A Study to Evaluate Efficacy and Safety of Upadacitinib in Adults With Axial Spondyloarthritis
- Registration Number
- NCT04169373
- Lead Sponsor
- AbbVie
- Brief Summary
This protocol includes 2 standalone studies with randomization, data collection, analysis and reporting conducted independently.
The main objectives of this protocol are:
* To evaluate the efficacy of upadacitinib compared with placebo on reduction of signs and symptoms in adults with active axial spondyloarthritis (axSpA) including biologic disease-modifying antirheumatic drug inadequate responders (bDMARD-IR) ankylosing spondylitis (AS) (Study 1) and non-radiographic axial spondyloarthritis (nr-axSpA) (Study 2).
* To assess the safety and tolerability of upadacitinib in adults with active axSpA including bDMARD-IR AS (Study 1) and nr-axSpA (Study 2).
* To evaluate the safety and tolerability of upadacitinib in extended treatment in adult participants with active axSpA including bDMARD-IR AS who have completed the Double-Blind Period (Study 1) and nr-axSpA who have completed the Double-Blind Period (Study 2).
* To evaluate the maintenance of disease control after withdrawal of upadacitinib.
- Detailed Description
Study 1 (bDMARD-IR AS) is comprised of a 14-week randomized, double-blind, parallel-group, placebo-controlled period (the Double-Blind Period); a 90-week open-label, long-term extension period (the Open-Label Extension Period); and a 30-day Follow-Up Visit (F/U Visit).
Study 2 (nr-axSpA) is comprised of a 52-week randomized, double-blind, parallel-group, placebo-controlled period (the Double-Blind Period); a 52-week open-label, long-term extension period (the Open-Label Extension Period); and a 30-day F/U Visit.
In the Double-Blind Period for both studies, participants are randomized in a 1:1 ratio to receive either upadacitinib or placebo once daily (QD).
Participants in the placebo group switch to upadacitinib 15 mg QD at Week 14 in the Open-Label Extension Period for Study 1 (bDMARD-IR AS) and Week 52 in the Open-Label Extension Period for Study 2 (nr-axSpA).
Participants in remission at Week 104 have the option to enroll in a remission-withdrawal period.
Study M19-944 protocol uses a common screening platform for determining eligibility into Study 1 and Study 2. Each study has its own objectives, hypothesis testing, randomization, data collection, and adequate power for primary and secondary endpoints. Analysis and reporting are conducted separately and independently for each study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 734
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Study 1:
- Must have a clinical diagnosis of ankylosing spondylitis (AS) and meet the modified New York Criteria for AS,
- Must not have total spinal ankylosis
- Must have been previously exposed to 1 or 2 bDMARDs (at least 1 tumor necrosis factor [TNF] inhibitor or 1 interleukin [IL]-17 inhibitor [IL-17i]), and must have discontinued the bDMARD therapy due to either lack of efficacy (after at least 12 weeks of treatment with a bDMARD at an adequate dose) or intolerance (irrespective of treatment duration). Prior exposure to two bDMARDs was allowed for no more than 30% of patients; among patients with prior exposure to two bDMARDs, a lack of efficacy to one bDMARD and intolerance to another was permitted, but a patient could not have a lack of efficacy to two bDMARDs
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Study 2:
- Must have a clinical diagnosis of nr-axSpA fulfilling the 2009 Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA but not meeting the radiologic criterion of the modified New York criteria for AS
- Must have objective signs of active inflammation consistent with axSpA on magnetic resonance imaging (MRI) of sacroiliac (SI) joints or based on high sensitivity C-reactive protein (hsCRP) > the upper limit of normal (ULN).
- Prior treatment with at most one bDMARD (either TNF inhibitor or IL-17i) is allowed for at least 20% but no more than 35% of enrolled patients who had to discontinue the prior bDMARD due to either lack of efficacy (after ≥ 12 weeks at an adequate dose) or intolerance (regardless of treatment duration).
-
Must have a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 at the Screening and Baseline Visits.
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Must have a Total Back Pain score ≥ 4 based on a 0 - 10 numerical rating scale at the Screening and Baseline Visits.
-
Has had an inadequate response to at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs) over an at least 4-week period in total at maximum recommended or tolerated doses, or has an intolerance to or contraindication for NSAIDs as defined by the Investigator.
- Must not have been exposed to any Janus kinase (JAK) inhibitor (including but not limited to upadacitinib [Rinvoq®], tofacitinib [Xeljanz®], baricitinib [Olumiant®], filgotinib, ruxolitinib [Jakafi®], abrocitinib [PF-04965842], and peficitinib [Smyraf®]).
- Prior bDMARD therapy must be washed out.
- Participant must not have a history of an allergic reaction or significant sensitivity to constituents of the study drug.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Study 1: Placebo Placebo Participants receive matching placebo for 14 weeks and then switch to receive 15 mg upadacitinib orally once a day for 90 weeks. Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment). Study 2: Placebo Placebo Participants receive matching placebo for 52 weeks and then switch to receive 15 mg upadacitinib orally once a day for 52 weeks. Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment). Study 1: Upadacitinib 15 mg Upadacitinib Participants receive 15 mg upadacitinib orally once a day for 104 weeks. Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment). Study 1: Placebo Upadacitinib Participants receive matching placebo for 14 weeks and then switch to receive 15 mg upadacitinib orally once a day for 90 weeks. Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment). Study 2: Upadacitinib 15 mg Upadacitinib Participants receive 15 mg upadacitinib orally once a day for 104 weeks. Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment). Study 2: Placebo Upadacitinib Participants receive matching placebo for 52 weeks and then switch to receive 15 mg upadacitinib orally once a day for 52 weeks. Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment).
- Primary Outcome Measures
Name Time Method Study 1: Percentage of Participants Achieving Assessment of SpondyloArthritis International Society 40 (ASAS40) Response at Week 14 Baseline and Week 14 ASAS40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of \> 0 units) in the potential remaining domain:
* Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity);
* Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
* Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
* Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).Study 2: Percentage of Participants Achieving an ASAS40 Response at Week 14 Baseline and Week 14 ASAS40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of \> 0 units) in the potential remaining domain:
* Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity);
* Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
* Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
* Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).
