A Study Comparing Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis on a Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response to csDMARDs Alone
- Registration Number
- NCT02675426
- Lead Sponsor
- AbbVie
- Brief Summary
The primary objectives of this study are to compare the efficacy, safety, and tolerability of upadacitinib 30 mg once daily (QD) and 15 mg QD versus placebo for the treatment of signs and symptoms of adults with moderately to severely active rheumatoid arthritis who were on a stable dose of csDMARDs and had an inadequate response to csDMARDs.
- Detailed Description
This Phase 3 multicenter study includes two periods. Period 1 is a 12-week, randomized, double-blind, parallel-group, placebo-controlled period designed to compare the safety and efficacy of upadacitinib 30 mg once daily and upadacitinib 15 mg once daily versus placebo for the treatment of signs and symptoms of adults with moderately to severely active rheumatoid arthritis (RA) who were on a stable dose of csDMARDs and had an inadequate response to csDMARDs.
Period 2 is a 248-week blinded long-term extension period to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 30 mg once daily and upadacitinib 15 mg once daily in participants who completed Period 1.
Participants were to be randomized in a 2:2:1:1 ratio using interactive response technology (IRT) to receive double-blind study drug in one of the following treatment groups:
* Group 1: Upadacitinib 30 mg QD in Period 1 → Upadacitinib 30 mg QD in Period 2
* Group 2: Upadacitinib 15 mg QD in Period 1 → Upadacitinib 15 mg QD in Period 2
* Group 3: Placebo in Period 1 → Upadacitinib 30 mg QD in Period 2
* Group 4: Placebo in Period 1 → Upadacitinib 15 mg QD in Period 2
Randomization was stratified by prior exposure to biological disease-modifying anti-rheumatic drug (bDMARD) (yes/no) and geographic region.
Following Protocol Amendment 6.0 approval in December 2019, all participants still on study received open-label upadacitinib 15 mg QD, including those on upadacitinib 30 mg QD, with the earliest switch occurring at the Week 168 visit.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 661
- Adult male or female, at least 18 years old.
- Diagnosis of rheumatoid arthritis (RA) for greater than or equal to 3 months.
- Subjects have been receiving conventional synthetic DMARD (csDMARD) therapy for greater than or equal to 3 months and on a stable dose for greater than or equal to 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide.
- Meets the following minimum disease activity criteria: greater than or equal to 6 swollen joints (based on 66 joint counts) and greater than or equal to 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
- Subjects with prior exposure to at most one biologic DMARD (bDMARD) may be enrolled (up to 20% of study population) if they have documented evidence of intolerance to bDMARDs or limited exposure (less than 3 months) and have satisfied required washout periods.
- Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
- History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted.
- Subjects who are considered inadequate responders to bDMARD therapy as determined by the Investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo / Upadacitinib 15 mg Placebo Period 1: Participants receive placebo once daily for 12 weeks. Period 2: Participants receive upadacitinib 15 mg once daily for 248 weeks. Placebo / Upadacitinib 30 mg Placebo Period 1: Participants receive placebo once daily for 12 weeks. Period 2: Participants receive upadacitinib 30 mg once daily for 248 weeks or until implementation of Protocol Amendment 6 at which time participants switch to receive upadacitinib 15 mg once daily. Upadacitinib 15 mg Upadacitinib Period 1: Participants receive upadacitinib 15 mg once daily for 12 weeks. Period 2: Participants continue to receive upadacitinib 15 mg once daily for an additional 248 weeks. Upadacitinib 30 mg Upadacitinib Period 1: Participants receive upadacitinib 30 mg once daily for 12 weeks. Period 2: Participants continue to receive upadacitinib 30 mg once daily for an additional 248 weeks or until implementation of Protocol Amendment 6 at which time participants switch to receive upadacitinib 15 mg once daily. Placebo / Upadacitinib 15 mg Upadacitinib Period 1: Participants receive placebo once daily for 12 weeks. Period 2: Participants receive upadacitinib 15 mg once daily for 248 weeks. Placebo / Upadacitinib 30 mg Upadacitinib Period 1: Participants receive placebo once daily for 12 weeks. Period 2: Participants receive upadacitinib 30 mg once daily for 248 weeks or until implementation of Protocol Amendment 6 at which time participants switch to receive upadacitinib 15 mg once daily.
