A Study of Tocilizumab in Comparison to Etanercept in Participants With Rheumatoid Arthritis and Cardiovascular Disease Risk Factors
- Registration Number
- NCT01331837
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This randomized, open-label, parallel-group, multicenter study will evaluate the rate of cardiovascular events with tocilizumab in comparison to etanercept in participants with rheumatoid arthritis (RA). Participants will be randomized to receive intravenous (IV) 8 milligrams per kilogram (mg/kg) tocilizumab every 4 weeks or subcutaneous 50 milligrams (mg) etanercept weekly, with or without non-biologic disease-modifying anti-rheumatic drug (DMARD).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3080
- Participants with moderate to severe RA of greater than or equal to (>=6) months duration
- Inadequate response to at least one non-biologic DMARD
- Positive for Rheumatoid Factor (RF) and/or anti-cyclic citrullinated peptide (CCP) antibodies at screening
- Have C-reactive protein (CRP) greater than (>) 0.3 milligrams per deciliter (mg/dL) at screening or at the baseline visit
- Swollen joint count (SJC) >=8 (66 joint count) and tender joint count (TJC) >= 8 (68 joint count) during screening or at the baseline visit
- History of Coronary Heart Disease (CHD) or presence of one or more additional CHD risk factors, including current cigarette smoking, hypertension, low High Density Lipoprotein (HDL) cholesterol, family history of premature CHD, diabetes, presence of extra-articular disease associated with rheumatoid arthritis
- At the time of randomization, will have discontinued infliximab, adalimumab, golimumab, or certolizumab for >= 4 weeks
- Major surgery (including joint surgery or coronary revascularization) within 8 weeks prior to screening or planned major surgery within 1 year of study start
- Rheumatic autoimmune disease other than RA
- History of or current inflammatory joint disease other than RA
- Current or recent (within past 3 months) evidence of serious uncontrolled concomitant cardiovascular or cerebrovascular disease (myocardial infarction, revascularization, stroke, transient ischemic attack, or acute coronary syndrome)
- Current or previous (within the past 2 years) evidence of serious uncontrolled concomitant pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or gastrointestinal disease
- Uncontrolled disease states, such as asthma or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
- Pre-existing central nervous system demyelinating or seizure disorders
- History of diverticulitis, diverticulosis requiring treatment or other lower gastrointestinal tract conditions that might predispose to perforations
- Current liver disease as determined by the investigator; a history of asymptomatic elevations in liver function tests (LFTs) is not considered an exclusion
- Active current infection or history of recurrent bacterial, viral, fungal, mycobacterial or other infections, including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds
- Any major episode of infection requiring hospitalization or treatment with IV antibiotics within four weeks of screening or oral antibiotics within two weeks prior to screening visit
- Active tuberculosis (TB) requiring treatment within 3 years prior to baseline
- Latent TB diagnosed during screening that has not been appropriately treated
- Primary or secondary immunodeficiency (history of or currently active)
- Moderate to severe heart failure
- Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including hematologic malignancies and solid tumors, except basal cell carcinoma of the skin that has been excised and cured), or breast cancer diagnosed within the previous 20 years
- Breast feeding mothers
- History of alcohol, drug or chemical abuse within the 6 months prior to screening
- Participants with lack of peripheral venous access
- Participants with a history of allergic reactions to latex
- Previous treatment with non-tumor necrosis factor (non-TNF)-inhibitor biologic therapy
- Treatment with any investigational agent within 4 weeks of screening visit
- Treatment with any cell depleting therapies within 1 year of baseline
- Treatment with IV gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline visit
- Immunization with a live/attenuated vaccine within 4 weeks prior to baseline visit
- Any previous treatment with alkylating agents, such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tocilizumab Tocilizumab - Etanercept Etanercept -
- Primary Outcome Measures
Name Time Method Time to First CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis From baseline up to 4.9 years Prospective comparison of time to first occurrence of any component of the composite of CV death (excluding events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analyses
Percentage of Patients Reporting a Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event From baseline up to 4.9 years Percentage of patients reporting any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke
Time to First CV-EAC Adjudicated Event - Sensitivity Analysis From Baseline up to 4.9 years Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analysis
Time to First CV-EAC Adjudicated Event Before Last Direct Contact Date From Baseline up to 4.9 years Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke before last direct contact date (i.e., latest date of visit, IVRS call, or site call).
Percentage of Participants With a CV-EAC Adjudicated Event Before Last Direct Contact Date From Baseline up to 4.9 years Percentage of participants with any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke before last direct contact date (i.e., latest date of visit, IVRS call, or site call).
Time to First Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event From baseline up to 4.9 years Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke.
Percentage of Patients With a CV-EAC Adjudicated Event - Sensitivity Analysis From Baseline up to 4.9 years Percentage of patients with any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analysis
Percentage of Patients With a CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis From baseline up to 4.9 years Percentage of patients with any component of the composite of CV death (excluding events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analyses
- Secondary Outcome Measures
Name Time Method The Time to First Occurrence of an Expanded CV Composite Endpoint From baseline up to 4.9 years Prospective comparison of the time to first ccurrence of the expanded composite endpoint. The expanded composite endpoint is defined as the CV composite of the primary endpoint with the addition of non-elective coronary revascularization procedures and hospitalization for unstable angina.
Percentages of Participants With an Expanded CV Composite Endpoint From baseline up to 4.9 years Percentages of participants with the expanded CV composite endpoint. The expanded composite endpoint is defined as the CV composite of the primary endpoint with the addition of non-elective coronary revascularization procedures and hospitalization for unstable angina.
Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction From baseline up to 4.9 years Prospective comparison of time to first occurrence of Individual component of primary endpoint: non-fatal Myocardial Infarction
Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction From baseline up to 4.9 years Percentage of patients reporting Individual component of primary endpoint: non-fatal Myocardial Infarction
Time to First Occurrence of Individual Component of Primary Endpoint: Cardiovascular Death From baseline up to 4.9 years Prospective comparison of time to first occurrence of Individual component of primary endpoint: cardiovascular death
Percentage of Patients With Individual Component of Primary Endpoint: Cardiovascular Death From baseline up to 4.9 years Percentage of patients reporting Individual component of primary endpoint: cardiovascular death
Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Stroke From baseline up to 4.9 years Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Stroke From baseline up to 4.9 years Prospective comparison of time to first occurrence of Individual component of primary endpoint: non-fatal stroke
Time to First Occurrence of Individual Component of Primary Endpoint: All-cause Mortality From baseline up to 4.9 years Prospective comparison of time to first occurrence of Individual component of primary endpoint: All-cause mortality
Percentage of Patients With Individual Component of Primary Endpoint: All-cause Mortality From baseline up to 4.9 years Percentage of patients reporting Individual component of primary endpoint: All-cause mortality
Trial Locations
- Locations (426)
Emory Uni ; Division of Rheumatology
🇺🇸Atlanta, Georgia, United States
Apex Medical Research, AMR, Inc.
🇺🇸Chicago, Illinois, United States
Columbus Arthritis Center
🇺🇸Columbus, Ohio, United States
University of Pittsburgh Medical Center Health System; Infectious Disease
🇺🇸Pittsburgh, Pennsylvania, United States
Clinical Center Bezanijska Kosa
🇷🇸Belgrade, Serbia
Hospital Privado Cordoba
🇦🇷Cordoba Pcia, Argentina
Fundación CIDEA
🇦🇷Buenos Aires, Argentina
Atencion Integral En Reumatologia Buenos Aires
🇦🇷Buenos Aires, Argentina
Krankenhaus Hietzing; 2.Med.Abteilung, Pav.3A
🇦🇹Wien, Austria
Clinica Alemana de Temuco
🇨🇱Temuco, Chile
Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza
🇭🇺Gyula, Hungary
Varosi Korhaz-Rendelointezet
🇭🇺Mor, Hungary
Fejer Megyei Szent Gyorgy Korhaz
🇭🇺Szekesfehervar, Hungary
The Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
L.Krumina GP practice
🇱🇻Bauska, Latvia
Hospital Pulau Pinang
🇲🇾Penang, Malaysia
Sime Darby Medical Centre
🇲🇾Selangor, Malaysia
Clinica Hospital Angeles Chapalita
🇲🇽Guadalajara, Mexico
Hospital Universitario de Saltillo
🇲🇽Saltillo, Mexico
Spitalul Clinic de Recuperare Iasi
🇷🇴Iasi, Romania
State institution of health care - Territorial Clinical Hospital
🇷🇺Barnaul, Russian Federation
City Hospital No.4
🇷🇺Moscow, Russian Federation
Spitalul Judetean de Urgenta Targoviste
🇷🇴Targoviste, Romania
Pharmax Research Clinic Inc.
🇺🇸Miami, Florida, United States
Advanced Biomedical Research of America
🇺🇸Las Vegas, Nevada, United States
Houston Inst. For Clinical Research
🇺🇸Houston, Texas, United States
Seattle Rheumatology Associates
🇺🇸Seattle, Washington, United States
Texas Arthritis Research Center
🇺🇸San Antonio, Texas, United States
Selah Medical Ctr
🇺🇸Boise, Idaho, United States
Rheumatology Associates of North Alabama
🇺🇸Huntsville, Alabama, United States
Clinical and Translational Research Center of Alabama, PC
🇺🇸Tuscaloosa, Alabama, United States
Arizona Arthritis & Rheumatology Associates, P.C.
🇺🇸Glendale, Arizona, United States
Arizona Arthritis & Rheumatology Research, Pllc
🇺🇸Paradise Valley, Arizona, United States
Advanced Arthritis Care & Research
🇺🇸Scottsdale, Arizona, United States
Camp Lowell Medical Specialists
🇺🇸Tucson, Arizona, United States
NEA Baptist Clinic
🇺🇸Jonesboro, Arkansas, United States
Allergy & Rheumatology Medical Clinic, Inc
🇺🇸La Jolla, California, United States
Samy Metyas, MD, Inc
🇺🇸Covina, California, United States
Talbert Medical Group
🇺🇸Huntington Beach, California, United States
Valerius Medical Group
🇺🇸Los Alamitos, California, United States
Dr. Brigid Freyne, MD
🇺🇸Murrieta, California, United States
Sharp Rees-Stealy Medical Group
🇺🇸Poway, California, United States
Purushotham & Akther Kotha Inc
🇺🇸San Diego, California, United States
San Diego Arthritis Med Clnc
🇺🇸San Diego, California, United States
Pacific Arthritis Ctr Med Grp
🇺🇸Santa Maria, California, United States
Orrin M. Troum, Md
🇺🇸Santa Monica, California, United States
Inland Rheumatology; Clinical Trials, Inc.
