A Study of Tocilizumab as Monotherapy and in Combination With Methotrexate Versus Methotrexate in Patients With Early Moderate to Severe Rheumatoid Arthritis
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT01007435
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This randomized, double-blind, parallel group study will assess the safety, disease remission, and prevention of structural joint damage in patients with early moderate to severe rheumatoid arthritis treated with tocilizumab as monotherapy or in combination with methotrexate, versus methotrexate alone. Patients will be randomized to receive either (A) tocilizumab (8 mg/kg iv every 4 weeks) plus placebo, (B) tocilizumab (8 mg/kg iv every 4 weeks) plus methotrexate (7.5-20 mg po weekly), (C) tocilizumab (4 mg/kg iv every 4 weeks) plus methotrexate (7.5-20 mg po weekly), or (D) placebo plus methotrexate (7.5-20 mg po weekly). Patients in groups C and D who have not achieved low disease activity at week 52 can receive tocilizumab 8 mg/kg iv every 4 weeks. Anticipated time on study treatment is 104 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1162
- Adult patients ≥ 18 years of age.
- Rheumatoid arthritis of ≤ 2 years duration.
- Disease Activity Score 28 (DAS28) > 3.2.
- Swollen joint count (SJC) ≥ 4 of 66 joints, tender joint count (TJC) ≥ 6 of 68 joints.
- Rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) positive (if RF and anti-CCP negative > 1 erosion required at screening).
- Erythrocyte sedimentation rate (ESR) ≥ 28 mm/h or C-reactive protein (CRP) ≥ 10 mg/L at screening.
- Previous treatment with tocilizumab.
- Previous treatment with methotrexate or biologic agent.
- Rheumatic autoimmune disease other than rheumatoid arthritis (RA).
- History of or current inflammatory joint disease other than RA.
- Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in RA.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description (A) Tocilizumab 8 mg/kg + placebo to methotrexate Tocilizumab Patients received tocilizumab 8 mg/kg iv every 4 weeks + placebo to methotrexate orally once a week for 104 weeks. (A) Tocilizumab 8 mg/kg + placebo to methotrexate Placebo to methotrexate Patients received tocilizumab 8 mg/kg iv every 4 weeks + placebo to methotrexate orally once a week for 104 weeks. (B) Tocilizumab 8 mg/kg + methotrexate Tocilizumab Patients received tocilizumab 8 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks. (C) Tocilizumab 4 mg/kg + methotrexate Tocilizumab Patients received tocilizumab 4 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks. (C) Tocilizumab 4 mg/kg + methotrexate Methotrexate Patients received tocilizumab 4 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks. (D) Placebo to tocilizumab + methotrexate Placebo to tocilizumab Patients received placebo tocilizumab intravenously (iv) every 4 weeks + methotrexate orally once a week for 104 weeks. (B) Tocilizumab 8 mg/kg + methotrexate Methotrexate Patients received tocilizumab 8 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks. (D) Placebo to tocilizumab + methotrexate Methotrexate Patients received placebo tocilizumab intravenously (iv) every 4 weeks + methotrexate orally once a week for 104 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 24 Week 24 A participant has a DAS28 remission response if their DAS28 \< 2.6. The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 52 Week 52 Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 Baseline to Weeks 24 and 52 Improvement must be seen in tender (68) and swollen (66) joint counts. Joints were assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation. Improvement must also be seen in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line "no disease activity" \[symptom-free and no arthritis symptoms\] and the extreme right end "maximum disease activity"; patient assessment of pain in previous the 24 hours on a VAS (extreme left end of the line "no pain" and the extreme right end "unbearable pain"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C-reactive protein (CRP), or erythrocyte sedimentation rate if CRP was missing.
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52 Baseline to Week 52 The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint, including subluxation, is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement.
Change From Baseline in Modified Sharp Erosion Score at Week 52 Baseline to Week 52 Change From Baseline in Sharp Joint Space Narrowing Score at Week 52 Baseline to Week 52 Percentage of Participants With a Major Clinical Response at Week 52 Baseline to Week 52 A major clinical response is defined as an ACR70 response that is maintained for 6 consecutive months (24 weeks) for any 24-week period between Week 2 and Week 52.