- Primary Outcome Measures
Name Time Method Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 Baseline and Week 12 The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria:
1. ≥ 20% improvement in 68-tender joint count;
2. ≥ 20% improvement in 66-swollen joint count; and
3. ≥ 20% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity;
* Patient global assessment of disease activity;
* Patient assessment of pain;
* Health Assessment Questionnaire - Disability Index (HAQ-DI);
* High-sensitivity C-reactive protein (hsCRP).Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 Week 12 The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was low disease activity, based on a Disease Activity Score 28 (DAS28)-CRP score of ≤ 3.2 at Week 12.
The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28 score less than or equal to 3.2 indicates low disease activity.
- Secondary Outcome Measures
Name Time Method Change From Baseline in in Disease Activity Score 28 (CRP) at Week 12 Baseline and Week 12 The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 Baseline and Week 12 The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.
A negative change from Baseline in the overall score indicates improvement.Change From Baseline in Short-Form 36 (SF-36) Physical Component Summary (PCS) Score at Week 12 Baseline and Week 12 The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The physical component summary score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement.Percentage of Participants Achieving Clinical Remission Based on DAS28 (CRP) at Week 12 Week 12 Clinical remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6.
DAS28 (CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12 Week 12 Low disease activity based on the clinical disease activity index (CDAI) is defined as a CDAI score ≤ 10.
CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.Change From Baseline in Duration of Morning Stiffness at Week 12 Baseline and Week 12 Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days.
Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Week 12 Baseline and week 12 The FACIT-Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a five point Likert scale from 0 (not at all) to 4 (very much). The FACIT-Fatigue scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from Baseline indicates improvement.
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 Baseline and Week 12 Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria:
1. ≥ 50% improvement in 68-tender joint count;
2. ≥ 50% improvement in 66-swollen joint count; and
3. ≥ 50% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity;
* Patient global assessment of disease activity;
* Patient assessment of pain;
* Health Assessment Questionnaire - Disability Index (HAQ-DI);
* High-sensitivity C-reactive protein (hsCRP).Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 Baseline and Week 12 Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria:
1. ≥ 70% improvement in 68-tender joint count;
2. ≥ 70% improvement in 66-swollen joint count; and
3. ≥ 70% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity;
* Patient global assessment of disease activity;
* Patient assessment of pain;
* Health Assessment Questionnaire - Disability Index (HAQ-DI);
* High-sensitivity C-reactive protein (hsCRP).Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1 Baseline and Week 1 Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria:
1. ≥ 20% improvement in 68-tender joint count;
2. ≥ 20% improvement in 66-swollen joint count; and
3. ≥ 20% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity;
* Patient global assessment of disease activity;
* Patient assessment of pain;
* Health Assessment Questionnaire - Disability Index (HAQ-DI);
* High-sensitivity C-reactive protein (hsCRP).
