Study Comparing Doses Of An Experimental Glucocorticoid Compound To Prednisone And Placebo In Rheumatoid Arthritis
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT01393639
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to compare the safety and efficacy of multiple doses of PF-04171327, an experimental glucocorticoid drug, to prednisone at 5 mg or 10 mg and placebo in the treatment of rheumatoid arthritis. All subjects will also be receiving background treatment of methotrexate for their rheumatoid arthritis. Study medication will be given for eight weeks followed by a 4 week period during which the dose of study medication will be gradually reduced. The efficacy of the study medications will be determined by assessing severity of the rheumatoid arthritis during the study and safety will be determined by adverse event reporting, laboratory tests and biomarker analysis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 323
- Subjects must have documented rheumatoid arthritis with a duration of at least 3 months as determined by the investigator using standardly accepted criteria, must have been receiving methotrexate for at least 3 months to treat their rheumatoid arthritis, and must be free of any signs or symptoms of infection.
- Subjects cannot enter the study if they have recently received treatment with certain medications which might interfere with study medications;
- subjects cannot enter if they have abnormalities in certain blood tests, history of cancer, recent bone fracture or other significant conditions.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PF-04171327 1 mg QD PF-04171327 - PF-04171327 5 mg QD PF-04171327 - PF-04171327 10 mg QD PF-04171327 - PF-04171327 15 mg QD PF-04171327 - placebo placebo - prednisone 10 mg QD prednisone - prednisone 5 mg QD prednisone -
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving a 20% Improvement in American College of Rheumatology (ACR) Criteria at Week 8 Week 8 ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).
Mean Percent Change From Baseline in 0 Hour Procollagen Type 1 N Terminal Propeptide (P1NP) at Week 8 (Comparisons to Prednisone 5 mg) Week 8 Change from baseline in P1NP at week 8 is presented in this outcome measure.
Mean Percent Change From Baseline in 0 Hour Urinary N Telopeptide/Urinary Creatinine (uNTx/uCr) at Week 8 (Comparisons to Prednisone 5 mg) Week 8 Change from baseline in uNTx/uCr at week 8 is presented in this outcome measure.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving ACR20 Response at Weeks 2, 4, and 12 (Comparisons to Placebo, and Prednisone 10 mg) Weeks 2, 4, and 12 (taper period) ACR20 response: greater than or equal to (≥) 90 percent (%) improvement in tender or swollen joint counts and 90% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Percentage of Participants Achieving ACR50 Response at Weeks 2, 4, 6, 8 and 12 (Comparisons to Placebo, and Prednisone 10 mg) Weeks 2, 4, 6, 8, and 12 (taper period) ACR50 response: greater than or equal to (≥) 50 percent (%) improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Percentage of Participants Achieving ACR70 Response at Weeks 2, 4, 6, 8 and 12 (Comparisons to Placebo, and Prednisone 10 mg) Weeks 2, 4, 6, 8, and 12 (taper period) ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Change From Baseline in Tender-Joint Counts at Weeks 2, 4, 6, 8 (Comparisons to Placebo, and Prednisone 10 mg) Weeks 2, 4, 6, and 8 Twenty-eight tender/painful joint count included the following joints: shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, and knees. Artificial joints were not assessed. These joints were assessed by a joint assessor, who was blinded to the participant's safety data, previous efficacy data and treatment randomization, to determine the number of joints that were considered tender or painful, and swollen.
Change From Baseline in Tender-Joint Counts at Week 12 (Descriptive Statistics) Week 12 Twenty-eight tender/painful joint count included the following joints: shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, and knees. Artificial joints were not assessed. These joints were assessed by a joint assessor, who was blinded to the participant's safety data, previous efficacy data and treatment randomization, to determine the number of joints that were considered tender or painful, and swollen.
