SPIRIT-H2H: A Study of Ixekizumab (LY2439821) Versus Adalimumab in Participants With Psoriatic Arthritis

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03151551
• Collaborator: (none)
• Enrollment: 566
• Locations: 131
• Arms: 2
• Actual Duration (Months): 24.3
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate the effectiveness and safety of ixekizumab versus adalimumab in participants with psoriatic arthritis (PsA) who are biologic disease-modifying anti-rheumatic drugs (DMARD) naive.

Condition or Disease	Intervention/Treatment	Phase
Psoriatic Arthritis	Drug: Ixekizumab; Drug: Adalimumab	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 566 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 52-Week Multicenter, Randomized, Open-Label, Parallel- Group Study Evaluating the Efficacy and Safety of Ixekizumab Versus Adalimumab in Patients With Psoriatic Arthritis Who Are Biologic Disease-Modifying Anti-Rheumatic Drug Naive
• Actual Study Start Date: Aug 24, 2017
• Actual Primary Completion Date: Nov 15, 2018
• Actual Study Completion Date: Sep 4, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ixekizumab 160 milligrams (mg) ixekizumab given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	Drug: Ixekizumab; Administered SC; Other Names: LY2439821
Active Comparator: Adalimumab 80 mg adalimumab given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.	Drug: Adalimumab; Administered SC

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Simultaneously Achieving American College of Rheumatology 50 (ACR50) and Psoriasis Area and Severity Index 100 (PASI100) [Week 24]

   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.

Secondary Outcome Measures

1. Percentage of Participants Achieving ACR50 [Week 24]

   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).

2. Percentage of Participants Achieving PASI100 [Week 24]

   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.

Other Outcome Measures

1. Change From Baseline in Tender Joint Count (TJC) [Baseline, Week 52]

   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.

2. Change From Baseline in Swollen Joint Count (SJC) [Baseline, Week 52]

   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.

3. Change From Baseline in Participant's Assessment of Pain Visual Analogue Score (VAS) [Baseline, Week 52]

   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.

4. Change From Baseline in Participant's Global Assessment of Disease Activity [Baseline, Week 52]

   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.

5. Change From Baseline in Physician's Global Assessment of Disease Activity [Baseline, Week 52]

   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.

6. Change From Baseline in C-Reactive Protein (CRP) [Baseline, Week 52]

   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.

7. Change From Baseline in HAQ-DI [Baseline, Week 52]

   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.

8. Percentage of Participants Simultaneously Achieving ACR50 and PASI100 [Week 52]

   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.

9. Change From Baseline in Disease Activity Score-CRP (DAS28-CRP) [Baseline, Week 52]

   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.

10. Percentage of Participants Achieving Minimal Disease Activity (MDA) [Week 52]

    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.

11. Percentage of Participants Achieving Psoriatic Arthritis Response Criteria (PsARC) [Week 52]

    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.

12. Change From Baseline in Modified Composite Psoriatic Disease Activity Index (mCPDAI) Score [Baseline, Week 52]

    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.

13. Change From Baseline in the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index in Participants With Enthesitis at Baseline [Baseline, Week 52]

    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.

14. Change From Baseline in the Leeds Enthesitis Index (LEI) in Participants With Enthesitis at Baseline [Baseline, Week 52]

    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.

15. Change From Baseline in the Leeds Dactylitis Index-Basic (LDI-B) in Participants With Dactylitis at Baseline [Baseline, Week 52]

    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.

16. Change From Baseline in Psoriasis Body Surface Area (BSA) [Baseline, Week 52]

    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.

17. Change From Baseline in the Nail Psoriasis Severity Index (NAPSI) Fingernails Score in the Subgroup of Participants With Fingernail Involvement at Baseline [Baseline, Week 52]

    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.

18. Change From Baseline in the Itch NRS [Baseline, Week 52]

    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.

19. Change From Baseline in Fatigue Severity NRS (Fatigue NRS) Score [Baseline, Week 52]

    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.

20. Change From Baseline in Medical Outcomes Study 36-item Short Form Health Survey (SF-36): Physical Component Summary (PCS) [Baseline, Week 52]

    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.

21. Change From Baseline in SF-36: Mental Component Summary (MCS) [Baseline, Week 52]

    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.

22. Change From Baseline in Measures of Health Utility (EuroQol-5 Dimensions 5 Level [EQ-5D 5L]) United Kingdom(UK) Population-Based Index Score [Baseline, Week 52]

    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.

23. Change From Baseline in Measures of Health Utility (EuroQol-5 Dimensions 5 Level [EQ-5D 5L]) VAS Score [Baseline, Week 52]

    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.

24. Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score [Baseline, Week 52]

    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.

25. Percentage of Participants Answering "Mostly Satisfied" to Each Question in Treatment Satisfaction Questionnaire (TSQ) [Week 52]

    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").

