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

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 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 Ps) to 72 (the most severe disease).

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 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 Ps) to 72 (the most severe disease).

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 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 Ps) to 72 (the most severe disease). LS mean change from baseline in PASI was calculated using Analysis of Covariance (ANCOVA) with modified Baseline- Observation- Carried Forward (mBOCF) and with terms for baseline and treatment.

The sPGA is the physician's determination of the participant's Psoriasis (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.

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), and a 5-point change from baseline is considered clinically relevant.

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), and a 5-point change from baseline is considered clinically relevant. LS mean change from baseline in DLQI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

The percentage involvement of psoriasis on each participant's body surface area was assessed by the investigator on a continuous 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.

LS mean change from baseline in BSA was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

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 PPASI) to 72 (most severe PPASI). The PPASI was only assessed if participants have palmoplantar psoriasis at baseline.

LS mean change from baseline in PPASI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

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).

LS mean change from baseline in PSSI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

The PBI assessment consists of 2 steps: before treatment, every patient defines his/her treatment needs according to a standardized list (Patient Needs Questionnaire [PNQ]). After treatment, the patient rates the degree of benefits achieved (Patient Benefits Questionnaire [PBQ]). 25 items are rated on a 5-point scale with values from 0 (not at all) to 4 (very), allowing for "did not apply to me" (5) and missing.

For each treatment goal the PNQ importance is derived by dividing the respective PNQ item by the sum of all PNQ items. The weighted sum of each PBQ item with its respective PNQ importance yields the PBI score.

LS mean was calculated using ANCOVA with LOCF and with a term for treatment.

The Itch NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching from psoriasis (Ps) is indicated by circling the number that best describes the worst level of itching in the past 24 hours.

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

The pain VAS is a participant-administered single-item scale designed to measure Skin pain from Psoriasis using a 100 millimeter (mm) horizontal VAS. Overall severity of participant's skin pain from Psoriasis is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no pain) to 100 mm (pain as severe as you can imagine).

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

QIDS-SR16 is a participant-administered, 16-item instrument intended to assess the existence and severity of symptoms of depression. A participant is asked to consider each statement as it relates to the way they have felt for the past 7 days and rate each on a 4-point scale: 0 (best) to 3 (worst). The sum of the 16 items corresponding to 9 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] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity. Whereas 0-5 indicates no symptoms.

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

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, lower scores = more disability, higher scores = less disability and better health. In this study, the SF-36 acute version was used, which has a 1-week recall period.

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

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, lower scores = more disability, higher scores = less disability and better health. In this study, the SF-36 acute version was used, which has a 1-week recall period.

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

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).

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

PSAB measure is a 3-item scale designed to measure the degree of bothersomeness of skin appearance due to Ps in participants with Ps. Participants are asked to indicate on 3 numeric rating scales (NRS) from 0 (not at all bothered) to 10 (extremely bothered) how bothered they are by any redness or discoloration, thickness, and scaling or flaking on their skin due to Ps.

The scores from the 3 NRS items are summed for a total score ranging from 0 to 30, where 0 indicating no bothersomeness and 30 indicating greater bothersomeness.

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

NAPPA is a clinical and participant-reported outcomes tool, and consists of 3 components: a questionnaire assessing nail-specific quality of life NAPPA-QoL (Nail Assessment in Psoriasis and Psoriatic Arthritis Quality of Life), a 2-part questionnaire assessing participant relevant needs and treatment benefits NAPPA-PBI (Nail Assessment in Psoriasis and Psoriatic Arthritis - Patient Benefit Index), and a clinical assessment of objective finger nail psoriasis severity NAPPA-CLIN.

Sum of all assessed finger and toes ranging between 0 (no involvement) to 16 (worst involvement).

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

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 EQ-5D-5L health states were converted into a single summary index by applying a crosswalk using a United Kingdom (UK) Population value set to each of the levels in each dimension. This produced participant-level index scores between -0.594 and 1.0 (worse to better health).

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

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).

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

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).

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

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. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment).

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

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. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment).

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

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. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment).

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

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. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment).

LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

Studying psoriasis involvement in the face, neck, and the genitals is of considerable interest for participants. These are locations that bear high potential for stigmatization and/or psychological distress, and, hence, effects in those regions are assumed to heavily influence participant's quality of life.

Following set of binary questions were asked to check the satisfaction of participants.

1. Does the participant currently have visible psoriasis on face/neck? (Yes/No)
2. Does the participant currently have psoriasis on the genital area? (Yes/No)

Studying psoriasis involvement in the face, neck, and the genitals is of considerable interest for participants. These are locations that bear high potential for stigmatization and/or psychological distress, and, hence, effects in those regions are assumed to heavily influence participant's quality of life.

Following set of binary questions were asked to check the satisfaction of participants.

1. Does the patient currently have visible psoriasis on face/neck? (Yes/No)
2. Does the patient currently have psoriasis on the genital area? (Yes/No) The genital area includes the labia majora (hair-bearing), labia minora modified mucus membrane, and perineum in female patients; and the penis glans, penis - shaft, and scrotum in male patients.

Systemic Therapy Adherence Questionnaire (STAQ) is a 38 item questionnaire that was developed by shortening and adapting the Topical Treatment Adherence Questionnaire (TTAQ) for administration to participants under systemic therapy. The following STAQ items are of special interest for this study.

1. STAQ item 13 (The treatment does not affect my sex life)
2. STAQ item 16 (I am enjoying life again as a result of the treatment)
3. STAQ item 20 (The side effects of the treatment were acceptable)
4. STAQ item 31 (I am satisfied with the efficacy of the treatment)
5. STAQ item 32 (I am satisfied with the tolerability of the treatment)
6. STAQ item 35 (The positive aspects of the treatment outweigh the negative ones).

The STAQ items are on a 4-point Likert scale with scores between 0 (strong disagreement) and 3 (strong agreement). LS mean was calculated using ANCOVA with term for treatment.