A Study to Compare Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) Monotherapy in Adults With Rheumatoid Arthritis (RA) Who Have Not Previously Taken Methotrexate
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT02706873
- Lead Sponsor
- AbbVie
- Brief Summary
The objectives of Period 1 were the following:
* To compare the safety and efficacy of upadacitinib 7.5 mg once daily (QD) monotherapy (for participants in Japan only), 15 mg QD monotherapy, and 30 mg QD monotherapy versus weekly methotrexate monotherapy for the treatment of signs and symptoms of RA in methotrexate-naïve adults with moderately to severely active RA;
* To compare the efficacy of upadacitinib 15 mg QD monotherapy and upadacitinib 30 mg QD monotherapy versus weekly methotrexate monotherapy for prevention of structural progression in methotrexate-naïve adults with moderately to severely active RA.
The objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 7.5 mg QD (for participants in Japan only), 15 mg QD, and 30 mg QD in adults with RA who have completed Period 1.
- Detailed Description
This study includes 2 periods (a 48-week double-blind treatment period and a long-term extension period) and a Japan substudy. In Period 1 participants will be randomized in a 1:1:1 ratio to treatment Groups 2, 3, and 4 below, except for participants from Japan, who will be randomized in a 2:1:1:1 ratio to Groups 1, 2, 3, and 4:
* Group 1: Upadacitinib 7.5 mg once daily (QD) monotherapy (participants in Japan only)
* Group 2: Upadacitinib 15 mg QD monotherapy
* Group 3: Upadacitinib 30 mg QD monotherapy
* Group 4: Methotrexate monotherapy
Rescue therapy is defined for Weeks 12 through 24, Week 26, and Weeks 36 through 40. Starting at Week 12 through Week 24, participants who do not achieve ≥ 20% improvement in both tender joint count (TJC) and swollen joint count (SJC) compared with baseline at two consecutive visits will continue on their blinded therapy and the Investigator should optimize (initiate or increase) background RA medications: non-steroidal anti-inflammatory drug(s) (NSAIDs), corticosteroids (oral ≤ 10 mg/day prednisone equivalent or prednisone equivalent ≤ 0.5 mg/kg/day for 3 consecutive days) and/or low-potency analgesics.
Rescue therapy for participants who meet the following criteria at Week 26 are as follows:
Participants who do not achieve clinical remission (CR) based on Clinical Disease Activity Index (CDAI) (defined as a CDAI score ≤ 2.8):
* but achieve ≥ 20% improvement in both TJC and SJC compared with baseline will continue on blinded study drug and the Investigator should optimize (initiate or increase) background RA medications: NSAIDs, corticosteroids (oral ≤ 10 mg/day prednisone equivalent and up to 2 local injections), low-potency analgesics and conventional synthetic disease-modifying anti-rheumatic drug(s) (csDMARDs) (only 1 of the following: sulfasalazine, hydroxychloroquine or chloroquine) throughout the remainder of Period 1 and until the study is unblinded.
* and do not achieve ≥ 20% improvement in both TJC and SJC compared with baseline and originally assigned to methotrexate will be re-randomized in a 1:1 ratio to receive blinded upadacitinib 15 mg QD or upadacitinib 30 mg QD (participants in Japan will be randomized 1:1:1 to receive upadacitinib 7.5 mg QD, 15 mg QD, or 30 mg QD) while continuing methotrexate treatment in a blinded manner until the study is unblinded. Participants originally assigned to upadacitinib will add methotrexate 10 mg/week (7.5 mg for Japan) to upadacitinib in a blinded manner and will remain on upadacitinib plus methotrexate 10 mg/week (7.5 mg for Japan) until the study is unblinded.
Starting at Week 36 through Week 40, participants who do not achieve ≥ 20% improvement in both TJC and SJC compared with baseline at two consecutive visits will continue on their blinded therapy and the Investigator should optimize (initiate or increase) background RA medications: NSAIDs, corticosteroids (oral ≤ 10 mg/day prednisone equivalent or prednisone equivalent ≤ 0.5 mg/kg/day for 3 consecutive days and up to 2 local injections), low-potency analgesics and csDMARDs (only 1 of the following: sulfasalazine, hydroxychloroquine or chloroquine).
Participants who complete the Week 48 visit (end of Period 1) will enter the long-term extension, Period 2 (212 weeks) and continue study treatment per assignment at the end of Period 1 in a blinded fashion. When the last participant completes the last visit of Period 1 (Week 48), study drug assignment in both periods may be unblinded, and participants will be dispensed study drug in an open-label fashion until the completion of Period 2. Starting with Protocol Amendment 6, participants receiving upadacitinib 15 mg and 30 mg QD will receive open-label upadacitinib 15 mg QD, and participants receiving methotrexate will receive open-label methotrexate.
A global analysis will be conducted for the comparisons of the primary and secondary efficacy endpoints between the upadacitinib 15 mg QD and 30 mg QD treatment groups versus the methotrexate treatment group for all participants (excluding the Japan specific upadacitinib 7.5 mg treatment group). Analyses will be conducted separately for United States (US)/Food and Drug Administration (FDA), European Union (EU)/European Medicines Agency (EMA), and Japan/Pharmaceuticals and Medical Devices Agency (PMDA) regulatory purposes, each according to a pre-specified sequence of primary and ranked secondary endpoints.
A separate Japan sub-study analysis will be conducted for the comparisons of the efficacy endpoints between the upadacitinib 7.5 mg QD, 15 mg QD, and 30 mg QD treatment groups versus the methotrexate treatment group for participants enrolled in Japan only.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1002
-
Duration of symptoms consistent with RA for ≥ 6 weeks who also fulfill the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA.
-
Naïve to Methotrexate (MTX) or, if already on MTX, have received no more than 3 weekly MTX doses with requirement to complete a 4-week MTX washout before the first dose of study drug.