🇺🇸Upland, California, United States
Harbor UCLA Medical Center
🇺🇸Torrance, California, United States
Medvin Clinical Research
🇺🇸Whittier, California, United States
Arthritis Assoc & Osteoporosis; Ctr of Colorado Springs
🇺🇸Colorado Springs, Colorado, United States
University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
Joao Nascimento
🇺🇸Bridgeport, Connecticut, United States
ZASA Clinical Research
🇺🇸Boynton Beach, Florida, United States
Arthritis & Osteoporosis Center Pc
🇺🇸Hamden, Connecticut, United States
DC Health Clinic
🇺🇸Coral Gables, Florida, United States
Tsai, Yong
🇺🇸Daytona Beach, Florida, United States
Jacksonville Center For Clinical Research
🇺🇸Jacksonville, Florida, United States
Arthritis/Osteoporosis Treatment Center
🇺🇸Orange Park, Florida, United States
Arthritis Rsrch of Florida, Inc.
🇺🇸Palm Harbor, Florida, United States
Baptist Hospital Clinical Research
🇺🇸Pensacola, Florida, United States
Pinellas Medical Research, LLC
🇺🇸Saint Petersburg, Florida, United States
Lovelace Scientific Resources
🇺🇸Sarasota, Florida, United States
Centre for Arthritis and Rheumatic Diseases
🇺🇸South Miami, Florida, United States
Sonora Clinical Research
🇺🇸Boise, Idaho, United States
North Georgia Rheumatology
🇺🇸Duluth, Georgia, United States
Harbin Clinic
🇺🇸Rome, Georgia, United States
St. Joseph'S/Candler Health System, Inc.; Office of Research
🇺🇸Savannah, Georgia, United States
St. Luke's Intermountain Research Center
🇺🇸Boise, Idaho, United States
Idaho Arthritis Center
🇺🇸Meridian, Idaho, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
Methodist Medical Center of Ilinois
🇺🇸Peoria, Illinois, United States
Northern Indiana Research Alliance
🇺🇸Fort Wayne, Indiana, United States
Diagnostic Rheumatology & Research
🇺🇸Indianapolis, Indiana, United States
Graves Gilbert Clinic
🇺🇸Bowling Green, Kentucky, United States
Memorial Medical Group Clinical Research
🇺🇸South Bend, Indiana, United States
Research Integrity
🇺🇸Owensboro, Kentucky, United States
Arthritis & Diabetes Clinic, Inc
🇺🇸Monroe, Louisiana, United States
Rheumatology Associates of Baltimore
🇺🇸Baltimore, Maryland, United States
Osteoporosis & Clinical Trials Center
🇺🇸Hagerstown, Maryland, United States
Center For Rheumatology & Bone Research
🇺🇸Wheaton, Maryland, United States
Phase Iii Clinical Research
🇺🇸Fall River, Massachusetts, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Clinical Pharmacology Study Group
🇺🇸Worcester, Massachusetts, United States
Rheumatology, P.C.; Medical Arts Building
🇺🇸Kalamazoo, Michigan, United States
Hurley Research Center
🇺🇸Flint, Michigan, United States
Advanced Rheumatology, PC
🇺🇸Lansing, Michigan, United States
Northern Michigan Regional Hospital
🇺🇸Petoskey, Michigan, United States
St. Paul Rheumatology
🇺🇸Eagan, Minnesota, United States
Va Medical Center
🇺🇸Minneapolis, Minnesota, United States
Jackson Arthritis Clinic
🇺🇸Flowood, Mississippi, United States
Glacier View Research Institute
🇺🇸Kalispell, Montana, United States
Innovative Health Research
🇺🇸Las Vegas, Nevada, United States
Dartmouth-Hitchcock Medical Center, Rheumatology 5C
🇺🇸Lebanon, New Hampshire, United States
Rheumatology Associates Of New Jersey
🇺🇸Teaneck, New Jersey, United States
Nashua Rheumatology - Foundation Medical Partners
🇺🇸Nashua, New Hampshire, United States
Summit Medical Group
🇺🇸Berkeley Heights, New Jersey, United States
Arthritis Rheumatic & Back Disease Associates
🇺🇸Voorhees, New Jersey, United States
SUNY Downstate Medical Center.
🇺🇸Brooklyn, New York, United States
Albuquerque Center For Rheumatology
🇺🇸Albuquerque, New Mexico, United States
Arthritis and Osteoporosis Associates of New Mexico
🇺🇸Las Cruces, New Mexico, United States
Arthritis & Osteoporosis Medical Associates, Pllc
🇺🇸Brooklyn, New York, United States
Joint & Muscle Research Institute
🇺🇸Charlotte, North Carolina, United States
Arthritis Health Associates; Clinical Research
🇺🇸Syracuse, New York, United States
DiGiovanna Inst for Med Ed&Res
🇺🇸North Massapequa, New York, United States
Southern Tier Arthritis & Rheumatism
🇺🇸Olean, New York, United States
Asheville Arthritis & Osteoporosis Center, PA
🇺🇸Asheville, North Carolina, United States
Carolina Bone & Joint P.A.
🇺🇸Charlotte, North Carolina, United States
Shanahan Rheumatology & Immunology, PLLC
🇺🇸Raleigh, North Carolina, United States
PMG Research of Hickory LLC
🇺🇸Hickory, North Carolina, United States
Durham Rheumatology
🇺🇸Durham, North Carolina, United States
Carolina Arthritis Associates, Pa
🇺🇸Wilmington, North Carolina, United States
Specialty Medical Clinic and Research Center
🇺🇸Sanford, North Carolina, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Cincinnati Rheumatic Disease Study Group
🇺🇸Cincinnati, Ohio, United States
Ohio State Univ Med Center
🇺🇸Columbus, Ohio, United States
Clinical Research Source, Inc.