- Secondary Outcome Measures
Name Time Method Study 1: Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 14 Baseline and Week 14 ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:
1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 \[none\] - 10 \[very severe\])
2. Patient global assessment of disease activity (NRS score 0 \[no activity\] - 10 \[severe activity\])
3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 \[none\] - 10 \[very severe\])
4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 \[0 hours\] - 10 \[2 or more hours\])
5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.
The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS include Inactive disease (ASDAS \< 1.3) and very high disease (ASDAS \> 3.5). A negative change from Baseline score indicates improvement in disease activity.Study 1: Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Week 14 Baseline and Week 14 The BASDAI assesses disease activity by asking the participant to answer 6 questions (each on an 11 point numeric rating scale \[NRS\]) pertaining to symptoms experienced for the past week. For Questions 1 to 5 (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10. Lower scores indicate less disease activity.
A BASDAI 50 response is defined as improvement of 50% or more from Baseline in BASDAI score.Study 1: Percentage of Participants With ASDAS Inactive Disease at Week 14 Week 14 ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:
1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 \[none\] - 10 \[very severe\])
2. Patient global assessment of disease activity (NRS score 0 \[no activity\] - 10 \[severe activity\])
3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 \[none\] - 10 \[very severe\])
4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 \[0 hours\] - 10 \[2 or more hours\])
5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.
The overall score ranges from 0 with no defined upper score. ASDAS Inactive Disease is defined as an ASDAS score \< 1.3.Study 1: Change From Baseline in Patient's Assessment of Nocturnal Back Pain at Week 14 Baseline and Week 14 Participants assessed the amount of back pain at night over the last week on a 0 to 10 NRS, where 0 represents no pain and 10 represents most severe pain.
Study 1: Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score at Week 14 Baseline and Week 14 The ASQoL consists of 18 items related to quality of life, including the impact of pain on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. Each item is answered as yes (scored as 1) or no (scored as 0).
Scores are summed to obtain the overall score which ranges from 0 to 18, where higher scores indicate a worse quality of life. A negative change from Baseline in ASQoL indicates improvement in quality of life.Study 2: Percentage of Participants With ASDAS Inactive Disease at Week 52 Week 52 ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:
1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 \[none\] - 10 \[very severe\])
2. Patient global assessment of disease activity (NRS score 0 \[no activity\] - 10 \[severe activity\])
3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 \[none\] - 10 \[very severe\])
4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 \[0 hours\] - 10 \[2 or more hours\])
5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.
The overall score ranges from 0 with no defined upper score. ASDAS Inactive Disease is defined as an ASDAS score \< 1.3.Study 1: Change From Baseline in Magnetic Resonance Imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) Score for the Spine at Week 14 Baseline and Week 14 In the SPARCC MRI assessment of the spine, the entire spine was evaluated for active inflammation (bone marrow edema). Six discovertebral units (DVU) representing the 6 most abnormal DVUs were selected to calculate the MRI Spine SPARCC score. For each of the 6 DVUs, 3 consecutive sagittal slices were assessed in 4 quadrants to evaluate the extent of inflammation in all three dimensions.
Each quadrant was scored for the presence (1) or absence (0) of edema. If edema was present in at least one quadrant of a DVU slice, it was also scored for intensity and depth of the edema representing that slice: An additional score of 1 was assigned if an intense signal was seen in any quadrant on a DVU slice. Slices that included a lesion demonstrating continuous increased signal of depth ≥ 1 cm extending from the endplate were scored as an additional 1 per slice.
The maximum (worst) overall score for all 6 DVUs is 108. A negative change from Baseline indicates improvement.Study 1: Change From Baseline in Linear Bath Ankylosing Spondylitis Metrology Index (BASMI[Lin]) at Week 14 Baseline and Week 14 The BASMI is a composite score based on 5 direct measurements of spinal mobility:
1. cervical rotation (measured in degrees),
2. tragus to wall distance (in centimeters \[cm\])
3. lumbar side flexion (in cm),
4. lumbar flexion (modified Schober's) (in cm) and
5. intermalleolar distance (in cm).
Each measurement is converted to a linear score between 0 and 10. The total BASMI(lin) score is the average of the 5 scores and ranges from 0 to 10; the higher the BASMI(lin) score the more severe the patient's limitation of movement due to their ankylosing spondylitis. A negative change from Baseline indicates improvement.Study 1: Percentage of Participants With an ASAS20 Response at Week 14 Baseline and Week 14 ASAS20 response was defined as an improvement of ≥ 20% and an absolute improvement of ≥ 1 unit (on a scale of 0 to 10) from Baseline in at least 3 of the following 4 domains, with no deterioration (defined as a worsening of ≥ 20% and a net worsening of ≥ 1 units \[on a scale of 0 to 10\]) in the remaining domain:
* Patient's global assessment of disease activity, measured on a NRS from 0 (no activity) to 10 (severe activity);
* Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
* Function, measured by the BASFI which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
* Inflammation, measured by the mean of the 2 morning stiffness-related BASDAI NRS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).Study 1: Percentage of Participants With ASDAS Low Disease Activity at Week 14 Week 14 ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:
1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 \[none\] - 10 \[very severe\])
2. Patient global assessment of disease activity (NRS score 0 \[no activity\] - 10 \[severe activity\])
3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 \[none\] - 10 \[very severe\])
4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 \[0 hours\] - 10 \[2 or more hours\])
5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.
The overall score ranges from 0 with no defined upper score. ASDAS Low Disease Activity is defined as an ASDAS score \< 2.1.Study 1: Change From Baseline in Patient's Assessment of Total Back Pain at Week 14 Baseline and Week 14 Participants assessed their total back pain during the last week on a 0 to 10 numerical rating scale (NRS), where 0 represents no pain and 10 represents most severe pain.