-
Participants with prior exposure to conventional synthetic disease-modifying anti-rheumatic drugs(csDMARDs) other than MTX may be enrolled if completed the washout period.
-
Participant meets both of the following minimum disease activity criteria:
-≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
-
high sensitivity C reactive protein (hsCRP) ≥ 5 mg/L (central lab, upper limit of normal [ULN] 2.87 mg/L at Screening Visit.
-
Greater than or equal to 1 bone erosion on x-ray (by local reading) OR in the absence of documented bone erosion, both positive rheumatoid factor (RF) and positive anti-cyclic citrullinated peptide (anti CCP) autoantibodies are required at Screening.
-
Stable dose of non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, oral corticosteroids (equivalent to prednisone ≤ 10 mg/day), or inhaled corticosteroids for stable medical conditions are allowed but must have been at a stable dose ≥ 1 week prior to the first dose of study drug.
- Intolerant to Methotrexate (MTX).
- Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
- Prior exposure to any biologic disease-modifying anti-rheumatic drugs (bDMARDs).
- History of any arthritis with onset prior to age 17 years or current diagnosis, inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms]. Current diagnosis of secondary Sjogren's Syndrome is permitted.
- Has been treated with intra-articular, intramuscular, intravenous, trigger point or tender point, intra-bursa, or intra-tendon sheath corticosteroids in the preceding 8 weeks prior to the first dose of study drug.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Upadacitinib 7.5 mg (Japan-only) Placebo to Methotrexate Period 1: Participants will receive upadacitinib 7.5 mg once daily and placebo to methotrexate once weekly for 48 weeks. Period 2: Participants will continue on upadacitinib 7.5 mg once daily and placebo to methotrexate once weekly until the study is unblinded, after which participants will receive open-label upadacitinib 7.5 mg up to Week 260. Upadacitinib 15 mg Placebo to Methotrexate Period 1: Participants will receive upadacitinib 15 mg once daily and placebo to methotrexate once weekly for 48 weeks. Period 2: Participants will continue on upadacitinib 15 mg once daily and placebo to methotrexate once weekly until the study is unblinded, after which participants will receive open-label upadacitinib 15 mg up to Week 260. Methotrexate Placebo to Upadacitinib Period 1: Participants will receive placebo to upadacitinib once daily and methotrexate once weekly for 48 weeks. Period 2: Participants will continue on placebo to upadacitinib once daily and methotrexate once weekly until the study is unblinded, after which participants will receive open-label methotrexate up to Week 260. Upadacitinib 30 mg Placebo to Methotrexate Period 1: Participants will receive upadacitinib 30 mg once daily and placebo to methotrexate once weekly for 48 weeks. Period 2: Participants will continue on upadacitinib 30 mg once daily and placebo to methotrexate once weekly until the study is unblinded, after which participants will receive open-label upadacitinib 30 mg once daily. After implementation of Protocol Amendment 6 participants will receive upadacitinib 15 mg once daily up to Week 260. Methotrexate Methotrexate Period 1: Participants will receive placebo to upadacitinib once daily and methotrexate once weekly for 48 weeks. Period 2: Participants will continue on placebo to upadacitinib once daily and methotrexate once weekly until the study is unblinded, after which participants will receive open-label methotrexate up to Week 260. Upadacitinib 7.5 mg (Japan-only) Upadacitinib Period 1: Participants will receive upadacitinib 7.5 mg once daily and placebo to methotrexate once weekly for 48 weeks. Period 2: Participants will continue on upadacitinib 7.5 mg once daily and placebo to methotrexate once weekly until the study is unblinded, after which participants will receive open-label upadacitinib 7.5 mg up to Week 260. Upadacitinib 15 mg Upadacitinib Period 1: Participants will receive upadacitinib 15 mg once daily and placebo to methotrexate once weekly for 48 weeks. Period 2: Participants will continue on upadacitinib 15 mg once daily and placebo to methotrexate once weekly until the study is unblinded, after which participants will receive open-label upadacitinib 15 mg up to Week 260. Upadacitinib 30 mg Upadacitinib Period 1: Participants will receive upadacitinib 30 mg once daily and placebo to methotrexate once weekly for 48 weeks. Period 2: Participants will continue on upadacitinib 30 mg once daily and placebo to methotrexate once weekly until the study is unblinded, after which participants will receive open-label upadacitinib 30 mg once daily. After implementation of Protocol Amendment 6 participants will receive upadacitinib 15 mg once daily up to Week 260.
- Primary Outcome Measures
Name Time Method Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Global Analysis Baseline to Week 24 The second primary endpoint for Japan/PMDA regulatory purposes was change from baseline in mTSS at Week 24.
The mTSS measures the level of joint damage from radiographs of the hands and feet. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers.
Joint erosion was assessed in 16 joints in each hand/wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
JSN was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst). A change from Baseline greater than 0 indicates progression.Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 - Global Analysis Baseline and Week 12 The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 50% response (ACR50) at Week 12. Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria:
1. ≥ 50% improvement in 68-tender joint count;
2. ≥ 50% improvement in 66-swollen joint count; and
3. ≥ 50% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity
* Patient global assessment of disease activity
* Patient assessment of pain
* Health Assessment Questionnaire - Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP).Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Global Analysis Week 24 The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was clinical remission, based on a Disease Activity Score 28 (DAS28)-CRP score of \< 2.6 at Week 24.
The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28 score less than 2.6 indicates clinical remission.Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 - Global Analysis Baseline and Week 12 The primary endpoint for Japan/Pharmaceuticals and Medical Devices Agency (PMDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria:
1. ≥ 20% improvement in 68-tender joint count;
2. ≥ 20% improvement in 66-swollen joint count; and
3. ≥ 20% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity
* Patient global assessment of disease activity
* Patient assessment of pain
* Health Assessment Questionnaire - Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP).
- Secondary Outcome Measures
Name Time Method Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Global Analysis Baseline to week 12 The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.
