A Study of Ixekizumab (LY2439821) Versus Adalimumab in Participants With Psoriatic Arthritis

ACR50 response is a ≥50% improvement from baseline for tender joint count(TJC)& swollen joint count (SJC)& in at least 3 of the following 5 criteria: Participant's(pts) assessment of joint pain Visual Analog Scale (VAS),Pts Global Assessment of Disease Activity (PatGA)VAS, Physician's Global Assessment of Disease Activity (PGA)VAS, Pts assessment of physical function using the Health Assessment Questionnaire-Disability Index(HAQ-DI), or High Sensitivity(assay)C-Reactive Protein (hs-CRP). PASI is an index combining assessments of the extent of body-surface involvement in head, trunk, arms, legs, and severity of desquamation, erythema and plaque thickness in each region, yielding overall score of 0-no involvement, to 72-most severe involvement. Pts achieving PASI100 were defined as having 100% improvement in the PASI score compared to baseline. Pts with active plaque PsO with a BSA≥3% & PASI=0 at baseline were considered PASI100 responders if they had achieved PASI=0 & BSA=0 at week 24.

Time frame: Week 24

Population: All randomized participants. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

ACR50 response is defined as a ≥50% improvement from baseline for tender joint count (TJC) and swollen joint count (SJC) and in at least 3 of the following 5 criteria: Participant's assessment of joint pain Visual Analog Scale (VAS), Participant's Global Assessment of Disease Activity (PatGA) VAS, Physician's Global Assessment of Disease Activity (PGA) VAS, participant's assessment of physical function using the Health Assessment Questionnaire-Disability Index (HAQ-DI), or High Sensitivity (assay) C-Reactive Protein (hs-CRP).

Time frame: Week 24

Population: All randomized participants. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

PASI is an index combining assessments of the extent of body-surface involvement in head, trunk, arms, legs, and severity of desquamation, erythema and plaque thickness in each region, yielding overall score of 0-no involvement, to 72-most severe involvement. Participants achieving PASI100 were defined as having 100% improvement in the PASI score compared to baseline. Any participants with active plaque psoriasis (PsO) with a BSA ≥3% and PASI = 0 at baseline were considered PASI100 responders if & only if they had achieved PASI=0 & BSA=0 at week 24.

Time frame: Week 24

Population: All randomized participants. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

CRP is the ACR Core Set laboratory measure of acute-phase reactant. It was measured with a high sensitivity assay at the central laboratory to help assess the effect of ixekizumab on the participant's PsA. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline CRP value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

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. The recall period of this scale is over the last week. 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. Scores range from 0 to 30 (less to more impairment), and a 4-point change from baseline is considered as the minimal clinically important difference threshold. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline DLQI value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The DAS28-CRP is a measure of disease activity in 28 joints that consists of a composite numerical score with the following variables: TJC28, SJC28, hs-CRP (measured in milligrams per liter), and Participant's Global Assessment of Disease Activity recorded by participants on a 0 to 100 VAS. For DAS28-CRP, the Tender Joint Count 28 (TJC28) and Swollen Joint Count (SJC28) are a subset of TJC and SJC, and include 14 joints on each side of the body: 2 shoulders, 2 elbows, 2 wrists, 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. DAS28 values range from 0 to 9.4. Higher values indicate more severe symptoms and greater functional impairment. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline DAS28-CRP value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The Fatigue Severity NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing no fatigue and 10 representing as bad as you can imagine. Participants rate their fatigue (weariness, tiredness) by circling the 1 number that described their worst level of fatigue during the past 24 hours. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline Fatigue NRS value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

HAQ-DI is a participant reported questionnaire that measures disease-associated disability (physical function). It consists of 24 questions with 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other daily activities. The disability section scores the participant's self-perception on the degree of difficulty (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do), covering the 8 domains. The reported use of special aids or devices and/or the need for assistance of another person to perform these activities is assessed. The HAQ-DI is a composite ranging from 0-3 with lower scores indicating less functional disability. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline HAQ-DI value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The EQ-5D-5L consists of 2 components: a descriptive system of the respondent's health and a rating of his/her current health state. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The descriptive part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.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 participant-level index scores between -0.594 and 1.0 (worse to better health). LS mean was calculated using MMRM model that included treatment group,concomitant csDMARD use at baseline,moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline EQ-5D 5L value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