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52 Baseline to Weeks 24 and 52 The Stanford HAQ-DI is a patient completed questionnaire specific for rheumatoid arthritis. The HAQ-DI assesses how well the patient is able to perform 8 activities: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The patient answers 20 questions with 1 of 4 responses with the past week as the time frame: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The highest score for any question in a category determines the category score. The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.
Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52 Baseline to Weeks 24 and 52 The SF-36 Health Survey (Version 2) is a standardized questionnaire consisting of 36 questions that measures patient-reported symptoms on 8 dimensions; it is used to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100. A positive change score indicates better HRQoL.
Trial Locations
- Locations (236)
Wenatchee Valley Hospital & Clinics
🇺🇸Wenatchee, Washington, United States
Royal Prince Alfred Hospital; Rheumatology
🇦🇺Camperdown, New South Wales, Australia
Ohio State University; Dept of Immunology
🇺🇸Columbus, Ohio, United States
Kaiser Franz Josef Spital; Ii. Medizinische Abt.
🇦🇹Wien, Austria
Unidad De Enfermedades; Cronico Degenerativas, SC.
🇲🇽Mexico, Mexico
Cork Uni Hospital; Dept of Rheumatology
🇮🇪Cork, Ireland
Joao Nascimento
🇺🇸Bridgeport, Connecticut, United States
Policlinico Umberto I - Universita' La Sapienza ; Cattedra Di Reumatologia - Dept. Terapia Medica
🇮🇹Roma, Lazio, Italy
Rheumapraxis an der Hase
🇩🇪Osnabrück, Germany
Pinnacle Research Group; Llc, Central
🇺🇸Anniston, Alabama, United States
Laiko General Hospital; Hematology Clinic
🇬🇷Athens, Greece
The Third Affiliated Hospital of Sun Yat-Sen University
🇨🇳Guangzhou, China
Hopital Porte Madeleine; Service de Rhumatologie
🇫🇷Orleans, France
Institut de Rhumatologie de Montreal
🇨🇦Montreal, Quebec, Canada
Klinik der Uni zu Köln; Klinik für Innere Medizin
🇩🇪Köln, Germany
Saskatoon Osteoporosis Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Dres. Florian Schuch, Ruediger de la Camp, Martin Hammerschmidt u.w.
🇩🇪Erlangen, Germany
Riesgo De Fractura; Rheumatology
🇨🇴Bogota, Colombia
Helsinki University Central Hospital; Rheumatology Clinic
🇫🇮Helsinki, Finland
St. Joseph'S Health Care Centre; Rheumatology
🇨🇦London, Ontario, Canada
Hopital emile muller; Rhumatologie
🇫🇷Mulhouse, France
Nexus Clinical Research Centre
🇨🇦St John's, Newfoundland and Labrador, Canada
Kerckhoff-Klinik; Rheumatologie&klin.Immunologie
🇩🇪Bad Nauheim, Germany
Hospital Pablo Tobon Uribe
🇨🇴Medellin-Antioquia, Colombia
Dr. William G. Bensen Medicine Professional Corporation
🇨🇦Hamilton, Ontario, Canada
Niagara Peninsula Arthritis Centre
🇨🇦St. Catharines, Ontario, Canada
Rheuma-Zentrum Baden-Baden Gmbh; Klinik Für Innere Medizin-Rheumatologie
🇩🇪Baden-Baden, Germany
Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III
🇩🇪Dresden, Germany
Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel
🇲🇽Mexicali, Mexico
St.Vincent's University Hospital; Rheumatology Department
🇮🇪Dublin, Ireland
University General Hospital of Larissa; Rheumatology Unit
🇬🇷Larissa, Greece
Markhot Ferenc Hospital; Dep. of Rheumatology