26. Number of Participants Who Answered "Yes" to Any 10 Questions in Columbia Suicide Severity Rating Scale (C-SSRS) [Week 52]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Presence of established diagnosis of active psoriatic arthritis for at least 6 months, and currently meets Classification for Psoriatic Arthritis (CASPAR) criteria

• Active PsA defined as the presence of at least 3 (out of 68) tender and at least 3 (out of 66) swollen joints

• Presence of active plaque psoriasis with a BSA ≥3%

• Men must agree to use a reliable method of birth control or remain abstinent during the study

• Women must agree to use reliable birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment

• Have had an inadequate response when treated with 1 or more conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)

Exclusion Criteria:

• Current or prior use of biologic agents for treatment of Ps or PsA

• Evidence of active inflammatory arthritic syndromes or spondyloarthropathies other than PsA

• Have participated in any study with interleukin 17 (IL-17) antagonists, including ixekizumab

• Serious disorder or illness other than psoriatic arthritis

• Serious infection within the last 3 months

• Active Crohn's disease or active ulcerative colitis

• Active vasculitis or uveitis

• Diagnosis of or history of malignant disease <5 years prior to randomization

• Women who are breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Atencion Integral en Reumatología	Ciudad Autonoma de Buenos Aire	Buenos Aires	Argentina	C1426AAL
2	Clinica Adventista de Belgrano	Ciudad de Buenos Aires	Buenos Aires	Argentina	C1430EGF
3	CER Instituto Medico	Quilmes	Buenos Aires	Argentina	B1878DVC
4	Instituto de Asist Reumatologica Integral	San Fernando	Buenos Aires	Argentina	B1646DBM
5	Centro Medico Privado de Reumatologia	San Miguel de Tucuman	Tucuman	Argentina	T4000AXL
6	Organizacion Medica de Investigacion - OMI	Ciudad Autonoma de Buenos Aire		Argentina	C1015ABO
7	Instituto Centenario	Ciudad Autonoma de Buenos Aire		Argentina	C1204AAD
8	Hospital Ramos Mejia	Ciudad Autonoma de Buenos Aire		Argentina	C1221ADC
9	Centro de Medicina Familiar Mindout Research	Ciudad Autonoma de Buenos Aire		Argentina	C1417EYG
10	CENUDIAB	Ciudad Autonoma de Buenos Aire		Argentina	C1440AAD
11	Consultora Integral de Salud S.R.L.	Cordoba		Argentina	5004
12	Centro Polivalente de Asistencia e Inv. Clinica CER-San Juan	San Juan		Argentina	J5402DIL
13	Combined Rheumatology Practice (CRP)	Kogarah	New South Wales	Australia	2217
14	Rheumatology, The Queen Elizabeth Hospital	Woodville South	South Australia	Australia	5011
15	Southern Clinical Research Pty Ltd	Hobart	Tasmania	Australia	7000
16	Emeritus Research	Camberwell	Victoria	Australia	3124
17	St Vincents Hospital Melbourne	Fitzroy	Victoria	Australia	3065
18	Zentrum für klinische Studien Dr. Ursula Hanusch GmbH	Wien		Austria	1060
19	AKH	Wien		Austria	1090
20	Rheuma-Zentrum Wien Oberlaa	Wien		Austria	1100
21	Reumaclinic	Genk		Belgium	3600
22	Universitair Ziekenhuis Gent	Gent		Belgium	9000
23	Saint Joseph Hospital	Gilly		Belgium	6060
24	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven		Belgium	3000
25	Hopital Ambroise Pare	Mons		Belgium	7000
26	The Waterside Clinic	Barrie	Ontario	Canada	L4M 6L2
27	SKiN Center for Dermatology	Peterborough	Ontario	Canada	K9J 5K2
28	Centre de Recherche Musculo-Squelettique	Trois-Rivieres	Quebec	Canada	G8Z 1Y2
29	Polmed Research Inc.	Saskatoon	Saskatchewan	Canada	S7K 0H6
30	Group de recherche en maladies osseuses	Quebec		Canada	G1V 3M7
31	Frederiksberg Hospital	Frederiksberg	Hovedstaden	Denmark	2000
32	Aalborg Universitetshospital - Psykiatrien	Aalborg		Denmark	9000
33	Helsinki University Hospital, HYKS	Helsinki		Finland	00029
34	Kiljava Medical Research	Hyvinkaa		Finland	05800
35	Terveystalo Kouvola	Kouvola		Finland	45100
36	Turun Yliopistollinen Keskussairaala	Turku		Finland	20521
37	Hôpital Trousseau, CHRU de Tours	Chambray-lès-Tours		France	37170
38	Centre Hospitalier de Vendee Les Oudairies	La Roche Sur Yon		France	85025
39	Hopital Edouard Herriot	Lyon Cedex 03		France	69003
40	Centre hospitalier universitaire Lapeyronie	Montpellier Cedex 5		France	34295
41	Nouvel Hôpital Orléans La Source	Orleans CEDEX 2		France	45067
42	Hôpital Pierre-Paul Riquet	Toulouse cedex 9		France	31059
43	Klinikum der Universität München	München	Bayern	Germany	80336
44	Klinikum der Johann Wolfgang Goethe-Universität Frankfurt	Frankfurt am Main	Hessen	Germany	60590
45	Rheumazentrum Ratingen	Ratingen	Nordrhein-Westfalen	Germany	40878
46	HRF Hamburger Rheuma Forschungszentrum	Hamburg		Germany	20095
47	Allergo-Derm Bakos Kft	Szolnok	Jasz-Nagykun-Szolnok	Hungary	5000
48	Obudai Egeszsegugyi Centrum Kft	Budapest		Hungary	1036
49	UNO Medical Trials Kft.	Budapest		Hungary	1135
50	Vital Medical Center	Veszprem		Hungary	8200
51	Care Hospital	Hyderabad	Andhra Pradesh	India	500035
52	King George Hospital	Visakhapatnam	Andhra Pradesh	India	530002
53	Sir Ganga Ram Hospital	New Delhi	Delhi	India	110060
54	Panchshil Hospital	Ahmedabad	Gujarat	India	380005
55	Byramjee Jeejeebhoy Medical College & Civil Hospital	Ahmedabad	Gujarat	India	380016