🇺🇸Toledo, Ohio, United States
Toledo Clinic
🇺🇸Toledo, Ohio, United States
Altoona Center For Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Ilumina Clinical Associates
🇺🇸Indiana, Pennsylvania, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Sentara Medical Group
🇺🇸Norfolk, Virginia, United States
Arthritis & Osteoporosis Clinic
🇺🇸Waco, Texas, United States
Rheum & Pulmonary Clinic
🇺🇸Beckley, West Virginia, United States
St. Joseph's Hospital
🇨🇦London, Ontario, Canada
Credit Valley, Rheumatology
🇨🇦Mississauga, Ontario, Canada
Centre de Recherche Musculo-Squelettique
🇨🇦Trois-rivieres, Quebec, Canada
Clinical Hospital Centre Zagreb
🇭🇷Zagreb, Croatia
Vilnius District Central Outpatient Clinic, Public Institution
🇱🇹Vilnius, Lithuania
Hospital Raja Permaisuri Bainun
🇲🇾Ipoh, Perak, Malaysia
Wojewodzki Szpital Zespolony w Elblagu
🇵🇱Elblag, Poland
Lecznica MAK-MED NZOZ
🇵🇱Nadarzyn, Poland
CMI Dr.Ciornohuz Adriana
🇷🇴Iasi, Romania
Spitalul Municipal Ploiesti
🇷🇴Ploiesti, Romania
Spitalul Clinic Colentina
🇷🇴Sector 2, Romania
Mediab SRL
🇷🇴Targu Mures, Romania
SEI of HPE "Altay State Medical University of Roszdrav"
🇷🇺Barnaul, Russian Federation
Spitalul Clinic Municipal de Urgenta Timisoara
🇷🇴Timisoara, Romania
SIH Kemerovo Regional Clinical Hospital
🇷🇺Kemerovo, Russian Federation
Head Clinical Hospital of Internal Affair Ministry of Russia
🇷🇺Moscow, Russian Federation
FSBI Scientific Research Institute of Clinical Immunology of SB of RAMS
🇷🇺Novosibirsk, Russian Federation
Hospital Infanta Sofia; Servicio de Reumatologia
🇪🇸San Sebastian de los Reyes, Madrid, Spain
Leicester Royal Infirmary NHS Trust
🇬🇧Leicester, United Kingdom
Royal Victoria Infirmary
🇬🇧Newcastle upon Tyne, United Kingdom
Trinity Health Center
🇺🇸Minot, North Dakota, United States
C Michael Neuwelt MD Inc
🇺🇸San Leandro, California, United States
Uni Of Alabama,Birmingham; Medicine - Rheumatology
🇺🇸Birmingham, Alabama, United States
Valley Arthritis Care
🇺🇸Phoenix, Arizona, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States
Russells Hall Hospital; Rheumatology Department
🇬🇧Dudley, United Kingdom
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
SW Florida Clinical Research
🇺🇸Tampa, Florida, United States
Healthpoint Medical group, Inc
🇺🇸Tampa, Florida, United States
Clinical Interventions Research Institute
🇺🇸Mission Viejo, California, United States
Arthritis & Rheumatology of Georgia
🇺🇸Atlanta, Georgia, United States
Ramesh Gupta - PP
🇺🇸Memphis, Tennessee, United States
Rheumatic Disease Clin Res Ctr
🇺🇸Houston, Texas, United States
South Carolina Research Center
🇺🇸Myrtle Beach, South Carolina, United States
Columbia Arthritis Center (Partnership Practice)
🇺🇸Columbia, South Carolina, United States
Pennsylvania Regional Center for Arthritis and Osteoporosis Research
🇺🇸Wyomissing, Pennsylvania, United States
Southwest Rheumatology
🇺🇸Mesquite, Texas, United States
Pivotal Clinical Research, Llc
🇺🇸Perkasie, Pennsylvania, United States
Instituto centenario
🇦🇷Buenos Aires, Argentina
Arthritis Group
🇺🇸Philadelphia, Pennsylvania, United States
Arthritis Centre; Suite 103
🇺🇸Racine, Wisconsin, United States
Mountain State Clinical Research
🇺🇸Clarksburg, West Virginia, United States
PMA Medical Specialists
🇺🇸Limerick, Pennsylvania, United States
CEMIC
🇦🇷Buenos Aires, Argentina
Amarillo Center For Clinical Research
🇺🇸Amarillo, Texas, United States
Allegheny Rheumatology
🇺🇸Wexford, Pennsylvania, United States
Office of George Krick, Md
🇺🇸Tacoma, Washington, United States
Clinical Research Center of Reading
🇺🇸Wyomissing, Pennsylvania, United States
Adriana Pop-Moody MD Clinic PA
🇺🇸Corpus Christi, Texas, United States
Metroplex Clinical Research
🇺🇸Dallas, Texas, United States
Brown Clinic
🇺🇸Watertown, South Dakota, United States
Arthritis and Rheumatic Disease Associates
🇺🇸Burke, Virginia, United States
Apex Clinical Research
🇺🇸Kennewick, Washington, United States
Organizacion Medica de Investigacion
🇦🇷Buenos Aires, Argentina
CEIM Consultorios Especializados en Investigaciones Médicas
🇦🇷Buenos Aires, Argentina
APRILLUS
🇦🇷Buenos Aires, Argentina
Centro de Investigaciones Reumatologicas y Osteologicas
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Sanatorio Parque de Rosario
🇦🇷Rosario, Argentina
CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
🇦🇷San Juan, Argentina
Medizinische Universität Wien
🇦🇹Wien, Austria
CHU St Pierre (St Pierre)
🇧🇪Brussels, Belgium
ZNA Jan Palfijn
🇧🇪Merksem, Belgium
Hospital General de Agudos Dr. J. M. Ramos Mejia
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Instituto Reumatológico Strusberg
🇦🇷Cordoba, Argentina
Hospital Italiano de Cordoba
🇦🇷Cordoba, Argentina
Centro de Investigaciones Médicas - CIM
🇦🇷Florencio Varela, Argentina
Hospital Municipal Nuestra Sra. de Lujan
🇦🇷Lujan, Argentina
Centro de Investigacion Pergamino SA
🇦🇷Pergamino, Argentina
Instituto Centralizado de Asistencia e Investigaci
🇦🇷Rosario, Santa Fe, Argentina
Centro Médico Privado de Reumatología
🇦🇷San Miguel de Tucuman, Argentina
Lkh-Univ. Klinikum Graz
🇦🇹Graz, Austria
Landesklinikum Weinviertel Stockerau; Rheumatologie
🇦🇹Stockerau, Austria
Rheuma-Zentrum Favoriten Wien
🇦🇹Wien, Austria
Royal Alexandra Hospital
🇨🇦Edmonton, Alberta, Canada
Arthur Karasik, MD
🇨🇦Etobicoke, Ontario, Canada
Revmatologicka ambulance
🇨🇿Praha 4, Czechia
Revmatologicka Ambulance
🇨🇿Hlucin, Czechia
Revmatologicka Ambulance-Terezin
🇨🇿Terezin, Czechia
Fakultni nemocnice u sv. Anny v Brne
🇨🇿Brno, Czechia
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium
The Medical Arts Health Research Group
🇨🇦Powell River, British Columbia, Canada
Mount Sinai Hospital
🇨🇦Toronto, Ontario, Canada
Nexus Clinical Research Centre
🇨🇦St John's, Newfoundland and Labrador, Canada
Niagara Peninsula Arthritis Centre
🇨🇦St. Catharines, Ontario, Canada
AZ Groeninge (Vercruysselaan)
🇧🇪Kortrijk, Belgium
CHU Sart-Tilman
🇧🇪Liège, Belgium
Hospital Clinico Pontificia Universidad Catolica de Chile
🇨🇱Santiago, Chile
St. Clare'S Mercy Hospital
🇨🇦St John's, Newfoundland and Labrador, Canada
Charlton Medical Center
🇨🇦Hamilton, Ontario, Canada
K-W Musculoskeletal Research
🇨🇦Kitchener, Ontario, Canada
University Clinical Center of the Republic of Srpska
🇧🇦Banja Luka, Bosnia and Herzegovina
Uni Hospital Center Tuzla
🇧🇦Tuzla, Bosnia and Herzegovina
Institut de Rhumatologie de Montreal
🇨🇦Montreal, Quebec, Canada
Hospital San Juan de Dios La Serena
🇨🇱La Serena, Chile
Interin
🇨🇱Santiago, Chile
Centre Re Recherche Saint-Louis
🇨🇦Quebec, Canada
Chus Hopital Fleurimont
🇨🇦Sherbrooke, Quebec, Canada
Groupe de Recherche En Rhumatologie Et Maladies Osseuses
🇨🇦Quebec City, Quebec, Canada
Centro Medico Prosalud
🇨🇱Santiago, Chile
Centro de Estudios Reumatológicos
🇨🇱Santiago, Chile
Centro de Investigacion Clinica del Sur
🇨🇱Temuco, Chile
Revmatologie MUDr. Klara Sirova s.r.o.
🇨🇿Ostrava - Moravska Ostrava, Czechia
Hospital Clinico Viña del Mar- Oncovida
🇨🇱Viña del Mar, Chile
Centro de Estudios Clinicos V Region Limitada
🇨🇱Viña del Mar, Chile
Clinical Hospital Centre Rijeka; Department of Rheumatology and Clinical Immunology
🇭🇷Rijeka, Croatia
Artroscan s.r.o.
🇨🇿Sokolov, Czechia
General Hospital Karlovac
🇭🇷Karlovac, Croatia
Special Hospital for Medical Rehabilitation
🇭🇷Krapinske Toplice, Croatia
Universtiy Hospital Dubrava
🇭🇷Zagreb, Croatia
PV - Medical, s.r.o.
🇨🇿Zlin, Czechia
Revmatologicky Ustav
🇨🇿Praha, Czechia
Interni a revmatologicka ordinace
🇨🇿Hostivice, Czechia
Revmatologicka a-interni ambulance
🇨🇿Kladno, Czechia
Schlosspark-Klinik
🇩🇪Berlin, Germany
CHU d'Amiens Hôpital Nord; Pharmacie Clinique
🇫🇷Amiens, France
Hospital Clínica Santa Inés
🇪🇨Cuenca, Ecuador
Centro de Reumatología y Rehabilitación
🇪🇨Guayaquil, Ecuador
OMNI Hospital
🇪🇨Guayaquil, Ecuador
Centro Medico Alcivar 4
🇪🇨Guayaquil, Ecuador
Centro Medico Picasso
🇪🇨Quito, Ecuador
Novaclinica Santa Cecilia; Reumatology
🇪🇨Quito, Ecuador
Ospedale Di Circolo E Fondazione Macchi
🇮🇹Varese, Lombardia, Italy
Groupe Hospitalier Pellegrin
🇫🇷Bordeaux, France
CHU Grenoble Sud
🇫🇷Echirolles, France
CHR Orleans, Hopital Madeleine
🇫🇷Orléans, France
Hôpital Sud - CHU de Rennes
🇫🇷Rennes, France
Hôpital Victor Provo
🇫🇷Roubaix, France
CHU de Rouen, Hopital de Bois Guillaume; Service de Rhumatologie
🇫🇷Rouen, France
CHU Saint-Etienne, Hopital Bellevue
🇫🇷Saint-Etienne, France
Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
🇩🇪Dresden, Germany
Hôpital Edouard Herriot; Service de Rhumatologie
🇫🇷Lyon, France
Laiko General Hospital Athen
🇬🇷Athens, Greece
Euroclinic of Athens; Internal Medicine & Immunology Dept.