🇭🇺Eger, Hungary
K-W Musculoskeletal Research
🇨🇦Kitchener, Ontario, Canada
CH Jean Rougier; Rhumato Reed Fonctionnelle
🇫🇷Cahors, France
Hopital Maisonneuve- Rosemont; Rheumatology
🇨🇦Montreal, Quebec, Canada
Sunshine Coast Rheumatology Research Unit
🇦🇺Maroochydore, Queensland, Australia
China-Japan Friendship Hospital
🇨🇳Beijing, China
Campus Charité Mitte Charité Centrum 12. Med.Klinik Abt.Rheumatologie u.Klin.Immunologie
🇩🇪Berlin, Germany
Fondation Hopital Saint Joseph; Rhumatologie
🇫🇷Marseille, France
Hopital Purpan; Rhumatologie
🇫🇷Toulouse, France
Reumalab Sas; Rheumatology
🇨🇴Medellin, Colombia
ASST FATEBENEFRATELLI SACCO; Reumatologia (Sacco)
🇮🇹Milano, Lombardia, Italy
Rheumapraxis PD Dr.med. Bernhard Heilig
🇩🇪Heidelberg, Germany
Hopital Lapeyronie; Immunologie Rhumatologie
🇫🇷Montpellier, France
Centre de Recherche Musculo-Squelettique
🇨🇦Trois-rivieres, Quebec, Canada
Barzilai; Rheumatology
🇮🇱Ashkelon, Israel
Gemeinschaftspraxis Dr. Von Hinueber/Dr. Demary; Rheumatologie
🇩🇪Hildesheim, Germany
Debreceni Egyetem Orvos- és Egészségtudományi Centrum; Belgyógyászati Intézet, Reumatológiai Tanszék
🇭🇺Debrecen, Hungary
Haemek Hospital; Rheumatology
🇮🇱Afula, Israel
Cliditer SA de CV
🇲🇽Miexico City, Mexico
Centro de Infusion Marbella; Consultorios Royal Center Num 214
🇵🇦Panama City, Panama
Adelaide and Meath Hospital; Rheumatology Department
🇮🇪Dublin, Ireland
Hospital Universitario de la Princesa; Servicio de Reumatologia
🇪🇸Madrid, Spain
Ryazan State Medical University Named after I.P.Pavlov
🇷🇺Ryazan, Russian Federation
St Augustines Hospital; Rheumatology
🇿🇦Durban, South Africa
Clinical Research Unit
🇿🇦Pretoria, South Africa
Bnei Zion Medical Center; Rheumatology
🇮🇱Haifa, Israel
Chaim Sheba Medical Center; Interna Dept B
🇮🇱Ramat-Gan, Israel
Clinic of Rheumatology; Clinical Centre Skopje
🇲🇰Skopje, Macedonia, The Former Yugoslav Republic of
Private Practice
🇬🇹Guatemala City, Guatemala
Ospedale S. Giovanni Bosco; S.C. A Direzione Uni Ria Di Immunologia Clinica
🇮🇹Torino, Piemonte, Italy
Netcare Private Hospital
🇿🇦Bloemfontein, South Africa
Chaim Sheba Medical Center; Rheumatology
🇮🇱Ramat Gan, Israel
Greenacres Hospital
🇿🇦Port Elizabeth, South Africa
Hadassah University Hospital, Ein Karem; Rheumatology
🇮🇱Jerusalem, Israel
FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences
🇷🇺Moscow, Russian Federation
Budai Irgalmasrendi Kórház KHT. II. Reumatológia
🇭🇺Budapest, Hungary
Hospital Universitario Reina Sofia; Servicio de Reumatologia
🇪🇸Cordoba, Spain
Hadassah Mount Scopus Hospital; Rheumatology
🇮🇱Jerusalem, Israel
Royal Hallamshire Hospital; Rheumatology
🇬🇧Sheffield, United Kingdom
Hospital Infanta Sofia; Servicio de Reumatologia
🇪🇸San Sebastian de los Reyes, Madrid, Spain
Unidad de Enfermedades Reumaticas y Cronicodegenerativas
🇲🇽Torreon, Mexico
Hospital General Universitario de Guadalajara; Servicio de Reumatologia
🇪🇸Guadalajara, Spain
Abk Reuma Srl- Medicentro
🇵🇪Lima, Peru
Szpital Specjalistyczny Nr 1; Oddzial Reumatologii I Rehabilitacji
🇵🇱Bytom, Poland
SBIH of Moscow "City Clinical Hospital #20 of Moscow Healthcare Department"
🇷🇺Moscow, Russian Federation
Karolinska University Hospital, Huddinge; Rheumatology
🇸🇪Huddinge, Sweden
Winelands Research Centre
🇿🇦Stellenbosch, South Africa