A negative change from Baseline in the overall score indicates improvement.Change From Baseline in DAS28 (CRP) at Week 24 - Global Analysis Baseline to Week 24 The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 - Global Analysis Baseline to Week 24 The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.
A negative change from Baseline in the overall score indicates improvement.Change From Baseline in DAS28 (CRP) at Week 12 - Global Analysis Baseline to Week 12 The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
Percentage of Participants With an ACR50 Response at Week 24 - Global Analysis Baseline and Week 24 Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria:
1. ≥ 50% improvement in 68-tender joint count;
2. ≥ 50% improvement in 66-swollen joint count; and
3. ≥ 50% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity
* Patient global assessment of disease activity
* Patient assessment of pain
* Health Assessment Questionnaire - Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP).Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Global Analysis Week 12 The DAS28(CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28(CRP) score less than or equal to 3.2 indicates low disease activity.Percentage of Participants With No Radiographic Progression at Week 24 - Global Analysis Week 24 No radiographic progression is defined as a change from Baseline in mTSS ≤ 0. The mTSS measures the level of joint damage from radiographs of the hands and feet. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers.
Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
Joint space narrowing (JSN) was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst).Percentage of Participants With an ACR20 Response at Week 24 - Global Analysis Baseline and Week 24 Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria:
1. ≥ 20% improvement in 68-tender joint count;
2. ≥ 20% improvement in 66-swollen joint count; and
3. ≥ 20% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity
* Patient global assessment of disease activity
* Patient assessment of pain
* Health Assessment Questionnaire - Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP).Percentage of Participants With an ACR70 Response at Week 24 - Global Analysis Baseline and Week 24 Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria:
1. ≥ 70% improvement in 68-tender joint count;
2. ≥ 70% improvement in 66-swollen joint count; and
3. ≥ 70% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity
* Patient global assessment of disease activity
* Patient assessment of pain
* Health Assessment Questionnaire - Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP).Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Global Analysis Baseline to week 12 The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 24 - Global Analysis Week 24 The DAS28(CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28(CRP) score less than or equal to 3.2 indicates low disease activity.Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 24 - Global Analysis Baseline to Week 24 The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 - Global Analysis Baseline and Week 12 Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria:
1. ≥ 70% improvement in 68-tender joint count;
2. ≥ 70% improvement in 66-swollen joint count; and
3. ≥ 70% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity
* Patient global assessment of disease activity
* Patient assessment of pain
* Health Assessment Questionnaire - Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP).Percentage of Participants With an ACR20 Response at Week 12 - Japan Sub-study Baseline and Week 12 Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria:
1. ≥ 20% improvement in 68-tender joint count;
2. ≥ 20% improvement in 66-swollen joint count; and
3. ≥ 20% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity
* Patient global assessment of disease activity
* Patient assessment of pain
* Health Assessment Questionnaire - Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP).Percentage of Participants With an ACR50 Response at Week 12 - Japan Sub-study Baseline and Week 12 Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria:
1. ≥ 50% improvement in 68-tender joint count;
2. ≥ 50% improvement in 66-swollen joint count; and
3. ≥ 50% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity
* Patient global assessment of disease activity
* Patient assessment of pain
* Health Assessment Questionnaire - Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP).Percentage of Participants With an ACR70 Response at Week 12 - Japan Sub-study Baseline and Week 12 Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria:
1. ≥ 70% improvement in 68-tender joint count;
2. ≥ 70% improvement in 66-swollen joint count; and
3. ≥ 70% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity
* Patient global assessment of disease activity
* Patient assessment of pain
* Health Assessment Questionnaire - Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP).Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Japan Sub-study Baseline to week 12 The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.
A negative change from Baseline in the overall score indicates improvement.Percentage of Participants With No Radiographic Progression at Week 24 - Japan Sub-study Week 24 No radiographic progression is defined as a change from Baseline in mTSS ≤ 0. The mTSS measures the level of joint damage from radiographs of the hands and feet. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers.
Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
Joint space narrowing (JSN) was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst).Change From Baseline in DAS28 (CRP) at Week 12 - Japan Sub-study Baseline to Week 12 The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Japan Sub-study Week 12 The DAS28(CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28(CRP) score less than or equal to 3.2 indicates low disease activity.Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Japan Sub-study Week 24 The DAS28(CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28 score less than 2.6 indicates clinical remission.Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Japan Sub-study Baseline to Week 12 The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Japan Sub-study Baseline to Week 24 The mTSS measures the level of joint damage from radiographs of the hands and feet. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers.
Joint erosion was assessed in 16 joints in each hand/wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
JSN was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst). A change from Baseline greater than 0 indicates progression.