Study 1: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 14 Baseline and Week 14 The Bath Ankylosing Spondylitis Functional Index is a validated index to determine the degree of functional limitation in patients with AS. BASFI consists of 10 questions assessing participants' ability to perform activities such as putting on socks, bending, reaching, getting up from the floor or an armless chair, standing, climbing and other physical activities. Each item is scored on a NRS ranging from 0 (easy to perform an activity) to 10 (impossible to perform an activity). The overall score is the mean of the 10 items and ranges from 0 to 10 with higher scores indicating more functional limitations. A negative change from Baseline in BASFI indicates improvement.
Study 1: Percentage of Participants With ASAS Partial Remission at Week 14 Week 14 ASAS partial remission (PR) is defined as an absolute score of ≤ 2 units on a 0 to 10 scale for each of the four following domains:
* Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity);
* Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
* Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
* Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).Study 1: Change From Baseline in ASAS Health Index at Week 14 Baseline and Week 14 The ASAS health index (HI) measures functioning and health across 17 aspects of health in patients with AS, including pain, emotional functions, sleep, sexual function, mobility, self care, and community life. Each of the 17 questions is answered by the participant as "I agree" (score = 1) or "I disagree" (score = 0). The responses to the 17 dichotomous items are summed up to give a total score ranging from 0 to 17, where a higher score indicates a worse health status. A negative change from Baseline indicates improvement.
Study 1: Change From Baseline in MRI SPARCC Score for Sacroiliac Joints at Week 14 Baseline and Week 14 In the SPARCC MRI assessment of the sacroiliac (SI) joints 6 consecutive sacroiliac joint image coronal slices representing the largest proportion of the synovial compartment of the SI joints were assessed for edema, intensity and depth of edema.
Each SI joint (left and right) was divided into quadrants for a total of 8 SI scoring locations. Each quadrant was scored for the presence (1) or absence (0) of edema, intensity of edema (a score of 1 was assigned for each SI joint (left and right) if an intense signal was seen in any quadrant of that joint for each slice), and a lesion was graded as deep (score of 1) if there was homogeneous and unequivocal increase in signal extending over a depth of at least 1 cm from the articular surface of the SI joint in any quadrant.
The total maximum (worst) score for all SI joints across 6 slices is 72. A negative change from Baseline indicates improvement.Study 2: Change From Baseline in MRI SPARCC Score for the Spine at Week 14 Baseline and Week 14 In the SPARCC MRI assessment of the spine, the entire spine is evaluated for active inflammation (bone marrow edema). Six discovertebral units (DVU) representing the 6 most abnormal DVUs were selected to calculate the MRI Spine SPARCC score. For each of the 6 DVUs, 3 consecutive sagittal slices were assessed in 4 quadrants to evaluate the extent of inflammation in all three dimensions.
Each quadrant was scored for the presence (1) or absence (0) of edema. If edema was present in at least one quadrant of a DVU slice, it was also scored for intensity and depth of the edema representing that slice: An additional score of 1 was assigned if an intense signal was seen in any quadrant on a DVU slice. Slices that included a lesion demonstrating continuous increased signal of depth ≥ 1 cm extending from the endplate were scored as an additional 1 per slice.
The maximum (worst) overall score for all 6 DVUs is 108. A negative change from Baseline indicates improvement.Study 2: Percentage of Participants With ASDAS Low Disease Activity at Week 52 Week 52 ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:
1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 \[none\] - 10 \[very severe\])
2. Patient global assessment of disease activity (NRS score 0 \[no activity\] - 10 \[severe activity\])
3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 \[none\] - 10 \[very severe\])
4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 \[0 hours\] - 10 \[2 or more hours\])
5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.
The overall score ranges from 0 with no defined upper score. ASDAS Low Disease Activity is defined as an ASDAS score \< 2.1.Study 1: Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Week 14 Baseline and Week 14 The MASES evaluation was conducted to assess the presence or absence of enthesitis (inflammation of the entheses, or sites where tendons or ligaments insert into the bone) at 13 different sites (first costochondral joint left/right, seventh costochondral joint left/right, posterior superior iliac spine left/right, anterior superior iliac spine left/right, iliac crest left/right, fifth lumbar spinous process, and proximal insertion of Achilles tendon left/right. Each site was scored for presence (1) or absence (0) of enthesitis. The MASES is the sum of the 13 site scores, and ranges from 0 to 13, with higher scores indicating more inflammation of the entheses. A negative change from Baseline indicates improvement.
Study 2: Change From Baseline in MRI SPARCC Score for SI Joints at Week 14 Baseline and Week 14 In the SPARCC MRI assessment of the sacroiliac (SI) joints 6 consecutive sacroiliac joint image coronal slices representing the largest proportion of the synovial compartment of the SI joints were assessed for edema, intensity and depth of edema.
Each SI joint (left and right) was divided into quadrants for a total of 8 SI scoring locations. Each quadrant was scored for the presence (1) or absence (0) of edema, intensity of edema (a score of 1 was assigned for each SI joint (left and right) if an intense signal was seen in any quadrant of that joint for each slice), and a lesion was graded as deep (score of 1) if there was homogeneous and unequivocal increase in signal extending over a depth of at least 1 cm from the articular surface of the SI joint in any quadrant.
The total maximum (worst) score for all SI joints across 6 slices is 72. A negative change from Baseline indicates improvement.Study 2: Percentage of Participants With BASDAI 50 Response at Week 14 Baseline and Week 14 The BASDAI assesses disease activity by asking the participant to answer 6 questions (each on an 11 point numeric rating scale \[NRS\]) pertaining to symptoms experienced for the past week. For Questions 1 to 5 (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10. Lower scores indicate less disease activity.
A BASDAI 50 response is defined as improvement of 50% or more from Baseline in BASDAI score.Study 2: Change From Baseline in Patient's Assessment of Total Back Pain at Week 14 Baseline and Week 14 Participants assessed their total back pain during the last week on a 0 to 10 numerical rating scale (NRS), where 0 represents no pain and 10 represents most severe pain.