Trafford General Hospital; Rheumatology
🇬🇧Manchester, United Kingdom
Arrowe Park Hospital; Rheumatology Dept
🇬🇧Wirral, United Kingdom
Waikato Hospital; Rheumatology Outpatients
🇳🇿Hamilton, New Zealand
Timaru Hospital
🇳🇿Timaru, New Zealand
Haywood Hospital; Staffordshire Rheumatology Centre
🇬🇧Stoke-on-trent, United Kingdom
State Institution of Healthcare of Tula Region "Tula Regional Clinical Hospital"
🇷🇺Tula, Russian Federation
Hospital Univ. Nuestra Señora de Valme; Servicio de Reumatologia
🇪🇸Sevilla, Spain
Medyczne Centrum Hetmanska; Indywidualna Specjalistyczna Praktyka Lekarska
🇵🇱Poznan, Poland
Maidstone Hospital; Dept of Rheumatology
🇬🇧Maidstone, United Kingdom
Iu Cerrahpasa Tip Fakultesi Ic Hastaliklari Anabilim Dali; Romatoloji Bilim Dali
🇹🇷Istanbul, Turkey
Hospital Universitario Virgen del Rocio; Servicio de Reumatologia
🇪🇸Sevilla, Spain
Russells Hall Hospital; Rheumatology Department
🇬🇧Dudley, United Kingdom
Hospital Univ. Central de Asturias; Servicio de Reumatologia
🇪🇸Oviedo, Asturias, Spain
HUC; Servico de Reumatologia
🇵🇹Coimbra, Portugal
Addenbrooke'S Hospital; Rheumatology Research Unit
🇬🇧Cambridge, United Kingdom
Royal Derby Hospital
🇬🇧Derby, United Kingdom
Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)
🇲🇽Culiacán Rosales, Sinaloa, Mexico
Sjællands Universitetshospital, Køge; Reumatologisk Afdeling
🇩🇰Køge, Denmark
General Hospital of Chinese PLA; Department of Hematology
🇨🇳Beijing, China
Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, China
Karolinska Sjukhuset; Reumatologkliniken D2-1
🇸🇪Stockholm, Sweden
Arcispedale Santa Maria Nuova; Reumatologia
🇮🇹Reggio Emilia, Emilia-Romagna, Italy
Ospedale Di Magenta Fornaroli; U.O. Di Reumatologia
🇮🇹Magenta, Lombardia, Italy
San Diego Arthritis Med Clnc
🇺🇸San Diego, California, United States
Denver Arthritis Clinic
🇺🇸Denver, Colorado, United States
Park Nicollet Inst. ; Rtrc
🇺🇸Minneapolis, Minnesota, United States
Durham Rheumatology
🇺🇸Durham, North Carolina, United States
Health Research of Oklahoma, Llc
🇺🇸Oklahoma City, Oklahoma, United States
Oklahoma Medical Research Foundation
🇺🇸Oklahoma City, Oklahoma, United States
Houston Inst. For Clinical Research
🇺🇸Houston, Texas, United States
Texas Arthritis Research Center; Center for Arthritis & Rheumatic Diseases
🇺🇸San Antonio, Texas, United States
Royal Victoria Infirmary; Clinical Research Facility
🇬🇧Newcastle Upon Tyne, United Kingdom
North Tyneside General Hospital
🇬🇧North Shields, United Kingdom
Ch Pitie Salpetriere; Rhumatologie
🇫🇷Paris, France
Centre Re Recherche Saint-Louis
🇨🇦Quebec, Canada
Rheumazentrum-Ruhrgebiet, St. Josefs-Krankenhaus; Rheumatologie
🇩🇪Herne, Germany
Schlosspark Klinik; Abt. Rheumatologie
🇩🇪Berlin, Germany
Klinikum der Universität München; Bereich Pettenkoferstr.; Rheumaeinheit der medizinischen Klinik IV
🇩🇪München, Germany
State institution of healthcare "Regional hospital for war veterans"
🇷🇺Saratov, Russian Federation
State Institution of Healthcare of Yaroslavl Region Clinical Hospital #8
🇷🇺Yaroslavl, Russian Federation
Meir Medical Center; Internal Dept A
🇮🇱Kfar Saba, Israel
Burnette & Silverfield, MDS
🇺🇸Tampa, Florida, United States
Rheumatology Associates of North Alabama
🇺🇸Huntsville, Alabama, United States
Arthrocare, Arthritis Care and Research, P.C.