Trial Locations
- Locations (290)
Hokkaido University Hospital /ID# 148262
🇯🇵Sapporo, Japan
TriWest Research Associates- La Mesa /ID# 143738
🇺🇸La Mesa, California, United States
Desert Medical Advances /ID# 143730
🇺🇸Palm Desert, California, United States
International Medical Research - Daytona /ID# 143748
🇺🇸Daytona Beach, Florida, United States
Millennium Research /ID# 143736
🇺🇸Ormond Beach, Florida, United States
Arthritis Research of Florida /ID# 143743
🇺🇸Palm Harbor, Florida, United States
Sarasota Arthritis Center /ID# 145978
🇺🇸Sarasota, Florida, United States
FL Med Clinic, PA /ID# 143744
🇺🇸Zephyrhills, Florida, United States
Deerbrook Medical Associates /ID# 143728
🇺🇸Vernon Hills, Illinois, United States
Ocean Rheumatology, PA /ID# 143737
🇺🇸Toms River, New Jersey, United States
Four Rivers Clinical Research /ID# 143741
🇺🇸Paducah, Kentucky, United States
STAT Research, Inc. /ID# 143750
🇺🇸Vandalia, Ohio, United States
Arthritis Rheumatic Back Disorder /ID# 143733
🇺🇸Voorhees, New Jersey, United States
Trinity Health Med Arts Clinic /ID# 143727
🇺🇸Minot, North Dakota, United States
Healthcare Research Consultant /ID# 143747
🇺🇸Tulsa, Oklahoma, United States
Advanced Rheumatology & Arthri /ID# 147947
🇺🇸Wexford, Pennsylvania, United States
Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 145653
🇺🇸Summerville, South Carolina, United States
Dr. Ramesh Gupta /ID# 143732
🇺🇸Memphis, Tennessee, United States
West Tennessee Research Inst /ID# 143723
🇺🇸Jackson, Tennessee, United States
Diagnostic Group Integrated He /ID# 152921
🇺🇸Beaumont, Texas, United States
Adriana Pop-Moody MD Clinic PA /ID# 147626
🇺🇸Corpus Christi, Texas, United States
SW Rheumatology Res. LLC /ID# 143745
🇺🇸Mesquite, Texas, United States
Rheumatic Disease Clin Res Ctr /ID# 151103
🇺🇸Houston, Texas, United States
Accurate Clinical Research /ID# 143749
🇺🇸Houston, Texas, United States
Doctor's Hosp at Renaissance /ID# 156407
🇺🇸Edinburg, Texas, United States
MedResearch Inc. /ID# 156409
🇺🇸El Paso, Texas, United States
Arthritis & Osteoporosis Clinic /ID# 159542
🇺🇸Waco, Texas, United States
Arthritis Clinic of Central TX /ID# 159541
🇺🇸San Marcos, Texas, United States
Arthritis Clinic of N. VA, P.C /ID# 143734
🇺🇸Arlington, Virginia, United States
Instituto CAICI /ID# 143141
🇦🇷Rosario, Santa FE, Argentina
Iari /Id# 148595
🇦🇷San isidro, Buenos Aires, Argentina
Org Medica de Investigacion /ID# 143142
🇦🇷Buenos Aires, Argentina
Consultora Integral de Salud S /ID# 143144
🇦🇷Cordoba, Argentina
Centro Integral de Reumatologi /ID# 143143
🇦🇷San Miguel de Tucuman, Argentina
Centro Medico Privado/Reuma /ID# 143140
🇦🇷San Miguel de Tucuman, Argentina
Rheumatology Research Unit /ID# 143147
🇦🇺Maroochydore, Queensland, Australia
Royal Prince Alfred Hospital /ID# 143149
🇦🇺Camperdown, New South Wales, Australia
The Queen Elizabeth Hospital /ID# 143148
🇦🇺Woodville, South Australia, Australia
Southern Clinical Research Pty /ID# 143150
🇦🇺Hobart, Tasmania, Australia
Emeritus Research /ID# 143146
🇦🇺Camberwell, Victoria, Australia
First City Clinical Hospital /ID# 159020
🇧🇾Minsk, Belarus
Rhumaconsult SPRL /ID# 143158
🇧🇪Charleroi, Hainaut, Belgium
UZ Gent /ID# 143157
🇧🇪Gent, Oost-Vlaanderen, Belgium
ReumaClinic Genk /ID# 143159
🇧🇪Genk, Belgium
CHU Ambroise Pare /ID# 152955
🇧🇪Mons, Belgium
Clinical Center University of Sarajevo /ID# 143164
🇧🇦Sarajevo, Bosnia and Herzegovina
Ceti - Centro de Estudos Em Terapias Inovadoras Ltda /Id# 143169
🇧🇷Curitiba, Parana, Brazil
LMK Sevicos Medicos S/S /ID# 143167
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
CIP - Centro Internacional de Pesquisa /ID# 143171
🇧🇷Goiânia, Goias, Brazil
UMHAT Pulmed OOD /ID# 143176
🇧🇬Plovdiv, Bulgaria
MHAT Trimontsium /ID# 143173
🇧🇬Plovdiv, Bulgaria
CCBR Brasil /ID# 150925
🇧🇷Rio de Janeiro, Brazil
MHAT Kaspela /ID# 143172
🇧🇬Plovdiv, Bulgaria
UMHAT Sv. Ivan Rilski /ID# 143175
🇧🇬Sofia, Bulgaria
Manitoba Clinic /ID# 143203
🇨🇦Winnipeg, Manitoba, Canada
CA Ctr for Clin Trials CCCT /ID# 159080
🇨🇦Thornhill, Ontario, Canada
