Efficacy at 24 Weeks With Long Term Safety, Tolerability and Efficacy up to 5 Years of Secukinumab in Patients of Active Psoriatic Arthritis

ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire \[HAQ-DI\] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their ACR20 was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Time frame: Week 24

Population: Full Analysis Set.

The DAS28 is a measure of disease activity based on Swollen and Tender Joint Counts, ESR or CRP and the Patient Global Assessment. A DAS28 score \> 5.1 implies active disease, ≤ 3.2 low disease activity, and \< 2.6 remission. The score can range from 0 - 9.4. The data collected after the patient switched to secukinumab were treated as missing for placebo patients and were analyzed using a mixed-effects repeated measures model. For secukinumab patients, the actual values were used in the analysis. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Time frame: Baseline, Week 24

Population: Full Analysis Set, including only participants with measurements at baseline and Week 24. Participants in the Placebo arm who switched to Secukinumab prior to Week 24 were treated as missing.

The SF-36 is an instrument to measure health-related quality of life among healthy patients and patients with acute and chronic conditions. Score range is from 0 (no problems) to 100 (unable to perform the activity). SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both physically and emotionally based. Two overall summary scores, the Physical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS was used. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Time frame: Baseline, Week 24

Population: Full Analysis Set, including only participants with measurements at baseline and Week 24. Participants in the Placebo arm who switched to Secukinumab prior to Week 24 were treated as missing.

The HAQ-DI assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, are you able to... perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Time frame: Baseline, Week 24

Population: Full Analysis Set, including only participants with measurements at baseline and Week 24. Participants in the Placebo arm who switched to Secukinumab prior to Week 24 were treated as missing.

ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 50% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire \[HAQ-DI\] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their ACR20 was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Time frame: Week 24

Population: Full Analysis Set

PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a 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 75 response was defined as participants achieving \>= 75% improvement from baseline. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their value was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias.

Time frame: Week 24

Population: Psoriasis Subset (≥3% skin involvement with psoriasis at baseline)

PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a 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 response was defined as participants achieving \>= 90% improvement from baseline. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their value was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias.

Time frame: Week 24

Population: Psoriasis Subset (≥3% skin involvement with psoriasis at baseline)

Resolution of dactylitis was evaluated in the subset of patients who had disease activity at baseline. In this analysis, a lower percentage is desirable and resolution is defined as complete absence of the symptom. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their assessment was set to nonresponse at Week 24 (presence of dactylitis). This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Time frame: Week 24

Population: Dactylitis Subset (participants with dactylitis at baseline)

Resolution of enthesitis was evaluated in the subset of patients who had disease activity at baseline. In this analysis, a lower percentage is desirable and resolution is defined as complete absence of the symptom. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their assessment was set to nonresponse at Week 24 (presence of enthesitis). This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Time frame: Week 24

Population: Enthesitis Subset (participants with enthesitis at baseline)