Analgesic Efficacy And Safety of Tanezumab Added On To Diclofenac SR In Patients With Osteoarthritis Of The Knee Or Hip
- Conditions
- Osteoarthritis
- Interventions
- Registration Number
- NCT00864097
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to investigate the analgesic efficacy and safety of tanezumab added on to diclofenac SR in patients with osteoarthritis of the knee or hip currently experiencing partial benefit from, and are tolerating, diclofenac 150 mg/day therapy.
- Detailed Description
This study was terminated on 16 Nov 2010 following a US FDA clinical hold for tanezumab osteoarthritis clinical studies which halted dosing and enrollment of patients on 23 June 2010 for potential safety issues.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 607
- Osteoarthritis of the knee or hip according to ACR criteria with Kellgren-Lawrence X-ray grade equal to, or greater than, 2.
- Patients must be experiencing some benefit from their current stable dose regimen of oral diclofenac 150 mg/day and be tolerating their diclofenac regimen.
- Pain and function levels as required by the protocol at Screening and Baseline.
- Willing to discontinue all non-study pain medications throughout the study except as permitted per protocol.
- Willing and able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests and other study procedures.
- Pregnant women.
- BMI greater than 39.
- History of other disease that may involve index knee or hip including inflammatory joint diseases, chrystalline disease (gout or pseudogout), endocrinopathies, metabolic joint diseases, lupus erythematosus, rheumatoid arthritis (RA), joint infections, neuropathic disorders, avascular necrosis, Paget's disease or tumors.
- Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy or other moderate to severe pain that may confound assessments or self-evaluation of the pain associated with OA.
- Signs and symptoms of clinically significant cardiac disease within 6 months prior to screening.
- Diagnosis or TIA within 6 months prior to screening or diagnosis of stroke with residual deficits that would preclude completion of required study activities.
- History, diagnosis , signs or symptoms of clinically significant neurological and/or psychiatric disease/disorder.
- At Screening: uncontrolled hypertension, hemoglobin A1c greater than or equal to 10%, ALT or AST greater than or equal to 3X upper limit of normal, creatinine exceeding 150 micro-mol/L in men or 133 micro-mol/L in women.
- Patients on warfarin or other coumadin anticoagulant therapy and/or lithium therapy within 30 days prior to Screening.
- Known hypersensitivity to NSAIDs (eg, diclofenac), cyclooxygenase inhibitors or paracetamol (acetaminophen).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tanezumab 5 mg + diclofenac tanezumab IV tanezumab 5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32) Tanezumab 10 mg + diclofenac tanezumab IV tanezumab 10 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32) Tanezumab 2.5 mg + diclofenac tanezumab IV tanezumab 2.5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32) IV placebo + diclofenac IV placebo IV placebo to match tanezumab every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32) IV placebo + diclofenac diclofenac IV placebo to match tanezumab every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32) Tanezumab 10 mg + diclofenac diclofenac IV tanezumab 10 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32) Tanezumab 5 mg + diclofenac diclofenac IV tanezumab 5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32) Tanezumab 2.5 mg + diclofenac diclofenac IV tanezumab 2.5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)
- Primary Outcome Measures
Name Time Method Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis Score at Week 16 Baseline, Week 16 Participants answered: "Considering all the ways your osteoarthritis in your index joint (knee/hip) affects you, how are you doing today?" Participants responded by using a 5-point Likert scale, where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher score indicated worst condition.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 16 Baseline, Week 16 WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. WOMAC physical function is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index knee or hip during past 48 hours. It is calculated as mean of the scores from 17 individual questions, each scored on a NRS of 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. Physical function refers to participant's ability to move around and perform usual activities of daily living.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16 Baseline, Week 16 WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis (OA). WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or hip during past 48 hours. It is calculated as mean of the scores from 5 individual questions, each scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response; LOCF Weeks 2, 4, 8, 12, 16, and 24 OMERACT-OARSI responder: participant has \>=50 percent (%) change and \>=2 absolute change from Baseline in either WOMAC pain or physical function subscale scores or at least 2 of the following being true: \>=20% change and \>=1 absolute change from Baseline in WOMAC pain subscale; \>=20% change and \>=1 absolute change from Baseline in the WOMAC physical function subscale; \>=20% change and \>=1 absolute change from Baseline in PGA of osteoarthritis. WOMAC pain and physical function score: 0 to 10 with higher score = worse response. PGA score: 1 = very good and 5 = very poor.
Percentage of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16 and 24 Baseline, Week 16 and 24 WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis (OA). WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or hip during past 48 hours. It is calculated as mean of the scores from 5 individual questions, each scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Greater percentage reduction indicates greater improvement. Percentage of participants with cumulative reduction (as percent) (greater than 0%; \>= 10, 20, 30, 40, 50, 60, 70, 80 and 90%; = 100 %) in WOMAC pain subscale from Baseline to Weeks 16 and 24 were reported.
