A Study of Ixekizumab (LY2439821) in Participants With Active Psoriatic Arthritis
- Conditions
- Psoriatic Arthritis
- Interventions
- Registration Number
- NCT02349295
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The main purpose of this study is to evaluate how effective and safe the study drug known as ixekizumab is in participants with active psoriatic arthritis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 363
- Presents with established diagnosis of active psoriatic arthritis (PsA) for at least 6 months, and currently meets Classification for Psoriatic Arthritis (CASPAR) criteria
- Active PsA defined as the presence of at least 3 tender and at least 3 swollen joints
- Presence of active psoriatic skin lesion or a history of plaque psoriasis (Ps)
- 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 been treated with 1 or more conventional disease-modifying antirheumatic drugs (cDMARDs)
- Have had prior treatment with at least 1 and not more than 2 tumor necrosis factor (TNF) inhibitors. The participant must have discontinued at least 1 TNF inhibitor due to either an inadequate response (based on a minimum of 12 weeks on therapy) or documented intolerance.
- Current use of biologic agents for treatment of Ps or PsA
- Inadequate response to greater than 2 biologic DMARDs
- Current use of more than one cDMARDs
- Diagnosis of active inflammatory arthritic syndromes or spondyloarthropathies other than PsA
- Have received treatment with interleukin (IL) -17 or IL12/23 targeted monoclonal antibody (MAb) therapy
- Serious disorder or illness other than psoriatic arthritis
- Serious infection within the last 3 months
- Breastfeeding or nursing (lactating) women
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ixekizumab 80 milligram (mg) every 2 Weeks (Q2W) Placebo Blinded Treatment Period (Week(wk) 0-24): Participants (pts) received a starting dose of 160 mg of ixekizumab (ixe) given as 2 subcutaneous (SC) injections at Wk 0 followed by 1 SC injection of 80 mg of ixe Q2W given on Wks 2,4,6,8,10,12,14,16,18,20,22, and 24.Week 16 inadequate responders (IR) from the placebo treatment group who were re-randomized (1:1) to ixe 80 mg Q2W and IR from ixekizumab 80 mg Q2W who continued on ixekizumab 80 mg Q2W. Pts receive rescue therapy while receiving ixekizumab given as 1 injection of 80 mg Q2W given on Wks 16,18,20,22,24. Extension Period (Wk24-156):Pts who were randomized to ixe 80 mg Q2W at week 0 and continued on ixe 80 mg Q2W during the Extension Period. Pts who received ixekizumab 80 mg Q2W,who were either completed the study or discontinued the study early entered the post-treatment follow-up period (12-24 weeks). Ixekizumab 80 mg Q4W Placebo Blinded Treatment Period (Week 0-24): Participants (pts) received a starting dose of 160 mg of ixekizumab (ixe) given as 2 subcutaneous (SC) injections at Wk 0 followed by 1 SC injection of 80 mg of ixe Q4W given on Wks 4, 8 and 12 alternating with placebo for ixe injections Q4W given on Wks 2,6,10,14,18, and 22.Week 16 inadequate responders (IR) from the placebo treatment group who were re-randomized (1:1) to ixe 80 mg Q4W and IR from ixekizumab 80 mg Q4W who continued on ixekizumab 80 mg Q4W. Pts receive rescue therapy while receiving ixekizumab given as 1 injection of 80 mg Q4W given on Wks 16 and 20 alternating with placebo for ixe injections Q4W given on Wks 18 and 22.Extension Period (Wk24-156):Pts who were randomized to ixe 80 mg Q4W at week 0 and continued on ixe 80 mg Q4W during the Extension Period.Pts who received ixekizumab 80 mg Q4W,who were either completed the study or discontinued the study early entered the post-treatment follow-up period (12-24 weeks). Placebo Placebo Blinded Treatment Period (Wk 0-24): Pts received placebo for Ixe as 2 SC injections followed by 1 SC injection Q2W given on Wks 2,4,6,8,10,12,14,16,18,20,22 and 24. Pts initially randomized to placebo treatment group in the double blind treatment period,flagged as IR at Wk 