A Long Term Extension Study of Ixekizumab (LY2439821) in Participants With Axial Spondyloarthritis

Phase 3

Completed

Conditions: Axial Spondyloarthritis

Interventions: Drug: Ixekizumab
Drug: Placebo

Registration Number: NCT03129100

Lead Sponsor: Eli Lilly and Company

Brief Summary: The purpose of this study is to evaluate, in participants having achieved a state of sustained remission, if the ixekizumab treatment groups are superior to the placebo group in maintaining response during the randomized withdrawal-retreatment period in participants with axial spondyloarthritis.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 773

Inclusion Criteria

Have completed the final study visit in Study RHBV (NCT02696785), RHBW (NCT02696798), or RHBX (NCT02757352).

(Note: Participants from Study RHBX are not eligible if they permanently discontinued ixekizumab and were receiving a tumor necrosis factor [TNF] inhibitor).

Must agree to use a reliable method of birth control.

Exclusion Criteria

Have significant uncontrolled disorders or abnormal laboratory values that, in the opinion of the investigator, pose an unacceptable risk to the participant if investigational product continues to be administered.
Have a known hypersensitivity to ixekizumab or any component of this investigational product.
Had investigational product permanently discontinued during a previous ixekizumab study.
Had temporary investigational product interruption at any time during or at the final study visit of a previous ixekizumab study and, in the opinion of the investigator, restarting ixekizumab poses an unacceptable risk for the participant's participation in the study.
Have any other condition that, in the opinion of the investigator, renders the participant unable to understand the nature, scope, and possible consequences of the study or precludes the participant from following and completing the protocol.
Are currently enrolled in any other clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ixekizumab (IXE) 80Q4W	Ixekizumab	Participants received 80 milligram (mg) of Ixekizumab subcutaneously (SC) every four weeks (Q4W).
Ixekizumab (IXE) 80Q2W	Ixekizumab	Participants received 80 milligram (mg) of Ixekizumab subcutaneously (SC) every two weeks (Q2W).
Placebo	Placebo	Participants received subcutaneous dose of placebo.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who do Not Experience a Flare (Combined Ixekizumab Treatment)	Week 64	A flare is defined as Ankylosing Spondylitis Disease Activity Score (ASDAS ≥2.1) at 2 consecutive visits, or ASDAS \>3.5 at any visit during Period 2. ASDAS is a composite index to assess disease activity in AS. The parameters used for the ASDAS (with high sensitivity C-reactive protein (CRP) as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). (CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who do Not Experience a Flare	Week 64	A flare is defined as Ankylosing Spondylitis Disease Activity Score (ASDAS ≥2.1) at 2 consecutive visits, or ASDAS \>3.5 at any visit during Period 2. ASDAS is a composite index to assess disease activity in AS. The parameters used for the ASDAS (with high sensitivity C-reactive protein (CRP) as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). (CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity.
Percentage of Participants With No New Syndesmophyte Formation	Week 56	Percentage of participants with no new syndesmophyte formation was measured using the average of 2 selected readers of 3 readers.
Change From Baseline in Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)	Baseline, 2 Years	The mSASSS is a four-point scoring system for lateral radiographs of the lumbar and cervical spine and has been shown to reliably track disease progression over time, where: 0 = normal; 1 = sclerosis, squaring or erosion; 2 = syndesmophyte; 3 = bony bridge. By the scoring system of mSASSS of the spinal x-rays, a total of 24 sites were scored on the lateral cervical and lumbar spine: the anterior corners of the vertebrae from lower border of C2 to upper border T1 (inclusive), and from lower border of T12 to upper border of S1 (inclusive). Each corner was scored from 0 to 3, resulting in a range from 0 \[no change\] to 72 \[progression\].
Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response	Week 64	The BASDAI is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to radiographic axial spondyloarthritis (rad-axSpA): 1) Fatigue, 2) Spinal pain, 3) Peripheral arthritis, 4) Enthesitis, 5) Intensity, and 6) Duration of morning stiffness. Participants need to score each item with a score from 0 to 10 (NRS). Total score is obtained from the average of symptom scores ranging 0 (no problem) to 10 (worst problem), with a higher score indicating more severe AS symptom. BASDAI50 represents an improvement of ≥50% of the BASDAI score from baseline.
Change From Baseline in Chest Expansion in Centimeters	Baseline, Week 64	Chest expansion is the difference, in centimeter (cm), between the circumference of the chest in maximal inspiration and maximal expiration. While participants have their hands resting on or behind the head, the assessor will measure the chest encircled length by centimeter (cm) at the fourth intercostal level anteriorly. Two tries were recorded. The better measurement (larger difference) of 2 tries (in centimeters) was used for analyses. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Change From Baseline on the Quick Inventory of Depressive Symptomatology Self-Report-16 (QIDS-SR16)	Baseline, Week 64	The 16-item QIDS-SR16 version is a widely used validated scale designed to assess the severity of depressive symptoms. The participant was asked to rate the severity and frequency of specific symptoms present over the last 7 days. The QIDS-SR16 total scores range from 0 to 27, where higher scores indicate higher severity of symptoms. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Percentage of Participants Achieving an ASAS40 Response	Week 64	ASAS40 is defined as a ≥40% improvement and an absolute improvement from baseline of ≥2 units (range of 0 to 10) in at least 3 of the following 4 domains without any worsening in the remaining domain. The following ASAS domains are used: Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). Bath Ankylosing Spondylitis Functional Index (BASFI): Participant asked to rate the difficulty associated with 10 individual basic functional activities. Participant response was captured using Numeric Rating Scale (NRS) (range 0 to 10) with a higher score indicating worse function. Inflammation based on mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Q5 \& Q6 (mean of intensity \& duration of stiffness): Score ranges from "0" (none) and "10" (very severe).
Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Score	Baseline, Week 64	The SPARCC enthesitis is an index used to measure the severity of enthesitis. The SPARCC assesses 16 sites for enthesitis using a score of "0" for no activity or "1" for activity. Sites assessed include Medial epicondyle (left/right \[L/R\]), Lateral epicondyle (L/R), Supraspinatus insertion into greater tuberosity of humerus (L/R), Greater trochanter (L/R), Quadriceps insertion into superior border of patella (L/R), Patellar ligament insertion into inferior pole of patella or tibial tubercle (L/R), Achilles tendon insertion into calcaneum (L/R), and Plantar fascia insertion into calcaneum (L/R). The SPARCC is the sum of all site scores (range 0 to 16). Higher scores indicate more severe enthesitis. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Change From Baseline in Severity of Peripheral Arthritis by Tender Joint Count (TJC) Score of 46 Joints	Baseline, Week 64	The number of tender and painful joints was determined by examination of 46 joints (23 joints on each side of the body). The 46 joints were assessed and classified as tender or not tender. Sum of all joints checked to be tender/painful divided by number of evaluable joints which was multiplied by 46 to obtain TJC score. The scores ranges from 0 (no tender/painful joints) to 46 (all joints tender/painful). LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Percentage of Participants With Change of Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥1.1 Units	Week 64	ASDAS is a composite index to assess disease activity in AS. The parameters used for the ASDAS (with CRP as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness +0.579×Ln(CRP+1). (CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity.
Change From Baseline in the Individual Components of the ASAS Criteria	Baseline, Week 64	Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). Bath Ankylosing Spondylitis Functional Index (BASFI): Participant asked to rate the difficulty associated with 10 individual basic functional activities. Participant response was captured using Numeric Rating Scale (NRS) (range 0 to 10) with a higher score indicating worse function. Inflammation based on Q5 \& Q6 mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (mean of intensity \& duration of stiffness): Score ranges from "0" (none) and "10" (very severe). LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Percentage of Participants With Inactive Disease on the ASDAS (<1.3 Units)	Week 64	ASDAS is a composite index to assess disease activity in AS. The parameters used for the ASDAS (with CRP as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). (CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity.
Change From Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP)	Baseline, Week 64	High sensitivity CRP is the measure of acute phase reactant. It was measured with a high sensitivity assay at the central laboratory to help assess the effect of ixekizumab on disease activity. High sensitivity CRP is a sensitive laboratory assay for serum levels of C-Reactive Protein, which is a biomarker of inflammation. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Percentage of Participants With Anterior Uveitis or Uveitis Flares	Week 64	Anterior uveitis is an inflammation of the middle layer of the eye. which includes the iris (colored part of the eye) and the adjacent tissue, known as the ciliary body.
Change From Baseline in ASAS Health Index (ASAS HI)	Baseline, Week 64	The ASAS Health Index (ASAS HI) is a disease specific health-index instrument designed to assess the impact of interventions for SpA, including axSpA. The 17 item instrument has scores ranging from 0 (good Health) to 17 (poor Health). Each item consists of 1 question that the participant needs to respond to with either "I agree" (score 1) or "I do not agree (score 0)." A score of "1" is given where the item is affirmed, indicating adverse health. All item scores are summed to give a total score or index. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS)20 Response	Week 64	ASAS20 response is defined as a ≥20% improvement and an absolute improvement from baseline of ≥1 units (range 0 to 10) in ≥3 of 4 domains, and no worsening of ≥20% and ≥1 unit (range 0 to 10) in the remaining domain. The following ASAS domains are used: Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). Bath Ankylosing Spondylitis Functional Index (BASFI): Participant asked to rate the difficulty associated with 10 individual basic functional activities. Participant response was captured using Numeric Rating Scale (NRS) (range 0 to 10) with a higher score indicating worse function. Inflammation based on mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Q5 \& Q6 (mean of intensity \& duration of stiffness): Score ranges from "0" (none) and "10" (very severe).
