TO ASSESS THE EFFICACY AND SAFETY OF PF-06650833, PF-06651600, AND TOFACITINIB ALONE AND IN COMBINATION IN PARTICIPANTS WITH ACTIVE RHEUMATOID ARTHRITIS WITH AN INADEQUATE RESPONSE TO METHOTREXATE
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT04413617
- Lead Sponsor
- Pfizer
- Brief Summary
Dual objectives of increased efficacy compared to currently available SoC RA drugs and maintaining a favourable benefit - risk relationship.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 460
- Male or female participants between the ages of 18 and 70 years.
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- Diagnosis of RA and meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA with a Total Score ≥6/10.
- The participant has active disease at both Screening and Randomization, as defined by both: ≥6 joints tender or painful on motion, AND ≥6 joints swollen; and fulfills 1 of the following 2 criteria: High sensitivity C reactive protein (hsCRP) >7 mg/L at Screening (Visit 1) as performed by the central laboratory OR Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm h.
- Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
- Participants with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
- Participants with any active or latent infections.
- Participants with positive hepatitis B surface antigen (HBsAg).
- Participants with positive HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA).
- Any history of either untreated or inadequately treated latent or active tuberculosis (TB) infection, current treatment for active or latent TB infection or evidence of currently active TB,
- History of a major organ transplant (eg, heart, lung, kidney and liver) or hematopoietic stem cell/marrow transplant.
- History of severe allergic or anaphylactoid reaction to kinase inhibitors, or corticosteroid preparations.
- Known history of diverticulitis or symptomatic diverticulosis, perineal abscess or fistulae.
- Participants with malignancy or history of malignancy (including lymphoma, leukemia, or lymphoproliferative disease).
- Pre-existing chronic autoimmune disease (eg, inflammatory bowel disease, systemic lupus erythematosus, moderate-severe atopic dermatitis, dermatomyositis) other than RA. Secondary Sjogren's Syndrome (due to RA) may be included.
- Participants with fibromyalgia will be excluded.
- Previous treatment with total lymphoid irradiation.
- Participants with an oral, tympanic, or temporal temperature of 38°C (100.4°F) or higher at baseline.
- Participants may not receive any live/attenuated vaccine from 30 days prior to randomization during the course of the study, or for 30 days after the last dose of study medication. Participants who have current routine household contact with children who have received varicella or oral polio vaccine within 2 months of first study dose are also excluded.
- History of any lymphoproliferative disorder.
- Have hearing loss with progression over the previous 5 years, sudden hearing loss, or middle or inner ear disease.
- History of any prior deep vein thrombosis (DVT) or pulmonary embolism [PE].
- Recent (within 6 months of screening) myocardial infarction, coronary revascularization, or percutaneous angioplasty with or without placement of a coronary artery stent; acute coronary syndrome; chronic uncompensated heart failure or New York Heart Association Functional Class III or IV; left ventricular assist devices; implanted defibrillators.
- Current severe chronic renal insufficiency or renal failure as defined by persistent (on repeated measurements) eGFR <60 mL/min per 1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) calculation.
- Any known coagulopathy or hypercoagulant syndrome.
- Presence of any of the following laboratory abnormalities at screening or within the 3 months prior to first study dose:
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥1.5 x the upper limit of normal (ULN); Participants with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ≤ ULN and other liver function assessments are normal; Absolute neutrophil count of <1.5 x 109/L (<1500/mm3). Participants with cyclic (benign ethnic) neutropenia will be excluded; Absolute lymphocyte count of <0.5 x 109/L (<500/mm3); Absolute white blood cell (WBC) count of <3.0 x 109/L (<3000/mm3); Hemoglobin <9.0 g/dL (90 g/L); Platelet count ≤100 x 109/L (100,000 cells/mm3) or ≥1000 x 109/L (1,000,000 cells/mm3); Thrombocytopenia, as defined by a platelet count <100 x 109/L (<100,000/mm3) at screening visit or within the 3 months prior to first study dose. [Screening laboratory tests with abnormal results may be repeated once to confirm abnormal results. If results return to normal protocol acceptable limits within the 4-week screening period, the participant may enter the study].