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 2 components: a descriptive system of the respondent's health and a rating of his/her current health state using a 0 (worst health you can imagine) to 100mm VAS (best health you can imagine). LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline EQ-5D 5L value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

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, with higher scores indicating better levels of function and/or better health. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline PCS value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The CPDAI is a validated instrument intended to assess composite psoriatic disease activity and response to therapy. Domains include peripheral arthritis as assessed by the number of tender and swollen joints and the HAQ-DI, skin as assessed by the PASI and the Dermatology Life Quality Index (DLQI), enthesitis as assessed by the number of sites with enthesitis and the HAQ-DI, and dactylitis as assessed by the number of digits affected. Each domain with the exception of spinal disease is scored from 0-3. Individual domain scores are summed to give an overall composite score (range 0-12) with a higher score indicating higher disease activity. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline CPDAI value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The pain VAS is a participant-administered single-item scale designed to measure current joint pain from Psoriatic arthritis (PsA) using a 100-millimeter(mm) horizontal VAS. Overall severity of participant's joint pain from PsA is indicated by marking a vertical tick on the horizontal 100-mm scale, where the left end from 0 mm (no pain) to right end 100 mm (worst possible joint pain). LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline VAS value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The patient's overall assessment of his or her PsA activity was recorded using a 100-mm horizontal VAS, where 0 represents no disease activity and 100 represents extremely active disease. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline VAS value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The investigator was asked to give an overall assessment of the severity of the participant's current PsA activity using a 100-mm horizontal VAS, where 0 represents no disease activity and 100 represents extremely active disease. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline VAS value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The investigator evaluates the percentage involvement of psoriasis on each participant's BSA on a continuous scale from 0% = no involvement to 100% = full involvement, where 1% corresponded to the size of the participant's handprint including the palm, fingers, and thumb. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline BSA value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

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, with higher scores indicating better levels of function and/or better health. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline MCS value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

SJC is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. LS mean was calculated using MMRM model that included treatment group, concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline SJC value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

TJC is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model that included treatment group, concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline TJC value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The Itch NRS is a participant-administered, 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 is indicated by circling the number that best described the worst level of itching in the past 24 hours. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline and at least one post-baseline NRS value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The LDI-B measures the severity of dactylitis.In each digit,the ratio of the circumference(cf) of the affected digit to the cf of the digit on the opposite hand or foot measured in mm. Each dactylitic digit is defined by a minimum increase of 10% in cf over the contra-lateral digit.If the same digits on each hand or foot were thought to be involved,the clinician referred to a table of normative values for a value which was used to provide the comparison.If the ratio is \>1.1,then subtract 1 from the calculated ratio and multiply it by 100 and the tenderness score of 0(not tender) or 1(tender).Otherwise,if the ratio of the cf of the digit is ≤1.1,then the LDI-B score is set to 0.LDI-B score can be \>=0 with higher numbers indicating worse dactylitis.LS mean was calculated using MMRM model: treatment group,concomitant csDMARD use at baseline,moderate-to-severe Ps involvement,visit as fixed factors,baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline dactylitis (LDI-B \>0). Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The LEI was developed specifically for use in PsA. It measures enthesitis at 6 sites (lateral epicondyle of humerus, right/left (R/L); medial femoral condyle,(R/L); Achilles tendon insertion, (R/L)). Each site is assigned a score of 0 (absent) or 1 (present); the results from each site are then added to produce a total score (range 0 to 6) with the higher scores indicating more severe enthesitis. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline enthesitis (LEI \>0). Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The NAPSI scale is used to evaluate the severity of fingernail bed Ps and fingernail matrix Ps by area of involvement. The fingernail is divided into quadrants. Each fingernail is given a score for fingernail bed Ps 0 (none) to 4 (Ps in 4 quadrants of the fingernail) and fingernail matrix Ps 0 (none) to 4 (Ps in 4 quadrants of the matrix), depending on the presence (score of 1) or absence (score of 0) of any of the features of fingernail bed or matrix Ps in each quadrant. The sum of all fingernails equals the total NAPSI score range is from 0 (no effect) to 80 (more severe psoriasis). LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had baseline fingernail involvement (NAPSI \>0). Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The SPARCC enthesitis index evaluates tenderness in a total of 16 entheseal sites: the greater trochanter (right/left \[R/L\]), quadriceps tendon insertion into the patella (R/L), patellar ligament insertion into the patella and tibial tuberosity (R/L), Achilles tendon insertion (R/L), plantar fascia insertion (R/L), medial epicondyles of humerus (R/L),Lateral epicondyle humerus (R/L) and the supraspinatus insertion (R/L). Tenderness at each site is quantified on a dichotomous basis: 0 = nontender and 1 = tender. The results from each site are then added to produce a total score (range 0 to 16) with the Higher scores indicating more severe enthesitis. LS mean was calculated using MMRM model that included treatment group, concomitant csDMARD use at baseline, moderate-to-severe plaque psoriasis involvement, visit as fixed factors, baseline value as covariate and baseline-by-visit and treatment-by-visit interactions terms.