16,re-randomized to ixe 80 mg Q2W/Q4W for the remainder of the current period and following period. Extended Treatment Period (Wk 24-156): Pts who were randomized to placebo at Week 0 then randomized to ixekizumab 80 mg Q2W/Q4W during the Extension Period.Pts who remained on placebo at the completion of the double blind treatment period received the first dose of ixe (160 mg starting dose) at Wk 24.Pts who were IRs at Wk 16 and were re-randomized to ixe at Wk 16 received the first dose of ixe (160 mg starting dose) at Wk 16. Pts who received placebo,who were either completed the study or discontinued the study early entered the post-treatment follow-up period (12-24 weeks). Ixekizumab 80 milligram (mg) every 2 Weeks (Q2W) Ixekizumab 80 mg Q2W Blinded Treatment Period (Week(wk) 0-24): Participants (pts) received a starting dose of 160 mg of ixekizumab (ixe) given as 2 subcutaneous (SC) injections at Wk 0 followed by 1 SC injection of 80 mg of ixe Q2W given on Wks 2,4,6,8,10,12,14,16,18,20,22, and 24.Week 16 inadequate responders (IR) from the placebo treatment group who were re-randomized (1:1) to ixe 80 mg Q2W and IR from ixekizumab 80 mg Q2W who continued on ixekizumab 80 mg Q2W. Pts receive rescue therapy while receiving ixekizumab given as 1 injection of 80 mg Q2W given on Wks 16,18,20,22,24. Extension Period (Wk24-156):Pts who were randomized to ixe 80 mg Q2W at week 0 and continued on ixe 80 mg Q2W during the Extension Period. Pts who received ixekizumab 80 mg Q2W,who were either completed the study or discontinued the study early entered the post-treatment follow-up period (12-24 weeks). Ixekizumab 80 mg Q4W Ixekizumab 80 mg Q4W Blinded Treatment Period (Week 0-24): Participants (pts) received a starting dose of 160 mg of ixekizumab (ixe) given as 2 subcutaneous (SC) injections at Wk 0 followed by 1 SC injection of 80 mg of ixe Q4W given on Wks 4, 8 and 12 alternating with placebo for ixe injections Q4W given on Wks 2,6,10,14,18, and 22.Week 16 inadequate responders (IR) from the placebo treatment group who were re-randomized (1:1) to ixe 80 mg Q4W and IR from ixekizumab 80 mg Q4W who continued on ixekizumab 80 mg Q4W. Pts receive rescue therapy while receiving ixekizumab given as 1 injection of 80 mg Q4W given on Wks 16 and 20 alternating with placebo for ixe injections Q4W given on Wks 18 and 22.Extension Period (Wk24-156):Pts who were randomized to ixe 80 mg Q4W at week 0 and continued on ixe 80 mg Q4W during the Extension Period.Pts who received ixekizumab 80 mg Q4W,who were either completed the study or discontinued the study early entered the post-treatment follow-up period (12-24 weeks).
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving American College of Rheumatology 20 Index (ACR20) Week 24 ACR20 response is defined as a greater than or equal to (≥) 20% 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 VAS (PatGA), Physician's Global Assessment of the Disease Activity VAS (PGA), Participant's Assessment of Physical Function using the Health Assessment Questionnaire Disability Index (HAQ-DI), or Acute Phase Reactant as measured by high sensitivity C-reactive protein (hs-CRP).
- Secondary Outcome Measures
Name Time Method Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Baseline, Week 24 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 degree of difficulty (0=without any difficulty,1=with some difficulty,2=with much difficulty,3=unable to do)covering the 8 domains.The HAQ-DI is a composite ranging from 0-3 with lower scores indicating less functional disability.The reported use of special aids/devices and/or the need for assistance of another person to perform these activities is assessed.Least Square (LS) mean calculated using Mixed Model Repeated Measurements (MMRM) analysis with treatment,baseline score,geographic region, TNFi experience,visit, treatment-by-visit interaction(itcn), geographic region-by-visit itcn,TNFi experience-by-visit itcn and baseline score-by-visit itcn.