🇺🇸Mesa, Arizona, United States
Clnical & Translational Reseach Center for Alabama, PC
🇺🇸Tuscaloosa, Alabama, United States
Sharp Rees-Stealy Medical Group
🇺🇸San Diego, California, United States
Uni of California - San Diego; Division of Rheumatology
🇺🇸La Jolla, California, United States
Talbert Medical Group
🇺🇸Huntington Beach, California, United States
Sun Valley Arthritis Center
🇺🇸Peoria, Arizona, United States
Valerius Medical Group & Research Ctr of Greater Long Beach
🇺🇸Los Alamitos, California, United States
Arthritis/Osteoporosis Treatment Center
🇺🇸Orange Park, Florida, United States
Arthritis Center Palm Harbor
🇺🇸Palm Harbor, Florida, United States
New England Research Associates
🇺🇸Trumbull, Connecticut, United States
Arthritis Rsrch of Florida, Inc.
🇺🇸Palm Harbor, Florida, United States
Illinois Bone & Joint Inst.
🇺🇸Morton Grove, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Deerbrook Medical Associates
🇺🇸Vernon Hills, Illinois, United States
Quad City Rheumatology, Sc
🇺🇸Moline, Illinois, United States
Via Christi Clinic, PA
🇺🇸Wichita, Kansas, United States
Physician'S Clinic of Iowa
🇺🇸Cedar Rapids, Iowa, United States
Baton Rouge Clinic, Amc
🇺🇸Baton Rouge, Louisiana, United States
Fiechtner Research Inc
🇺🇸Lansing, Michigan, United States
Harbor Arthritis Center
🇺🇸Petoskey, Michigan, United States
Osteoporosis & Clinical Trials Center
🇺🇸Cumberland, Maryland, United States
Borgess Rheumatology
🇺🇸Kalamazoo, Michigan, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Jackson Arthritis Clinic
🇺🇸Flowood, Mississippi, United States
Mark Fisher Md, Facr, Llc
🇺🇸Haddon Heights, New Jersey, United States
NJP Clinical Research
🇺🇸Clifton, New Jersey, United States
North Mississippi Medical Ctr; Internal Medicine Associates
🇺🇸Tupelo, Mississippi, United States
Dartmouth-Hitchcock Medical Center, Rheumatology 5C
🇺🇸Lebanon, New Hampshire, United States
Depaul Medical Group-SSM Healthcare
🇺🇸Florissant, Missouri, United States
Arthritis Health Associates; Clinical Research
🇺🇸Syracuse, New York, United States
Arthritis and Osteoporosis Associates of New Mexico
🇺🇸Las Cruces, New Mexico, United States
Southwest Rheumatology & Research Group, LLC
🇺🇸Middleburg Heights, Ohio, United States
Asheville Arthritis & Osteoporosis Center, PA
🇺🇸Asheville, North Carolina, United States
Healthcare Research Consultants
🇺🇸Tulsa, Oklahoma, United States
East Penn Rheumatology Associates, Pc
🇺🇸Bethlehem, Pennsylvania, United States
Altoona Center For Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Piedmont Arthritis Clinic
🇺🇸Greenville, South Carolina, United States
Clinical Research Center of Reading
🇺🇸Wyomissing, Pennsylvania, United States
Amarillo Center For Clinical Research
🇺🇸Amarillo, Texas, United States
Arthritis & Osteoporosis Associates, LLP
🇺🇸Lubbock, Texas, United States
Accurate Clinical Research
🇺🇸Houston, Texas, United States