Ctr de Inv Clinica del Sur /ID# 143208
🇨🇱Temuco, Araucania, Chile
Someal /Id# 143207
🇨🇱Providencia, Santiago, Chile
Quantum Research LTDA. /ID# 143210
🇨🇱Puerto Varas, Chile
Quantum Research Stgo. /ID# 145651
🇨🇱Santiago, Chile
1st Aff Hosp of Bengbu Med Col /ID# 162974
🇨🇳Bengbu, Anhui, China
Investigaciones Medicas SSMSO /ID# 151685
🇨🇱Santiago, Chile
1st Aff Hosp of Shantou Univ /ID# 162968
🇨🇳Shantou, Guangdong, China
Riesgo de Fractura S.A - CAYRE /ID# 143212
🇨🇴Bogota, Colombia
Fund Inst de Reum F. Chalem /ID# 159544
🇨🇴Bogotá, Colombia
Medicity S.A.S. /ID# 143213
🇨🇴Bucaramanga, Colombia
Klinicki bolnicki centar Split /ID# 143216
🇭🇷Split, Croatia
Clinical Hospital Dubrava /ID# 143217
🇭🇷Zagreb, Croatia
Poliklinika Bonifarm /ID# 143215
🇭🇷Zagreb, Croatia
L.K.N. Arthrocentrum, s.r.o /ID# 143224
🇨🇿Hlučín, Moravskoslezsky Kraj, Czechia
CTCenter MaVe, s.r.o. /ID# 143226
🇨🇿Olomouc, Olomoucky Kraj, Czechia
Nuselská poliklinika, Revmatologie /ID# 143232
🇨🇿Prague 4, Praha 4, Czechia
Nuselská poliklinika, Revmatologie /ID# 143233
🇨🇿Prague 4, Praha 4, Czechia
Thomayerova nemocnice /ID# 143228
🇨🇿Prague, Praha 4, Czechia
PV MEDICAL Services s.r.o. /ID# 143234
🇨🇿Zlín 1, Zlin, Czechia
RHEUMA s.r.o. /ID# 143230
🇨🇿Breclav, Czechia
Revmatologie, s.r.o. /ID# 143223
🇨🇿Brno, Czechia
Revmatologie Bruntal, s.r.o /ID# 143220
🇨🇿Bruntál, Czechia
Nemocnice Slany /ID# 143221
🇨🇿Slany, Czechia
Medical Plus, s.r.o. /ID# 143219
🇨🇿Uherské Hradište, Czechia
Center of Clinical and Basic Research /ID# 143239
🇪🇪Tallinn, Harjumaa, Estonia
Paernu Hospital /ID# 143238
🇪🇪Pärnu, Estonia
East Tallinn Central Hospital /ID# 143240
🇪🇪Tallinn, Estonia
Praxis Walter, Rendsburg /ID# 143250
🇩🇪Rendsburg, Schleswig-Holstein, Germany
Rheumazentrum Ruhrgebiet /ID# 145652
🇩🇪Herne, Nordrhein-Westfalen, Germany
Rheumaforschungszentrum II /ID# 143247
🇩🇪Hamburg, Germany
Uniklinik Koln /ID# 143248
🇩🇪Köln, Nordrhein-Westfalen, Germany
LMU Klinikum der Universität München /ID# 143249
🇩🇪Munich, Germany
Schoen Klinikum Hamburg Eilbek /ID# 143251
🇩🇪Hamburg, Germany
Clinicas Hospital Herrera Ller /ID# 153715
🇬🇹Ciudad de Guatemala, Guatemala
Clin Especializada Med Interna /ID# 153716
🇬🇹Ciudad de Guatemala, Guatemala
Clinica Medica Reumatologia /ID# 153714
🇬🇹Ciudad de Guatemala, Guatemala
Queen Mary Hospital /ID# 143255
🇭🇰Hong Kong, Hong Kong
CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 143258
🇭🇺Miskolc, Borsod-Abauj-Zemplen, Hungary
Markusovszky Egyetemi Oktatókórház /ID# 143261
🇭🇺Szombathely, Vas, Hungary
Fejer Megyei Szent Gyorgy Korh /ID# 144724
🇭🇺Szekesfehervar, Hungary
St Vincent's University Hosp /ID# 143262
🇮🇪Dublin, Ireland
Barzilai Medical Center /ID# 144725
🇮🇱Ashkelon, Israel
Azienda Ospedaliera Luigi Sacc /ID# 143270
🇮🇹Milan, Italy
Rambam Health Care Campus /ID# 143263
🇮🇱Haifa, Israel
Istituto Clinico Humanitas /ID# 147531
🇮🇹Rozzano, Milano, Italy
Sheba Medical Center /ID# 145975
🇮🇱Ramat Gan, Israel
Fondazione IRCCS Policlinico /ID# 143265
🇮🇹Pavia, Italy
Nagoya University Hospital /ID# 148031
🇯🇵Nagoya-shi, Aichi, Japan
A.O.U.I. di Verona Policlinico /ID# 143266
🇮🇹Verona, Italy
NHO Kyushu Medical Center /ID# 148263
🇯🇵Fukuoka-shi, Fukuoka, Japan
NHO Kyushu Medical Center /ID# 148264
🇯🇵Fukuoka-shi, Fukuoka, Japan
Teikyo University Chiba Medical Center /ID# 159618
🇯🇵Ichihara, Chiba, Japan
National Hospital Organization Sagamihara National Hospital /ID# 148019
🇯🇵Sagamihara-shi, Kanagawa, Japan
Kobe University Hospital /ID# 153461
🇯🇵Kobe, Hyogo, Japan
Center for Arthritis and Clinical Rheumatology Matsubara Clinic /ID# 148254
🇯🇵Kumamoto-shi, Kumamoto, Japan
Bay Side Misato Medical Center /ID# 148256
🇯🇵Kochi-shi, Kochi, Japan
Kumamoto Orthopaedic Hospital /ID# 148054
🇯🇵Kumamoto-shi, Kumamoto, Japan
Nagaoka Red Cross Hospital /ID# 148018
🇯🇵Nagaoka-shi, Niigata, Japan
Japanese Red Cross Okayama Hospital /ID# 159619
🇯🇵Okayama-shi, Okayama, Japan
Kumamoto Shinto General Hospital /ID# 148266
🇯🇵Kumamoto-shi, Kumamoto, Japan
Sasebo Chuo Hospital /ID# 148261
🇯🇵Sasebo-city, Nagasaki, Japan