Percentage of Participants Achieving ACR20 Week 12 ACR20 response is defined as a ≥20% improvement from baseline for TJC and SJC and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain VAS, Participant's Global Assessment of Disease Activity VAS, Physician's Global Assessment of the Disease Activity VAS, Participant's Assessment of Physical Function using the HAQ-DI, or hs-CRP.
Percentage of Participants Achieving American College of Rheumatology 50 Index (ACR50) Week 24 ACR50 response is defined as a ≥50% improvement from baseline for TJC and SJC and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain VAS, Participant's Global Assessment of Disease Activity VAS, Physician's Global Assessment of the Disease Activity VAS, Participant's Assessment of Physical Function using the HAQ-DI, or hs-CRP.
Percentage of Participants Achieving American College of Rheumatology 70 Index (ACR70) Week 24 ACR70 response is defined as a ≥70% improvement from baseline for TJC and SJC and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain VAS, Participant's Global Assessment of Disease Activity VAS, Physician's Global Assessment of the Disease Activity VAS, Participant's Assessment of Physical Function using the HAQ-DI, or hs-CRP.
Percentage of Participants With Psoriasis Area and Severity Index (PASI) 75 Week 12 The PASI is an index that combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation, erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 75 were defined as having an improvement of at least 75% in the PASI compared to their baseline measures.
Percentage of Patients Achieving Minimal Disease Activity (MDA) Week 24 It uses a composite of 7 key outcome measures (includes PASI) used in PsA to encompass all of the domains of the disease to measure the overall state of a patients' disease. The LEI is used to assess tender entheseal points. Patients are classified as achieving MDA if they fulfill 5 of 7 outcome measures: 1. TJC ≤1, 2. SJC ≤1, 3. PASI total score ≤1 or BSA ≤3, 4. patient pain VAS score of ≤15, 5. patient global VAS score of ≤20, 6. HAQ-DI score ≤0.5, 7. tender entheseal points (6 entheseal points) ≤1.
Percentage of Patients Achieving Complete Resolution in Enthesitis as Assessed by the Leeds Enthesitis Index (LEI) Week 24 The LEI was developed specifically for use in PsA. It measures enthesitis at 6 sites (lateral epicondyle, left and right; medial femoral condyle, left and right; Achilles tendon insertion, left and right). Each site was assigned a score of 0 (absent) or 1 (present); the results from each site were then added to produce a total score (range 0 to 6). So, "0" indicates good score here.
Change From Baseline in Itch Numeric Rating Scale (NRS) Baseline, Week 12 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 participants itching from psoriasis was indicated by circling the number that best described the worst level of itching in the past 24 hours. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.
Change From Baseline in Tender Joint Count (TJC) Baseline, Week 24 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. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.
Change From Baseline in Swollen Joint Count (SJC) Baseline, Week 24 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 analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.
Change From Baseline in Participants Assessment of Pain Visual Analog Scale (VAS) Baseline, Week 24 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 analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.
Change From Baseline in Patients Global Assessment of Disease Activity VAS Baseline, Week 24 The patient's overall assessment of his or her PsA activity will be 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 analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.
Change From Baseline in Physicians Global Assessment of Disease Activity VAS Baseline, Week 24 The investigator will be 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 analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.
Change From Baseline in C-Reactive Protein (CRP) Baseline, Week 24 C-reactive protein (CRP) is a disease related biomarker and measured in milligrams per liter. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.
Change From Baseline in Disease Activity Score-CRP (DAS28-CRP) Baseline, Week 24 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 mg/L), and Participant's Global Assessment of Disease Activity recorded by participants on a 0 to 100 millimeter (mm) 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 analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.
Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score Baseline, Week 24 The BASDAI is a self-administered measure used to answer 6 questions with a 0 to 10 centimeter (cm) VAS pertaining to the 5 major symptoms of axial activity. To give each symptom equal weighting, the mean of the 2 scores relating to morning stiffness was taken. The resulting 0 to 50 score was divided by 5 to give a final 0 to 10 BASDAI Score. BASDAI ranges from 0-10. Higher scores represent greater disease activity. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.
Change From Baseline in Fatigue Severity Numeric Rating Scale (NRS) Score Baseline, Week 24 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 rated their fatigue (feeling tired or worn out) by circling the 1 number that described their worst level of fatigue during the past 24 hours. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Scores: Physical Component Summary (PCS) Baseline, Week 24 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. In this study, the SF-36 acute version was used, which has a 1 week recall period. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Scores: Mental Component Summary (MCS) Baseline, Week 24 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. In this study, the SF-36 acute version was used, which has a 1 week recall period. LS mean was calculated using MMRM analysis with treatment, baseline score, geographic region, TNFi experience, visit, treatment-by-visit interaction, geographic region-by-visit interaction, TNFi experience-by-visit interaction, and baseline score-by-visit interaction.
Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) Week 24 Number of participants with positive treatment emergent anti-ixekizumab antibodies was summarized by treatment group.
Pharmacokinetics (PK):Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Ixekizumab All immunogenicity samples post the first Ixekizumab dose (Week 4, 12, 24, 36, and 52) and PK samples collected per dedicated sparse sampling plan (4-5 samples per patient) across Weeks 1 through 24 and Early termination visit (ETV) The Ctrough is the minimum observed serum concentration at steady state of Ixekizumab. The Ctrough at Week 24 was reported.
Pharmacokinetics: Area Under the Concentration-Time Curve for Dosing Interval (Tau) at Steady State [AUC(Tau,Steady State)] of Ixekizumab All immunogenicity samples post the first Ixekizumab dose (Week 4, 12, 24, 36, and 52) and PK samples collected per dedicated sparse sampling plan (4-5 samples per patient) across Weeks 1 through 24 and Early termination visit (ETV) The AUC(Tau,Steady State) is the area under the concentration-time curve for dosing interval (Tau) at steady state of ixekizumab (Tau is 28 days for 80 mg Q4W cohort, and is 14 days for 80mg Q2W cohort, respectively).
Percentage of Participants Achieving ACR 20 Week 52 and Week 156 ACR20 response is defined as a ≥20% improvement from baseline for TJC and SJC and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain VAS, Participant's Global Assessment of Disease Activity VAS, Physician's Global Assessment of the Disease Activity VAS, Participant's Assessment of Physical Function using the HAQ-DI, or hs-CRP.
Percentage of Participants Achieving ACR 50 Week 52 and Week 156 ACR50 response is defined as a ≥50% improvement from baseline for TJC and SJC and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain VAS, Participant's Global Assessment of Disease Activity VAS, Physician's Global Assessment of the Disease Activity VAS, Participant's Assessment of Physical Function using the HAQ-DI, or hs-CRP.
Percentage of Participants Achieving ACR 70 Week 52 and Week 156 ACR70 response is defined as a ≥70% improvement from baseline for TJC and SJC and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain VAS, Participant's Global Assessment of Disease Activity VAS, Physician's Global Assessment of the Disease Activity VAS, Participant's Assessment of Physical Function using the HAQ-DI, or hs-CRP.
Trial Locations
- Locations (105)
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Office: Dr Robin K Dore
🇺🇸Tustin, California, United States
Rheumatology Associates of South Florida
🇺🇸Boca Raton, Florida, United States
Johns Hopkins Arthritis Center
🇺🇸Baltimore, Maryland, United States
Klein and Associates MD, PA
🇺🇸Hagerstown, Maryland, United States
Arthritis, Rheumatic & Back Disease Associates
🇺🇸Voorhees, New Jersey, United States
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Baden-Württemberg, Germany
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
Pioneer Research Solutions
🇺🇸Houston, Texas, United States
Houston Institute for Clinical Research
🇺🇸Houston, Texas, United States
MEDICAL PLUS, s.r.o.