Change From Baseline in Occiput to Wall Distance	Baseline, Week 64	The participant is to make a maximum effort to touch the head against the wall when standing with heels and back against the wall (occiput). Then the distance from occiput to wall is measured. Two tries will be recorded. The better (smaller) measurement of 2 tries (in centimeters) will be used for analyses. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Change From Baseline in Severity of Peripheral Arthritis by Swollen Joint Count (SJC) Score of 44 Joints	Baseline, Week 64	The number of swollen joints was determined by examination of 44 joints (22 joints on each side of the body). The 44 joints were assessed and classified as swollen or not swollen. Sum of all joints checked to be swollen divided by number of evaluable joints which was multiplied by 44 to obtain SJC score. The SJC score ranges from 0 (no swollen joints) to 44 (all joints swollen). LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Change From Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ)	Baseline, Week 64	The Jenkins Sleep Evaluation Questionnaire (JSEQ) is a 4 item scale designed to estimate sleep problems in clinical research. The JSEQ assesses the frequency of sleep disturbance in 4 categories: 1) trouble falling asleep, 2) waking up several times during the night, 3) having trouble staying asleep (including waking up far too early), and 4) waking up after the usual amount of sleep feeling tired and worn out. Participants report the numbers of days they experience each of these problems in the past month on a 6 point Likert Scale ranging from 0 = "no days" to 5 = "22-30 days. The total JSEQ score ranges from 0 to 20, with higher scores indicating greater sleep disturbance. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)	Baseline, Week 64	BASMI is a combined index comprising of the following 5 clinical measurements of spinal mobility in participants with radiographic axial spondyloarthritis (rad-axSpA). 1. Lateral Spinal Flexion 2. Tragus-to-wall distance 3. Lumbar Flexion (modified Schober) 4. Maximal intermalleolar distance and 5. Cervical rotation. The BASMI linear result is the average of the 5 assessments and ranges from 0 to 10. The higher the BASMI score the more severe the participant's limitation of movement due to their AS. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score	Baseline, Week 64	The SF-36 is a 36-item participant administered measure designed to be a short, multipurpose assessment of health in the areas of physical functioning, role - physical, role - emotional, bodily pain, vitality, social functioning, mental health, and general health. The 2 overarching domains of mental well- being and physical well-being are captured by the Mental Component Summary and Physical Component Summary scores. T-scores are used for analysis. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Change From Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores	Baseline, Week 64	The WPAI-SpA consists of 6 questions to determine employment status, hours missed from work because of SpA, hours missed from work for other reasons, hours actually worked, the degree to which SpA affected work productivity while at work, and the degree to which SpA affected activities outside of work. The WPAI-SpA has been validated in the rad-axSpA participant population. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. The computed percentage range for each sub-scale was from 0-100, with higher scores indicating greater impairment and less productivity. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)	Baseline, Week 64	The MASES is an index used to measure the severity of enthesitis. The MASES assesses 13 sites for enthesitis using a score of "0" for no activity or "1" for activity. Sites assessed include costochondral 1 (right/left), costochondral 7 (right/left), spinal iliaca anterior superior (right/left), crista iliaca (right/left), spina iliaca posterior (right/left), processus spinosus L5, and Achilles tendon proximal insertion (right/left). The MASES is the sum of all site scores (range 0 to 13); higher scores indicate more severe enthesitis. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Change From Baseline in the Fatigue Numeric Rating Scale (NRS) Score	Baseline, Week 64	The fatigue severity NRS is a participant administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing "no fatigue" and 10 representing "as bad as you can imagine". Participants rate their fatigue (feeling tired or worn out) by circling the 1 number that describes their worst level of fatigue during the previous 24 hours. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Change From Baseline in SF-36 Mental Component Summary (MCS) Score	Baseline, Week 64	The SF-36 is a 36-item participant administered measure designed to be a short, multipurpose assessment of health in the areas of physical functioning, role - physical, role - emotional, bodily pain, vitality, social functioning, mental health, and general health. The 2 overarching domains of mental well- being and physical well-being are captured by the Mental Component Summary and Physical Component Summary scores. T-scores are used for analysis. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Change From Baseline in the European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) UK Population-based Index Score	Baseline, Week 64	The European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of 2 components: a descriptive system of the respondent's health and a rating of his/her current health state using a 0- to 100-mm visual analog scale (VAS). The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors.
Percentage of Participants With Anti-Ixekizumab Antibodies	Baseline, Week 64	A treatment emergent - antidrug antibody (TE-ADA) positive participant is defined as: a) a participant with a \>= 4-fold increase over a positive baseline antibody titer; or b) for a negative baseline titer, a participant with an increase from the baseline to a level of \>= 1:10. Percentage was calculated based on the number of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-ixekizumab antibodies / number of evaluable participants \* 100%.