Kansai Medical University Hospital /ID# 159622
🇯🇵Hirakata-shi, Osaka, Japan
Saitama Medical Center, Saitama Medical University /ID# 148015
🇯🇵Kawagoe-shi, Saitama, Japan
Osaka Medical College Hospital /ID# 159624
🇯🇵Takatsuki -shi, Osaka, Japan
Juntendo University Hospital /ID# 148050
🇯🇵Bunkyo-ku, Tokyo, Japan
Jichi Medical University Hospital /ID# 159620
🇯🇵Shimotsuke-shi, Tochigi, Japan
Toho University Ohashi Medical Center /ID# 148027
🇯🇵Meguro-ku, Tokyo, Japan
Keio University Hospital /ID# 148057
🇯🇵Shinjuku-ku, Tokyo, Japan
Tokito Clinic Rheumatology and Orthopaedics Surgery /ID# 148052
🇯🇵Shimonoseki-shi, Yamaguchi, Japan
Sugimoto Rheumatology and Internal Medicine Clinic /ID# 148047
🇯🇵Fukui, Japan
Shono Rheumatism Clinic /ID# 148046
🇯🇵Fukuoka, Japan
Matsubara Mayflower Hospital /ID# 148033
🇯🇵Kato, Japan
St. Mary's Hospital /ID# 148038
🇯🇵Kurume, Japan
Oribe Clinic of Rheumatology and Internal Medicine /ID# 156035
🇯🇵Oita, Japan
Osaka City General Hospital /ID# 159617
🇯🇵Osaka, Japan
Sapporo City General Hospital /ID# 148037
🇯🇵Sapporo, Japan
Azuma Rheumatology Clinic /ID# 161050
🇯🇵Sayama, Japan
Hikarigaoka Spellman Hospital /ID# 148020
🇯🇵Sendai, Japan
FL Med Ctr and Research, Inc. /ID# 143724
🇺🇸Miami, Florida, United States
Sun Research Institute /ID# 159546
🇺🇸San Antonio, Texas, United States
Accurate Clinical Management /ID# 159543
🇺🇸San Antonio, Texas, United States
NextGen Clinical Trials LLP /ID# 150930
🇺🇸San Antonio, Texas, United States
National Hospital Organization Tokyo Medical Center /ID# 148040
🇯🇵Tokyo, Japan
Takaoka Rheumatic Orthopedic Clinic /ID# 148022
🇯🇵Takaoka, Japan
JSC Nat Scientific Med Res Ctr /ID# 143272
🇰🇿Astana, Kazakhstan
Karaganda State Medical Univ /ID# 153431
🇰🇿Karaganda, Kazakhstan
LTD M+M Centers /ID# 143279
🇱🇻Adazi, Latvia
Vilnius University Hospital /ID# 143584
🇱🇹Vilnius, Lithuania
Clinstile, S.A. de C.V. /ID# 143591
🇲🇽Cuauhtemoc, Ciudad De Mexico, Mexico
RM Pharma Specialists, S.A de C.V /ID# 143593
🇲🇽Mexico City, Mexico
Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 143592
🇲🇽Mexico City, Mexico
Centro Especializado en Diabetes, Obesidad y Prevención de Enfermedades Cardiova /ID# 143589
🇲🇽Mexico City, Mexico
Centro Reumatologico de Queret /ID# 149493
🇲🇽Queretaro, Mexico
Waikato Hospital /ID# 143602
🇳🇿Hamilton, Waikato, New Zealand
Timaru Medical Specialists Ltd /ID# 143599
🇳🇿Timaru, New Zealand
Porter Rheumatology Ltd /ID# 143601
🇳🇿Nelson, New Zealand
Middlemore Clinical Trials /ID# 143600
🇳🇿Auckland, New Zealand
WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 143606
🇵🇱Wrocław, Dolnoslaskie, Poland
Silmedic Sp z o.o /ID# 143605
🇵🇱Katowice, Slaskie, Poland
Centro Hospitalar Lisboa Ocidental, EPE /ID# 151009
🇵🇹Lisbon, Lisboa, Portugal
Ponce School of Medicine /ID# 145657
🇵🇷Ponce, Puerto Rico
GCM Medical Group /ID# 143618
🇵🇷San Juan, Puerto Rico
Spitalul Clinic Dr. I. Cantacuzino /ID# 143622
🇷🇴Bucharest, Bucuresti, Romania
School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 143619
🇵🇷San Juan, Puerto Rico
Spitalul Clinic Sf. Maria /ID# 143623
🇷🇴Bucuresti, Romania
Spitalul Clinic de Recuperare /ID# 143620
🇷🇴Iasi, Romania
LLC Medical Center /ID# 143647
🇷🇺Novosibirsk, Novosibirskaya Oblast, Russian Federation
Kazan State Medical University /ID# 143645
🇷🇺Kazan, Tatarstan, Respublika, Russian Federation
Tver Regional Clinical Hosp. /ID# 143639
🇷🇺Tver, Tverskaya Oblast, Russian Federation
Russian National Research Medi /ID# 143642
🇷🇺Moscow, Russian Federation
Orenburg Regional Clinical Hos /ID# 143630
🇷🇺Orenburg, Russian Federation
Reg Clin Hosp n.a. Kuvatova G. /ID# 143632
🇷🇺UFA, Russian Federation
Ryazan State Medical Universit /ID# 143646
🇷🇺Ryazan, Russian Federation
Samara Regional Clinical Hosp /ID# 150928
🇷🇺Samara, Russian Federation
Voronezh State Medical Univers /ID# 150926
🇷🇺Voronezh, Russian Federation
MEDMAN s.r.o. /ID# 143661
🇸🇰Martin, Slovakia
Reumatologická ambulancia Reum.hapi s.r.o. /ID# 143657
🇸🇰Nové Mesto Nad Váhom, Slovakia
TIMMED spol. s r.o. /ID# 143664
