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

• ClinicalTrials.gov Identifier: NCT03151551
• Recruitment Status: Completed
• First Posted: May 12, 2017
• Results First Posted: April 2, 2019
• Last Update Posted: November 3, 2020
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

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 (Clinical Trial)
• 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: August 24, 2017
• Actual Primary Completion Date: November 15, 2018
• Actual Study Completion Date: September 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 Name: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.

    1. Wish to be dead
    2. Non-specific active suicidal thoughts
    3. Active suicidal ideation with any methods (not plan) without intent to act
    4. Active suicidal ideation with some intent to act, without specific plan
    5. Active suicidal ideation with specific plan and intent
    6. Preparatory acts or behavior
    7. Aborted attempt
    8. Interrupted attempt
    9. Non-fatal suicide attempt
    10. Completed suicide

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Argentina

Atencion Integral en Reumatología

Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina, C1426AAL

Clinica Adventista de Belgrano

Ciudad de Buenos Aires, Buenos Aires, Argentina, C1430EGF

CER Instituto Medico

Quilmes, Buenos Aires, Argentina, B1878DVC

Instituto de Asist Reumatologica Integral

San Fernando, Buenos Aires, Argentina, B1646DBM

Centro Medico Privado de Reumatologia

San Miguel de Tucuman, Tucuman, Argentina, T4000AXL

Organizacion Medica de Investigacion - OMI

Ciudad Autonoma de Buenos Aire, Argentina, C1015ABO

Instituto Centenario

Ciudad Autonoma de Buenos Aire, Argentina, C1204AAD

Hospital Ramos Mejia

Ciudad Autonoma de Buenos Aire, Argentina, C1221ADC

Centro de Medicina Familiar Mindout Research

Ciudad Autonoma de Buenos Aire, Argentina, C1417EYG

CENUDIAB

Ciudad Autonoma de Buenos Aire, Argentina, C1440AAD

Consultora Integral de Salud S.R.L.

Cordoba, Argentina, 5004

Centro Polivalente de Asistencia e Inv. Clinica CER-San Juan

San Juan, Argentina, J5402DIL

Australia, New South Wales

Combined Rheumatology Practice (CRP)

Kogarah, New South Wales, Australia, 2217

Australia, South Australia

Rheumatology, The Queen Elizabeth Hospital

Woodville South, South Australia, Australia, 5011

Australia, Tasmania

Southern Clinical Research Pty Ltd

Hobart, Tasmania, Australia, 7000

Australia, Victoria

Emeritus Research

Camberwell, Victoria, Australia, 3124

St Vincents Hospital Melbourne

Fitzroy, Victoria, Australia, 3065

Austria

Zentrum für klinische Studien Dr. Ursula Hanusch GmbH

Wien, Austria, 1060

AKH

Wien, Austria, 1090

Rheuma-Zentrum Wien Oberlaa

Wien, Austria, 1100

Belgium

Reumaclinic

Genk, Belgium, 3600

Universitair Ziekenhuis Gent

Gent, Belgium, 9000

Saint Joseph Hospital

Gilly, Belgium, 6060

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

Leuven, Belgium, 3000

Hopital Ambroise Pare

Mons, Belgium, 7000

Canada, Ontario

The Waterside Clinic

Barrie, Ontario, Canada, L4M 6L2

SKiN Center for Dermatology

Peterborough, Ontario, Canada, K9J 5K2

Canada, Quebec

Centre de Recherche Musculo-Squelettique

Trois-Rivieres, Quebec, Canada, G8Z 1Y2

Canada, Saskatchewan

Polmed Research Inc.

Saskatoon, Saskatchewan, Canada, S7K 0H6

Canada

Group de recherche en maladies osseuses

Quebec, Canada, G1V 3M7

Denmark

Frederiksberg Hospital

Frederiksberg, Hovedstaden, Denmark, 2000

Aalborg Universitetshospital - Psykiatrien

Aalborg, Denmark, 9000

Finland

Helsinki University Hospital, HYKS

Helsinki, Finland, 00029

Kiljava Medical Research

Hyvinkaa, Finland, 05800

Terveystalo Kouvola

Kouvola, Finland, 45100

Turun Yliopistollinen Keskussairaala

Turku, Finland, 20521

France

Hôpital Trousseau, CHRU de Tours

Chambray-lès-Tours, France, 37170

Centre Hospitalier de Vendee Les Oudairies

La Roche Sur Yon, France, 85025

Hopital Edouard Herriot

Lyon Cedex 03, France, 69003

Centre hospitalier universitaire Lapeyronie

Montpellier Cedex 5, France, 34295

Nouvel Hôpital Orléans La Source

Orleans CEDEX 2, France, 45067

Hôpital Pierre-Paul Riquet

Toulouse cedex 9, France, 31059

Germany

Klinikum der Universität München

München, Bayern, Germany, 80336

Klinikum der Johann Wolfgang Goethe-Universität Frankfurt

Frankfurt am Main, Hessen, Germany, 60590

Rheumazentrum Ratingen

Ratingen, Nordrhein-Westfalen, Germany, 40878

HRF Hamburger Rheuma Forschungszentrum

Hamburg, Germany, 20095

Hungary

Allergo-Derm Bakos Kft

Szolnok, Jasz-Nagykun-Szolnok, Hungary, 5000

Obudai Egeszsegugyi Centrum Kft

Budapest, Hungary, 1036

UNO Medical Trials Kft.