Change From Baseline in Swollen-Joint Counts at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg) Weeks 2, 4, 6, and 8 Twenty-eight tender/painful joint count included the following joints: shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, and knees. Artificial joints were not assessed. These joints were assessed by a joint assessor, who was blinded to the participant's safety data, previous efficacy data and treatment randomization, to determine the number of joints that were considered tender or painful, and swollen.
Change From Baseline in Swollen-Joint Counts at Week 12 (Descriptive Statistics) Week 12 Twenty-eight tender/painful joint count included the following joints: shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, and knees. Artificial joints were not assessed. These joints were assessed by a joint assessor, who was blinded to the participant's safety data, previous efficacy data and treatment randomization, to determine the number of joints that were considered tender or painful, and swollen.
Change From Baseline in C Reactive Protein (CRP) at Weeks 2, 4, 6, and 8 (Comparisons to Placebo and Prednisone 10 mg) Weeks 2, 4, 6, and 8 The CRP was collected at each applicable clinic visit and analyzed by a central laboratory. In order to assist with the data clean-up at the end of the study, the CRP results were unblinded to the sponsor at the time of the last subject's last visit. All statistics presented below are derived from mixed model with fixed effects for treatment, visit, treatment-by-visit interaction and baseline value; unstructured covariance matrix was used.
Change From Baseline of CRP at Week 12 (Descriptive Statistics) Week 12 The CRP was collected at each applicable clinic visit and analyzed by a central laboratory. In order to assist with the data clean-up at the end of the study, the CRP results were unblinded to the sponsor at the time of the last subject's last visit.
Change From Baseline in Patient Global Assessment of Arthritis at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg) Weeks 2, 4, 6, and 8 Participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The subject's response was recorded using a 100 mm Visual Analog Scale (VAS), where 0 mm = no pain and 100 mm = most severe pain.
Change From Baseline in Patient Global Assessment of Arthritis at Week 12 (Descriptive Statistics) Week 12 Participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The subject's response was recorded using a 100 mm Visual Analog Scale (VAS), where 0 mm = no pain and 100 mm = most severe pain.
Change From Baseline in Physician Global Assessment of Arthritis at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg) Weeks 2, 4, 6, and 8 The investigator assessed how the participant's overall arthritis appears at the time of the visit. This was an evaluation based on the participant's disease signs, functional capacity and physical examination, and was independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS, where 0 mm = no pain and 100 mm = most severe pain.
Change From Baseline in Physician Global Assessment of Arthritis at Week 12 (Descriptive Statistics) Week 12 The investigator assessed how the participant's overall arthritis appears at the time of the visit. This was an evaluation based on the participant's disease signs, functional capacity and physical examination, and was independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS, where 0 mm = no pain and 100 mm = most severe pain.
Change From Baseline in Pain VAS at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg) Weeks 2, 4, 6, and 8 Participants assessed the severity of their arthritis pain using a 100 mm VAS placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponds to the magnitude of their pain.
Change From Baseline in Pain VAS at Week 12 (Descriptive Statistics) Week 12 Participants assessed the severity of their arthritis pain using a 100 mm VAS placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponds to the magnitude of their pain.
Change From Baseline in HAQ-DI at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg) Weeks 2, 4, 6, and 8 Health Assessment Questionnaire-Disability Index (HAQ-DI): participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Change From Baseline in HAQ-DI at Week 12 (Descriptive Statistics) Week 12 Health Assessment Questionnaire-Disability Index (HAQ-DI): participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Change From Baseline in Disease Activity Score (DAS) 28-3 CRP at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg) Weeks 2, 4, 6, and 8 DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) \<= 3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) \<2.6 = remission.
Change From Baseline in DAS 28-3 CRP at Week 12 (Descriptive Statistics) Week 12 DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) \<= 3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) \<2.6 = remission.
Change From Baseline in DAS28-4(CRP) at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg) Weeks 2, 4, 6, and 8 DAS28-4 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) \<= 3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) \<2.6 = remission. All statistics presented below are derived from mixed model with fixed effects for treatment, visit, treatment-by-visit interaction and baseline value; unstructured covariance matrix was used.