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Weeks 2, 4, 8, 12 and 24 Baseline, Weeks 2, 4, 8, 12, and 24 WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or hip during past 48 hours. It is calculated as mean of the scores from 5 individual questions, each scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain.
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Weeks 2, 4, 8, 12, and 24 Baseline, Weeks 2, 4, 8, 12, and 24 WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. WOMAC physical function is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index knee or hip during past 48 hours. It is calculated as mean of the scores from 17 individual questions, each scored on a NRS of 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. Physical function refers to participant's ability to move around and perform usual activities of daily living.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Weeks 2, 4, 8, 12, 16, and 24 Baseline, Weeks 2, 4, 8, 12, 16, and 24 WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in index knee or hip during past 48 hours. It is calculated as mean of the scores from 2 individual questions scored on NRS of (no stiffness) to 10 (extreme stiffness), with higher scores indicate higher stiffness. Total score range for WOMAC stiffness subscale score is (no stiffness) to 10 (extreme stiffness), where higher scores indicate higher stiffness. Stiffness is defined as a sensation of decreased ease in movement of knee/hip. Negative change indicated an improvement.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Walking on a Flat Surface at Weeks 2, 4, 8, 12, 16, and 24 Baseline, Week 2, 4, 8, 12, 16, 24 Participants answered the question: "How much pain have you had when walking on a flat surface?" Participants responded by using an 11-point scale where 0 = no pain and 10 = extreme pain. Where 0 is the best response and negative change indicated an improvement.
Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis Score at Weeks 2, 4, 8, 12, and 24 Baseline, Weeks 2, 4, 8, 12, and 24 Participants answered: "Considering all the ways your osteoarthritis in your index joint (knee/hip) affects you, how are you doing today?" Participants responded by using a 5-point Likert scale, where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher score indicated worst condition.
Percentage of Participants With Improvement of at Least 2 Points in Patient Global Assessment (PGA) of Osteoarthritis; LOCF Weeks 2, 4, 8, 12, 16, and 24 Participants answered: "Considering all the ways your osteoarthritis in your index joint (knee/hip) affects you, how are you doing today?" Participants responded by using a 5-point Likert scale, where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher score indicated worst condition. A decrease of at least 2 points on the 5-point scale relative to baseline value indicated improvement.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16, and 24 Baseline, Weeks 2, 4, 8, 12, 16, and 24 WOMAC Index: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain (5 items), stiffness (2 items), and physical function (17 items) in participants with osteoarthritis of the hip and/or knee. WOMAC average score is the mean of the WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, with higher score indicating worse response. Greater reduction in WOMAC average score indicated greater improvement.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Downstairs at Weeks 2, 4, 8, 12, 16, and 24 Baseline, Weeks 2, 4, 8, 12, 16, and 24 Participants answered the question: "How much pain have you had when going up or down the stairs?" Participants responded by using an 11-point scale, where 0 = no pain and 10 = extreme pain. Where 0 is the best response and negative change indicated an improvement.
Number of Participants With Change From Baseline in European Quality of Life - 5 Dimension (EQ-5D) Individual Health State Profile at Week 24 Baseline, Week 24 EQ-5D was a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme dysfunction) and a single index value characterizing current health status using a visual analog scale with score ranging from 0 (worst) to 100 (best). Baseline EQ-5D individual health state profile was determined as number of participants "no dysfunction, moderate or some dysfunction and extreme dysfunction" and change from baseline in EQ-5D individual health state profile was determined as number of participants "improved, no change or worsened".
Time to Discontinuation (TTD) Due to Lack of Efficacy Baseline up to Week 16 and 24 Median time to discontinuation due to lack of efficacy was estimated using Kaplan-Meier method.
Percentage of Participants With At Least 30%, 50%, 70% and 90% Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score; LOCF Baseline, Weeks 2, 4, 8, 12, 16, and 24 WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis (OA). WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or hip during past 48 hours. It is calculated as mean of the scores from 5 individual questions, each scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Greater percentage reduction indicates greater improvement. Percentage of participants with reduction in WOMAC pain intensity of at least (\>=) 30%, 50%, 70% and 90% at Weeks 2, 4, 8, 12, 16, 24 and 32 compared to baseline were classified as responders to WOMAC pain subscale and are reported here.
Percentage of Participants With Improvement of at Least 2 Points in Patient Global Assessment (PGA) of Osteoarthritis; Baseline Observation Carried Forward (BOCF) Weeks 2, 4, 8, 12, 16, and 24 Participants answered: "Considering all the ways your osteoarthritis in your index joint (knee/hip) affects you, how are you doing today?" Participants responded by using a 5-point Likert scale, where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher score indicated worst condition. A decrease of at least 2 points on the 5-point scale relative to baseline value indicates improvement.