- Grade 3 or greater laboratory abnormality based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 toxicity scale, except for the following that are allowed: Grade 3 prothrombin time (PT) secondary to warfarin treatment; Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy.
- Participants previously treated with a biologic DMARD (except for up to 25% of participants who may have been treated with 1, and only 1 prior TNF inhibitor) or any other recent DMARD treatment (eg, a JAK inhibitor), or participants currently treated with any other prohibited medications will be excluded.
- Prior use of tofacitinib or other JAK inhibitor in the context of a clinical trial is excluded. Concomitant use of tofacitinib (other than as prescribed by the randomization scheme) or other JAK inhibitor is prohibited.
- Participants who have previously been treated with other, non-TNFa inhibiting biologic DMARDs [including, abatacept (Orencia®), tocilizumab (Actemra®), Sarilumab (Kevzara®), anakinra (Kineret®), rituximab (Rituxan®) or other selective B lymphocyte depleting agents, or other lymphocyte depleting agents/therapies (such as alemtuzab [CamPath®], natalizumab (Tysabri®), alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation) are excluded from participation in the study.
- Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of IP used in this study (whichever is longer).
- Any 12-lead electrocardiogram (ECG) performed prior to randomization that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PF-06650833 + tofacitinib PF-06650833 - PF-06650833 + tofacitinib Tofacitinib - PF-06651600 PF-06651600 - Tofacitinib Tofacitinib - PF-06650833 + PF-06651600 PF-06650833 - PF-06650833 + PF-06651600 PF-06651600 - PF-06650833 PF-06650833 -
- Primary Outcome Measures
Name Time Method Change From Baseline (BL) in Disease Activity Score (DAS)28-C Reactive Protein (CRP) at Week 12 BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 12 DAS28 is a measure based on assessment of 28 joints for tenderness and swelling (tender and swollen joint counts). Disease Activity Score 28-C reactive protein (DAS28-CRP) is derived using differential weighting given to 4 components: tender joint count (range: 0-28), swollen joint count (range: 0-28), patient global assessment (recorded on a visual analog scale \[VAS\] scale of 0-100 mm), and CRP (milligram per liter). DAS28-CRP score ranges from 0 to 9.4. The lower the DAS28-CRP score is, the better the participant has response (remission = score\<2.6, low disease activity = score≤3.2). A negative value in change from BL indicates an improvement. Mixed Model Repeated Measures was used for statistical analysis, which used the change from BL of DAS28-CRP as an outcome and treatment, scheduled study visit, BL value of DAS28-CRP, treatment by visit interaction and BL by visit interaction as fixed effects. The model used the unstructured covariance matrix.
- Secondary Outcome Measures
Name Time Method DAS28-CRP Remission (<2.6) Rates at Week 24 Week 24 DAS28-CRP is derived using differential weighting given to 4 components: tender joint count, swollen joint count, patient global assessment, and CRP. Remission is defined as DAS28-CRP score \<2.6. Remission rate = the number of responders (who had remission) / (number of responders + non-responders + non-responder assigned by non-responder imputation \[NRI\] after removal of missingness due to COVID-19 and missing components at a given visit)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs), and Withdrawals Due to TEAEs From first dose of study intervention (Day 1) to Week 28 An adverse event (AE) was any untoward medical occurrence in a patient or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. TEAEs were events between first dose of study drug and up to follow-up visit that were absent before treatment or that worsened after treatment. AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE.
Number of Participants With Clinical Laboratory Abnormalities (Hematology and Chemistry, Without Regard to Baseline Abnormality) From BL to Week 28 Clinical laboratory abnormality was determined at the investigator's discretion.
