Efficacy and Safety of Subcutaneous Secukinumab for Moderate to Severe Chronic Plaque-type Psoriasis for up to 1 Year

A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is the current benchmark of primary endpoints for most clinical trials of psoriasis. PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).

Time frame: 12 weeks

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe. Treatment success was defined as achievement of IGA mod 2001 score of 0 or 1. IGA score of 0 or 1 as an indicator of efficacy.

Time frame: 12 weeks

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

The Psoriasis Symptom Diary©, a 16-item patient reported outcome (PRO) measure developed and validated in accordance with the FDA PRO Guidance (FDA Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims, 2009), demonstrated favorable psychometric properties and usefulness for treatment efficacy evaluation alongside other measures of disease severity in clinical trials for chronic plaque psoriasis.Weekly averages will be derived for each of the 16 questions of the Psoriasis Diary up to Week 12. A weekly average is the sum of the scored item over the course of the study week divided by the number of days on which the item was completed and will be set to missing if four or more daily assessments were missing of the corresponding question. A reduction in score from baseline shows efficacy. Each question has a score of 0 (no symptoms) up to 10 (Severe symptoms)

Time frame: Week 12

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

The EQ-5D is an instrument used to assess a participant's health status. The instrument includes a descriptive profile and a visual analog scale (VAS). The descriptive profile includes 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 3 response levels: no problems, some problems and severe problems. The VAS is a vertical scale that assesses the health status from 0 (worst possible health state) to 100 (best possible health state). This outcome measures the percent change in VAS score. Positive mean percent changes indicate improvement.

Time frame: Baseline, Week 4,8, 12

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

The EQ-5D is an instrument used to assess a participant's health status. The instrument includes a descriptive profile and a visual analog scale (VAS). The descriptive profile includes 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 3 response levels: no problems, some problems and severe problems. The VAS is a vertical scale that assesses the health status from 0 (worst possible health state) to 100 (best possible health state). This outcome measures the percent change in VAS score. Positive mean percent changes indicate improvement.

Time frame: Week 12, 24, 36, 52

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). A negative mean percentage change indicates improvement.

Time frame: Week 13,14,15,16,20,24,28,32,36,40,44,48,52

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). A negative mean percentage change indicates improvement.

Time frame: Baseline, Week 1,2,3,4,8,12,

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe. Treatment success was defined as achievement of IGA mod 2001 score of 0 or 1.

Time frame: 12 and 52 weeks

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).

Time frame: 12 and 52 weeks

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

The development of anti-secunimubab anti-bodies would decrease a participant's ability to respond to secukinumab treatment.

Time frame: Week 12

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). Not relevant is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. A negative mean percentage change from baseline indicates improvement.

Time frame: Baseline, Week 4, 8 & 12

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). Not relevant is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. A negative mean percentage change from baseline indicates improvement.

Time frame: Week 12,24, 36 & 52

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (max). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving ≥ 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe.

Time frame: Week 13,14,15,16,20,24,28,32,36,40,44,48,52

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (max). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving ≥ 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe.

Time frame: Week 1,2,3,4,8,12,

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

PASI is an assessment of lesion severity & affected area into a single score:0(no disease)to 72(max. disease).Body is divided into 4 areas for scoring(head,arms,trunk,legs)each area is scored separately & then added for final PASI.For each area, % of skin involved is estimated:0(0%)to 6(90-100%)& severity is estimated by clinical signs, erythema,induration & desquamation;scale 0(none) to 4(max). Final PASI=sum of severity parameters for each area\* area score weight of section(head:0.1,arms:0.2 body:0.3 legs:0.4).PASI 75, 90 is patients achieving≥75%or90% improvement from baseline.The IGA mod 2011 scale is static, exclusively to the patients disease at assessment,& not with any of the patient's previous disease states at other visits.The scores are:0=clear,1=almost clear,2= mild,3=moderate&4=severe.Response variables PASI 75,90, IGA mod 2011 0 or 1 response at wk 12 was scored versus previous psoriasis systemic therapy & response to previous biologic systemic therapy by treatment

Time frame: Week 12

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe.

Time frame: Week 13,14,15,16,20,24,28,32,36,40,44,48,52

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe.

Time frame: Baseline, Week 1,2,3,4,8,12,

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 90 was defined as participants who achievied ≥ 90% improvement from baseline.

Time frame: 12 weeks

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). Not relevant is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. A negative mean percentage change from baseline indicates improvement.

Time frame: Week 4, 8, 12

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). Not relevant is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. A negative mean percentage change from baseline indicates improvement.

Time frame: Week 12,24,36, & 52

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.

PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (max). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 75 was defined as participants achieving ≥ 75% improvement from baseline.

Time frame: Week 12

Population: Full analysis set (FAS): The FAS was comprised of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization. If the actual stratum was different to the assigned stratum in IRT, the actual stratum was used in analyses.