Change From Baseline in DAS28-4(CRP) at Week 12 (Descriptive Statistics) Week 12 DAS28-4 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) \<= 3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) \<2.6 = remission.
Change From Baseline in SF-36v2 Mental Component Scores at Weeks 4 and 8 (Comparisons to Placebo, and Prednisone 10 mg) Weeks 4 and 8 The 36 item Short Form Health Survey (SF-36) (Versions 2, acute version) is a 36 item generic health status measure. It measures 8 general health concepts: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. These concepts can also be summarized as physical component score (PCS) and mental component score (MCS). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). This questionnaire was completed by the participant prior to any procedures being performed at the visit, if possible. The form was then checked by site staff for completeness.
Change From Baseline in SF-36v2 Mental Component Scores at Week 12 (Descriptive Statistics) Week 12 The 36 item Short Form Health Survey (SF-36) (Versions 2, acute version) is a 36 item generic health status measure. It measures 8 general health concepts: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. These concepts can also be summarized as physical component score (PCS) and mental component score (MCS). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). This questionnaire was completed by the participant prior to any procedures being performed at the visit, if possible. The form was then checked by site staff for completeness.
Change From Baseline in SF-36v2 Physical Component Scores at Weeks 4 and 8 (Comparisons to Placebo, and Prednisone 10 mg) Weeks 4 and 8 The 36 item Short Form Health Survey (SF-36) (Versions 2, acute version) is a 36 item generic health status measure. It measures 8 general health concepts: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. These concepts can also be summarized as physical component score (PCS) and mental component score (MCS). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). This questionnaire was completed by the participant prior to any procedures being performed at the visit, if possible. The form was then checked by site staff for completeness.
Change From Baseline in SF-36v2 Physical Component Scores at Week 12 (Descriptive Statistics) Week 12 The 36 item Short Form Health Survey (SF-36) (Versions 2, acute version) is a 36 item generic health status measure. It measures 8 general health concepts: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. These concepts can also be summarized as physical component score (PCS) and mental component score (MCS). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). This questionnaire was completed by the participant prior to any procedures being performed at the visit, if possible. The form was then checked by site staff for completeness.
Trial Locations
- Locations (91)
Revmatologichno Otdelenie, MBAL - Plovdiv
🇧🇬Plovdiv, Bulgaria
MBAL "Sveti Ivan Rilski" Sofia; Klinika po Revmatologia
🇧🇬Sofia, Bulgaria
Centro de Estudios de Investigacion Basica y Clinica SC.
🇲🇽Guadalajara, Jalisco, Mexico
Unidad de Investigacion Biomedica del CEM
🇲🇽Merida, Yucatan, Mexico
Reumalab S.A.S
🇨🇴Medellin, Antioquia, Colombia
Alastair C. Kennedy, MD
🇺🇸Vero Beach, Florida, United States
Centrum Kliniczno-Badawcze J. Brzezicki, B. Górniakiewicz-Brzezicka Lekarze Spółka Partnerska
🇵🇱Elbląg, Poland
Clinical Hospital of Emergency Care N.V. Soloviev
🇷🇺Yaroslavl, Russian Federation
Smolensk Regional Clinical Hospital
🇷🇺Smolensk, Russian Federation
Catalina Pointe Clinical Research, Inc.
🇺🇸Tucson, Arizona, United States
C. Michael Neuwelt, MD, Inc.
🇺🇸San Leandro, California, United States
Javed Rheumatology Associates, Inc.
🇺🇸Newark, Delaware, United States
Allergy, Asthma, Arthritis, and Lung Center
🇺🇸Daytona Beach, Florida, United States
Millennium Research
🇺🇸Ormond Beach, Florida, United States
Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Arthritis and Osteoporosis Medical Associates, PLLC
🇺🇸Brooklyn, New York, United States
The Center for Arthritis and Rheumatism
🇺🇸Vero Beach, Florida, United States
Cincinnati Rheumatic Disease Study Group, Inc.