Number of Participants With Change From Baseline in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria From BL to Week 28 Abnormality in change from BL in vital signs included: sitting/semi-supine diastolic blood pressure (BP) increase and decrease from BL of \>=20mmHg, systolic BP increase and decrease from BL of \>=30mmHg
Number of Participants With Adverse Events of Special Interest From first dose of study intervention (Day 1) to Week 28 These AEs included severe and opportunistic infection AEs; herpes virus infection AEs; clinically significant categorical increases in hepatic enzymes AST, and ALT and total bilirubin, and potential cases meeting Hy's Law criteria for increased risk of drug induced liver injury (DILI); major adverse cardiovascular events, including pulmonary embolism and deep vein thrombosis, cerebrovascular accident; AEs for decreased renal function, acute kidney injury, clinically significant increases in serum creatinine (Scr) and decreases in estimated glomerular filtration rate (eGFR). Only participants with AEs mentioned above were reported in the table below.
Change From Baseline in DAS28-CRP at Week 24 BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 24 DAS28 is a measure based on assessment of 28 joints for tenderness and swelling (tender and swollen joint counts). DAS28-CRP is derived using differential weighting given to 4 components: tender joint count (range: 0-28), swollen joint count (range: 0-28), patient global assessment (recorded on a visual analog scale \[VAS\] scale of 0-100 mm), and CRP (milligram per liter). DAS28-CRP score ranges from 0 to 9.4. The lower the DAS28-CRP score is, the better the participant has response (remission = score\<2.6, low disease activity = score≤3.2). A negative value in change from BL indicates an improvement.
American College of Rheumatology (ACR)20, ACR 50, ACR 70, and ACR 90 Responder Rates at Week 12 and Week 24 BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 12, Week 24 The American College of Rheumatology's definition for calculating improvement in rheumatoid arthritis (ACR20) is calculated as a \>=20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and CRP. Similarly, ACR50, ACR70, and ACR 90 were calculated with the respective percent improvement. Responder rate = number of responders (who had ACR20/50/70/90 response)/(number of responders + non-responders + non-responder assigned by non-responder imputation \[NRI\] after removal of missingness due to COVID-19 and missing components at a given visit)
Change From Baseline in the Tender/Painful and Swollen Joint Count at Week 12 and Week 24 BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 12, Week 24 The endpoint included Tender/Painful Joint Count 68 (TJC68) and 28 (TJC28). TJC68 was assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful in upper body and upper/lower extremity. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). The 28-joints set is the subset of 68 joints set including the following joints: shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, and knees. TJC28 was calculated by Pfizer from TJC68. Higher scores indicate higher level of disability.
Change From Baseline in the Physician's Global Assessment (PhGA) of Arthritis at Week 12 and Week 24 BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 12, Week 24 PhGA of Arthritis is an evaluation done by investigator based on the participant's disease signs, functional capacity and physical examination, and should be independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS. Physician's Global Assessment score ranges from 0 to 100. Higher scores indicate higher level of disability. A negative value in change from BL indicates an improvement.
Trial Locations
- Locations (143)
Independent Medical Diagnostic Laboratory Mediscan EOOD
🇧🇬Plovdiv, Bulgaria
MHAT Plovdiv AD
🇧🇬Plovdiv, Bulgaria
DCC Sveti Georgi EOOD
🇧🇬Plovdiv, Bulgaria
UMHAT "Kanev" AD
🇧🇬Ruse, Bulgaria
MHAT "Lyulin" EAD
🇧🇬Sofia, Bulgaria
Medical Center "Spectar" OOD
🇧🇬Sofia, Bulgaria
UMHAT "Sveti Ivan Rilski" EAD
🇧🇬Sofia, Bulgaria
"DCC 17 - Sofia" EOOD
🇧🇬Sofia, Bulgaria
Manitoba Clinic
🇨🇦Winnipeg, Manitoba, Canada
Centro Radiologico San Vicente de Paul
🇨🇱Santiago, Region Metropolitana, Chile
CTR Estudios
🇨🇱Santiago, Region Metropolitana, Chile
IMARED
🇨🇱Santiago, Region Metropolitana, Chile
REVMACLINIC s.r.o.
🇨🇿Brno, Czechia
MRI Lekarsky servis s.r.o.
🇨🇿Havirov, Czechia
HV Medical s.r.o., ORL ambulance pro deti a dospele
🇨🇿Brno, Czechia
Poliklinika AMO - Audiologie
🇨🇿Ostrava - Kuncice, Czechia
Vesalion s.r.o.