Trial Locations
- Locations (167)
Hospital Clin Univ San Carlos /ID# 138993
🇪🇸Madrid, Spain
Houston Institute for Clin Res /ID# 138716
🇺🇸Houston, Texas, United States
AZ Sint Lucas /ID# 141338
🇧🇪Brugge, Belgium
Diagnostic Consultative Center /ID# 138882
🇧🇬Sofia, Bulgaria
Immanuel-Krankenhaus /ID# 139059
🇩🇪Berlin, Germany
Klinicka bolnica Sveti Duh /ID# 152812
🇭🇷Zagreb, Croatia
Asklepios Klinik Altona /ID# 140466
🇩🇪Hamburg, Germany
Centro Peninsular de Investigación Clínica SCP /ID# 148160
🇲🇽Colonia Centro, Yucatan, Mexico
Klaipeda University Hospital /ID# 141416
🇱🇹Klaipeda, Lithuania
Nemocnica Kosice Saca, a.s. /ID# 138918
🇸🇰Kosice, Slovakia
St. Augustine's Medical Centre /ID# 141352
🇿🇦Berea, Kwazulu-Natal, South Africa
Cincinnati Rheumatic Disease Study Group, Inc. /ID# 138868
🇺🇸Cincinnati, Ohio, United States
SunValley Arthritis Center, Lt /ID# 140452
🇺🇸Peoria, Arizona, United States
Allergy and Rheum Med Clin /ID# 146082
🇺🇸La Jolla, California, United States
Suncoast Clinical Research /ID# 138633
🇺🇸New Port Richey, Florida, United States
Pacific Arthritis Ctr Med Grp /ID# 138744
🇺🇸Los Angeles, California, United States
Robin K. Dore MD, Inc /ID# 138688
🇺🇸Tustin, California, United States
Clinical Investigation Special /ID# 139696
🇺🇸Skokie, Illinois, United States
Springfield Clinic /ID# 138602
🇺🇸Springfield, Illinois, United States
Four Rivers Clinical Research /ID# 141134
🇺🇸Paducah, Kentucky, United States
Indiana Univ School of Med /ID# 140077
🇺🇸Indianapolis, Indiana, United States
Health Research Oklahoma /ID# 138535
🇺🇸Oklahoma City, Oklahoma, United States
PMG Research of Wilmington LLC /ID# 140951
🇺🇸Wilmington, North Carolina, United States
Denver Arthritis Clinic /ID# 139876
🇺🇸Denver, Colorado, United States
Altoona Ctr Clinical Res /ID# 138741
🇺🇸Duncansville, Pennsylvania, United States
T. Joseph Raoof, MD, Inc. /ID# 140964
🇺🇸Encino, California, United States
Arizona Research Center, Inc. /ID# 140448
🇺🇸Phoenix, Arizona, United States
Clinical Res of West FL, Inc. /ID# 138854
🇺🇸Clearwater, Florida, United States
OrthoIllinois /ID# 139695
🇺🇸Rockford, Illinois, United States
Deerbrook Medical Associates /ID# 139694
🇺🇸Vernon Hills, Illinois, United States
Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 138689
🇺🇸Summerville, South Carolina, United States
Comprehensive Arthritis Care, a division of Comprehensive Rheumatology Care PLLC /ID# 141021
🇺🇸Hendersonville, Tennessee, United States
Metroplex Clinical Research /ID# 138698
🇺🇸Dallas, Texas, United States
Accurate Clinical Management /ID# 139338
🇺🇸San Antonio, Texas, United States
Mautalen Salud e Investigacion /ID# 141419
🇦🇷Buenos Aires, Argentina
Wilhelminenspital der Stadt Wien /ID# 138788
🇦🇹Wien, Austria
Arthritis Consultants, P.A. /ID# 141138
🇺🇸Killeen, Texas, United States
Diag Consult Ctr 17 Sofia EOOD /ID# 141006
🇧🇬Sofia, Bulgaria
L.K.N. Arthrocentrum, s.r.o /ID# 141340
🇨🇿Hlučín, Moravskoslezsky Kraj, Czechia
Inst. Rheumatologic Strusberg /ID# 145648
🇦🇷Cordoba, Argentina