🇺🇸Cincinnati, Ohio, United States
Accurate Clinical Research, Inc.
🇺🇸Houston, Texas, United States
Tricounty Radiology
🇺🇸Charleston, South Carolina, United States
Low Country Rheumatology, PA
🇺🇸Charleston, South Carolina, United States
Arthritis Northwest, PLLC
🇺🇸Spokane, Washington, United States
Revmatologichen kabinet, DKTs Sv. Pantaleimon OOD
🇧🇬Pleven, Bulgaria
Hospital Pablo Tobon Uribe
🇨🇴Medellin, Antioquia, Colombia
Preventive Care SAS
🇨🇴Chía, Cundinamarca, Colombia
Revmatologie Bruntal, S.R.O.
🇨🇿Bruntal, Czechia
Revmatologicka ambulance
🇨🇿Praha 4, Czechia
Thomayerova nemocnice
🇨🇿Praha 4, Czechia
CIRI GmbH
🇩🇪Frankfurt am Main, Germany
Klinische Forschung Berlin-Buch GmbH
🇩🇪Berlin, Germany
Revita Reumatologiai Rendelo
🇭🇺Budapest, Hungary
Qualiclinic Kft.
🇭🇺Budapest, Hungary
Budai Irgalmasrendi Korhaz, Reumatologia I.
🇭🇺Budapest, Hungary
Fejer Megyei Szent Gyorgy Korhaz Reumatologia
🇭🇺Szekesfehervar, Hungary
Shirdi Sai Hospital
🇮🇳Bangalore, Karnataka, India
MAV Korhaz es Rendelointezet, Reumatologiai szakrendeles
🇭🇺Szolnok, Hungary
Krishna Institute of Medical Sciences Ltd
🇮🇳Secunderabad, Andra Pradesh, India
Dapartment of Rheumatology
🇮🇳Lucknow, Uttar Pradesh, India
KyungHee University Hospital
🇰🇷Seoul, Korea, Korea, Republic of
Daegu Catholic University Medical Center, Department of Rheumatology
🇰🇷Daegu, Korea, Republic of
Inha University Hospital, Medicine/Rheumatology
🇰🇷Incheon, Korea, Republic of
Seoul National University Hospital, Rheumatology, Internal Medicine
🇰🇷Seoul, Korea, Republic of
Hospital Raja Permaisuri Bainun
🇲🇾Ipoh, Perak, Malaysia
Konkuk University Medical Center, Department of Rheumatology
🇰🇷Seoul, Korea, Republic of
Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.
🇲🇽San Luis Potosi, Mexico
Sunway Medical Centre
🇲🇾Petaling Jaya, Selangor Darul Ehsan, Malaysia
Wojewodzki Zespol Reumatologiczny im. dr J. Titz-Kosko
🇵🇱Sopot, Poland
Spitalul Clinic "Sfanta Maria", Clinica de Medicina Interna si Reumatologie
🇷🇴Bucuresti, Romania
Spitalul Clinic Judetean de Urgenta "Sfantul Apostol Andrei"
🇷🇴Galati, Romania
Territorial Clinical Hospital
🇷🇺Barnaul, Russian Federation
Spitalul Clinic Judetean de Urgenta Targu Mures, Reumatologic
🇷🇴Tg Mures, Romania
Sverdlovsk Regional Clinical Hospital # 1
🇷🇺Ekaterinburg, Russian Federation
GBUZ of Kemerovo region Regional clinical hospital for was veterans
🇷🇺Kemerovo, Russian Federation
FSBI Scientific - Research Institute of Rheumatology RAMS n.a. V.A. Nasonova.