Study 2: Change From Baseline in ASDAS at Week 14 Baseline and Week 14 ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:
1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 \[none\] - 10 \[very severe\])
2. Patient global assessment of disease activity (NRS score 0 \[no activity\] - 10 \[severe activity\])
3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 \[none\] - 10 \[very severe\])
4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 \[0 hours\] - 10 \[2 or more hours\])
5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.
The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS include Inactive disease (ASDAS \< 1.3) and very high disease (ASDAS \> 3.5). A negative change from Baseline score indicates improvement in disease activity.Study 2: Percentage of Participants With ASDAS Inactive Disease at Week 14 Week 14 ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:
1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 \[none\] - 10 \[very severe\])
2. Patient global assessment of disease activity (NRS score 0 \[no activity\] - 10 \[severe activity\])
3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 \[none\] - 10 \[very severe\])
4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 \[0 hours\] - 10 \[2 or more hours\])
5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.
The overall score ranges from 0 with no defined upper score. ASDAS Inactive Disease is defined as an ASDAS score \< 1.3.Study 2: Percentage of Participants With ASDAS Low Disease Activity at Week 14 Week 14 ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:
1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 \[none\] - 10 \[very severe\])
2. Patient global assessment of disease activity (NRS score 0 \[no activity\] - 10 \[severe activity\])
3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 \[none\] - 10 \[very severe\])
4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 \[0 hours\] - 10 \[2 or more hours\])
5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.
The overall score ranges from 0 with no defined upper score. ASDAS Low Disease Activity is defined as an ASDAS score \< 2.1.Study 2: Percentage of Participants With ASAS Partial Remission at Week 14 Week 14 ASAS partial remission (PR) is defined as an absolute score of ≤ 2 units on a 0 to 10 scale for each of the four following domains:
* Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity);
* Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
* Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
* Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).Study 2: Change From Baseline in Patient's Assessment of Nocturnal Back Pain at Week 14 Baseline and Week 14 Participants assessed the amount of back pain at night over the last week on a 0 to 10 NRS, where 0 represents no pain and 10 represents most severe pain.
Study 2: Change From Baseline in BASFI at Week 14 Baseline and Week 14 The Bath Ankylosing Spondylitis Functional Index is a validated index to determine the degree of functional limitation in patients with AS. BASFI consists of 10 questions assessing participants' ability to perform activities such as putting on socks, bending, reaching, getting up from the floor or an armless chair, standing, climbing and other physical activities. Each item is scored on a NRS ranging from 0 (easy to perform an activity) to 10 (impossible to perform an activity). The overall score is the mean of the 10 items and ranges from 0 to 10 with higher scores indicating more functional limitations. A negative change from Baseline in BASFI indicates improvement.
Study 2: Change From Baseline in ASQoL at Week 14 Baseline and Week 14 The ASQoL consists of 18 items related to quality of life, including the impact of pain on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. Each item is answered as yes (scored as 1) or no (scored as 0).
Scores are summed to obtain the overall score which ranges from 0 to 18, where higher scores indicate a worse quality of life. A negative change from Baseline in ASQoL indicates improvement in quality of life.Study 2: Change From Baseline in ASAS Health Index at Week 14 Baseline and Week 14 The ASAS HI measures functioning and health across 17 aspects of health in patients with AS, including pain, emotional functions, sleep, sexual function, mobility, self care, and community life. Each of the 17 questions is answered by the participant as "I agree" (score = 1) or "I disagree" (score = 0). The responses to the 17 dichotomous items are summed up to give a total score ranging from 0 to 17, where a higher score indicates a worse health status. A negative change from Baseline indicates improvement.
Study 2: Percentage of Participants Achieving an ASAS20 Response at Week 14 Baseline and Week 14 ASAS20 response was defined as an improvement of ≥ 20% and an absolute improvement of ≥ 1 unit (on a scale of 0 to 10) from Baseline in at least 3 of the following 4 domains, with no deterioration (defined as a worsening of ≥ 20% and a net worsening of ≥ 1 units \[on a scale of 0 to 10\]) in the remaining domain:
* Patient's global assessment of disease activity, measured on a NRS from 0 (no activity) to 10 (severe activity);
* Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
* Function, measured by the BASFI which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
* Inflammation, measured by the mean of the 2 morning stiffness-related BASDAI NRS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).Study 2: Change From Baseline in BASMI(Lin) at Week 14 Baseline and Week 14 The BASMI is a composite score based on 5 direct measurements of spinal mobility:
1. cervical rotation (measured in degrees),
2. tragus to wall distance (in centimeters \[cm\])
3. lumbar side flexion (in cm),
4. lumbar flexion (modified Schober's) (in cm) and
5. intermalleolar distance (in cm).
Each measurement is converted to a linear score between 0 and 10. The total BASMI(lin) score is the average of the 5 scores and ranges from 0 to 10; the higher the BASMI(lin) score the more severe the patient's limitation of movement due to their ankylosing spondylitis. A negative change from Baseline indicates improvement.Study 2: Change From Baseline in MASES at Week 14 Baseline and Week 14 The MASES evaluation was conducted to assess the presence or absence of enthesitis (inflammation of the entheses, or sites where tendons or ligaments insert into the bone) at 13 different sites (first costochondral joint left/right, seventh costochondral joint left/right, posterior superior iliac spine left/right, anterior superior iliac spine left/right, iliac crest left/right, fifth lumbar spinous process, and proximal insertion of Achilles tendon left/right. Each site was scored for presence (1) or absence (0) of enthesitis. The MASES is the sum of the 13 site scores, and ranges from 0 to 13, with higher scores indicating more inflammation of the entheses. A negative change from Baseline indicates improvement.
Study 2: Percentage of Participants Achieving an ASAS40 Response at Week 52 Baseline and Week 52 ASAS40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of \> 0 units) in the potential remaining domain:
* Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity);
* Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
* Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
* Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).Study 2: Percentage of Participants Who Initiated Rescue Treatment Between Week 24 and Week 52 Week 24, Week 32, Week 40, and Week 52 Participants who did not achieve an ASAS20 response at any 2 consecutive scheduled visits from Week 24 through Week 52 were to be rescued with standard of care treatment as described in the protocol.