56	Shalby Hospital	Ahmedabad	Gujarat	India	532004
57	Government Medical College & Sir Sayajirao General Hospital	Vadodara	Gujarat	India	390001
58	Artemis Hospital	Gurgaon	Haryana	India	122001
59	Narayana Hrudayalaya Hospital	Bangalore	Karnataka	India	560099
60	Kokilaben Dhirubhai Ambani Hospital &Medical Research Inst.	Mumbai	Maharashtra	India	400053
61	Ruby Hall Clinic and Grant Medical Foundation	Pune	Maharashtra	India	411001
62	Krishna Institute of Medical Sciences Ltd.	Secunderabad	Telengana	India	500003
63	Apollo Gleneagles Hospitals	Kolkata	West Bengal	India	700054
64	Barzilai Medical Center	Ashkelon		Israel	78278
65	Rambam Medical Center	Haifa		Israel	3109601
66	Carmel Medical Center	Haifa		Israel	3436212
67	Meir Medical Center	Kfar Saba		Israel	4428164
68	Rabin Medical Center	Petach Tikva		Israel	4941492
69	Sheba Medical Center	Ramat Gan		Israel	5266202
70	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	6423906
71	Assaf Harofeh Medical Center	Zerifin		Israel	6093000
72	Istituto Clinico Humanitas	Rozzano	Milano	Italy	20089
73	Istituto Ortopedico Rizzoli	Bologna		Italy	40136
74	Presidio Ospedaliero Vittorio Emanuele	Catania		Italy	95124
75	Fondazione Universitaria degli Studi G D'Annunzio	Chieti		Italy	66100
76	Policlinico di Tor Vergata	Roma		Italy	00133
77	Complesso Integrato Columbus	Roma		Italy	00168
78	Ospedale Policlinico Giambattista Rossi, Borgo Roma	Verona		Italy	37134
79	Centro Medico del Angel S.C.	Mexicali	Baja California	Mexico	21100
80	Ctro Inv en Artritis y Osteoporosis SC	Mexicali	Baja California	Mexico	21200
81	CIMAB S.A. de C.V.	Torreon	Coahuila	Mexico	27000
82	Grupo Médico CAMINO S.C.	México City	Distrito Federal	Mexico	03310
83	Clínica Enfermedades Crónicas y Procedimientos Especiales SC	Morelia	Michoacan	Mexico	58249
84	Centro Investigacion de Tratam Innovadores de Sinaloa SC	Culiacan	Sinaloa	Mexico	80000
85	Cemdeicy S.C.P.	Merida	Yucatán	Mexico	97130
86	RM Pharma Specialists S.A. de C.V.	Distrito Federal		Mexico	3100
87	Antonius Ziekenhuis	Sneek		Netherlands	8601 ZK
88	NZOZ Centrum Reumatologiczne Ind. Prak.	Elblag		Poland	82-300
89	"Dermed" Centrum Medyczne Sp. z o.o.	Lodz		Poland	90-265
90	Twoja Przychodnia-Centrum Medyczne Nowa Sol	Nowa Sol		Poland	67100
91	Rheuma Medicus Zakład Opieki Zdrowotnej	Warsaw		Poland	02-118
92	DermMEDICA Sp. z o.o.	Wroclaw		Poland	51-318
93	Greenacres Hospital	Port Elizabeth	Eastern Cape	South Africa	6045
94	Clinresco Centres (Pt) Ltd	Johannesburg	Gauteng	South Africa	1619
95	Suite 509 Umhlanga Netcare Medical Centre	Durban	KwaZulu-Natal	South Africa	4319
96	Arthritis Clinical Research Trial Unit	Pinelands	Western Cape	South Africa	7405
97	Winelands Medical Research Centre	Stellenbosch	Western Cape	South Africa	7600
98	St Augustines Hospital	Durban		South Africa	4001
99	Emmed Research	Muckleneuk		South Africa	0135
100	Prof Ally	Pretoria		South Africa	0002
101	Suite 209A Jakaranda Hospital	Pretoria		South Africa	0002
102	Hospital Marina Baixa	La Vila Joiosa	Alicante	Spain	03570
103	Hospital Clinico Universitario de Santiago	Santiago de Compostela	La Coruna	Spain	15706
104	Hospital Del Sagrado Coraz	Barcelona		Spain	08029
105	Complexo Hospitalario Universitario A Coruña, CHUAC	La Coruna		Spain	15006
106	Hospital Infanta Luisa	Sevilla		Spain	41010
107	Reumatologikliniken Västmanlands Sjukhus	Västerås	Västmanland	Sweden	72189
108	Reumatologiska Kliniken Skånes universitetssjukhus Malmö	Malmo		Sweden	205 02
109	Centrum för reumatologi	Stockholm		Sweden	102 35
110	Reumatologiska Kliniken Karolinska Universitetssjukhuset Solna	Stockholm		Sweden	171 76
111	Kantonsspital St. Gallen	St. Gallen	Sankt Gallen	Switzerland	9007
112	HUG-Hôpitaux Universitaires de Genève	Genève		Switzerland	1206
113	Regional Clinical Hospital Center for Emergency medical care	Kharkiv		Ukraine
114	National Scientific Center "Strazhesko institute of cardio"	Kyiv		Ukraine	03680
115	Kyiv City Clinical Hospital #3	Kyiv		Ukraine
116	Multifield Medical Center of Odesa NMU (University Clinic#1)	Odesa		Ukraine	65026
117	Municipal Institution of Ternopil Regional Council	Ternopil		Ukraine	46002
118	Vinnytsya Regional Clinical Hospital	Vinnytsya		Ukraine	21018
119	Regional Clinical Hospital of Zaporizhzhia	Zaporizhzhia		Ukraine	69600
120	Addenbrookes Hospital	Cambridge	Cambridgeshire	United Kingdom	CB2 0QQ
121	Royal Cornwall Hospital	Truro	Cornwall	United Kingdom	TR1 3LJ
122	Southampton General Hospital	Southampton	Hants	United Kingdom	SO16 6YD
123	Wythenshawe Hospital	Wythenshawe	Manchester	United Kingdom	M23 9LT
124	Wishaw General Hospital	Wishaw	North Lanarkshire	United Kingdom	ML2 0DP
125	Western General Hospital	Edinburgh	Scotland	United Kingdom	EH4 2XU
126	Whipps Cross University Hospital	London	Surrey	United Kingdom	E11 1NR
127	North Tyneside General Hospital	North Shields	Tyneside	United Kingdom	NE29 8NH
128	The Dudley Group NHS Foundation Trust	Dudley	West Midlands	United Kingdom	DY1 2HQ
129	New Cross Hospital	Wolverhampton	West Midlands	United Kingdom	WV10 0QP
130	St Lukes Hospital	Bradford	West Yorkshire	United Kingdom	BD5 0NA
131	The Great Western Hospital	Swindon	Wiltshire	United Kingdom	SN3 6BB