🇨🇿Uherske Hradiste, Czechia
CCBR Czech Prague, s.r.o.
🇨🇿Praha, Czechia
Kadlec Clinic Rheumatology
🇺🇸Kennewick, Washington, United States
Hopital Purpan
🇫🇷Toulouse, France
Azienda Ospedaliera - Universitaria Pisana
🇮🇹Pisa, Italy
Emeritus Research
🇦🇺Camberwell, Victoria, Australia
Complexo Hospitalario Universitario A Coruña, CHUAC
🇪🇸La Coruña, Spain
Rheumazentrum Ruhrgebiet
🇩🇪Herne, Nordrhein-Westfalen, Germany
Centro de Salud Mental Parc Tauli
🇪🇸Sabadell, Barcelona, Spain
Hospital Universitario Marques De Valdecilla
🇪🇸Santander, Cantabria, Spain
Medica pro Familia Sp z o.o. S.K.A
🇵🇱Warszawa, Poland
AI Centrum Medyczne
🇵🇱Poznan, Poland
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Hôpital Trousseau, CHRU de Tours
🇫🇷Chambray-lès-Tours, France
Universität Leipzig - Universitätsklinikum
🇩🇪Leipzig, Sachsen, Germany
Hopital Cochin
🇫🇷Paris CEDEX 14, France
Universitätsklinikum Würzburg
🇩🇪Würzburg, Bayern, Germany
Arthritis Northwest PLLC
🇺🇸Spokane, Washington, United States
Coast Joint Care
🇦🇺Maroochydore, Queensland, Australia
Princess Alexandra Hospital
🇬🇧Harlow, Essex, United Kingdom
Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
🇩🇪Frankfurt am Main, Hessen, Germany
CHU de Montpellier-Hopital Arnaud de Villeneuve
🇫🇷Montpellier Cedex 5, France
Chru De Nantes Hotel-Dieu
🇫🇷Nantes Cedex 1, France
Hospital De Fuenlabrada
🇪🇸Fuenlabrada, Madrid, Spain
Malopolskie Centrum Medyczne S.C.
🇵🇱Krakow, Poland
Chang Gung Memorial Hospital - Kaohsiung
🇨🇳Kaohsiung City (r.o.c), Taiwan
Chang Gung Memorial Hospital - Linkou
🇨🇳Taoyuan City, Taiwan
Hospital Infanta Luisa
🇪🇸Sevilla, Andalucia, Spain
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Sachsen, Germany
Chung Shan Medical University Hospital
🇨🇳Taichung City, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Istituto Ortopedico Gaetano Pini
🇮🇹Milano, Italy
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Hospital De Basurto
🇪🇸Bilbao, Vizcaya, Spain
Universitätsklinikum Schleswig-Holstein
🇩🇪Lübeck, Schleswig-Holstein, Germany
King George Hospital
🇬🇧Goodmayes, Essex, United Kingdom
Basildon and Thurrock University Hospital
🇬🇧Basildon, Essex, United Kingdom
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
New Cross Hospital
🇬🇧Wolverhampton, West Midlands, United Kingdom
HRF Hamburger Rheuma Forschungszentrum
🇩🇪Hamburg, Germany
Hospital Regional Universitario de Málaga
🇪🇸Malaga, Spain
Arizona Arthritis & Rheumatology Research, PLLC
🇺🇸Mesa, Arizona, United States
Little Rock Diagnostic Clinic
🇺🇸Little Rock, Arkansas, United States
University of California - San Diego
🇺🇸La Jolla, California, United States
Purushotham & Akther Kotha MD Inc
🇺🇸La Mesa, California, United States
Stanford University Hospital
🇺🇸Palo Alto, California, United States
Florida Medical Clinic PA
🇺🇸Zephyrhills, Florida, United States
Arthritis & Osteoporosis Treatment Center, PA
🇺🇸Orange Park, Florida, United States
Heartland Research Associates
🇺🇸Wichita, Kansas, United States
Physicians Clinic of Iowa
🇺🇸Cedar Rapids, Iowa, United States
North MS Medical Clinics, Inc.
