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

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

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.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Drug: Ixekizumab; Drug: Adalimumab

• Study Type: Interventional
• Enrollment (Actual): 566
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Simultaneously Achieving American College of Rheumatology 50 (ACR50) and Psoriasis Area and Severity Index 100 (PASI100)	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.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving ACR50	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).	Week 24
Percentage of Participants Achieving PASI100	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.	Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Tender Joint Count (TJC)	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.	Baseline, Week 52
Change From Baseline in Swollen Joint Count (SJC)	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.	Baseline, Week 52
Change From Baseline in Participant's Assessment of Pain Visual Analogue Score (VAS)	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.	Baseline, Week 52
Change From Baseline in Participant's Global Assessment of Disease Activity	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.	Baseline, Week 52
Change From Baseline in Physician's Global Assessment of Disease Activity	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.	Baseline, Week 52
Change From Baseline in C-Reactive Protein (CRP)	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.	Baseline, Week 52
Change From Baseline in HAQ-DI	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.	Baseline, Week 52
Percentage of Participants Simultaneously Achieving ACR50 and PASI100	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.	Week 52
Change From Baseline in Disease Activity Score-CRP (DAS28-CRP)	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.	Baseline, Week 52
Percentage of Participants Achieving Minimal Disease Activity (MDA)	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.	Week 52
Percentage of Participants Achieving Psoriatic Arthritis Response Criteria (PsARC)	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.	Week 52
Change From Baseline in Modified Composite Psoriatic Disease Activity Index (mCPDAI) Score	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.	Baseline, Week 52
Change From Baseline in the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index in Participants With Enthesitis at Baseline	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.	Baseline, Week 52
Change From Baseline in the Leeds Enthesitis Index (LEI) in Participants With Enthesitis at Baseline	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.	Baseline, Week 52
Change From Baseline in the Leeds Dactylitis Index-Basic (LDI-B) in Participants With Dactylitis at Baseline	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.	Baseline, Week 52
Change From Baseline in Psoriasis Body Surface Area (BSA)	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.	Baseline, Week 52
Change From Baseline in the Nail Psoriasis Severity Index (NAPSI) Fingernails Score in the Subgroup of Participants With Fingernail Involvement at Baseline	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.	Baseline, Week 52
Change From Baseline in the Itch NRS	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.	Baseline, Week 52
Change From Baseline in Fatigue Severity NRS (Fatigue NRS) Score	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.	Baseline, Week 52
Change From Baseline in Medical Outcomes Study 36-item Short Form Health Survey (SF-36): Physical Component Summary (PCS)	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.	Baseline, Week 52
Change From Baseline in SF-36: Mental Component Summary (MCS)	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.	Baseline, Week 52
Change From Baseline in Measures of Health Utility (EuroQol-5 Dimensions 5 Level [EQ-5D 5L]) United Kingdom(UK) Population-Based Index Score	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.	Baseline, Week 52
Change From Baseline in Measures of Health Utility (EuroQol-5 Dimensions 5 Level [EQ-5D 5L]) VAS Score	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.	Baseline, Week 52
Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score	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.	Baseline, Week 52
Percentage of Participants Answering "Mostly Satisfied" to Each Question in Treatment Satisfaction Questionnaire (TSQ)	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").	Week 52
Number of Participants Who Answered "Yes" to Any 10 Questions in Columbia Suicide Severity Rating Scale (C-SSRS)	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	Week 52

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 24, 2017
• Primary Completion (ACTUAL): November 15, 2018
• Study Completion (ACTUAL): September 4, 2019

Study Registration Dates

• First Submitted: May 4, 2017
• First Submitted That Met QC Criteria: May 11, 2017
• First Posted (ACTUAL): May 12, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 3, 2020
• Last Update Submitted That Met QC Criteria: October 9, 2020
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Anti-Inflammatory Agents; Antirheumatic Agents; Dermatologic Agents; Adalimumab; Ixekizumab
• Other Study ID Numbers: 16687; I1F-MC-RHCF (OTHER: Eli Lilly and Company); 2016-004585-25 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing 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.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No