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - May 26, 2017
• Statistical Analysis Plan - Dec 3, 2018

More Information

Additional Information:

• A Study of Ixekizumab (LY2439821) Versus Adalimumab in Participants With Psoriatic Arthritis (Spirit-H2H)

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03151551
• Other Study ID Numbers: 16687; I1F-MC-RHCF; 2016-004585-25
• First Posted: May 12, 2017
• Last Update Posted: Nov 3, 2020
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Arthritis; Arthritis, Psoriatic; Adalimumab; Ixekizumab

Study Results

Participant Flow

Recruitment Details	Per protocol and statistical analysis plan (SAP), the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together.
Pre-assignment Detail	Open-Label Treatment Period from Week 0 to Week 52 inclusive followed by Post-Treatment Follow-Up Period of up to a minimum of 12 weeks.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps. Follow-up: Participants did not receive drug during the Post-Treatment Follow-Up Period.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps. Follow-up: Participants did not receive drug during the Post-Treatment Follow-Up Period.
Period Title: Open-Label Treatment Period
STARTED	283	283
Received at Least One Dose of Study Drug	283	283
IXE 160 mg at Baseline, 80 mg Q2W/Q4W	49	0
IXE 160 mg at Baseline, 80 mg Q4W	218	0
ADA 80 mg at Baseline, 40 mg Q2W	0	51
ADA 40 mg at Baseline, 40 mg Q2W	0	219
COMPLETED	265	259
NOT COMPLETED	18	24
Period Title: Open-Label Treatment Period
STARTED	265	258
COMPLETED	240	230
NOT COMPLETED	25	28