🇨🇿Ostrava, Czechia
ORL - sluchadla s.r.o.
🇨🇿Pardubice, Czechia
JSC "Evex Hospitals"
🇬🇪Tbilisi, Georgia
LTD "MediClub Georgia"
🇬🇪Tbilisi, Georgia
LTD "Institute of Clinical Cardiology"
🇬🇪Tbilisi, Georgia
Mammut Egeszsegkozpont, Ful-orr- gegeszet
🇭🇺Budapest, Hungary
Trial Pharma Kft.
🇭🇺Bekescsaba, Hungary
Vasutegeszsegugyi Nonprofit Kozhasznu Tarsasag
🇭🇺Bekescsaba, Hungary
LTD "Multi-Profile Clinic Consilium Medulla"
🇬🇪Tbilisi, Georgia
Betegapolo Irgalmasrend Budai Irgalmasrendi Korhaz
🇭🇺Budapest, Hungary
Budai Irgalmasrendi Korhaz
🇭🇺Budapest, Hungary
Qualiclinic Kft.
🇭🇺Budapest, Hungary
Revita Reumatologiai Rendelo
🇭🇺Budapest, Hungary
Affidea Magyarország Kft. Bank Center Központ
🇭🇺Budapest, Hungary
Magyar Honvédség Egészségügyi Központ
🇭🇺Budapest, Hungary
Affidea Magyarorszag Kft. Vaci Greens Egeszsegkozpont
🇭🇺Budapest, Hungary
Mediszintech Audiologia Kft.
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Sanitas Diagnosztikai es Rehabilitacios Kozpont
🇭🇺Gyula, Hungary
Debreceni Egyetem Klinikai Központ
🇭🇺Debrecen, Hungary
Huniko Kereskedelmi és Egészségügyi Szolgáltató Kft.
🇭🇺Miskolc, Hungary
Szegedi Tudomanyegyetem
🇭🇺Szeged, Hungary
Szegedi Tudomanyegyetem Reumatologiai Klinika
🇭🇺Szeged, Hungary
Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺Szeged, Hungary
Csolnoky Ferenc Korhaz, Ful- Orr- Gegeszeti Osztaly
🇭🇺Veszprem, Hungary
Nzoz Zdrowie Osteo-Medic
🇵🇱Bialystok, Poland
Podlaskie Centrum Sluchu i Mowy Sluchmed
🇵🇱Bialystok, Poland
VITAL MEDICAL CENTER (VITÁL-MEDICINA Kft.)
🇭🇺Veszprém, Hungary
Lar-Med
🇵🇱Bialystok, Poland
NZOZ Kendron
🇵🇱Bialystok, Poland
Tomma Diagnostyka obrazowa
🇵🇱Bialystok, Poland
ClinicMed Daniluk, Nowak Sp. J.
🇵🇱Bialystok, Poland
Nzoz McD Voxel
🇵🇱Bydgoszcz, Poland
Klinika Foniatrii i Audiologii, Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Klinika Reumatologii i Ukladowych Chorob Tkanki Lacznej
🇵🇱Bydgoszcz, Poland
Centrum Medyczne Pratia Gdynia
🇵🇱Gdynia, Poland
Portowy Zaklad Opieki Zdrowotnej Sp. z o.o.
🇵🇱Gdynia, Poland
Centrum Medyczne Enel-Med., Oddzial Alfa Plaza - Gdynia
🇵🇱Gdynia, Poland
Samodzielny Publiczny Specjalistyczny Szpital Zachodni im. sw. Jana Pawla II
🇵🇱Grodzisk Mazowiecki, Poland
MCBK
🇵🇱Grodzisk Mazowiecki, Poland
LUX MED.
🇵🇱Krakow, Poland
Malopolskie Badania Kliniczne
🇵🇱Krakow, Poland
Centrum Badan Klinicznych JCI
🇵🇱Krakow, Poland
Centrum medyczne PLEJADY
🇵🇱Krakow, Poland
LUXMED
🇵🇱Krakow, Poland
FONMED
🇵🇱Nowa Sol, Poland
Pratia MCM Krakow
🇵🇱Krakow, Poland
Centrum Medycyny Profilaktycznej Sp. z o. o.