Aurora Rheumatology and Immunotherapy Center /ID# 139306
🇺🇸Franklin, Wisconsin, United States
Optimus Clinical Research Pty. /ID# 138769
🇦🇺Kogarah, New South Wales, Australia
Coffs Clinical Trials /ID# 138747
🇦🇺Coffs Harbour, New South Wales, Australia
Barwon Rheumatology /ID# 138772
🇦🇺Geelong, Victoria, Australia
Manitoba Clinic /ID# 139086
🇨🇦Winnipeg, Manitoba, Canada
Poliklinika Bonifarm /ID# 141415
🇭🇷Zagreb, Croatia
Medical Center Kuna-Peric /ID# 140365
🇭🇷Zagreb, Croatia
PV-MEDICAL s.r.o. /ID# 138913
🇨🇿Zlin, Czechia
Kiljava Medical Research /ID# 139260
🇫🇮Hyvinkaa, Finland
Charité Universitätsmedizin Campus Mitte /ID# 139052
🇩🇪Berlin, Germany
Nemocnice Slany /ID# 141112
🇨🇿Slany, Czechia
Paernu Hospital /ID# 138961
🇪🇪Pärnu, Estonia
East Tallinn Central Hospital /ID# 140618
🇪🇪Tallinn, Estonia
South Karelia Central Hospital /ID# 139973
🇫🇮Lappeenranta, Finland
Hopital Saint Joseph /ID# 149188
🇫🇷Marseille CEDEX 08, Bouches-du-Rhone, France
Uniklinik Koln /ID# 139084
🇩🇪Köln, Nordrhein-Westfalen, Germany
St Vincent's University Hosp /ID# 138562
🇮🇪Dublin, Ireland
Vilnius University Hospital /ID# 141348
🇱🇹Vilnius, Lithuania
McBk Sc /Id# 138360
🇵🇱Grodzisk Mazowiecki, Mazowieckie, Poland
Universita di Catanzaro Magna Graecia /ID# 139316
🇮🇹Catanzaro, Calabria, Italy
JSC Nat Scientific Med Res Ctr /ID# 140575
🇰🇿Astana, Kazakhstan
Hanyang University Seoul Hospi /ID# 138655
🇰🇷Seoul, Seongdong-gu, Korea, Republic of
School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 139328
🇵🇷San Juan, Puerto Rico
NZOZ Centrum Reumatologiczne /ID# 138353
🇵🇱Elblag, Warminsko-mazurskie, Poland
Samara Regional Clinical Hosp /ID# 148642
🇷🇺Samara, Russian Federation
REUMA-GLOBAL, s.r.o. /ID# 139912
🇸🇰Trnava, Slovakia
Yaroslavi State Medical Univer /ID# 139908
🇷🇺Yaroslavl, Russian Federation
Slovak research center Team Member, Thermium s.r.o. /ID# 139924
🇸🇰Pieštany, Slovakia
Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 140869
🇨🇳Kaohsiung, Taiwan
Odessa National Medical Univ /ID# 139179
🇺🇦Odesa, Ukraine
HFR Fribourg - Hopital Canton /ID# 139155
🇨🇭Fribourg, Switzerland
Far Eastern Memorial Hospital /ID# 140871
🇨🇳New Taipei City, Taiwan
Taipei Veterans General Hosp /ID# 139234
🇨🇳Taipei City, Taiwan
National Taiwan Univ Hosp /ID# 141443
🇨🇳Taipei City, Taipei, Taiwan
Ankara Numune Training and Res /ID# 139237
🇹🇷Ankara, Turkey
Warrington + Halton Hosp NHS /ID# 139195
🇬🇧Warrington, United Kingdom
Arthritis Northwest, PLLC /ID# 138539
🇺🇸Spokane, Washington, United States
Trinity Universal Research Association /ID# 148649
🇺🇸Plano, Texas, United States
Arthritis Assoc of NW Ohio /ID# 140953
🇺🇸Toledo, Ohio, United States
Baylor College of Medicine /ID# 138682
🇺🇸Houston, Texas, United States
Trinity Universal Res Assoc /ID# 149271
🇺🇸Carrollton, Texas, United States
Arthritis & Osteoporosis Clinic /ID# 138703
🇺🇸Waco, Texas, United States
Revmatologie, s.r.o. /ID# 138899
🇨🇿Brno, Czechia
Inland Rheum Clin Trials Inc. /ID# 138853
🇺🇸Upland, California, United States
Covina Arthritis Clinic /ID# 139881