🇬🇷Athens, Greece
University General Hospital of Larissa; Rheumatology Unit
🇬🇷Larissa, Greece
Clinfan Szolgaltato Kft.
🇭🇺Szekszard, Hungary
Manipal Hospital
🇮🇳Bangalore, India
St.John's Medical College Hospital
🇮🇳Banglore, India
Arthritis Super Speciality Centre
🇮🇳Hubli, India
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Chaim Sheba Medical Center; Rheumatology
🇮🇱Ramat Gan, Israel
CHU Hopital Gabriel Montpied
🇫🇷Clermont Ferrand, France
Centre Hospitalier Sud Francilien
🇫🇷Corbeil Essonnes, France
Universitaetsklinikum Hamburg-Eppendorf; Medizinische Klinik Nephrologie/Rheumatologie
🇩🇪Hamburg, Germany
Universitaetsklinikum Frankfurt
🇩🇪Frankfurt, Germany
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris, France
Hopital Cochin; Gastro Enterologie
🇫🇷Paris, France
Universitätsklinikum Erlangen; Augenklinik
🇩🇪Erlangen, Germany
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
Praxiszentrum St. Bonifatius
🇩🇪Muenchen, Germany
Schön Klinik Hamburg-Eilbek Klinik für Rheumatologie
🇩🇪Hamburg, Germany
Rheumatologische Gemeinschaftspraxis
🇩🇪Osnabrueck, Germany
Shalby Hospital Limited
🇮🇳Ahmedabad, Gujarat, India
Gemeinschaftspraxis Dr. Von Hinueber/Dr. Demary; Rheumatologie
🇩🇪Hildesheim, Germany
Rheumazentrum Ruhrgebiet; St. Josefs-Krankenhaus
🇩🇪Herne, Germany
Evangelisches Fachkrankenhaus
🇩🇪Ratingen, Germany
University General Hospital of Heraklion
🇬🇷Crete, Greece
Euromedica Kyanous Stavros General Hospital
🇬🇷Thessaloniki, Greece
424 Military Training Hospital-Egnatia
🇬🇷Thessaloniki, Greece
Zala Megyei Korhaz; Reumatologia
🇭🇺Zalaegerszeg, Hungary
Hôpital Saint-Antoine; Service de Psychiatrie
🇫🇷Paris, France
Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)
🇫🇷Toulouse, France
Hôpital General - CHRU de Dijon
🇫🇷Strasbourg, France
Charité Universitaetsmedizin Berlin, Campus Charité Mitte
🇩🇪Berlin, Germany
Ludwig Maximilians; Universitaet
🇩🇪München, Germany
Universitätsklinikum Köln, Klinik I für Innere Medizin
🇩🇪Koeln, Germany
Praxisgemeinschaft Rheumatologie-Nephrologie Erlangen PGRN
🇩🇪Erlangen, Germany
General Hospital of Thessaloniki Hippokration
🇬🇷Thessaloniki, Greece
Clinexpert Egeszsegugyi Szolgaltato es Kereskedelmi Kft
🇭🇺Budapest, Hungary
Országos Fizioterápiás És Reumatológiai Intézet; I. Reumatológiai És Metabolikus Osteológiai Osztály
🇭🇺Budapest, Hungary
Obudai Egeszsegugyi Centrum Kft.
🇭🇺Budapest, Hungary
Debreceni Egyetem, Klinikai Kozpont, Tudogyogyaszati Klinika
🇭🇺Debrecen, Hungary
Fondazione Salvatore Maugeri IRCCS; Istituto Scientifico di Riabilitazione di Telese
🇮🇹Telese Terme, Campania, Italy
Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
🇮🇹Milano, Lombardia, Italy
Presidio Ospedaliero Vittorio Emanuele
🇮🇹Catania, Sicilia, Italy
Ospedale Misericordia e Dolce
🇮🇹Prato, Toscana, Italy
Azienda Ospedaliera A. Cardarelli
🇮🇹Napoli, Campania, Italy
Vedanta Institute; Medical Sciences
🇮🇳Ahmedabad, India
Ospedale San Giovanni Bosco; Divisione di Reumatologia
🇮🇹Napoli, Campania, Italy
Ospedali Riuniti di Bergamo
🇮🇹Bergamo, Lombardia, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Toscana, Italy
Azienda Ospedaliero Universitaria San Martino
🇮🇹Genova, Liguria, Italy
Care Institute of Medical Sciences
🇮🇳Hyderabad, India
Jasleen Hospital
🇮🇳Nagpur, India
Tel-Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Daugavpils Regional Hospital
🇱🇻Daugavpils, Latvia
Alytus Regional S. Kudirkos Hospital, Public Institution
🇱🇹Alytus, Lithuania
D.Saulite-Kandevica Private Practice
🇱🇻Liepaja, Latvia
Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)
🇲🇽Culiacán Rosales, Sinaloa, Mexico
Clinic ORTO
🇱🇻Riga, Latvia
Private Practice EHOKG
🇱🇻Riga, Latvia
Riga East Clinical University Hospital; Clinic Gailezers
🇱🇻Riga, Latvia
P. Stradins Clinical University Hospital
🇱🇻Riga, Latvia
Klaipeda Seamen's Hospital, Public Institution
🇱🇹Klaipeda, Lithuania
Klaipeda University Hospital; Public Institution
🇱🇹Klaipeda, Lithuania
Hospital Selayang
🇲🇾Kuala Lumpur, Malaysia
Centro de Investigacion del Noroeste SC
🇲🇽Tijuana, Baja California, Mexico
Hospital Umum Sarawak
🇲🇾Kuching, Malaysia
Unidad de Atencion Medica e Investigacion en Salud S.C.