Study 2: Percentage of Participants With ASDAS Major Improvement at Week 52 Baseline and Week 52 ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:
1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 \[none\] - 10 \[very severe\])
2. Patient global assessment of disease activity (NRS score 0 \[no activity\] - 10 \[severe activity\])
3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 \[none\] - 10 \[very severe\])
4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 \[0 hours\] - 10 \[2 or more hours\])
5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.
The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS include Inactive disease (ASDAS \< 1.3) and very high disease (ASDAS \> 3.5). Major Improvement is defined as a change from Baseline of ≤ -2.0.
Trial Locations
- Locations (212)
Clinic of Robert Hozman/Clinical Investigation Specialists /ID# 215055
🇺🇸Skokie, Illinois, United States
Arthritis & Rheumatic Disease Specialties /ID# 215306
🇺🇸Aventura, Florida, United States
Toronto Western Hospital /ID# 215041
🇨🇦Toronto, Ontario, Canada
Great Lakes Clinical Trials /ID# 215790
🇺🇸Chicago, Illinois, United States
Kyiv Railway Clinical Hosp No.2 /ID# 214779
🇺🇦Kyiv, Ukraine
PI "Poltava Regional Clinical Hospital n.a. M.V.Sklifosovsky" /ID# 214151
🇺🇦Poltava, Ukraine
MI Kryvyi Rih City Clinical Hospital No.2 /ID# 214152
🇺🇦Kryvyi Rih, Ukraine
MNI KRC Kyiv Regional Clinical Hospital /ID# 214156
🇺🇦Kyiv, Ukraine
Ternopil University Hospital /ID# 214705
🇺🇦Ternopil, Ukraine
Percuro Clinical Research, Ltd /ID# 215302
🇨🇦Victoria, British Columbia, Canada
Narodny ustav reumatickych chorob /ID# 214674
🇸🇰Piestany, Slovakia
Hospital Marina Baixa /ID# 215970
🇪🇸Villajoyosa, Alicante, Spain
Far Eastern Memorial Hospital /ID# 215384
🇨🇳New Taipei City, Taiwan
Centro de Enfermedades del Hígado y Aparato Digestivo /ID# 214556
🇦🇷Rosario, Santa Fe, Argentina
St.Luke's International Hospital /ID# 215414
🇯🇵Chuo-ku, Tokyo, Japan
Instituto CAICI /ID# 215242
🇦🇷Rosario, Santa Fe, Argentina
Juntendo University Hospital /ID# 214929
🇯🇵Bunkyo-ku, Tokyo, Japan
CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 215217
🇲🇽Mexico City, Ciudad De Mexico, Mexico
Kaohsiung Veterans General Hos /ID# 214332
🇨🇳Kaohsiung, Taichung, Taiwan
Osteo-Medic S.C. /ID# 214351
🇵🇱Bialystok, Podlaskie, Poland
MUDr. Zuzana Cizmarikova s.r.o. /ID# 215220
🇸🇰Poprad, Slovakia
China Medical University Hospital /ID# 214019
🇨🇳Taichung City, Taiwan
Chung Shan Medical University Hospital /ID# 214018
🇨🇳Taichung, Taiwan
Cathay General Hospital /ID# 214183
🇨🇳Taipei, Taiwan
CMiP - Centro Mineiro de Pesquisa Ltda - ME /ID# 215277
🇧🇷Juiz de Fora, Minas Gerais, Brazil
UZ Gent /ID# 215004
🇧🇪Gent, Oost-Vlaanderen, Belgium
STAT Research, Inc. /ID# 215264
🇺🇸Springboro, Ohio, United States
Altoona Ctr Clinical Res /ID# 214770
🇺🇸Duncansville, Pennsylvania, United States
Arthritis and Osteoporosis Clinic Of Brazos Valley /ID# 215805
🇺🇸College Station, Texas, United States
Trinity Universal Research Associates, Inc /ID# 215189
🇺🇸Plano, Texas, United States
West Virginia Research Inst /ID# 214921
🇺🇸South Charleston, West Virginia, United States
West Texas Clinical Research /ID# 215928
🇺🇸Lubbock, Texas, United States
Rheumatology and Pulmonary Clinic /ID# 214946
🇺🇸Beckley, West Virginia, United States
Debreceni Egyetem Klinikai Kozpont /ID# 215187
🇭🇺Debrecen, Hajdu-Bihar, Hungary
Monash Medical Centre /ID# 215509
🇦🇺Clayton, Victoria, Australia
Rheuma Research Lausitz, Dr. Mario Sutowicz /ID# 214218
🇩🇪Cottbus, Germany
BJC Health /ID# 215510
🇦🇺Paramatta, New South Wales, Australia
Centre de recherche du CHUQ /ID# 215038
🇨🇦Quebec, Canada
Bnai Zion Medical Center /ID# 215856
🇮🇱Haifa, Israel
Praxisgemeinschaft Rheumatologie Nephrologie Erlangen /ID# 214212
🇩🇪Erlangen, Germany
CMED Rehabilitacios es Diagnosztikai Kozpont /ID# 215181
🇭🇺Szekesfehervar, Hungary
UMHAT Sveti Ivan Rilski /ID# 214806
🇧🇬Sofia, Bulgaria
Daido Clinic /ID# 214735
🇯🇵Nagoya-shi, Aichi, Japan
MVZ Rheumatologie und Autoimmunmedizin Hamburg GmbH /ID# 214208
🇩🇪Hamburg, Germany
LMK Sevicos Medicos S/S /ID# 215112
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Diagnostic consultative center 17 Sofia /ID# 214808
🇧🇬Sofia, Bulgaria
Reum.hapi s.r.o. /ID# 224268
