 (high level of anxiety or depression). Each subscale score ranges from 0 to 21 with higher scores indicating greater symptom severity. The classification is defined: 0-7 normal, 8-10 Borderline, 11-21 Abnormal. LS mean was calculated using the analysis of covariance (ANCOVA) model including treatment as fixed effect and baseline as covariate.

The QIDS-SR16 is a self-administered, 16-item instrument in which a participant is asked to consider each statement as it relates to the way they have felt for the past 7 days. There is a 4-point scale for each item ranging from 0 (best) to 3 (worst). The 16 items are scored to give 9 individual depression domains (sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance [initial, middle and late insomnia or hypersomnia], decrease/increase in appetite/weight, and psychomotor agitation/retardation), which are summed to give a single score ranging from 0 to 27, with higher scores denoting greater symptom severity. The LS Mean (no multiplicity adjustments) are presented for each treatment versus placebo comparison at each visit and use an analysis of covariance (ANCOVA) model including baseline as a covariate and treatment as fixed effect in the model.

The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been). The LS Mean (no multiplicity adjustments) are presented for each treatment versus placebo comparison at each visit and use an analysis of covariance (ANCOVA) model including baseline as a covariate and treatment as fixed effect in the model.

The pain VAS is a participant-administered single-item scale designed to measure current joint pain from psoriatic arthritis (PsA) using a 100- millimeter (mm) horizontal VAS. Overall severity of participant's joint pain from PsA is indicated by placing a single mark on the horizontal 100-mm scale from 0mm (no pain) to 100 mm (pain as severe as you can imagine). A mixed effects model for repeated measures analysis was used. Least Squares (LS) Mean values were calculated using MMRM and were controlled for baseline as a covariate, visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured.

MOS-S provides a concise assessment of important dimensions of sleep, including initiation, maintenance, respiratory problems, quantity, perceived adequacy, and somnolence during the past 4 weeks. Scoring based on 7 subscales: sleep disturbance, snoring, awakened short of breath or with headache, sleep adequacy, and somnolence (range:0-100,with higher scores for more impairment); sleep quantity (range:0-24), and optimal sleep (yes:1, no:0). Six(6) and 9 item index measures of sleep disturbance were constructed to provide composite scores. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range * 100); total score range: 0 to 100; higher score = higher scores indicate greater problems with the attribute.The LS Mean (no multiplicity adjustments) was calculated using an analysis of covariance (ANCOVA) model including baseline as a covariate and treatment as fixed effect in the model.

The PMRU is a 3-item participant-reported questionnaire on health care resource utilization due to psoriasis for physician/clinic visits, emergency room visits, and inpatient hospital admissions since the last study visit.

The WPAI questionnaire has six questions to assess whether the participant was currently employed (Q1); how many hours from work were missed due to problems associated with psoriasis (Q2) or any other reason (Q3); hours actually worked (Q4); degree that psoriasis affected productivity while working (Q5); and degree that psoriasis affected regular activities (Q6) over the past 7 days. Four separate overall scores were calculated, Absenteeism (work time missed) = (Q2/(Q2+Q4))*100, Presenteeism(impairment at work/reduced on-the-job effectiveness) = (Q5/10) *100, Work productivity loss(overall work impairment /absenteeism plus presenteeism) = (Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))x(Q5/10)]) * 100 and Activity Impairment = (Q6/10) * 100. Each score ranges from 0 to 100 with higher scores indicating greater impairment and less productivity ( worse outcomes). The LS Mean was calculated using ANCOVA model including baseline as a covariate and treatment as fixed effect in the model.

The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. The recall period was the past 4 weeks. The LS Mean was calculated using ANCOVA model including baseline as a covariate and treatment as fixed effect in the model.

The NAPSI is physician-rated and quantifies the severity of nail psoriasis by evaluating the presence or absence of psoriatic manifestations on the nail matrix and nail bed. Each finger nail is divided with imaginary lines into quadrants and scored for both nail matrix and nail bed psoriasis (range from 0 [absence of psoriasis] to 4 [presence of psoriasis in all 4 quadrants]). Participant's fingers and toes were evaluated and the sum of the scores was added resulting in a range of 0 to 160; higher scores indicate greater severity. If an individual toe or finger assessment was missing (not done), the average of the remaining measured digits was imputed and added to the sum. If <50% of the toes or finger assessments were missing, the imputation was performed. If >50% of the assessments were missing, then the sum of the scores was left as missing. LS mean was calculated using MMRM with baseline score as covariate, visit, treatment and visit by treatment interaction as fixed effects.

The PPASI is a physician-assessed composite score derived from the summed scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement. The PPASI score ranges from 0 to 72, with higher scores representing greater severity of palmoplantar psoriasis.LS mean was calculated using MMRM with baseline score as covariate, visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to symmetric.

The PSSI is a physician-assessed composite score derived from the summed scores for erythema, induration, and desquamation multiplied by a score for the extent of scalp area involved. The PSSI score ranges from 0 to 72, with higher scores representing greater severity of scalp psoriasis.LS mean was calculated using MMRM with baseline score as covariate, visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured.

The population pharmacokinetic (PK) modeling value for systemic clearance was based on data from week 1 to week 32 for all participants in all ixekizumab treatment arms.

The DLQI is a 10-item, participant-administered dermatology-specific questionnaire that assess health related quality of life that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The DLQI items response categories are scored 0 (not relevant) to 3 (very much) with a total score range of 0 to 30; higher scores indicate poor quality of life and a 5-point change from baseline is considered clinically relevant. The LS Mean(no multiplicity adjustments) are presented for each treatment versus placebo comparison at each visit and use an analysis of covariance (ANCOVA) model including baseline as a covariate and treatment as fixed effect in the model.