Budapest, Hungary, 1135

Vital Medical Center

Veszprem, Hungary, 8200

India

Care Hospital

Hyderabad, Andhra Pradesh, India, 500035

King George Hospital

Visakhapatnam, Andhra Pradesh, India, 530002

Sir Ganga Ram Hospital

New Delhi, Delhi, India, 110060

Panchshil Hospital

Ahmedabad, Gujarat, India, 380005

Byramjee Jeejeebhoy Medical College & Civil Hospital

Ahmedabad, Gujarat, India, 380016

Shalby Hospital

Ahmedabad, Gujarat, India, 532004

Government Medical College & Sir Sayajirao General Hospital

Vadodara, Gujarat, India, 390001

Artemis Hospital

Gurgaon, Haryana, India, 122001

Narayana Hrudayalaya Hospital

Bangalore, Karnataka, India, 560099

Kokilaben Dhirubhai Ambani Hospital &Medical Research Inst.

Mumbai, Maharashtra, India, 400053

Ruby Hall Clinic and Grant Medical Foundation

Pune, Maharashtra, India, 411001

Krishna Institute of Medical Sciences Ltd.

Secunderabad, Telengana, India, 500003

Apollo Gleneagles Hospitals

Kolkata, West Bengal, India, 700054

Israel

Barzilai Medical Center

Ashkelon, Israel, 78278

Rambam Medical Center

Haifa, Israel, 3109601

Carmel Medical Center

Haifa, Israel, 3436212

Meir Medical Center

Kfar Saba, Israel, 4428164

Rabin Medical Center

Petach Tikva, Israel, 4941492

Sheba Medical Center

Ramat Gan, Israel, 5266202

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel, 6423906

Assaf Harofeh Medical Center

Zerifin, Israel, 6093000

Italy

Istituto Clinico Humanitas

Rozzano, Milano, Italy, 20089

Istituto Ortopedico Rizzoli

Bologna, Italy, 40136

Presidio Ospedaliero Vittorio Emanuele

Catania, Italy, 95124

Fondazione Universitaria degli Studi G D'Annunzio

Chieti, Italy, 66100

Policlinico di Tor Vergata

Roma, Italy, 00133

Complesso Integrato Columbus

Roma, Italy, 00168

Ospedale Policlinico Giambattista Rossi, Borgo Roma

Verona, Italy, 37134

Mexico

Centro Medico del Angel S.C.

Mexicali, Baja California, Mexico, 21100

Ctro Inv en Artritis y Osteoporosis SC

Mexicali, Baja California, Mexico, 21200

CIMAB S.A. de C.V.

Torreon, Coahuila, Mexico, 27000

Grupo Médico CAMINO S.C.

México City, Distrito Federal, Mexico, 03310

Clínica Enfermedades Crónicas y Procedimientos Especiales SC

Morelia, Michoacan, Mexico, 58249

Centro Investigacion de Tratam Innovadores de Sinaloa SC

Culiacan, Sinaloa, Mexico, 80000

Cemdeicy S.C.P.

Merida, Yucatán, Mexico, 97130

RM Pharma Specialists S.A. de C.V.

Distrito Federal, Mexico, 3100

Netherlands

Antonius Ziekenhuis

Sneek, Netherlands, 8601 ZK

Poland

NZOZ Centrum Reumatologiczne Ind. Prak.

Elblag, Poland, 82-300

"Dermed" Centrum Medyczne Sp. z o.o.

Lodz, Poland, 90-265

Twoja Przychodnia-Centrum Medyczne Nowa Sol

Nowa Sol, Poland, 67100

Rheuma Medicus Zakład Opieki Zdrowotnej

Warsaw, Poland, 02-118

DermMEDICA Sp. z o.o.