🇸🇰Nove Mesto nad Vahom, Slovakia
ALBAMED s.r.o. /ID# 215248
🇸🇰Zvolen, Slovakia
Consorci Corporacio Sanitaria Parc Tauli Sabadell /ID# 214967
🇪🇸Sabadell, Barcelona, Spain
Hevizgyogyfurdo es Szent Andras Reumakorhaz /ID# 215184
🇭🇺Heviz, Hungary
Omsk Regional Clinic Hospital /ID# 214464
🇷🇺Omsk, Russian Federation
Ryazan State Medical University named after academician I.P. Pavlov /ID# 214418
🇷🇺Ryazan, Russian Federation
Family Clinic /ID# 214737
🇷🇺Yekaterinburg, Sverdlovskaya Oblast, Russian Federation
Meir Medical Center /ID# 217255
🇮🇱Kfar Saba, Israel
Kazan State Medical University /ID# 214421
🇷🇺Kazan, Tatarstan, Respublika, Russian Federation
Seoul National University Hospital /ID# 214532
🇰🇷Seoul, Korea, Republic of
Japanese Red Cross Okayama Hospital /ID# 214732
🇯🇵Okayama-shi, Okayama, Japan
Okinawa Prefectural Chubu Hospital /ID# 215575
🇯🇵Uruma-shi, Okinawa, Japan
LLC Novaya Klinika /ID# 214420
🇷🇺Pyatigorsk, Stavropol Skiy Kray, Russian Federation
Waikato Hospital /ID# 215503
🇳🇿Hamilton, Waikato, New Zealand
Chelyabinsk Regional Clinical Hospital /ID# 214463
🇷🇺Chelyabinsk, Chelyabinskaya Oblast, Russian Federation
Univerzitna nemocnica Bratislava Nemocnica Stare Mesto /ID# 214675
🇸🇰Bratislava, Slovakia
Nasz Lekarz Przychodnie Medyczne /ID# 214352
🇵🇱Torun, Kujawsko-pomorskie, Poland
Middlemore Clinical Trials /ID# 215502
🇳🇿Papatoetoe, Auckland, New Zealand
LLC Family Outpatient Clinic № /ID# 214455
🇷🇺Korolev, Moskva, Russian Federation
Hospital Universitario Reina Sofia /ID# 214968
🇪🇸Cordoba, Spain
Central City Hospital #7 /ID# 214741
🇷🇺Yekaterinburg, Sverdlovskaya Oblast, Russian Federation
MNPE Chernihiv Regional Hospital of the Chernihiv Region Council /ID# 214145
🇺🇦Chernihiv, Ukraine
Hospital Meixoeiro (CHUVI) /ID# 214969
🇪🇸Vigo, Pontevedra, Spain
Hacettepe Universitesi Tip Fak /ID# 214898
🇹🇷Sihhiye, Ankara, Turkey
Medical Center LLC Institute of Rheumatology /ID# 214146
🇺🇦Kyiv, Ukraine
CNE Vinnytsya Regional Clinical Hospital named after N.I.Pirogov /ID# 214147
🇺🇦Vinnytsia, Ukraine
West Suffolk Hospital /ID# 215529
🇬🇧Bury St Edmunds, Suffolk, United Kingdom
Clinic of Scientific Research Institute of Invalid Rehabilitation /ID# 214148
🇺🇦Vinnytsia, Ukraine
Minerva Health Centre /ID# 216226
🇬🇧Preston, Lancashire, United Kingdom
Norfolk and Norwich University Hospitals NHS Foundation Trust /ID# 214865
🇬🇧Norwich, Norfolk, United Kingdom
The first affiliated hospital of bengbu medical college /ID# 216609
🇨🇳Bengbu, Anhui, China
Anhui Provincial Hospital /ID# 216631
🇨🇳Hefei, Anhui, China
The First Affiliated Hospital of Shantou University Medical College /ID# 217883
🇨🇳Shantou, Guangdong, China
The First Affiliated Hospital of Soochow University /ID# 216607
🇨🇳Suzhou, Jiangsu, China
First Affiliated Hospital of Kunming Medical University /ID# 217945
🇨🇳Kunming, China
AZ Arthritis and Rheumotology Research, PLLC /ID# 215113
🇺🇸Phoenix, Arizona, United States
Denver Arthritis Clinic /ID# 215346
🇺🇸Denver, Colorado, United States
Wayne State University Health Center /ID# 215930
🇺🇸Detroit, Michigan, United States
Health Research of Oklahoma /ID# 215117
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health and Science University /ID# 216446
🇺🇸Portland, Oregon, United States
Memorial Rheumatology /ID# 216311
🇺🇸Houston, Texas, United States
Biopharma Informatic, LLC /ID# 215885
🇺🇸Houston, Texas, United States
Biopharma Informatic - Park Row /ID# 215907
🇺🇸Houston, Texas, United States
Applied Medical Informatics Research Inc. (AMIR) /ID# 215303
🇨🇦Montréal, Quebec, Canada
Centre de Recherche Musculo-Squelettique /ID# 215096
🇨🇦Trois-rivières, Quebec, Canada
EDUMED Educacao em Saude S/S L /ID# 215111
🇧🇷Curitiba, Parana, Brazil
CPCLIN - Centro de Pesquisas Clínicas /ID# 215175
🇧🇷Sao Paulo, Brazil
Kuwana City Medical Center /ID# 215196
🇯🇵Kuwana-shi, Mie, Japan
Olla-Med Clinic /ID# 214460
🇷🇺Moscow, Russian Federation
Alliance Biomedical Ural Group /ID# 214457
🇷🇺Izhevsk, Udmurtskaya Respublika, Russian Federation
Ulyanovsk Regional Clinical Hospital /ID# 214458
🇷🇺Ulyanovsk, Russian Federation
Universitaetsklinikum Erlangen /ID# 214281
🇩🇪Erlangen, Bayern, Germany
Rheumatologische Schwerpunktpraxis Brandt-Juergens /ID# 214282
🇩🇪Berlin, Germany