Baseline Characteristics

Arm/Group Title	Ixekizumab	Adalimumab	Total
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.	Total of all reporting groups
Overall Participants	283	283	566
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	47.5 (12.02)	48.3 (12.30)	47.9 (12.15)
Sex: Female, Male (Count of Participants)
Female	121 42.8%	133 47%	254 44.9%
Male	162 57.2%	150 53%	312 55.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	63 22.3%	65 23%	128 22.6%
Not Hispanic or Latino	198 70%	194 68.6%	392 69.3%
Unknown or Not Reported	22 7.8%	24 8.5%	46 8.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	27 9.5%	27 9.5%	54 9.5%
Asian	29 10.2%	33 11.7%	62 11%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 0.4%	1 0.2%
White	222 78.4%	211 74.6%	433 76.5%
More than one race	5 1.8%	11 3.9%	16 2.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Argentina	31 11%	27 9.5%	58 10.2%
Hungary	15 5.3%	18 6.4%	33 5.8%
Ukraine	15 5.3%	11 3.9%	26 4.6%
United Kingdom	13 4.6%	7 2.5%	20 3.5%
Switzerland	1 0.4%	3 1.1%	4 0.7%
India	20 7.1%	26 9.2%	46 8.1%
Spain	24 8.5%	18 6.4%	42 7.4%
Canada	5 1.8%	5 1.8%	10 1.8%
Sweden	3 1.1%	3 1.1%	6 1.1%
Austria	4 1.4%	4 1.4%	8 1.4%
Netherlands	2 0.7%	1 0.4%	3 0.5%
Belgium	6 2.1%	5 1.8%	11 1.9%
Finland	5 1.8%	6 2.1%	11 1.9%
Poland	24 8.5%	29 10.2%	53 9.4%
Denmark	1 0.4%	3 1.1%	4 0.7%
Mexico	32 11.3%	33 11.7%	65 11.5%
South Africa	15 5.3%	21 7.4%	36 6.4%
Italy	14 4.9%	25 8.8%	39 6.9%
Israel	14 4.9%	14 4.9%	28 4.9%
Australia	12 4.2%	5 1.8%	17 3%
France	9 3.2%	3 1.1%	12 2.1%
Germany	18 6.4%	16 5.7%	34 6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Simultaneously Achieving American College of Rheumatology 50 (ACR50) and Psoriasis Area and Severity Index 100 (PASI100)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	283	283
Number (95% Confidence Interval) [percentage of participants]	36 12.7%	27.9 9.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments	After data lock and initial analysis run, a medical inconsistency in baseline PASI data was identified (PASI=0 but BSA≥3%). The scenario was not anticipated or described in protocol or SAP. The inconsistency was resolved using medical judgment. The impacted participants had met baseline criteria for active psoriasis. Therefore, in the primary analysis, participants with baseline PASI=0 & BSA≥3% were considered PASI100 responders if, and only if, PASI=0 & BSA=0 achieved at week 24.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.036
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	8.1
	Confidence Interval	(2-Sided) 95%; 0.5 to 15.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Achieving ACR50
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	283	283
Number (95% Confidence Interval) [percentage of participants]	50.5 17.8%	46.6 16.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower bound of the 2-sided 95% confidence Interval (CI) for the difference in proportions of responders on IXE minus ADA is greater than the pre-specified margin -12%, IXE will be deemed non-inferior to ADA.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	3.9
	Confidence Interval	(2-Sided) 95%; -4.3 to 12.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants Achieving PASI100
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	283	283
Number (95% Confidence Interval) [percentage of participants]	60.1 21.2%	46.6 16.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments	After data lock and initial analysis run, a medical inconsistency in baseline PASI data was identified (PASI=0 but BSA≥3%). The scenario was not anticipated or described in protocol or SAP. The inconsistency was resolved using medical judgment. The impacted participants had met baseline criteria for active psoriasis. Therefore, in the primary analysis, participants with baseline PASI=0 & BSA≥3% were considered PASI100 responders if, and only if, PASI=0 & BSA=0 achieved at week 24.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	13.4
	Confidence Interval	(2-Sided) 95%; 5.3 to 21.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Other Pre-specified Outcome

Title	Change From Baseline in Tender Joint Count (TJC)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	242	239
Least Squares Mean (Standard Error) [score on a scale]	-15.91 (0.566)	-14.88 (0.569)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.155
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.03
	Confidence Interval	(2-Sided) 95%; -2.46 to 0.39
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.725
	Estimation Comments

5. Other Pre-specified Outcome

Title	Change From Baseline in Swollen Joint Count (SJC)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	242	239
Least Squares Mean (Standard Error) [score on a scale]	-9.58 (0.196)	-9.53 (0.198)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.823
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.54 to 0.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.249
	Estimation Comments

6. Other Pre-specified Outcome

Title	Change From Baseline in Participant's Assessment of Pain Visual Analogue Score (VAS)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	242	246
Least Squares Mean (Standard Error) [millimeters (mm)]	-37.21 (1.623)	-36.54 (1.621)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.752
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -4.80 to 3.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.104
	Estimation Comments

7. Other Pre-specified Outcome

Title	Change From Baseline in Participant's Global Assessment of Disease Activity
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	242	246
Least Squares Mean (Standard Error) [Millimeter (mm)]	-40.61 (1.594)	-37.82 (1.596)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.177
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.79
	Confidence Interval	(2-Sided) 95%; -6.83 to 1.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.060
	Estimation Comments

8. Other Pre-specified Outcome

Title	Change From Baseline in Physician's Global Assessment of Disease Activity
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	223	230
Least Squares Mean (Standard Error) [Millimeter (mm)]	-48.15 (1.113)	-46.79 (1.097)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.332
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.35
	Confidence Interval	(2-Sided) 95%; -4.08 to 1.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.391
	Estimation Comments

9. Other Pre-specified Outcome

Title	Change From Baseline in C-Reactive Protein (CRP)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	234	238
Least Squares Mean (Standard Error) [Milligram per Liter (mg/L)]	-5.68 (0.462)	-6.01 (0.461)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.592
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.32
	Confidence Interval	(2-Sided) 95%; -0.86 to 1.50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.599
	Estimation Comments

10. Other Pre-specified Outcome

Title	Change From Baseline in HAQ-DI
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	242	246
Least Squares Mean (Standard Error) [score on a scale]	-0.68 (0.035)	-0.62 (0.035)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.176
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.045
	Estimation Comments