Time frame: Baseline, Week 52

Population: All randomized participants who had a baseline SPARCC score \> 0. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The C-SSRS is a scale that captures the occurrence, severity, and frequency of suicide-related ideations and behaviors during the assessment period. 1. Wish to be dead 2. Non-specific active suicidal thoughts 3. Active suicidal ideation with any methods (not plan) without intent to act 4. Active suicidal ideation with some intent to act, without specific plan 5. Active suicidal ideation with specific plan and intent 6. Preparatory acts or behavior 7. Aborted attempt 8. Interrupted attempt 9. Non-fatal suicide attempt 10. Completed suicide

Time frame: Week 52

Population: All randomized participants. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

MDA is a composite of 7 key outcome measures: TJC ≤1; SJC ≤1; psoriasis activity and severity index (PASI total score) ≤1 or BSA ≤3; participant pain VAS score of ≤15; participant global disease activity VAS score of ≤20; HAQ-DI score ≤0.5; and tender entheseal points ≤1. Participants are classified as achieving MDA if they fulfill 5 of 7 outcome measures.

Time frame: Week 52

Population: All randomized participants who had a baseline and at least one post-baseline MDA value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The PsARC is a composite criteria reported in terms of the percentage of participants achieving response according to the following criterion: TJC, SJC, PGA, and PatGA. Overall response is defined by improvement from baseline assessment in 2 of 4 criteria, 1 of which must be a joint count; there must not be worsening in any of the 4 criteria: at least 30% reduction in TJC, at least 30% reduction in SJC, at least a 20 millimeter (mm) reduction in PGA and at least a 20 mm reduction in PatGA.

Time frame: Week 52

Population: All randomized participants who had a baseline and at least one post-baseline PsARC value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

The TSQ is a clinician-administered questionnaire that provides an assessment of the patient's opinion of the effectiveness, safety, and overall satisfaction of the study medication. Participants were asked to respond to questionnaire items using a 4-point Likert scale (from mostly satisfied to mostly dissatisfied).

Time frame: Week 52

Population: All randomized participants who had a baseline and at least one post-baseline TSQ value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.

ACR50 response is a ≥50% improvement from baseline for TJC and SJC and in at least 3 of the following 5 criteria: Participant's assessment of VAS, Pts Global Assessment of Disease Activity (PatGA) VAS, Physician's Global Assessment of Disease Activity (PGA)VAS, participant assessment of physical function using the HAQ-DI, or High Sensitivity(assay) C-Reactive Protein (hs-CRP). PASI is an index combining assessments of the extent of body-surface involvement in head, trunk, arms, legs, and severity of desquamation, erythema and plaque thickness in each region, yielding overall score of 0-no involvement, to 72-most severe involvement. Participant achieving PASI100 were defined as having 100% improvement in the PASI score compared to baseline. Pts achieving PASI100 were defined as having 100% improvement in the PASI score compared to baseline. Pts with active plaque PsO with a BSA≥3% & PASI=0 at baseline were considered PASI100 responders if they had achieved PASI=0 & BSA=0 at week 52.

Time frame: Week 52

Population: All randomized participants who had a baseline and at least one post-baseline ACR50 and PASI100 value. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.