🇵🇱Krakow, Poland
Centrum Medyczne iMed24
🇵🇱Krakow, Poland
Ai Centrum Medyczne
🇵🇱Poznan, Poland
LIVMED Sp. z.o.o.
🇵🇱Nowy Tomysl, Poland
Twoja Przychodnia - Centrum Medyczne Nowa Sol
🇵🇱Nowa Sol, Poland
Tomma Diagnostyka Obrazowa S.A.
🇵🇱Poznan, Poland
GEERS Dobry Sluch
🇵🇱Poznan, Poland
Prywatna Praktyka Lekarska Prof. dr hab. med. Pawel Hrycaj
🇵🇱Poznan, Poland
Centrum Mowy i Sluchu Medincus
🇵🇱Warszawa, Poland
Rex Medica Sport
🇵🇱Warszawa, Poland
Medycyna Kliniczna
🇵🇱Warszawa, Poland
"MTZ CLINICAL RESEARCH" Spolka z ograniczona odpowiedzialnoscia
🇵🇱Warszawa, Poland
Tomma Diagnostyka Obrazowa
🇵🇱Warszawa, Poland
Spoldzielnia Pracy Specjalistow Rentgenologow im. prof. W. Zawadowskiego
🇵🇱Warszawa, Poland
ArtAna Anna Piotrowska
🇵🇱Warszawa, Poland
Dermatovenerologicka ambulancia
🇸🇰Bratislava, Slovakia
Szpital LUX MED
🇵🇱Warszawa, Poland
ORL ambulancia RHINO s.r.o.
🇸🇰Bratislava, Slovakia
Oddelenie radiodiagnostiky a zobrazovacich metod, UNLP
🇸🇰Kosice, Slovakia
ARTROMAC n. o.
🇸🇰Kosice, Slovakia
Poliklinika Terasa s.r.o.
🇸🇰Kosice, Slovakia
Dermabene, s.r.o
🇸🇰Martin, Slovakia
ORL ML, s.r.o
🇸🇰Martin, Slovakia
Jessenius - Diagnosticke centrum
🇸🇰Nitra, Slovakia
Otorinolaryngologicka ambulancia MUDr. Olga Salgova
🇸🇰Partizanske, Slovakia
MEDICENTRUM Piestany, s.r.o.
🇸🇰Piestany, Slovakia
REUMACENTRUM s.r.o.
🇸🇰Partizanske, Slovakia
PARDERM, s. r. o., Dermatovenerologicka ambulancia
🇸🇰Partizanske, Slovakia
Narodny ustav reumatickych chorob
🇸🇰Piestany, Slovakia
Vseobecna nemocnica Rimavska Sobota
🇸🇰Rimavska Sobota, Slovakia
Nemocnica Alexandra Wintera n.o.
🇸🇰Piestany, Slovakia
Spinn, s.r.o.
🇸🇰Ruzomberok, Slovakia
Dg.s.r.o. - Diagnosticke- centrum
🇸🇰Rimavska Sobota, Slovakia
Clinica Gaias - Santiago
🇪🇸Santiago de Compostela, A Coruna, Spain
Clinica Sagrada Familia
🇪🇸Barcelona, Spain
Hospital General Universitario de Elche
🇪🇸Elche, Alicante, Spain
Communal non-profit enterprise "Chernihiv Regional Hospital" of Chernihiv Regional Council
🇺🇦Chernihiv, Ukraine
Hospital Clinico Universitario Santiago de Compostela
🇪🇸Santiago de Compostela, Spain
Hospital Quironsalud Infanta Luisa
🇪🇸Sevilla, Spain
Communal Non-commercial Enterprise of Kharkiv Regional Council
🇺🇦Kharkiv, Ukraine
Medical Center 'Ok!Clinic+' of International Institute of Clinical Research LLC
🇺🇦Kyiv, Ukraine
Medical сепtег of "Medical Clinic "Blagomed" LLC
🇺🇦Kyiv, Ukraine
Communal non-profit enterprise "Kyiv City Clinical Hospital #3" of executive body of Kyiv
🇺🇦Kyiv, Ukraine
Limited Liability Company "Medical Centre "Consilium Medical"
🇺🇦Kyiv, Ukraine
Clinic of the State Institution "DF Chebotaryov Institute of Gerontology of the NAMS of Ukraine"
🇺🇦Kyiv, Ukraine
Communal Non-Commercial Enterprise "Odesa Regional Clinical Hospital" of Odesa Regional Council
🇺🇦Odesa, Ukraine
Comunal Enterprise "Poltava Regional Clinical Hospital n. a. M.S. Sklifosovskogo of Poltava
🇺🇦Poltava, Ukraine
LLC "Modern Clinic"
🇺🇦Zaporizhzhya, Ukraine
CCR Czech a.s.