🇺🇸Covina, California, United States
The Center for Rheumatology /ID# 138746
🇺🇸Albany, New York, United States
PMG Research of Salisbury /ID# 141023
🇺🇸Salisbury, North Carolina, United States
Arth and Osteo Clin Brazo Valley /ID# 147809
🇺🇸College Station, Texas, United States
Klinicki bolnicki centar Rijeka /ID# 138649
🇭🇷Rijeka, Primorsko-goranska Zupanija, Croatia
Groupe de Recherche en Maladies Osseuses /ID# 138906
🇨🇦Sainte-foy, Quebec, Canada
Dr. Latha Naik /ID# 139089
🇨🇦Saskatoon, Saskatchewan, Canada
Center of Clinical and Basic Research /ID# 141116
🇪🇪Tallinn, Harjumaa, Estonia
Artroscan s.r.o. /ID# 138833
🇨🇿Ostrava, Czechia
Helsinki Univ Central Hospital /ID# 140381
🇫🇮Helsinki, Finland
Welcker, Planegg, DE /ID# 140467
🇩🇪Planegg, Germany
Revita Reumatologiai Rendelo /ID# 140761
🇭🇺Budapest, Hungary
Fejer Megyei Szent Gyorgy Korh /ID# 138554
🇭🇺Szekesfehervar, Hungary
Chonnam National University Hospital /ID# 138651
🇰🇷Gwangju, Jeonranamdo, Korea, Republic of
NZOZ Nasz Lekarz /ID# 138374
🇵🇱Toruń, Kujawsko-pomorskie, Poland
Centro Hospitalar Lisboa Ocidental, EPE /ID# 140594
🇵🇹Lisbon, Lisboa, Portugal
Osteo-Medic spolka cywilna /ID# 138371
🇵🇱Białystok, Podlaskie, Poland
Spitalul Municipal Ploiesti /ID# 138405
🇷🇴Ploiesti, Romania
Republican Clin Hos n.a. Baran /ID# 139273
🇷🇺Petrozavodsk, Russian Federation
Voronezh State Medical Univers /ID# 148431
🇷🇺Voronezh, Russian Federation
Hospital Regional de Malaga /ID# 138975
🇪🇸Málaga, Malaga, Spain
Arthritis Clinical Research Tr /ID# 138945
🇿🇦Cape Town, Western Cape, South Africa
Hospital General Univ de Elche /ID# 138991
🇪🇸Elche, Spain
National Cheng Kung University Hospital /ID# 140868
🇨🇳Tainan City, Tainan, Taiwan
MNCE "Lviv City Clinical Hospital #4" /ID# 139873
🇺🇦Lviv, Ukraine
Western General Hospital /ID# 139524
🇬🇧Edinburgh, United Kingdom
The Royal Free Hospital /ID# 139191
🇬🇧London, London, City Of, United Kingdom
Hosp Nuestra Senora Esperanza /ID# 138997
🇪🇸Santiago de Compostela, Spain
LLC Revmocentr /ID# 139872
🇺🇦Kyiv, Ukraine
Southampton General Hospital /ID# 139169
🇬🇧Southampton, United Kingdom
China Medical University Hosp /ID# 139232
🇨🇳Taichung City, Taichung, Taiwan
Whipps Cross Univ Hospital /ID# 139523
🇬🇧London, London, City Of, United Kingdom
AZ Arthritis and Rheum Assoc /ID# 148651
🇺🇸Mesa, Arizona, United States
University of Arizona Cancer Center - North Campus /ID# 140451
🇺🇸Tucson, Arizona, United States
Institute of Arthritis Res /ID# 138548
🇺🇸Idaho Falls, Idaho, United States
AZ Arthritis and Rheum Researc /ID# 138500
🇺🇸Phoenix, Arizona, United States
AZ Arthritis and Rheum Researc /ID# 139286
🇺🇸Phoenix, Arizona, United States
AZ Arthritis & Rheuma Research /ID# 138598
🇺🇸Phoenix, Arizona, United States
Ctr Arthritis & Rheumatic Dise /ID# 141696
🇺🇸Miami, Florida, United States
Medallion Clinical Research Institute, LLC /ID# 140074
🇺🇸Naples, Florida, United States
Arthritis Center, Inc. /ID# 141363
🇺🇸Palm Harbor, Florida, United States
Physician Res. Collaboration /ID# 138533
🇺🇸Lincoln, Nebraska, United States