11. Other Pre-specified Outcome

Title	Percentage of Participants Simultaneously Achieving ACR50 and PASI100
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	283	283
Number (95% Confidence Interval) [percentage of participants]	39.2 13.9%	26.1 9.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments	After data lock and initial analysis run, a medical inconsistency in baseline PASI data was identified (PASI=0 but BSA≥3%). The scenario was not anticipated or described in protocol or SAP. The inconsistency was resolved using medical judgment. The impacted participants had met baseline criteria for active psoriasis. Therefore, in the primary analysis, participants with baseline PASI=0 & BSA≥3% were considered PASI100 responders if, and only if, PASI=0 & BSA=0 achieved at week 52.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	13.1
	Confidence Interval	(2-Sided) 95%; 5.4 to 20.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Other Pre-specified Outcome

Title	Change From Baseline in Disease Activity Score-CRP (DAS28-CRP)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	226	228
Least Squares Mean (Standard Error) [score on a scale]	-2.45 (0.071)	-2.36 (0.071)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.368
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.26 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.091
	Estimation Comments

13. Other Pre-specified Outcome

Title	Percentage of Participants Achieving Minimal Disease Activity (MDA)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	283	283
MDA-6 Entheseal Points	48.1 17%	42.8 15.1%
MDA-18 Entheseal Points	47.3 16.7%	41.0 14.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments	MDA-18 Entheseal Points
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.108
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	6.4
	Confidence Interval	(2-Sided) 95%; -1.8 to 14.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments	MDA-6 Entheseal Points
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.179
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	5.3
	Confidence Interval	(2-Sided) 95%; -2.9 to 13.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Other Pre-specified Outcome

Title	Percentage of Participants Achieving Psoriatic Arthritis Response Criteria (PsARC)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	283	283
Number (95% Confidence Interval) [percentage of participants]	66.8 23.6%	65.7 23.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.846
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -8.9 to 6.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Other Pre-specified Outcome

Title	Change From Baseline in Modified Composite Psoriatic Disease Activity Index (mCPDAI) Score
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	237	234
Least Squares Mean (Standard Error) [score on a scale]	-4.35 (0.136)	-3.85 (0.136)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -0.83 to -0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.170
	Estimation Comments

16. Other Pre-specified Outcome

Title	Change From Baseline in the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index in Participants With Enthesitis at Baseline
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	163	139
Least Squares Mean (Standard Error) [score on a scale]	-3.93 (0.234)	-4.06 (0.241)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.687
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; -0.48 to 0.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.305
	Estimation Comments

17. Other Pre-specified Outcome

Title	Change From Baseline in the Leeds Enthesitis Index (LEI) in Participants With Enthesitis at Baseline
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	141	121
Least Squares Mean (Standard Error) [score on a scale]	-1.93 (0.113)	-2.02 (0.116)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.507
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.144
	Estimation Comments

18. Other Pre-specified Outcome

Title	Change From Baseline in the Leeds Dactylitis Index-Basic (LDI-B) in Participants With Dactylitis at Baseline
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	35	47
Least Squares Mean (Standard Error) [score on a scale]	-52.28 (11.495)	-48.89 (9.855)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.820
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.40
	Confidence Interval	(2-Sided) 95%; -32.78 to 25.99
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 14.951
	Estimation Comments

19. Other Pre-specified Outcome

Title	Change From Baseline in Psoriasis Body Surface Area (BSA)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	246	246
Least Squares Mean (Standard Error) [units on a scale]	-12.33 (0.623)	-10.79 (0.613)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.052
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.54
	Confidence Interval	(2-Sided) 95%; -3.09 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.790
	Estimation Comments

20. Other Pre-specified Outcome

Title	Change From Baseline in the Nail Psoriasis Severity Index (NAPSI) Fingernails Score in the Subgroup of Participants With Fingernail Involvement at Baseline
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	169	154
Least Squares Mean (Standard Error) [score on a scale]	-17.78 (0.731)	-15.08 (0.742)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.70
	Confidence Interval	(2-Sided) 95%; -4.57 to -0.84
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.949
	Estimation Comments

21. Other Pre-specified Outcome

Title	Change From Baseline in the Itch NRS
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	242	246
Least Squares Mean (Standard Error) [score on a scale]	-3.83 (0.159)	-3.54 (0.159)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.158
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -0.68 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.202
	Estimation Comments

22. Other Pre-specified Outcome

Title	Change From Baseline in Fatigue Severity NRS (Fatigue NRS) Score
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	241	246
Least Squares Mean (Standard Error) [score on a scale]	-3.03 (0.161)	-2.95 (0.161)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.711
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.49 to 0.33
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.21
	Estimation Comments

23. Other Pre-specified Outcome

Title	Change From Baseline in Medical Outcomes Study 36-item Short Form Health Survey (SF-36): Physical Component Summary (PCS)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	240	246
Least Squares Mean (Standard Error) [score on a scale]	10.07 (0.526)	9.55 (0.524)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.439
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; -0.80 to 1.85
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.674
	Estimation Comments

24. Other Pre-specified Outcome

Title	Change From Baseline in SF-36: Mental Component Summary (MCS)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	240	246
Least Squares Mean (Standard Error) [score on a scale]	5.23 (0.660)	4.77 (0.656)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.594
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; -1.23 to 2.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.860
	Estimation Comments