Wroclaw, Poland, 51-318

South Africa

Greenacres Hospital

Port Elizabeth, Eastern Cape, South Africa, 6045

Clinresco Centres (Pt) Ltd

Johannesburg, Gauteng, South Africa, 1619

Suite 509 Umhlanga Netcare Medical Centre

Durban, KwaZulu-Natal, South Africa, 4319

Arthritis Clinical Research Trial Unit

Pinelands, Western Cape, South Africa, 7405

Winelands Medical Research Centre

Stellenbosch, Western Cape, South Africa, 7600

St Augustines Hospital

Durban, South Africa, 4001

Emmed Research

Muckleneuk, South Africa, 0135

Prof Ally

Pretoria, South Africa, 0002

Suite 209A Jakaranda Hospital

Pretoria, South Africa, 0002

Spain

Hospital Marina Baixa

La Vila Joiosa, Alicante, Spain, 03570

Hospital Clinico Universitario de Santiago

Santiago de Compostela, La Coruna, Spain, 15706

Hospital Del Sagrado Coraz

Barcelona, Spain, 08029

Complexo Hospitalario Universitario A Coruña, CHUAC

La Coruna, Spain, 15006

Hospital Infanta Luisa

Sevilla, Spain, 41010

Sweden

Reumatologikliniken Västmanlands Sjukhus

Västerås, Västmanland, Sweden, 72189

Reumatologiska Kliniken Skånes universitetssjukhus Malmö

Malmo, Sweden, 205 02

Centrum för reumatologi

Stockholm, Sweden, 102 35

Reumatologiska Kliniken Karolinska Universitetssjukhuset Solna

Stockholm, Sweden, 171 76

Switzerland

Kantonsspital St. Gallen

St. Gallen, Sankt Gallen, Switzerland, 9007

HUG-Hôpitaux Universitaires de Genève

Genève, Switzerland, 1206

Ukraine

Regional Clinical Hospital Center for Emergency medical care

Kharkiv, Ukraine

National Scientific Center "Strazhesko institute of cardio"

Kyiv, Ukraine, 03680

Kyiv City Clinical Hospital #3

Kyiv, Ukraine

Multifield Medical Center of Odesa NMU (University Clinic#1)

Odesa, Ukraine, 65026

Municipal Institution of Ternopil Regional Council

Ternopil, Ukraine, 46002

Vinnytsya Regional Clinical Hospital

Vinnytsya, Ukraine, 21018

Regional Clinical Hospital of Zaporizhzhia

Zaporizhzhia, Ukraine, 69600

United Kingdom

Addenbrookes Hospital

Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ

Royal Cornwall Hospital

Truro, Cornwall, United Kingdom, TR1 3LJ

Southampton General Hospital

Southampton, Hants, United Kingdom, SO16 6YD

Wythenshawe Hospital

Wythenshawe, Manchester, United Kingdom, M23 9LT

Wishaw General Hospital

Wishaw, North Lanarkshire, United Kingdom, ML2 0DP

Western General Hospital

Edinburgh, Scotland, United Kingdom, EH4 2XU

Whipps Cross University Hospital

London, Surrey, United Kingdom, E11 1NR

North Tyneside General Hospital

North Shields, Tyneside, United Kingdom, NE29 8NH

The Dudley Group NHS Foundation Trust

Dudley, West Midlands, United Kingdom, DY1 2HQ

New Cross Hospital

Wolverhampton, West Midlands, United Kingdom, WV10 0QP

St Lukes Hospital

Bradford, West Yorkshire, United Kingdom, BD5 0NA

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)

Documents provided by Eli Lilly and Company:

Study Protocol  [PDF] May 26, 2017

Statistical Analysis Plan  [PDF] December 3, 2018

More Information

Additional Information:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Deodhar AA, Combe B, Accioly AP, Bolce R, Zhu D, Gellett AM, Sprabery AT, Burmester GR. Safety of ixekizumab in patients with psoriatic arthritis: data from four clinical trials with over 2000 patient-years of exposure. Ann Rheum Dis. 2022 Jul;81(7):944-950. doi: 10.1136/annrheumdis-2021-222027. Epub 2022 Apr 7.

Elewski BE, Blauvelt A, Gallo G, Wolf E, McKean-Matthews M, Burge R, Merola JF, Gottlieb AB, Guenther LC. Simultaneous Nail and Skin Clearance in Ixekizumab Head-to-Head Trials for Moderate-to-Severe Psoriasis and Psoriatic Arthritis. Dermatol Ther (Heidelb). 2022 Apr;12(4):911-920. doi: 10.1007/s13555-022-00704-2. Epub 2022 Mar 13.

Smolen JS, Sebba A, Ruderman EM, Schulze-Koops H, Sapin C, Gellett AM, Sprabery AT, Li L, de la Torre I, Gallo G, Liu-Leage S, Pillai S, Reis P, Nash P. Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naive Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study. Rheumatol Ther. 2020 Dec;7(4):1021-1035. doi: 10.1007/s40744-020-00250-3. Epub 2020 Nov 16.

Smolen JS, Mease P, Tahir H, Schulze-Koops H, de la Torre I, Li L, Hojnik M, Sapin C, Okada M, Caporali R, Gratacos J, Goupille P, Liu Leage S, Pillai S, Nash P. Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naive to biological disease-modifying antirheumatic drug: final results by week 52. Ann Rheum Dis. 2020 Oct;79(10):1310-1319. doi: 10.1136/annrheumdis-2020-217372. Epub 2020 Jul 13.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03151551
• Other Study ID Numbers: 16687; I1F-MC-RHCF ( Other Identifier: Eli Lilly and Company ); 2016-004585-25 ( EudraCT Number )
• First Posted: May 12, 2017
• Results First Posted: April 2, 2019
• Last Update Posted: November 3, 2020
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• 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; Joint Diseases; Musculoskeletal Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Adalimumab; Ixekizumab; Tumor Necrosis Factor Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Dermatologic Agents