Charite Universitaetsklinikum Berlin - Campus Benjamin Franklin /ID# 214211
🇩🇪Berlin, Germany
Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 214207
🇩🇪Dresden, Germany
Rehavita Kft HU /ID# 215188
🇭🇺Kormend, Zala, Hungary
MVZ für Rheumatologie Dr. M. Welcker GmbH /ID# 214261
🇩🇪Planegg, Germany
Orenburg State Medical University /ID# 214408
🇷🇺Orenburg, Russian Federation
Arizona Arthritis & Rheumatology Associates, P.C. /ID# 215282
🇺🇸Flagstaff, Arizona, United States
Arizona Arthritis & Rheumatology Research, PLLC /ID# 214731
🇺🇸Tucson, Arizona, United States
Newport Huntington Medical Group /ID# 216281
🇺🇸Huntington Beach, California, United States
Inland Rheum & Osteo Med Grp /ID# 215807
🇺🇸Upland, California, United States
Tekton Research /ID# 215054
🇺🇸Fort Collins, Colorado, United States
Sweet Hope Research Specialty Inc /ID# 215931
🇺🇸Hialeah, Florida, United States
Innovation Medical Research Center /ID# 216068
🇺🇸Palmetto Bay, Florida, United States
Conquest Research /ID# 215804
🇺🇸Winter Park, Florida, United States
Greater Chicago Specialty Physicians /ID# 216213
🇺🇸Schaumburg, Illinois, United States
Klein and Associates MD /ID# 214767
🇺🇸Hagerstown, Maryland, United States
Tufts Medical Center /ID# 215925
🇺🇸Boston, Massachusetts, United States
Clinical Pharmacology Study Group /ID# 215293
🇺🇸Worcester, Massachusetts, United States
Advanced Rheumatology, PC /ID# 214973
🇺🇸Lansing, Michigan, United States
NYU Langone Orthopedic Center /ID# 215594
🇺🇸New York, New York, United States
Clinvest Research LLC /ID# 215785
🇺🇸Springfield, Missouri, United States
CenterPointe Institute of Research /ID# 215793
🇺🇸Saint Louis, Missouri, United States
St. Paul Rheumatology /ID# 215537
🇺🇸Eagan, Minnesota, United States
St. Lawrence Health System /ID# 215844
🇺🇸Potsdam, New York, United States
Cape Fear Arthritis Care /ID# 215927
🇺🇸Leland, North Carolina, United States
Marietta Memorial Hospital /ID# 215929
🇺🇸Marietta, Ohio, United States
Trinity Universal Research Associates - Carrollton /ID# 214948
🇺🇸Carrollton, Texas, United States
Hospital Cordoba /ID# 215846
🇦🇷Cordoba, Argentina
Centro de Investigaciones Medicas Tucuman /ID# 214559
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
JPS Rheumatology Clinic /ID# 215962
🇺🇸Fort Worth, Texas, United States
Organizacion Medica de Investigacion (OMI) /ID# 214557
🇦🇷Ciudad Autonoma de Buenos Aire, Ciuadad Autonoma De Buenos Aires, Argentina
Instituto Medico Strusberg /ID# 215239
🇦🇷Cordoba, Argentina
Cimer /Id# 215240
🇦🇷San Miguel de Tucuman, Argentina
Emeritus Research Sydney /ID# 215507
🇦🇺Botany, New South Wales, Australia
ReumaClinic /ID# 215005
🇧🇪Genk, Belgium
Emeritus Research /ID# 215506
🇦🇺Camberwell, Victoria, Australia
Universitair Ziekenhuis Leuven /ID# 215006
🇧🇪Leuven, Vlaams-Brabant, Belgium
UMHAT Kaspela EOOD /ID# 214803
🇧🇬Plovdiv, Bulgaria
Medical center Unimed /ID# 214816
🇧🇬Plovdiv, Bulgaria
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto /ID# 215176
🇧🇷Sao Jose Do Rio Preto, Sao Paulo, Brazil
Medical center Teodora /ID# 214813
🇧🇬Ruse, Bulgaria
MHAT Plovdiv /ID# 214815
🇧🇬Plovdiv, Bulgaria
Medical center Excelsior /ID# 214805
🇧🇬Sofia, Bulgaria
UMHAT Sveti Ivan Rilski /ID# 214804
🇧🇬Sofia, Bulgaria
Peking Union Medical College Hospital /ID# 216545
🇨🇳Beijing, Beijing, China
Guangdong Provincial People's Hospital /ID# 216645
🇨🇳Guangzhou, Guangdong, China
Zhuzhou Central Hospital /ID# 216644
🇨🇳Zhuzhou, Hunan, China
Shenzhen People's Hospital /ID# 225438
🇨🇳Shenzhen, Guangdong, China
The First Affiliated Hospital of BaoTou Medical College, Inner Mongolia Universi /ID# 216612
🇨🇳Baotou, Inner Mongolia, China
Huashan Hospital, Fudan University /ID# 216646
🇨🇳Shanghai, Shanghai, China
REVMACLINIC s.r.o. /ID# 215153
🇨🇿Brno, Czechia
Revmatologie, s.r.o. /ID# 215309
🇨🇿Brno, Czechia
Fakultni Nemocnice v Motole /ID# 215160
🇨🇿Praha, Czechia
Revmacentrum MUDr. Mostera, s.r.o. /ID# 215161
🇨🇿Brno, Czechia
Revmatologicky ustav v Praze /ID# 215154
🇨🇿Praha, Czechia
PV MEDICAL Services s.r.o. /ID# 215119
🇨🇿Praha, Czechia
ARTHROHELP, s.r.o. /ID# 215224
🇨🇿Pardubice, Czechia
Revmatologicka ambulance - MUDr. Zuzana Urbanova /ID# 215652
🇨🇿Praha, Czechia
CCR Ostrava, s.r.o. /ID# 215226
🇨🇿Ostrava, Czechia
Thomayerova nemocnice /ID# 215118
🇨🇿Praha, Czechia