Texas Research Center
🇺🇸Sugar Land, Texas, United States
Arthritis & Osteoporosis Clinic
🇺🇸Waco, Texas, United States
Arthritis Northwest, Spokane
🇺🇸Spokane, Washington, United States
Tacoma Center For Arthritis Research
🇺🇸Tacoma, Washington, United States
Rheumatic Disease Center
🇺🇸Glendale, Wisconsin, United States
Inst. de Rehabilitacion Psicofisica; Reumathology
🇦🇷Buenos Aires, Argentina
Caici; Rheumatology
🇦🇷Rosario, Argentina
Centro Medico Privado de Reumatologia; Reumathology
🇦🇷San Miguel, Argentina
Organizacion Medica de Investigacion
🇦🇷Buenos Aires, Argentina
Cabrini Medical Centre; Rheumatology
🇦🇺Malvern, Victoria, Australia
Queen Elizabeth Hospital; Rheumatology
🇦🇺Woodville, South Australia, Australia
Menzies Research Institute
🇦🇺Hobart, Tasmania, Australia
Worthing Hospital
🇦🇺Murdoch, Western Australia, Australia
Lkh innsbruck - univ. Klinikum innsbruck - Tiroler landeskrankenanstalten ges.m.b.h.; Innere Medizin
🇦🇹Innsbruck, Austria
Krankenhaus der stadt wien hietzing; ii. Med. Abt. / zentrum für rheumatologie
🇦🇹Wien, Austria
Hospital das Clinicas - UFG;Reumatologia
🇧🇷Goiania, GO, Brazil
Centro Internacional de Pesquisa; Reumatologia
🇧🇷Goiania, GO, Brazil
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, RS, Brazil
Centro Mineiro de Pesquisa - CMIP
🇧🇷Juiz de Fora, MG, Brazil
Centro de Estudos em Terapias Inovadoras - CETI
🇧🇷Curtiba, PR, Brazil
Hospital e Maternidade Celso Pierro - PUCCamp; Reumatologia
🇧🇷Campinas, SP, Brazil
Universidade Federal de Sao Paulo - UNIFESP; Reumatologia
🇧🇷Sao Paulo, SP, Brazil
Arthritis Research Centre
🇨🇦Vancouver, British Columbia, Canada
Centro Paulista de Investigacao Clinica - CEPIC
🇧🇷Sao Paulo, SP, Brazil
Laurel Medical Clinic
🇨🇦Vancouver, British Columbia, Canada
Manitoba Clinic
🇨🇦Winnipeg, Manitoba, Canada
Rheumatology Research Associates
🇨🇦Ottawa, Ontario, Canada
Evangelisches Fachkrankenhaus; Rheumaklinik
🇩🇪Ratingen, Germany
Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Rheumatologie/Immunologie
🇩🇪Würzburg, Germany
Clinica Medica Del Dr Eduardo Alfredo Samayoa
🇬🇹Guatemala City, Guatemala
Tuen Mun Hospital; Medicine & Geriatrics
🇭🇰Tuen Mun, Hong Kong
Campus Bio-Medico; Immunologia e Allergologia
🇮🇹Roma, Lazio, Italy
Policlinico Universitario; Cattedra Di Reumatologia, Edificio 3
🇮🇹Napoli, Campania, Italy
Policlinico Universitario Di Cagliari
🇮🇹Monserrato, Sardegna, Italy
Centro de Estudios de Investigacion Basica Y Clinica S.C.; Reumatologia
🇲🇽Guadalajara, Mexico
North Shore Hospital, STAR Unit; Rheumatology Department
🇳🇿Auckland, New Zealand
Hospital de Sao Joao; Servico de Reumatologia
🇵🇹Porto, Portugal
Ponce School of Medicine; Caimed Center
🇵🇷Ponce, Puerto Rico
Municipal Autonomous Institution of Healthcare "City Clinical Hospital #40"
🇷🇺Ekaterinburg, Russian Federation
SBIH of Moscow "City clinical hospital #1 n.a. N.I. Pirogov" of Moscow Healthcare Department