🇸🇰Stará Lubovna, Slovakia
MEDEOS s.r.o. /ID# 143656
🇸🇰Trencin, Slovakia
Slovak Research Center /ID# 143659
🇸🇰Puchov, Slovakia
Reumatologicka ambulancia, LER /ID# 143660
🇸🇰Topolcany, Slovakia
ALBAMED s.r.o. /ID# 143654
🇸🇰Zvolen, Slovakia
REUMA-GLOBAL, s.r.o. /ID# 143655
🇸🇰Trnava, Slovakia
Reuma -MUDr. Maria Palasthyova /ID# 143662
🇸🇰Žiar nad Hronom, Slovakia
Univ Medical Ctr Ljubljana /ID# 143667
🇸🇮Ljubljana, Slovenia
Jakaranda Hosp, Emmed Research /ID# 143668
🇿🇦Pretoria, Gauteng, South Africa
Jakaranda Hosp, Emmed Research /ID# 145976
🇿🇦Pretoria, Gauteng, South Africa
H. Un. Marques de Valdecilla /ID# 143671
🇪🇸Santander, Cantabria, Spain
Hospital Univ Vall d'Hebron /ID# 143675
🇪🇸Barcelona, Spain
Comple Hosp Univ de A Coruna /ID# 143672
🇪🇸A Coruna, Spain
Hospital Clin Univ San Carlos /ID# 143674
🇪🇸Madrid, Spain
Clinica Gaias /ID# 143673
🇪🇸Santiago de Compostela, Spain
Hosp Nuestra Senora Esperanza /ID# 143677
🇪🇸Santiago de Compostela, Spain
HFR Fribourg - Hopital Canton /ID# 143700
🇨🇭Fribourg, Switzerland
China Medical University Hosp /ID# 143703
🇨🇳Taichung City, Taichung, Taiwan
Dalin Tzu Chi General Hospital /ID# 153535
🇨🇳Dalin, Taiwan
Hopital Mongi Slim /ID# 152870
🇹🇳La Marsa, Tunisia
Institut Mohamed Kassab /ID# 152869
🇹🇳Manouba, Tunisia
Hopital Farhat Hached /ID# 152868
🇹🇳Sousse, Tunisia
Uludag Universitesi Ataturk Rehabilitasyon ve Uygulama Merkezi /ID# 143705
🇹🇷Osmangazi, Bursa, Turkey
Izmir Tepecik Training and Research Hospital /ID# 157863
🇹🇷Konak, Izmir, Turkey
Lviv Regional Clinical Hospita /ID# 154449
🇺🇦Lviv, Lvivska Oblast, Ukraine
Izmir Katip Celebi Ataturk Training & Research Hospital /ID# 143704
🇹🇷Izmir, Turkey
Vinnytsia Regional Clinical Hospital n.a. M.I.Pyrogov /ID# 143714
🇺🇦Vinnytsia, Vinnytska Oblast, Ukraine
Regional Clinical Hospital /ID# 152029
🇺🇦Ivano-frankivsk, Ukraine
LLC Revmocentr /ID# 143710
🇺🇦Kyiv, Ukraine
Leicester Royal Infirmary /ID# 143718
🇬🇧Leicester, England, United Kingdom
Odessa National Medical Univ /ID# 143715
🇺🇦Odesa, Ukraine
Zaporizhzhia Regional Clinical /ID# 143712
🇺🇦Zaporizhia, Ukraine
Whipps Cross Univ Hospital /ID# 143721
🇬🇧London, London, City Of, United Kingdom
Western General Hospital /ID# 144431
🇬🇧Edinburgh, United Kingdom
Queen Alexandra Hospital /ID# 143722
🇬🇧Portsmouth, United Kingdom
Chapel Allerton Hospital /ID# 143717
🇬🇧Leeds, United Kingdom
Southampton General Hospital /ID# 143716
🇬🇧Southampton, United Kingdom
The 1st Aff Hosp Xiamen Univ /ID# 162076
🇨🇳Xiamen, Fujian, China
Hospital de Clinicas de Porto Alegre /ID# 143168
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
NHO Chiba-East-Hospital /ID# 148035
🇯🇵Chiba, Japan
Algemeen Stedelijk Ziekenhuis /ID# 153504
🇧🇪Aalst, Oost-Vlaanderen, Belgium
Soc. de Prestaciones medicas y Paramedicas Goecke /ID# 143209
🇨🇱Santiago, Chile
Centro de Estudios Clinicos Qu /ID# 152913
🇨🇱Vina Del Mar, Chile
Sagawa Akira Rheumatology Clin /ID# 148043
🇯🇵Sapporo, Japan
Ctr Int de Reum del Caribe SAS /ID# 143211
🇨🇴Barranquilla, Colombia
University General Hospital Attikon /ID# 143252
🇬🇷Athens, Attiki, Greece
Tuen Mun Hospital /ID# 143256
🇭🇰Tuen Mun, Hong Kong
NHO Toyohashi Medical Center /ID# 161033
🇯🇵Toyohashi-shi, Aichi, Japan
National Hospital Organization Asahikawa Medical Center /ID# 148021
🇯🇵Asahikawa, Hokkaido, Japan
St.Luke's International Hospital /ID# 148041
🇯🇵Chuo-ku, Tokyo, Japan
Daido Hospital /ID# 160868
🇯🇵Nagoya, Japan
Shirahama Hamayu Hospital /ID# 148253
🇯🇵Nishimura, Japan
Klaipeda University Hospital /ID# 143583
🇱🇹Klaipeda, Lithuania
Invest y Biomed de Chihuahua /ID# 143595
🇲🇽Chihuahua, Mexico
Centrum Medyczne Pratia Gdynia /ID# 143607
🇵🇱Gdynia, Pomorskie, Poland
NZOZ Centrum Reumatologiczne /ID# 143603
🇵🇱Elblag, Warminsko-mazurskie, Poland
Aprillus Asistencia e Investig /ID# 149179
🇦🇷Capital Federal, Buenos Aires, Argentina
Hokkaido Medical Center for Rheumatic Diseases /ID# 148259
🇯🇵Sapporo, Japan
City Clinical Hospital #9 /ID# 145650
🇧🇾Minsk, Belarus
Diagnostic Consultative Center /ID# 143174
🇧🇬Sofia, Bulgaria