CHU Toulouse /ID# 214780
🇫🇷Toulouse, Occitanie, France
MEDICAL PLUS, s.r.o. /ID# 215324
🇨🇿Uherske Hradiste, Czechia
CHU Bordeaux - Hopital Pellegrin /ID# 214784
🇫🇷Bordeaux, France
Hopital Ambroise Pare /ID# 214783
🇫🇷Boulogne Billancourt, France
AP-HP - Hopital Cochin /ID# 214782
🇫🇷Paris, France
Betegapolo Irgalmasrend Budai Irgalmasrendi Korhaz /ID# 215183
🇭🇺Budapest, Hungary
Medizinische Hochschule Hannover /ID# 214209
🇩🇪Hannover, Germany
Vital Medical Center Orvosi es Fogaszati Kozpont /ID# 215182
🇭🇺Veszprém, Veszprem, Hungary
Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz /ID# 215186
🇭🇺Gyula, Hungary
Tel Aviv Sourasky Medical Center /ID# 216956
🇮🇱Tel Aviv-Yafo, Tel-Aviv, Israel
The Chaim Sheba Medical Center /ID# 215854
🇮🇱Ramat Gan, Tel-Aviv, Israel
Pest Megyei Flor Ferenc Korhaz /ID# 214501
🇭🇺Kistarcsa, Hungary
Matsuyama Red Cross Hospital /ID# 216021
🇯🇵Matsuyama-shi, Ehime, Japan
Kita-harima Medical Center /ID# 216069
🇯🇵Ono-shi, Hyogo, Japan
Kobe University Hospital /ID# 214598
🇯🇵Kobe-shi, Hyogo, Japan
Hokkaido University Hospital /ID# 215221
🇯🇵Sapporo-shi, Hokkaido, Japan
Hyogo College of Medicine College Hospital /Id# 215638
🇯🇵Nishinomiya-shi, Hyogo, Japan
National Hospital Organization Asahikawa Medical Center /ID# 214930
🇯🇵Asahikawa-shi, Hokkaido, Japan
Sasebo Chuo Hospital /ID# 214703
🇯🇵Sasebo-shi, Nagasaki, Japan
National Hospital Organization Osaka Minami Medical Center /ID# 214205
🇯🇵Kawachinagano Shi, Osaka, Japan
Nagasaki University Hospital /ID# 215947
🇯🇵Nagasaki-shi, Nagasaki, Japan
Osaka City General Hospital /ID# 215640
🇯🇵Osaka-shi, Osaka, Japan
The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 214295
🇰🇷Seoul, Korea, Republic of
Ajou University Hospital /ID# 214533
🇰🇷Suwon, Gyeonggido, Korea, Republic of
Gachon University Gil Medical Center /ID# 214534
🇰🇷Incheon, Korea, Republic of
Hanyang University Seoul Hospital /ID# 214297
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Kyunghee University Hospital at Gangdong /ID# 214296
🇰🇷Seoul, Korea, Republic of
Asan Medical Center /ID# 214294
🇰🇷Seoul, Korea, Republic of
REUMED Sp.z o.o. Filia nr 1 /ID# 214353
🇵🇱Lublin, Lubelskie, Poland
WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 215093
🇵🇱Wroclaw, Dolnoslaskie, Poland
ETYKA-Osrodek Badan Klinicznych /ID# 215572
🇵🇱Olsztyn, Warminsko-mazurskie, Poland
Immanuel Kant Baltic Federal University /ID# 218259
🇷🇺Kaliningrad, Kaliningradskaya Oblast, Russian Federation
LLC Medical Center /ID# 214410
🇷🇺Novosibirsk, Novosibirskaya Oblast, Russian Federation
Research Institute of Rheumatology named after V.A. Nasonova /ID# 214459
🇷🇺Moscow, Moskva, Russian Federation
Nort-Western State Medical University n.a. Mechnikov /ID# 214454
🇷🇺St. Petersburg, Sankt-Peterburg, Russian Federation
RZD-Medicine Saratov /ID# 214465
🇷🇺Saratov, Russian Federation
City Clinical Hospital n.a. O.M. Filatov /ID# 214486
🇷🇺Moscow, Russian Federation
Clinical Rheumatologic Hospital No 25 /ID# 214488
🇷🇺St. Petersburg, Russian Federation
Hospital Unversitario Marques de Valdecilla /ID# 214965
🇪🇸Santander, Cantabria, Spain
Hospital Universitario La Paz /ID# 216032
🇪🇸Madrid, Spain
Hospital Universitario y Politecnico La Fe /ID# 214966
🇪🇸Valencia, Spain
Istanbul University Cerrahpasa Faculty of Medicine /ID# 214895
🇹🇷Cerrahpasa, Turkey
Mugla Sitki Kocman University Medical Faculty /ID# 215358
🇹🇷Mugla, Turkey
Khmelnytskyi Regional Hospital /ID# 214153
🇺🇦Khmelnytskyi, Ukraine
Municipal Non-Commercial Enterprise Odesa Regional Clinical Hospital of the Od /ID# 214159
🇺🇦Odesa, Ukraine
Medical Center CONSILIUM MEDICAL /ID# 216234
🇺🇦Kyiv, Ukraine
Doncaster Royal Infirmary /ID# 214971
🇬🇧Armthorpe Road, United Kingdom
AI Centrum Medyczne Sp. z o.o. sp.k. /ID# 214354
🇵🇱Poznan, Wielkopolskie, Poland
Multifield Medical Centre of ONMU /ID# 214149
🇺🇦Odesa, Ukraine
State Institution L.T. Malaya Therapy National Institute of the NAMS of Ukraine /ID# 214155
🇺🇦Kharkiv, Ukraine
CNCE of Kharkiv Regional Council Regional Clinical Hospital /ID# 214158
🇺🇦Kharkiv, Ukraine
MNI City Multidisciplinary Hospital #18 /ID# 214154
🇺🇦Kharkiv, Ukraine
Tekton Research, Inc. /ID# 214923
🇺🇸Austin, Texas, United States
Barwon Rheumatology Services /ID# 215508
🇦🇺Geelong, Victoria, Australia