25. Other Pre-specified Outcome

Title	Change From Baseline in Measures of Health Utility (EuroQol-5 Dimensions 5 Level [EQ-5D 5L]) United Kingdom(UK) Population-Based Index Score
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	240	245
Least Squares Mean (Standard Deviation) [score on a scale]	0.21 (0.013)	0.21 (0.013)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.979
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.017
	Estimation Comments

26. Other Pre-specified Outcome

Title	Change From Baseline in Measures of Health Utility (EuroQol-5 Dimensions 5 Level [EQ-5D 5L]) VAS Score
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	240	245
Least Squares Mean (Standard Deviation) [millimeters (mm)]	22.26 (1.37)	17.48 (1.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.78
	Confidence Interval	(2-Sided) 95%; 1.28 to 8.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.782
	Estimation Comments

27. Other Pre-specified Outcome

Title	Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	241	246
Least Squares Mean (Standard Error) [score on a scale]	-8.03 (0.273)	-6.91 (0.272)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.12
	Confidence Interval	(2-Sided) 95%; -1.78 to -0.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.335
	Estimation Comments

28. Other Pre-specified Outcome

Title	Percentage of Participants Answering "Mostly Satisfied" to Each Question in Treatment Satisfaction Questionnaire (TSQ)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	283	283
Effectiveness of Medication	64.3 22.7%	58.7 20.7%
Effectiveness over Time of Medication	62.9 22.2%	56.2 19.9%
Long Term Safety of Medication	63.3 22.4%	58.7 20.7%
Overall Satisfaction with Medication	64.0 22.6%	59.0 20.8%
Mostly Satisfied to any Questions	70.0 24.7%	67.8 24%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments	Effectiveness of Medication
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.165
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	5.7
	Confidence Interval	(2-Sided) 95%; -2.4 to 13.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments	Effectiveness over Time of Medication
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.098
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	6.7
	Confidence Interval	(2-Sided) 95%; -1.4 to 14.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments	Long Term Safety of Medication
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.241
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	4.6
	Confidence Interval	(2-Sided) 95%; -3.4 to 12.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments	Overall Satisfaction with Medication
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.215
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	4.9
	Confidence Interval	(2-Sided) 95%; -3.1 to 13.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Adalimumab
	Comments	Mostly Satisfied to any Questions
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.561
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95%; -5.5 to 9.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

29. Other Pre-specified Outcome

Title	Number of Participants Who Answered "Yes" to Any 10 Questions in Columbia Suicide Severity Rating Scale (C-SSRS)
Description	The C-SSRS is a scale that captures the occurrence, severity, and frequency of suicide-related ideations and behaviors during the assessment period. Wish to be dead Non-specific active suicidal thoughts Active suicidal ideation with any methods (not plan) without intent to act Active suicidal ideation with some intent to act, without specific plan Active suicidal ideation with specific plan and intent Preparatory acts or behavior Aborted attempt Interrupted attempt Non-fatal suicide attempt Completed suicide
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixekizumab	Adalimumab
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.	80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.
Measure Participants	283	283
Count of Participants [Participants]	9 3.2%	7 2.5%