PASI combines the extent of body surface involvement in 4 anatomical regions(head,trunk,arms,and legs).For each region the percent area of skin involved was estimated from 0(0%) to 6(90%-100%) and severity was estimated by clinical signs of erythema,induration and scaling with a scores range from 0(none) to 4(very severe).Each area is scored by itself and the scores were then combined for the final PASI.Final PASI calculated as:sum of severity parameters for each region*area score*weighing factor (head[0.1],upper limbs[0.2],trunk[0.3],lower limbs [0.4]).Overall scores range from 0(no psoriasis) to 72(most severe disease).The LS mean are presented for each treatment versus placebo comparison at each visit and use ANCOVA model including baseline PASI covariate and treatment as fixed effect in the model.Results at Week 12 are summarized as Improvement in PASI which is defined as a reduction in the PASI calculated score at a visit as compared to the score calculated at the baseline visit.

PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (none) to 4 (very severe). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor (head [0.1], upper limbs [0.2], trunk [0.3], lower limbs [0.4]). Overall scores range from 0 (no psoriasis) to 72 (the most severe disease). Participants achieving PASI 75 were defined as having an improvement of ≥75% in the PASI score compared to baseline.

The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (none) to 4 (very severe). Each area is scored by itself and the scores were then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor (head [0.1], upper limbs [0.2], trunk [0.3], lower limbs [0.4]). Overall scores range from 0 (no psoriasis) to 72 (the most severe disease). Improvement in PASI is defined as improvement in the PASI calculated score at a visit as compared to the score calculated at the baseline visit.

The sPGA of psoriasis is scored on a 6-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 6-point severity scale (0 [clear] to 5 [severe]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the sPGA score and category (0=clear; 1=minimal; 2=mild; 3=moderate; 4=marked; 5 = severe). As defined by protocol, a responder is a participant who has a post-baseline sPGA score of '0' or a post-baseline score of '1' with at least a 2 point improvement from baseline.

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%.

The sPGA of psoriasis is scored on a 6-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 6-point severity scale (0 [clear] to 5 [severe]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the sPGA score and category (0=clear; 1=minimal; 2=mild; 3=moderate; 4=marked; 5 = severe). As defined by protocol, a responder is a participant who has a post-baseline sPGA score of '0' or a post-baseline score of '1' with at least a 2 point improvement from baseline.

Treatment-emergent adverse events (TEAEs) are events which were not present at baseline or pre-existing conditions at baseline that worsened in severity following the start of treatment. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.

The HADS is a 14-item, participant self-reported scale that consists of an anxiety scale and a depression scale, each with 7 items. Items are rated on a 4-point Likert-type scale ranging from 0 (low level of anxiety or depression) to 3 (high level of anxiety or depression). Each subscale score ranges from 0 to 21 with higher scores indicating greater symptom severity. The classification is defined: 0-7 normal, 8-10 Borderline, 11-21 Abnormal.

The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been).

The pain VAS is a participant-administered single-item scale designed to measure current joint pain from psoriatic arthritis (PsA) using a 100- millimeter (mm) horizontal VAS. Overall severity of participant's joint pain from PsA is indicated by placing a single mark on the horizontal 100-mm scale from 0mm (no pain) to 100 mm (pain as severe as you can imagine). A mixed effects model for repeated measures analysis was used.

The NAPSI is physician-rated and quantifies the severity of nail psoriasis by evaluating the presence or absence of psoriatic manifestations on the nail matrix and nail bed. Each finger nail is divided with imaginary lines into quadrants and scored for both nail matrix and nail bed psoriasis (range from 0 [absence of psoriasis] to 4 [presence of psoriasis in all 4 quadrants]). Participant's fingers and toes were evaluated and the sum of the scores was added resulting in a range of 0 to 160; higher scores indicate greater severity. If an individual toe or finger assessment was missing (not done), the average of the remaining measured digits was imputed and added to the sum. If <50% of the toes or finger assessments were missing, the imputation was performed. If >50% of the assessments were missing, then the sum of the scores was left as missing.

Baseline is defined as the last available value prior to the first dose in Part A of the study.

The PSSI is a physician-assessed composite score derived from the summed scores for erythema, induration, and desquamation multiplied by a score for the extent of scalp area involved. The PSSI score ranges from 0 to 72, with higher scores representing greater severity of scalp psoriasis.

Baseline is defined as the last available value prior to the first dose in Part A of the study.

The PPASI is a physician-assessed composite score derived from the summed scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement. The PPASI score ranges from 0 to 72, with higher scores representing greater severity of palmoplantar psoriasis.LS mean was calculated using MMRM with baseline score as covariate, visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to symmetric.

PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (none) to 4 (very severe). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor (head [0.1], upper limbs [0.2], trunk [0.3], lower limbs [0.4]). Overall scores range from 0 (no psoriasis) to 72 (the most severe disease).Participants achieving PASI 75 were defined as having an improvement of ≥75% in the PASI score compared to baseline.

The DLQI is a 10-item, participant-administered dermatology-specific questionnaire that assess health related quality of life that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The DLQI items response categories are scored 0 (not relevant) to 3 (very much) with a total score range of 0 to 30; higher scores indicate poor quality of life and a 5-point change from baseline is considered clinically relevant.

Baseline is defined as the last available value prior to the first dose in Part A of the study.