🇺🇸Tupelo, Mississippi, United States
Glacier View Research Institute
🇺🇸Kalispell, Montana, United States
Beals Institute PC
🇺🇸Lansing, Michigan, United States
Atlantic Coastal Research
🇺🇸Toms River, New Jersey, United States
Physician Research Collaboration, LLC
🇺🇸Lincoln, Nebraska, United States
The Center for Rheumatology
🇺🇸Albany, New York, United States
Allergy Asthma Immunology of Rochester, AAIR Research Ctr
🇺🇸Rochester, New York, United States
Weill Cornell Medical College
🇺🇸Brooklyn, New York, United States
PMG Research of Hickory, LLC
🇺🇸Hickory, North Carolina, United States
STAT Research
🇺🇸Dayton, Ohio, United States
Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Clinical Research Center of Reading, LLC
🇺🇸Wyomissing, Pennsylvania, United States
Pennsylvania Regional Center for Arthritis & Osteoarthritis
🇺🇸Wyomissing, Pennsylvania, United States
Ramesh C. Gupta MD
🇺🇸Memphis, Tennessee, United States
Methodist Healthcare
🇺🇸Memphis, Tennessee, United States
Arthritis Care & Diagnostic Center P.A.
🇺🇸Dallas, Texas, United States
Accurate Clinical Research
🇺🇸League City, Texas, United States
Arthritis & Osteoporosis Associates LLP
🇺🇸Lubbock, Texas, United States
Rheumatology and Immunotherapy Center
🇺🇸Franklin, Wisconsin, United States
PV-MEDICAL s.r.o. Revmatologicka ambulance
🇨🇿Zlin, Czechia
CHU Brabois
🇫🇷Vandoeuvre Les Nancy, France
Krankenhaus Dresden-Friedrichstadt Städtisches Klinikum
🇩🇪Dresden, Sachsen, Germany
Rheuma Medicus Zakład Opieki Zdrowotnej
🇵🇱Warszawa, Poland
Hospital Universitario Nuestra Señora de Valme
🇪🇸Sevilla, Spain
Chi-Mei Hospital, Liouying
🇨🇳Tainan City, Yongkang Dist, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Whipps Cross University Hospital
🇬🇧London, Surrey, United Kingdom
Chapel Allerton Hospital
🇬🇧Leeds, West Yorkshire, United Kingdom
Jeffrey Alper MD Research
🇺🇸Naples, Florida, United States
New Jersey Physicians
🇺🇸Clifton, New Jersey, United States
Rheumatology Associates of Long Island
🇺🇸Smithtown, New York, United States
Arthritis and Osteoporosis Consultants of the Carolinas
🇺🇸Charlotte, North Carolina, United States
PMA Medical Specialists, LLC
🇺🇸Limerick, Pennsylvania, United States
DJL Clinical Research, PLLC
🇺🇸Charlotte, North Carolina, United States
Rheumatology Associates PC
🇺🇸Birmingham, Alabama, United States
Arizona Arthritis & Rheumatology Research
🇺🇸Phoenix, Arizona, United States
East Bay Rheumatology Medical Group
🇺🇸San Leandro, California, United States
Diagnostic Rheumatology and Research
🇺🇸Indianapolis, Indiana, United States
Bluegrass Community Research. Inc
🇺🇸Lexington, Kentucky, United States
Albuquerque Rehabilitation & Rheumatology, PC
🇺🇸Albuquerque, New Mexico, United States
Health Research Institute
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Austin Rheumatology Research PA
🇺🇸Austin, Texas, United States
Austin Regional Clinic
🇺🇸Austin, Texas, United States