Adverse Events

Time Frame	Up To Week 52
Adverse Event Reporting Description	All participants who received at least one dose of study drug. Per protocol and statistical analysis plan, the primary and secondary analysis were performed to compare all ixekizumab participants together versus all adalimumab participants together. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly
Arm/Group Title	Ixekizumab		Adalimumab		Ixekizumab Follow-up		Adalimumab Follow-up
Arm/Group Description	160 milligrams (mg) ixekizumab (IXE) given subcutaneously (SC) at baseline for all participants. 80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps. 80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.		80 mg adalimumab (ADA) given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps. 40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.		Follow-up: Participants did not receive drug during the Post-Treatment Follow-Up Period.		Follow-up: Participants did not receive drug during the Post-Treatment Follow-Up Period.
All Cause Mortality
	Ixekizumab		Adalimumab		Ixekizumab Follow-up		Adalimumab Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/283 (0%)		0/283 (0%)		0/265 (0%)		0/260 (0%)
Serious Adverse Events
	Ixekizumab		Adalimumab		Ixekizumab Follow-up		Adalimumab Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/283 (4.2%)		35/283 (12.4%)		7/265 (2.6%)		4/260 (1.5%)
Blood and lymphatic system disorders
Anaemia	0/283 (0%)	0	0/283 (0%)	0	0/265 (0%)	0	1/260 (0.4%)	1
Cardiac disorders
Angina unstable	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Atrial fibrillation	1/283 (0.4%)	1	1/283 (0.4%)	1	0/265 (0%)	0	1/260 (0.4%)	1
Atrial flutter	0/283 (0%)	0	0/283 (0%)	0	1/265 (0.4%)	1	0/260 (0%)	0
Cardiac failure congestive	0/283 (0%)	0	0/283 (0%)	0	1/265 (0.4%)	1	0/260 (0%)	0
Myocardial infarction	0/283 (0%)	0	0/283 (0%)	0	1/265 (0.4%)	1	0/260 (0%)	0
Myocardial ischaemia	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Gastrointestinal disorders
Acute abdomen	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Gastritis	0/283 (0%)	0	0/283 (0%)	0	1/265 (0.4%)	1	0/260 (0%)	0
General disorders
Asthenia	0/283 (0%)	0	0/283 (0%)	0	0/265 (0%)	0	1/260 (0.4%)	1
Injection site rash	1/283 (0.4%)	1	0/283 (0%)	0	0/265 (0%)	0	0/260 (0%)	0
Non-cardiac chest pain	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Pyrexia	2/283 (0.7%)	2	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Hepatobiliary disorders
Cholecystitis chronic	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Cholelithiasis	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Infections and infestations
Abscess	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Appendicitis	1/283 (0.4%)	1	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Arthritis bacterial	1/283 (0.4%)	1	0/283 (0%)	0	0/265 (0%)	0	0/260 (0%)	0
Cellulitis	1/283 (0.4%)	1	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Large intestine infection	1/283 (0.4%)	1	0/283 (0%)	0	0/265 (0%)	0	0/260 (0%)	0
Lower respiratory tract infection	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Lymph node tuberculosis	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Meningitis viral	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Pneumonia	1/283 (0.4%)	1	0/283 (0%)	0	0/265 (0%)	0	0/260 (0%)	0
Pneumonia legionella	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Pyelonephritis	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Pyoderma	0/283 (0%)	0	0/283 (0%)	0	1/265 (0.4%)	1	0/260 (0%)	0
Sepsis	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Staphylococcal sepsis	0/283 (0%)	0	0/283 (0%)	0	1/265 (0.4%)	1	0/260 (0%)	0
Viral infection	0/283 (0%)	0	0/283 (0%)	0	0/265 (0%)	0	1/260 (0.4%)	1
Injury, poisoning and procedural complications
Ankle fracture	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Fall	0/283 (0%)	0	2/283 (0.7%)	2	0/265 (0%)	0	0/260 (0%)	0
Hip fracture	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Humerus fracture	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Maternal exposure during pregnancy	0/121 (0%)	0	1/133 (0.8%)	1	0/111 (0%)	0	0/123 (0%)	0
Road traffic accident	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Tendon rupture	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Upper limb fracture	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Investigations
Hepatic enzyme increased	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Metabolism and nutrition disorders
Diabetic ketoacidosis	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Musculoskeletal and connective tissue disorders
Bursitis	1/283 (0.4%)	1	0/283 (0%)	0	0/265 (0%)	0	0/260 (0%)	0
Osteoarthritis	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Pain in extremity	1/283 (0.4%)	1	0/283 (0%)	0	0/265 (0%)	0	0/260 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Gastrointestinal stromal tumour	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Pituitary tumour benign	1/283 (0.4%)	1	0/283 (0%)	0	0/265 (0%)	0	0/260 (0%)	0
Rectal adenocarcinoma	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Squamous cell carcinoma of skin	0/283 (0%)	0	0/283 (0%)	0	1/265 (0.4%)	1	0/260 (0%)	0
Nervous system disorders
Haemorrhagic stroke	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Polyneuropathy	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Radiologically isolated syndrome	1/283 (0.4%)	1	0/283 (0%)	0	0/265 (0%)	0	0/260 (0%)	0
Sciatica	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Seizure	0/283 (0%)	0	0/283 (0%)	0	0/265 (0%)	0	1/260 (0.4%)	1
Transient ischaemic attack	1/283 (0.4%)	1	0/283 (0%)	0	0/265 (0%)	0	0/260 (0%)	0
Psychiatric disorders
Depression	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Renal failure	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Reproductive system and breast disorders
Menometrorrhagia	1/121 (0.8%)	1	0/133 (0%)	0	0/111 (0%)	0	0/123 (0%)	0
Prostatitis	0/162 (0%)	0	1/150 (0.7%)	1	0/154 (0%)	0	0/137 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/283 (0%)	0	0/283 (0%)	0	1/265 (0.4%)	1	0/260 (0%)	0
Vocal cord thickening	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Skin and subcutaneous tissue disorders
Erythrodermic psoriasis	0/283 (0%)	0	0/283 (0%)	0	1/265 (0.4%)	1	0/260 (0%)	0
Vascular disorders
Necrosis ischaemic	0/283 (0%)	0	1/283 (0.4%)	2	0/265 (0%)	0	0/260 (0%)	0
Peripheral artery occlusion	0/283 (0%)	0	1/283 (0.4%)	1	0/265 (0%)	0	0/260 (0%)	0
Other (Not Including Serious) Adverse Events
	Ixekizumab		Adalimumab		Ixekizumab Follow-up		Adalimumab Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/283 (23%)		44/283 (15.5%)		8/265 (3%)		5/260 (1.9%)
General disorders
Injection site reaction	16/283 (5.7%)	30	4/283 (1.4%)	9	0/265 (0%)	0	0/260 (0%)	0
Infections and infestations
Nasopharyngitis	38/283 (13.4%)	46	23/283 (8.1%)	26	5/265 (1.9%)	5	3/260 (1.2%)	3
Upper respiratory tract infection	18/283 (6.4%)	21	18/283 (6.4%)	23	3/265 (1.1%)	3	2/260 (0.8%)	2

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.