MMP Women's Health /ID# 141542
🇺🇸Portland, Maine, United States
Justus J. Fiechtner, MD, PC /ID# 138697
🇺🇸Lansing, Michigan, United States
Westroads Clinical Research /ID# 138304
🇺🇸Omaha, Nebraska, United States
Mansfield Health Center /ID# 141357
🇺🇸Mansfield, Massachusetts, United States
Advanced Rheumatology, PC /ID# 140071
🇺🇸Lansing, Michigan, United States
Rheuma Zentrum Favoriten GmbH /ID# 138787
🇦🇹Vienna, Austria
Emeritus Research /ID# 138773
🇦🇺Camberwell, Victoria, Australia
Rhumaconsult SPRL /ID# 138813
🇧🇪Charleroi, Hainaut, Belgium
UZ Gent /ID# 138806
🇧🇪Gent, Oost-Vlaanderen, Belgium
University Clinical Centre of the Republic of Srpska /ID# 138819
🇧🇦Banja Luka, Republika Srpska, Bosnia and Herzegovina
Eastern Health /ID# 140431
🇨🇦St. John's, Newfoundland and Labrador, Canada
CHRU Tours - Hopital Trousseau /ID# 138969
🇫🇷Chambray Les Tours, France
University General Hospital of Heraklion "PA.G.N.I" /ID# 139115
🇬🇷Heraklion, Greece
Inha University Hospital /ID# 149310
🇰🇷Incheon, Gwang Yeogsi, Korea, Republic of
Chungnam National University Hospital /ID# 138653
🇰🇷Daejeon, Korea, Republic of
LTD M+M Centers /ID# 138818
🇱🇻Adazi, Latvia
Seoul National University Hospital /ID# 138659
🇰🇷Seoul, Korea, Republic of
Asan Medical Center /ID# 140579
🇰🇷Seoul, Korea, Republic of
Ajou University Hospital /ID# 149311
🇰🇷Suwon-si, Gyeonggido, Korea, Republic of
Cath Univ Seoul St Mary's Hosp /ID# 138652
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Daegu Catholic University Med /ID# 139249
🇰🇷Daegu, Korea, Republic of
Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 138841
🇲🇽Mexico City, Mexico
Porter Rheumatology Ltd /ID# 138347
🇳🇿Nelson, New Zealand
Rheuma Medicus /ID# 138372
🇵🇱Warsaw, Poland
Instituto Portugues De Reumatologia /ID# 148315
🇵🇹Lisbon, Lisboa, Portugal
Spitalul Clinic Judetean de Urgenta /ID# 138407
🇷🇴Cluj, Romania
Spitalul Clinic Judetean de Ur /ID# 138393
🇷🇴Sibiu, Romania
LLC Novaya Klinika /ID# 139269
🇷🇺Pyatigorsk, Stavropol Skiy Kray, Russian Federation
Kazan State Medical University /ID# 138413
🇷🇺Kazan, Tatarstan, Respublika, Russian Federation
Narodny ustav reumatickych chorob Piestany /ID# 138427
🇸🇰Pieštany, Slovakia
Ulyanovsk Regional Clin Hosp /ID# 139279
🇷🇺Ulyanovsk, Russian Federation
ARTROMAC n.o. /ID# 138428
🇸🇰Kosice, Slovakia
Winelands Medical Research Ctr /ID# 138944
🇿🇦Stellenbosch, Western Cape, South Africa
Omega Research Consultants /ID# 139877
🇺🇸Orlando, Florida, United States
Tekton Research, Inc. /ID# 141428
🇺🇸Austin, Texas, United States
Bluegrass Community Research /ID# 138295
🇺🇸Lexington, Kentucky, United States
The Center for Rheumatology & /ID# 139203
🇺🇸Wheaton, Maryland, United States
Western Washington Arthritis C /ID# 138728
🇺🇸Bothell, Washington, United States
University Clinical Centre of the Republic of Srpska /ID# 140372
🇧🇦Banja Luka, Republika Srpska, Bosnia and Herzegovina
Leicester Royal Infirmary /ID# 139184
🇬🇧Leicester, England, United Kingdom
Prince of Wales Hospital /ID# 139314
🇭🇰Sha Tin, Hong Kong