Simedics IPS SAS /ID# 152572
🇨🇴Bogota, Colombia
North Estonian Medical Centre /ID# 145456
🇪🇪Tallinn, Estonia
Kagawa University Hospital /ID# 148016
🇯🇵Kyoto, Japan
Semey State Medical University /ID# 152661
🇰🇿Semey, Kazakhstan
Centro Hospitalar Lisboa Norte, EPE /ID# 143613
🇵🇹Lisboa, Portugal
Hevizgyogyfurdo es Szent Andra /ID# 143257
🇭🇺Heviz, Hungary
Pest Megyei Flor Ferenc Korhaz /ID# 143260
🇭🇺Kistarcsa, Hungary
Katayama Orthopedic Rheumatology Clinic /ID# 148029
🇯🇵Asahikawa, Hokkaido, Japan
NHO Osaka Minami Med Ctr /ID# 148042
🇯🇵Osaka, Kawachinagano-shi, Japan
Sanuki Municipal Hospital /ID# 158842
🇯🇵Sanuki, Japan
Regional Clinical Hospital /ID# 147173
🇰🇿Shymkent, Kazakhstan
Medyczne Centrum Hetmanska /ID# 144726
🇵🇱Poznań, Wielkopolskie, Poland
Centro Hospitalar de Sao Joao, EPE /ID# 153575
🇵🇹Porto, Portugal
Ecomed SRL /ID# 143629
🇷🇴Oradea, Romania
Ulyanovsk Regional Clin Hosp /ID# 143644
🇷🇺Ulyanovsk, Russian Federation
Clinical Center Serbia /ID# 143649
🇷🇸Belgrade, Beograd, Serbia
Slovak research center Team Member, Thermium s.r.o. /ID# 143663
🇸🇰Pieštany, Slovakia
National Hospital Organization Shimoshizu National Hospital /ID# 148258
🇯🇵Yotsukaido, Japan
University Clinical Centre of the Republic of Srpska /ID# 143161
🇧🇦Banja Luka, Republika Srpska, Bosnia and Herzegovina
Winelands Medical Research Ctr /ID# 143669
🇿🇦Stellenbosch, Western Cape, South Africa
Centro de Investigacion en Reumatologia y Especialidades Medicas- CIREEM SAS /ID# 143214
🇨🇴Bogota, Cundinamarca, Colombia
Medical Center Kuna-Peric /ID# 143218
🇭🇷Zagreb, Croatia
Clinica Medica Reumatologia /ID# 153931
🇬🇹Ciudad de Guatemala, Guatemala
Qualiclinic Kft. /ID# 143259
🇭🇺Budapest, Pest, Hungary
National Hospital Organization Beppu Medical Center /ID# 161058
🇯🇵Beppu, Japan
Yu Family Clinic /ID# 148048
🇯🇵Miyagi, Japan
Hosp Lithuanian Univ Health Sc /ID# 143582
🇱🇹Kaunas, Kovno, Lithuania
CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 153562
🇲🇽Mexico City, Ciudad De Mexico, Mexico
Instituto Portugues De Reumatologia /ID# 148313
🇵🇹Lisbon, Lisboa, Portugal
Unidade Local De Saude Do Alto Minho /ID# 143611
🇵🇹Viana Do Castelo, Portugal
Spitalul Clinic Sf. Maria /ID# 143625
🇷🇴Bucuresti, Romania
Family Outpatient clinic#4,LLC /ID# 151010
🇷🇺Korolev, Moskva, Russian Federation
Creer /Id# 153713
🇬🇹Ciudad de Guatemala, Guatemala
Centrum Medyczne AMED /ID# 143604
🇵🇱Warsaw, Mazowieckie, Poland
Centrum Medyczne Pratia Warszawa /ID# 143608
🇵🇱Warsaw, Mazowieckie, Poland
Centro Hosp de Tondela-Viseu /ID# 143612
🇵🇹Viseu, Portugal
Clinical Hospital No.1 n.a. N.I.Pirogov /ID# 143641
🇷🇺Moscow, Moskva, Russian Federation
NSC-Strazhesko Ist Cardiology /ID# 152026
🇺🇦Kiev, Ukraine
Centro Hospitalar De Vila Nova /ID# 143615
🇵🇹Vila Nova De Gaia, Porto, Portugal
National Taiwan Univ Hosp /ID# 143702
🇨🇳Taipei City, Taipei, Taiwan
Centro Hospitalar Baixo Vouga /ID# 153726
🇵🇹Porto, Portugal
LLC Novaya Klinika /ID# 143631
🇷🇺Pyatigorsk, Stavropol Skiy Kray, Russian Federation
Republican Clin Hos n.a. Baran /ID# 143634
🇷🇺Petrozavodsk, Russian Federation
Charles Nicolle Univ Hosp /ID# 152866
🇹🇳Tunis, Tunisia
Spitalul Clinic Sf. Maria /ID# 143627
🇷🇴Bucuresti, Romania
REUMACENTRUM s.r.o. /ID# 143653
🇸🇰Partizanske, Slovakia
MNCE "Lviv City Clinical Hospital #4" /ID# 143711
🇺🇦Lviv, Ukraine
Special Hospital for Rheuma /ID# 143648
🇷🇸Novi Sad, Vojvodina, Serbia
Arthritis Clinical Research Tr /ID# 143670
🇿🇦Cape Town, Western Cape, South Africa
Clinical Center Serbia /ID# 143650
🇷🇸Belgrade, Beograd, Serbia
Hospital La Rabta /ID# 152867
🇹🇳Tunis, Tunisia
Kondo Clinic for Ortho & Rheum /ID# 148032
🇯🇵Nagoya, Japan
Rheumatology Research Assoc /ID# 143206
🇨🇦Edmonton, Alberta, Canada
Ciads /Id# 143205
🇨🇦Winnipeg, Manitoba, Canada
Ctr. de Rheum de l'est du QC /ID# 151317
🇨🇦Rimouski, Quebec, Canada
CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos Ltda /ID# 143166
🇧🇷São Paulo, Sao Paulo, Brazil
University Clinical Centre of the Republic of Srpska /ID# 143162
🇧🇦Banja Luka, Republika Srpska, Bosnia and Herzegovina