🇲🇽Mérida, Yucatan, Mexico
Hospital CIMA Chihuahua; Reumatologia
🇲🇽Chihuahua, Mexico
Hospital Privado San Jose de Ciudad Obregon SA de CV
🇲🇽Ciudad Obregon, Mexico
Private Practice Dr. Cortes
🇲🇽Cuernavaca, Mexico
RM pharma specialist SA de CV
🇲🇽Delegacion Benito Juarez, Mexico
Mentrials S.A. de C.V
🇲🇽Distrito Federal, Mexico
Centro de Investigacion y Atencion Integral Durango CIAID
🇲🇽Durango, Mexico
Mundo Fisico
🇲🇽Guadalajara, Mexico
Centro de Investigacion en Enfermedades Reumaticas y Osteoporosis
🇲🇽Mexicali, Mexico
Inst. Mexicano de Investigacion Clinica
🇲🇽Mexico City, Mexico
Instituto Nacional de Cardiologia Ignacio Chavez
🇲🇽Mexico City, Mexico
Mexico Centre for Clinical Research
🇲🇽Mexico, Mexico
Chong Hua Hospital, Cebu City
🇵🇭Cebu City, Philippines
Szpital Uniwersytecki; nr 2 im. Dr J. Biziela
🇵🇱Bydgoszcz, Poland
Albert Schweitzer Ziekenhuis ; Dordwijk
🇳🇱Dordrecht, Netherlands
Cebu Doctors' University Hospital- North General Hospital
🇵🇭Cebu City, Philippines
St. Paul Hospital; Arthritis Center
🇵🇭Iloilo City, Philippines
Hospital Mocel
🇲🇽Mexico Df, Mexico
Cliditer SA de CV
🇲🇽Miexico City, Mexico
Jan Van Breemen Instituut
🇳🇱Amsterdam, Netherlands
Mary Mediatrix Medical Center
🇵🇭Lipa City, Philippines
Makati Medical Center
🇵🇭Makati City, Philippines
Comite Mexicano Para la Prevencion de Osteoporosis AC
🇲🇽Mexico, Mexico
Vlietland Hospital
🇳🇱Schiedam, Netherlands
Unidad de Enfermedades Reumaticas y Cronicodegenerativas
🇲🇽Torreon, Mexico
Franciscus Ziekenhuis
🇳🇱Roosendaal, Netherlands
NZOZ REUMED Sp. z o.o.
🇵🇱Lublin, Poland
Slaski Szpital Reumatologiczno; Rehabilitacyjny; Iii Oddzial Reumatologiczny
🇵🇱Ustron, Poland
ARS Rheumatica Sp.z o. o
🇵🇱Warszawa, Poland
Rheuma Medicus Zaklad Opieki Zdrowotnej
🇵🇱Warszawa, Poland
Akademicki Szpital Kliniczny im. Jana Mikulicza Radeckiego
🇵🇱Wroclaw, Poland
Spitalul Clinic Dr. I Cantacuzino
🇷🇴Bucharest, Romania
Spitalul Clinic Sf. Maria; Dept Interna si Reumatologie
🇷🇴Bucuresti, Romania
Centrul de Boli Reumatismale Dr. Ioan Stoia
🇷🇴Bucuresti, Romania
Medex SRL
🇷🇴Cluj-Napoca, Romania
Spitalul Clinic Judetean de Urgenta Cluj-Napoca, Clinica de Medicina Muncii
🇷🇴Cluj-Napoca, Romania
Scient Res Inst Rheumat RAMS
🇷🇺Moscow, Russian Federation
Moscow State Medical Stomatological University
🇷🇺Moscow, Russian Federation
Chris Hani Baragwanath Hospital; Rheumatology Department
🇿🇦Diepkloof, South Africa
Charlotte Maxeke Academic Hospital
🇿🇦Johannesburg, South Africa
University of Pretoria; Clinical Trial Unit
🇿🇦Pretoria, South Africa
MHI City Clinical Hospital#19
🇷🇺Novosibirsk, Russian Federation
Ryazan Regional Clinincal Cardiology Dispensary
🇷🇺Ryazan, Russian Federation
State institution of healthcare "Regional hospital for war veterans"
🇷🇺Saratov, Russian Federation
Leningradskaya Regional Clinical Hospital; Rheumatology Dept
🇷🇺St Petersburg, Russian Federation
Stavropol State Medical Academy
🇷🇺Stavropol, Russian Federation
Tomsk Regional Clinical Hospital
🇷🇺Tomsk, Russian Federation
Voronezh Regional Clinical Hospital #1
🇷🇺Voronezh, Russian Federation
Hospital Universitario de Canarias
🇪🇸S. Cristobal de la Laguna, Tenerife, Spain
Corporacio Sanitaria Parc Tauli
🇪🇸Sabadell, Barcelona, Spain
Hospital Sierrallana
🇪🇸Torrelavega, Cantabria, Spain
Hospital Regional Universitario Carlos Haya
🇪🇸Málaga, Malaga, Spain
Military Medical Academy
🇷🇸Belgrade, Serbia
Groote Schuur Hospital; Rheumatology Unit
🇿🇦Cape Town, South Africa