🇷🇺Moscow, Russian Federation
Kemerovo Regional Clinical Hospital
🇷🇺Kemerovo, Russian Federation
LLC Consultative and Diagnostic Rheumatological Center Healthy Joints
🇷🇺Novosibirsk, Russian Federation
GBOU VPO "Orenburg State Medical Academy of Ministry of Healthcare of Russian Federation"
🇷🇺Orenburg, Russian Federation
Clinical Rheumatological Hospital #25
🇷🇺Saint-Petersburg, Russian Federation
Republican Hospital V.A.Baranov
🇷🇺Petrozavodsk, Russian Federation
Ryazan Regional Clinical Cardiological Dispensary
🇷🇺Ryazan, Russian Federation
MUZ City Clinical Hospital #12
🇷🇺Saratov, Russian Federation
Tomsk Regional Clinical Hospital
🇷🇺Tomsk, Russian Federation
Vladimir Regional Clinical Hospital
🇷🇺Vladimir, Russian Federation
Institute of Rheumatology
🇷🇸Belgrade, Serbia
Yaroslavl Regional Clinical Hospital
🇷🇺Yaroslavl, Russian Federation
AAGS, s.r.o. , nestatne zdravotnicke zariadenie
🇸🇰Dunajska Streda, Slovakia
Nestatna reumatologicka ambulancia
🇸🇰Zilina, Slovakia
Reumatologicka ambulancia, REUMEX, s.r.o.
🇸🇰Rimavska Sobota, Slovakia
Reumaglobal s.r.o.
🇸🇰Trnava, Slovakia
Panorama Medical Centre
🇿🇦Panorama, Cape Town, South Africa
Emmed Research
🇿🇦Pretoria, Gauteng, South Africa
Hospital SANITAS CIMA.
🇪🇸Barcelona, Spain
Municipal Medical Institution "City Clinical Hospital #3"
🇺🇦Chernivtsi, Ukraine
Municipal Medicoprophylactic Institution "Donetsk City Clinical Hospital #5".
🇺🇦Donetsk, Ukraine
Complejo Hospitalario Universitario A Coruña. Hospital Materno Infantil Teresa Herrera
🇪🇸La Coruna, Spain
National Scientific Centre "Institute of Cardiology n.a. M.D. Strazheska of NAMS of Ukraine".
🇺🇦Kiev, Ukraine
Komunalnyi zaklad Kyivskoi oblasnoi rady "Kyivska oblasna klinichna likarnia"
🇺🇦Kyiv, Ukraine
Komunalna ustanova "Odeska oblasna klinichna likarnia"
🇺🇦Odesa, Ukraine
Municipal Establishment "City Clinical Hospital #9 n.a. O.I. Minakov", Department of Rheumatology
🇺🇦Odesa, Ukraine
Vinnytsya regional clinical hospital named after M.I. Pyrogova; Department of rheumatology
🇺🇦Vinnytsya, Ukraine
Clinical Hospital #122 L.G. Sokolov
🇷🇺Saint-Petersburg, Russian Federation
Municilap Institution Central Clinical Hospital 6
🇷🇺Ekaterinburg, Russian Federation
Charite Universitaetsmedizin Berlin, Klinik fuer Rheumatologie
🇩🇪Berlin, Germany
Centro Integral de Reumatologia e Inmunologia CIREI
🇨🇴Bogota, Cundinamarca, Colombia
Spitalul Clinic de Recuperare
🇷🇴Iasi, Romania
Komunalnyi zaklad Lvivskoi oblasnoi rady "Lvivskyi oblasnyi klinichnyi diahnostychnyi tsentr"
🇺🇦Lviv, Ukraine
MBAL Sveti Ivan Rilski Sofia; Klinika po Revmatologia
🇧🇬Sofia, Bulgaria
Nzoz "Lecznica Mak-Med S.C."
🇵🇱Nadarzyn, Poland
Institute for treatment and rehabilitation Niska Banja
🇷🇸Niska Banja, Serbia
Dr. Rethy Pal Korhaz es Rendelointezet, II. Reumatologia Szakrendeles
🇭🇺Bekescsaba, Hungary
Municipal Institution:"Zaporizhzhya Regional Clinical Hospital",Rheumatology Dep.
🇺🇦Zaporizhzhya, Ukraine