A Study of Ixekizumab (LY2439821) in Participants With Moderate-to-Severe Plaque Psoriasis

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 (no involvement) to 4 (severe involvement). 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 Ps) to 72 (the most severe disease).

Time frame: Week 12

Population: All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline measurement for PASI 90. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.

The European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of a descriptive system of the respondent's health which comprises the following 5 dimensions: 1) mobility 2) self-care 3) usual activities 4) pain/discomfort 5) anxiety/depression. The Bolt On PSO is an addition to the EQ-5D-5L that consists of 2 dimensions specific to psoriatic disease: 6) skin irritation (itching) and 7) self-confidence. Index scores for the Bolt On PSO range from 0.0042 to 1.0 (worse to better health). ANCOVA model was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline measurement for EQ-5D 5L Bolt On PSO-Index.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

The EQ-5D-5L descriptive system comprises 5 dimensions, each with 5 levels. The EQ-5D-5L health states were converted into a single summary index by applying a crosswalk using a UK Population value set to each of the levels in each dimension. This produced patient-level index scores between -0.594 and 1.0 (worse to better health). ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug \& had baseline \& post-baseline EQ-5D 5L UK population-based index score measurement.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

The EQ-5D 5L is a standardized measure of health status that includes a descriptive system of the respondent's health and a rating of his/her current health state using a 0 (worst health imaginable)- to 100 (best health imaginable)-millimeter (mm) Visual Analog Scale (VAS). ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline measurement for EQ-5D 5L VAS.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 (no itch) and 10 (worst itch imaginable). Overall severity of a participant's itching from Ps is indicated by circling the number that best describes the worst level of itching in the past 24 hours. ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug and had a post-baseline measurement for Itch NRS.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

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. Items from 8 domains contribute to the PCS. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. SF-36 acute version was used, which has a 1 week recall period. ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline measurement for SF36 MCS score.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

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. Items from 8 domains contribute to the PCS. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. SF-36 acute version was used, which has a 1 week recall period. ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline measurement for SF-36 PCS score.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

NAPSI is a numeric, reproducible, objective tool for evaluation of fingernail(fn) Ps. This scale is used to evaluate severity of fn bed Ps & fn matrix Ps by area of involvement in the fn unit. fn is divided with imaginary horizontal & longitudinal lines into quadrants. Each fn is given a score for fn bed Ps 0(none) to 4(Ps in 4 quadrants of the fn) & fn matrix Ps 0(none) to 4(Ps in 4 quadrants in matrix), depending on presence (score of 1) or absence (score of 0) of any of the features of fn bed or matrix Ps in each quadrant.NAPSI score of a fn is sum of scores in fn bed & fn matrix from each quadrant (maximum of 8). Each fn is evaluated, then the sum of all fn equals the total NAPSI score with a range from range 0 to 80. Higher scores indicate more severe ps. ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who had nail psoriasis at baseline \& received at least 1 dose of study drug and had baseline \& post-baseline NAPSI measurement.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

The Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 (no Ps) to 72. (the most severe disease) The PPASI was only assessed if participants have palmoplantar psoriasis at baseline. ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants(Pts) who had psoriasis in palmoplantar regions at baseline \& received at least 1 dose of study drug \& had baseline \& post-baseline PPASI data.~mBOCF:Pts who discontinued treatment due to AE were imputed by their baseline observation, Pts who discontinued due to other reasons were imputed by their last observation.

The percentage involvement of psoriasis on each participant's body surface area was assessed by the investigator on a scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand including palm, fingers and thumb. ANCOVA model with modified baseline observation carried forward (mBOCF) was used to produce Least Square (LS) mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug \& had a baseline \& post-baseline measurement for BSA affected by Ps.~mBOCF: Participants who discontinued treatment due to Adverse Event (AE) were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (\<10%) to 6 (90%-100%) with a total score ranging from 0 (less severity) to 72 (more severity). ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who had psoriasis in scalp region at baseline \& received at least 1 dose of study drug \& had baseline \& post-baseline PSSI data.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

The Patient Global Assessment of Disease Severity is a single-item participant-reported outcome measure on which participants are asked to rate the severity of their psoriasis today from 0 (Clear) = no psoriasis, to 5 (Severe) = the worst their psoriasis has ever been. ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline measurement for PatGA.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 items questionnaire, each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal. ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for HADS anxiety subscale.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 items questionnaire, each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal. ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline measurement for HADS depression subscale.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Skin Pain VAS is a participant administered scale designed to measure skin pain from psoriasis using a 100-millimeter (mm) horizontal VAS. Overall severity of a participant's skin pain from psoriasis at the present time is indicated by placing a single mark on the horizontal scale (0 = no skin pain; 100 = severe skin pain). ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline measurement for skin pain VAS.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work & WPAI-PSO absenteeism score is derived from these questions. Each WPAI score is expressed as an impairment percentage (0-100), with higher scores representing greater impairment (worse outcomes). ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for WPAI-PSO absenteeism score.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work & WPAI-PSO impairment in activities performed outside of work score is derived from these questions. each WPAI score is expressed as an impairment percentage (0-100), with higher scores representing greater impairment (worse outcomes). ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants(Pts) who received at least 1 dose of study drug \& had baseline \& post-baseline data for WPAI-PSO impairment in activities performed outside work.~mBOCF:Pts who discontinued treatment due to AE were imputed by their baseline observation, pts who discontinued due to other reasons were imputed by their last observation.

The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work & WPAI-PSO Presenteeism score is derived from these questions. each WPAI score is expressed as an impairment percentage (0-100), with higher scores representing greater impairment (worse outcomes). ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline measurement for WPAI-PSO presenteeism score.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work & WPAI-PSO work impairment score is derived from these questions. each WPAI score is expressed as an impairment percentage (0-100), with higher scores representing greater impairment (worse outcomes). ANCOVA model with mBOCF was used to produce LS mean with baseline, treatment group, region weight group as fixed effects.

Time frame: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline measurement for WPAI-PSO work impairment score.~mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

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 (no involvement) to 4 (severe involvement). 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 Ps) to 72 (the most severe disease).

Time frame: Week 12

Population: All randomized participants who received at least 1 dose of study drug and had a post-baseline measurement for PASI 100. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for Non-Responder Imputation (NRI) analysis.

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 (no involvement) to 4 (severe involvement). Each area is scored by itself 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 Ps) to 72 (the most severe disease).

Time frame: Week 12

Population: All randomized participants who received at least 1 dose of study drug and had a post-baseline measurement for PASI 75. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for Non-Responder Imputation (NRI) analysis.

The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA assessed as 0, indicates complete resolution of plaque Ps.

Time frame: Week 12

Population: All randomized participants who received at least 1 dose of study drug and had a post-baseline measurement for sPGA (0). Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for Non-Responder Imputation (NRI) analysis.

The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of 0 or 1 with at least a 2-point improvement from baseline.

Time frame: Week 12

Population: All randomized participants with baseline sPGA \>=3 \& received at least 1 dose of study drug and had a post-baseline measurement for sPGA. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for Non-Responder Imputation (NRI) analysis.

The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include not at all, a lot, and very much, with corresponding scores of 1, 2, and 3, respectively, and unanswered (not relevant) responses scored as 0. Totals range from 0 to 30 (less to more impairment). A score of 0 or 1 indicates no impact of disease on a participants quality of life.

Time frame: Week 12

Population: All randomized participants who received at least 1 dose of study drug and had a post-baseline measurement for DLQI. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for Non-Responder Imputation (NRI) analysis.