Number of Participants Who Discontinued Due to Lack of Efficacy Baseline up to end of study (Week 32) Number of participants who discontinued due to lack of efficacy were reported.
Change From Baseline in Average Pain Score in the Index Knee or Hip at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24 Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24 Participants were asked to assess index joint (knee/hip) pain during the past 24 hours on an 0-10 point integer scale ranging from 0 (no pain) to 10 (worst possible pain). Baseline score was calculated as the mean of the scores in the index joint over the 3 days days in the initial pain assessment period and a weekly mean was calculated using the daily pain scores in the index joint within each study week. The change from Baseline was calculated using the difference between each post-baseline weekly mean and the baseline mean score, where negative change indicated an improvement.
Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 12 and 24 Baseline, Week 12, and 24 SF-36v2 was a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and role limitations due to emotional problems, bodily pain, general health, vitality, and mental health. The total score and the score for a section was an average of the individual question scores, which were scaled 0-100. Higher scores reflected better participant status and positive change indicated an improvement.
Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 12 and 24 Baseline, Week 12 and 24 SF-36v2: standardized survey evaluating 8 aspects of functional health and wellbeing (physical and social functioning, role limitations due to physical and emotional problems, bodily pain, general health, vitality, mental health). Total score for each aspect were scaled 0-100. Higher scores reflect better participant status and positive change indicated an improvement. For obtaining physical and mental component scores, z-score for each scale=(observed score - mean score for general 1990 United States \[US\] population)/corresponding standard deviation. The 2 component scores were obtained by multiplying each aspect z-score by physical or mental factor score coefficient (1990 general US population) and summing the eight products. Component scores indicated how many standard deviations higher (in case of positive z-score \[better functioning\])/lower (in case of negative z-score \[worse functioning\]) participant's value was relative to the mean of the reference population.
Change From Baseline in European Quality of Life - 5 Dimension (EQ-5D) Index Score at Week 24 Baseline, Week 24 EQ-5D was a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme dysfunction) and a single index value characterizing current health status using a visual analog scale with score ranging from 0 (worst) to 100 (best). EQ-5D summary index was obtained with a formula that weights each level of the dimensions. The index-based score was interpreted along a continuum of 0 (death) to 1 (perfect health). Negative change from baseline represented worsening.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline up to 112 days after last intravenous dose (up to Week 32) An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 112 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included SAEs as well as non-serious AEs which occurred during the trial.
Trial Locations
- Locations (73)
Nuhr Zentrum
🇦🇹Senftenberg, Austria
ClinPharm International GmbH
🇦🇹Wien, Austria
Medizinische Universitaet Wien/AKH
🇦🇹Wien, Austria
Rheuma Zentrum Favoriten
🇦🇹Wien, Austria
Hopital Lariboisiere
🇫🇷Paris, France
Viereck-Apotheke
🇩🇪Berlin-Buch, Germany
Charité-Universitaetsmedizin Berlin
🇩🇪Berlin, Germany
CHU de Nantes
🇫🇷Nantes cedex 1, France
Apotheke
🇩🇪Berlin, Germany
Klinische Forschung Berlin-Buch GmbH
🇩🇪Berlin, Germany
Synexus ClinParm GmbH
🇩🇪Potsdam, Germany
Apotheke im Arztehaus Mickten
🇩🇪Dresden, Germany
Schiller Apotheke & Stadt Apotheke
🇩🇪Goeppingen, Germany
Synexus ClinPharm GmbH
🇩🇪Magdeburg, Germany
Schmerz- und Palliativzentrum Goeppingen
🇩🇪Goeppingen, Germany
Klinische Forschung Hamburg GmbH
🇩🇪Hamburg, Germany
Falken Apotheke Hoheluft
🇩🇪Hamburg, Germany
Klinische Forschung Hannover - Mitte GmbH
🇩🇪Hannover, Germany
Loewen-Apotheke
🇩🇪Hannover, Germany
Arkana Apotheke OHG
🇩🇪Leipzig, Germany
Apotheke des Ernst von Bergmann Klinikums
🇩🇪Potsdam, Germany
Apotheke im MSZ
🇩🇪Magdeburg, Germany
Kirchsteig Apotheke
🇩🇪Potsdam, Germany
"Centrum Medyczne MEDENS S.C. Niepubliczny Zaklad
🇵🇱Chelm Slaski, Poland
Malopolskie Centrum Medyczne s.c.
🇵🇱Krakow, Poland
Centrum Medyczne OSTEOMED Sp. z o. o.