MCHI Medical Sanitary Unit of Yaroslavl Diesel Apparatus Plant
🇷🇺Yaroslavl, Russian Federation
Institute of Rheumatology
🇷🇸Belgrade, Serbia
Hospital de Merida ;Servicio de Reumatologia
🇪🇸Merida, Badajoz, Spain
Hospital Universitario Virgen Macarena
🇪🇸Seville, Sevilla, Spain
Hospital Gregorio Marañon
🇪🇸Madrid, Spain
Hospital de Cruces; Servicio de Reumatologia
🇪🇸Barakaldo, Vizcaya, Spain
Wrightington Hospital
🇬🇧Wrightington, United Kingdom
Trakya University Medical Faculty
🇹🇷Edirne, Turkey
King'S College Hospital
🇬🇧London, United Kingdom
Hospital General de Castellon; Servicio de Reumatologia
🇪🇸Castellon, Spain
Hospital Universitario Basurto
🇪🇸Bilbao, Vizcaya, Spain
Selly Oak Hospital; Rheumatology Dept
🇬🇧Birmingham, United Kingdom
Addenbrooke's NHS Trust
🇬🇧Cambridge, United Kingdom
Cannock Chase Hospital; Rheumatology
🇬🇧Cannock, United Kingdom
Akdeniz Univesity Medical Faculty
🇹🇷Antalya, Turkey
Ataturk University Med Faculty
🇹🇷Erzurum, Turkey
Salford Royal NHS Foundation Trust
🇬🇧Salford, United Kingdom
Southampton General Hospital; Rheumatology
🇬🇧Southampton, United Kingdom
Southend Hospital; Rheumatology Department
🇬🇧Westcliffe-on-sea, United Kingdom
Karadeniz Tecnical Uni. Med. Fac.
🇹🇷Trabzon, Turkey
Royal London Hospital Outpatients Department
🇬🇧London, United Kingdom
Whipps Cross Hospital; Rheumatology Dept
🇬🇧London, United Kingdom
Fakultni Thomayerova nemocnice s poliklinikou
🇨🇿Praha, Czechia
Leading Edge Research, PA; Office of Dr. Burbano
🇺🇸Richardson, Texas, United States
Hospital Clinico Universitario de Santiago
🇪🇸Santiago de Compostela, La Coruña, Spain
The University of Arizona
🇺🇸Tucson, Arizona, United States
OrthoArkansas; Orthopedics & Sports Medicine
🇺🇸Little Rock, Arkansas, United States
Sun Valley Arthritis Center
🇺🇸Peoria, Arizona, United States
Coeur D'Alene Arthritis Clinic
🇺🇸Coeur d'Alene, Idaho, United States
North Mississippi Med Clinics, Inc.
🇺🇸Tupelo, Mississippi, United States
Univ of Nebraska Medical Ctr
🇺🇸Omaha, Nebraska, United States
Hospital Britanico de Buenos Aires
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Centro de Investigaciones Reumatologicas Tucuman
🇦🇷Tucuman, Argentina
General Hospital Prim.dr.Abdulah Nakas
🇧🇦Sarajevo, Bosnia and Herzegovina
University Clinic Ctr Sarajevo
🇧🇦Sarajevo, Bosnia and Herzegovina
Baker, Milton F.
🇨🇦Victoria, British Columbia, Canada
Markhot Ferenc Eu. Szolg. Nonprofit Kiem. Kozh. Kft.
🇭🇺Eger, Hungary
Synexus Magyarorszag Kft
🇭🇺Budapest, Hungary
Assaf Harofeh Medical Center
🇮🇱Beer Yaacov, Israel
Siauliai Republican Hospital Public Institution
🇱🇹Siauliai, Lithuania
Sunway Medical Centre
🇲🇾Selangor, Malaysia
Hospital Christus Muguerza del Parque; Reumatologia
🇲🇽Chihuahua, Mexico
Hospital Central Dr. Ignacio Morones Prieto
🇲🇽San Luis Potosi S.L.P., Mexico
Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.
🇲🇽San Luis Potosí, Mexico
Szpital Specjalistyczny Im J. Dietla Malopolskie Centrum Reumat; Oddzial Rumatologii
🇵🇱Krakow, Poland
Szpital Specjalistyczny im. J. Dietla
🇵🇱Krakow, Poland
SP Szpital Kliniczny nr 1 Pomorskiej Akademii Medycznej im. prof. Tadeusza Sokolowskiego
🇵🇱Szczecin, Poland
Spitalul Clinic Judetean de Urgenta Brasov
🇷🇴Brasov, Romania
Scientific and research medical complex Your Health
🇷🇺Kazan, Russian Federation
Institute of Rheumatology and Cardiovascular Diseases; Rheumatology
🇷🇸Niska Banja, Serbia
Ochsner Health System
🇺🇸New Orleans, Louisiana, United States
Ospedale La Colletta
🇮🇹Arenzano, Liguria, Italy