🇷🇺Moscow, Russian Federation
FSBI "FSCC of particularized sorts of medical care and medical technologies of FMBA"
🇷🇺Moscow, Russian Federation
Budget Institution of Healthcare of Voronezh Region "Voronezh Regional Clinical Hospital #1"
🇷🇺Voronezh, Russian Federation
SBEI of HPE "Northwestern State Medical University n.a. I.I.Mechnikov" of MoH of RF
🇷🇺Saint-Petersburg, Russian Federation
Ramathibodi Hospital, Mahidol Uni ; Allergy, Immunology & Rheumatology, Dept of Medicine
🇹🇭Bangkok, Thailand
Phramongkutklao Hospital; Dept. of Medicine, Rheumatology
🇹🇭Bangkok, Thailand
Cannock Chase Hospital; Rheumatology
🇬🇧Cannock, United Kingdom
Torbay Hospital; Dept of Rhematology
🇬🇧Torquay, United Kingdom
Reuma-Centro
🇬🇹Guatemala City, Guatemala
Centro de Investigación Clínica de Morelia, S.C.; Reumatologia
🇲🇽Morelia, Mexico
Jose Reyes Memorial Medical Center
🇵🇭Manila, Philippines
Wojewodzki Szpital Zespolony; Oddzial Reumatologii
🇵🇱Elblag, Poland
Klinika Reumatologii I Chorób Wewn. Pum W Szczecinie; Samodzielny Publiczny Szpital Kliniczny Nr 1
🇵🇱Szczecin, Poland
Università Degli Studi Di Genova - Dimi; Reumatologia
🇮🇹Genova, Liguria, Italy
Hospital Universitario de Saltillo
🇲🇽Saltillo, Mexico
Philippine General Hospital; Rheumatology
🇵🇭Manila, Philippines
Kiljavan Lääketutkimus Oy
🇫🇮Hyvinkää, Finland
Hospital de Santa Maria; Servico de Reumatologia
🇵🇹Lisboa, Portugal
Hospital de Merida ;Servicio de Reumatologia
🇪🇸Merida, Badajoz, Spain
Chulalongkorn Hospital; Division of Rheumatology - Medicine
🇹🇭Bangkok, Thailand
Centro especializado de rehabilitacion fisica y del dolor cerfid - unidad de inv. En reumatologia
🇵🇪Lima, Peru
Centro de Investigaciones Medicas/Hospital Maria Auxiliadora
🇵🇪San Juan de Miraflores, Peru
Uni of Santo Tomas Hospital; Rheumatology
🇵🇭Manila, Philippines
NZOZ REUMED Sp. z o.o.
🇵🇱Lublin, Poland
Instytut Reumatologii im. Prof. Dr hab. Eleonory Reicher; Oddzial Wczesnej Diagnostyki Stawow
🇵🇱Warszawa, Poland
National University Hospital; Dept of Medicine
🇸🇬Singapore, Singapore
Songklanagarind Hospital; Department of Internal Medicine, Division of Rheumatology
🇹🇭Songkhla, Thailand
Albuquerque Center For Rheumatology
🇺🇸Albuquerque, New Mexico, United States
Schön Klinik Hamburg-Eilbek Klinik für Rheumatologie
🇩🇪Hamburg, Germany
Istituto Ortopedico Rizzoli; Unità di Reumatologia
🇮🇹Bologna, Emilia-Romagna, Italy
FSBI "National medico-surgical Centre n.a. N.I. Pirogov" of the Ministry of Healthcare
🇷🇺Moscow, Russian Federation
Hospital Universitario Marques de Valdecilla; Servicio de Reumatologia
🇪🇸Santander, Cantabria, Spain
Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Reumatologia
🇪🇸Las Palmas de Gran Canaria, Las Palmas, Spain
QUEEN MARY HOSPITAL; Division of Rheumatology & Clinical Immunology
🇭🇰Hong Kong, Hong Kong
Pamela Youde Nethersole Eastern Hospital; Department of Medicine
🇭🇰Hong Kong, Hong Kong