A Study of Mirikizumab (LY3074828) in Participants With Moderate to Severe Plaque Psoriasis

PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. 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 PsO) to 72 (the most severe disease).

Time frame: Week 16

Population: All participants who received at least one dose of study drug.

The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (MCS and PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning. Least Squares Mean (LS Mean) was calculated using Analysis of covariance (ANCOVA) model with treatment, geographic region (US/OUS), and previous therapy (yes/no) as fixed factors and baseline value as covariate.

Time frame: Baseline, Week 16

Population: All participants who received at least one dose of study drug with a baseline value and at least 1 post-baseline value.

The DLQI is a patient-reported, 10-question, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include Not at all, A little, A lot, and Very much, with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of Not relevant which is scored as 0. For all questions, if unanswered the question is scored as 0. Totals range from 0 to 30 (less to more impairment). Least Square (LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, geographic region (US/OUS), previous therapy (yes/no), baseline value, visit, and the interaction treatment-by-visit as fixed factors, covariance structure = unstructured.

Time frame: Baseline, Week 16

Population: All participants who received at least one dose of study drug who had baseline and at least one post-baseline DLQI observation.

PSS is a patient-administered assessment of 4 symptoms (itch, pain, stinging, and burning); 3 signs (redness, scaling, and cracking); and 1 item on the discomfort related to symptoms/signs. The overall severity for each individual symptom/sign from the patient's psoriasis is indicated by selecting the number from a numeric rating scale (NRS) of 0 to 10 that best describes the worst level of each symptom/sign in the past 24 hours, where 0=no symptom/sign and 10=worst imaginable symptom/sign. The total score was calculated by summing the 8 individual items and ranged from 0 to 80, higher scores indicated greater symptom/sign severity. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, geographic region \[United States/Outside United States (US/OUS)\], previous therapy (yes/no), baseline value, visit, and the interaction treatment-by-visit as fixed factors, covariance structure = heterogeneous autoregressive.

Time frame: Baseline, Week 16

Population: All participants who received at least one dose of study drug who had baseline and at least one post-baseline PSS observation.

The Patient's 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. Least Square (LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, geographic region (US/OUS), previous therapy (yes/no), baseline value, visit, and the interaction treatment-by-visit as fixed factors, covariance structure = unstructured.

Time frame: Baseline, Week 16

Population: All participants who received at least one dose of study drug who had baseline and at least one post-baseline Patient Global Assessment observation.

The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no PsO to 72 for the most severe disease. 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 PsO) to 72 (the most severe disease).

Time frame: Week 16

Population: All participants who received at least one dose of study drug.

The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no PsO to 72 for the most severe disease. 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 PsO) to 72 (the most severe disease).

Time frame: Week 16

Population: All participants who received at least one dose of study drug.

The sPGA is the physician's determination of the participant's PsO lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's PsO was 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. Participants who did not meet the clinical response criteria or had missing data at Week 16 were considered non-responders for non-responder Imputation (NRI) analysis.

Time frame: Week 16

Population: All participants who received at least one dose of drug.

Pharmacokinetics (PK): Area Under the Curve (AUC) of Mirikizumab From Baseline through Week 104

Time frame: Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 52, Week 56, Week 64, Week 72, Week 80, Week 88, Week 96, Week 100, Week 104

Population: All participants who received at least one dose of study drug and had evaluable PK data.