🇨🇿Pardubice, Vychodocesky KRAJ, Czechia
Poliklinika Vektor
🇨🇿Pardubice, Czechia
Revmatologicky ustav
🇨🇿Praha 2, Czechia
Thomayerova nemocnice
🇨🇿Praha 4, Czechia
ORL ambulance
🇨🇿Uherske Hradiste, Czechia
Uherskohradistska nemocnice, a.s.
🇨🇿Uherske Hradiste, Czechia
Medical Plus s.r.o.
🇨🇿Uherske Hradiste, Czechia
,,UMHAT - Georgi Stranski" EAD
🇧🇬Pleven, Bulgaria
Revmacentrum MUDr. Mostera, s.r.o.
🇨🇿Brno, Czechia
Medical Diagnostic Laboratory Rusev EOOD
🇧🇬Plovdiv, Bulgaria
"Medical Center-Teodora" EOOD
🇧🇬Ruse, Bulgaria
Centre de Rhumatologie de l'Est du Quebec (CREQ)
🇨🇦Rimouski, Quebec, Canada
Medical Center "N.I. Pirogov" EOOD
🇧🇬Sofia, Bulgaria
CCR Ostrava, s.r.o.
🇨🇿Ostrava, Czechia
LTD "Cardioclinic - Digomi Medical Center"
🇬🇪Tbilisi, Georgia
Affidea Magyarorszag Kft.
🇭🇺Budapest, Hungary
Pest Megyei Flór Ferenc Kórház Fül- Orr- Gégészet és Gyermek Fül-Orr-Gégészet
🇭🇺Kistarcsa, Hungary
Pracownia Rezonansu Magnetycznego i RTG
🇵🇱Poznan, Poland
"Reumatika - Centrum Reumatologii" NZOZ
🇵🇱Warszawa, Poland
AZIMED-ORL s.r.o.
🇸🇰Rimavska Sobota, Slovakia
Grupo Hospitalario La Rosaleda - Hospital Nuestra Senora de la Esperanza
🇪🇸Santiago de Compostela, A Coruna, Spain
"Revmocenter" LLC
🇺🇦Kyiv, Ukraine
Mestka nemocnice Ostrava
🇨🇿Ostrava, Czechia
Pest Megyei Flór Ferenc Kórház Reumatológiai es Fizioterápiás Osztály
🇭🇺Kistarcsa, Hungary
Centro de Estudios Reumatologicos (CER)
🇨🇱Santiago, Region Metropolitana, Chile
Klinika dermatovenerologie UNLP
🇸🇰Kosice, Slovakia
Enroll SpA
🇨🇱Santiago, Region Metropolitana, Chile
Centro Radiologico Plaza Baquedano
🇨🇱Santiago, Region Metropolitana, Chile
REUMEX s.r.o.
🇸🇰Rimavska Sobota, Slovakia
ROMJAN, s.r.o.
🇸🇰Bratislava, Slovakia
MEDMAN, s. r. o.,
🇸🇰Martin, Slovakia
Zdravomak s.r.o. Topoľčany
🇸🇰Topolcany, Slovakia