🇵🇱Warszawa, Poland
Niepubliczny Zaklad Opieki Zdrowotnej "POLIMEDICA"
🇵🇱Zgierz, Poland
Clinical Emergency Military Hospital "Dr. Carol Davila"
🇷🇴Bucharest, Romania
Duo Medical srl
🇷🇴Bucharest, Romania
Medical Center "SANA"
🇷🇴Bucharest, Romania
Center of Rheumatology "Dr Ion Stoia"
🇷🇴Bucharest, Romania
County Emergency Clinic Hospital "Sf. Apostol Andrei"
🇷🇴Galati, Romania
St. Petersburg State Healthcare Institution "City Hospital #25 City Rheumatology Center"
🇷🇺St. Petersburg, Russian Federation
St. Petersburg State Healthcare Institution "City Pokrovskaya Hospital"
🇷🇺St. Petersburg, Russian Federation
Hospital Nuestra Señora de la Esperanza
🇪🇸Santiago de Compostela, A Coruna, Spain
Hospital de Basurto
🇪🇸Bilbao, Vizcaya, Spain
Hospital Comarcal de Elda
🇪🇸Elda Alicante, Spain
Hospital Universitario Getafe
🇪🇸Getafe-Madrid, Spain
Hospital G. U. Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Clinico Universitario Santiago
🇪🇸Santiago de Compostela, Spain
Me3plus AB
🇸🇪Goteborg, Sweden
Center for Lakemedelsstudier
🇸🇪Malmo, Sweden
Medicinskt Centrum
🇸🇪Norrkoping, Sweden
Road Clinical Hospital at Dnipropetrovsk station, Department of Rheumatology
🇺🇦Dnipropetrovsk, Ukraine
Institute of Urgent and Recovery Surgery named after V.K. Gusaka AMS Ukraine
🇺🇦Donetsk, Ukraine
Central City Clinical Hospital#1, Department of Therapy,
🇺🇦Donetsk, Ukraine
Ivano-Frankivsk Regional Clinical Hospital
🇺🇦Ivano-Frankivsk, Ukraine
City Clinical Hospital #8, Department of reumatology,
🇺🇦Kharkiv, Ukraine
State Institution "Institute of Gerontology AMS of Ukraine"
🇺🇦Kiev, Ukraine
Kyiv Central Basin Clinical Hospital, Department of cardiology,
🇺🇦Kyiv, Ukraine
City communal clinical hospital #5, Dept. of Therapy, Danylo Galytskiy Lviv National Med. University
🇺🇦Lviv, Ukraine
Communal Institution Ternopil regional council, "Ternopil Regional Clinical Hospital"
🇺🇦Ternopil, Ukraine
Communal institution "City Hospital #7", Department of Therapy,
🇺🇦Zaporizhzhia, Ukraine
Barnsley Hospital NHS Trust
🇬🇧Barnsley, South Yorkshire, United Kingdom
Wrightington Hospital
🇬🇧Wigan, United Kingdom
Herz Apotheke
🇩🇪Bochum, Germany
LKH-Medizinische Universitatsklinik Graz
🇦🇹Graz, Austria
Center polyclinic of Federal State Institution
🇷🇺Arkhangelsk, Russian Federation
Chair of Hospital Therapy of Ryazan State Medical University
🇷🇺Ryazan, Russian Federation
Chernivtsi Regional Clinical Hospital,Department of Rheumatology
🇺🇦Chernivtsi, Ukraine
Department of Rheumatology
🇬🇧Dudley, West Midlands, United Kingdom
State Educational Institution of Additional Professional Education
🇷🇺St. Petersburg, Russian Federation
Institution of Russian Academy of Sciences "St. Petersburg Clinical Hospital of RAS"
🇷🇺St. Petersburg, Russian Federation
Municipal Hospital No. 1 "Schuller"
🇷🇴Ploiesti, District Prahova, Romania
Clinical Hospital "Sf. Maria"
🇷🇴Bucharest, Romania
4th City Communal Clinical Hospital, Department of Rheumatology,
🇺🇦Lviv, Ukraine
Vinnytsya regional clinical hospital named after M.I. Pyrogova
🇺🇦Vinnytsya, Ukraine
Synexus SCM Sp. z o.o.
🇵🇱Wroclaw, Poland
Centro Salud Petrer 1
🇪🇸Petrer, Alicante, Spain
Clinical Emergency County Hospital Constanta
🇷🇴Constanta, Romania
St. Petersburg State Healthcare Institution "City Outpatient Clinical #51"
🇷🇺St. Petersburg, Russian Federation
State Healthcare Institution of Moscow city "City Clinical Hospital #15 n.a. O. M. Filatov"
🇷🇺Moscow, Russian Federation
Oleksandrivska Clinical Hospital in Kyiv-Department of Rheumatology # 1
🇺🇦Kyiv, Ukraine