Trial Locations

Locations (126): Physician Research Collaboration, LLC
🇺🇸
Lincoln, Nebraska, United States
Arthritis Rheumatic Disease Specialties
🇺🇸
Aventura, Florida, United States
University of Alberta Hospital
🇨🇦
Edmonton, Alberta, Canada
Klein and Associates MD, PA
🇺🇸
Hagerstown, Maryland, United States
Arthritis Northwest PLLC
🇺🇸
Spokane, Washington, United States
Centre hospitalier universitaire Lapeyronie
🇫🇷
Montpellier Cedex 5, France
CIP - Centro Internacional de Pesquisa
🇧🇷
Goiás, Brazil
Shanahan Rheumatology & Immunotherapy, PLLC
🇺🇸
Raleigh, North Carolina, United States
Sarasota Arthritis Center
🇺🇸
Sarasota, Florida, United States
Consultorios Reumatologicos Pampa
🇦🇷
Ciudad Autonoma de Buenos Aire, Argentina
Care Access Research - Huntington Beach
🇺🇸
Huntington Beach, California, United States
Carolina Arthritis Associates
🇺🇸
Wilmington, North Carolina, United States
Revmaclinic, s.r.o
🇨🇿
Brno, Czechia
Rambam Medical Center
🇮🇱
Haifa, Israel
Charité Universitätsmedizin Berlin
🇩🇪
Berlin, Germany
Arcispedale Santa Maria Nuova Azienda Ospedaliera di Reggio Emilia
🇮🇹
Reggio Emilia, Italy
Hôpital Trousseau, CHRU de Tours
🇫🇷
Chambray-lès-Tours, France
Asan Medical Center
🇰🇷
Songpa-gu, Seoul, Korea, Republic of
Revmatologicky ustav
🇨🇿
Praha 2, Czechia
Group de recherche en maladies osseuses
🇨🇦
Quebec, Canada
CCBR Brasil Centro de Analises e Pesquisas Clínicas LTDA
🇧🇷
Rio de Janeiro, RJ, Brazil
Seoul St. Mary's Hospital
🇰🇷
Seoul, Korea, Korea, Republic of
HRF Hamburger Rheuma Forschungszentrum
🇩🇪
Hamburg, Germany
Helsinki University Hospital, HYKS
🇫🇮
Helsinki, Finland
Hospital General Universitario Gregorio Marañon
🇪🇸
Madrid, Spain
MEDICAL PLUS, s.r.o.
🇨🇿
Uherske Hradiste, Czechia
Arthrohelp s.r.o
🇨🇿
Pardubice, Czechia
Kyung Hee University Hospital
🇰🇷
Seoul, Korea, Korea, Republic of
Japanese Red Cross Okayama Hospital
🇯🇵
Okayama, Japan
Hanyang University Medical Center
🇰🇷
Seoul, Korea, Republic of
St. Lukes International Hospital
🇯🇵
Chuo-Ku, Tokyo, Japan
Chungnam National University Hospital
🇰🇷
Daejeon, Korea, Republic of
Investigación y Biomedicina de Chihuahua, SC
🇲🇽
Chihuahua, Mexico
Antonius Ziekenhuis
🇳🇱
Sneek, Netherlands
Centrum Medyczne AMED
🇵🇱
Warszawa, Poland
Konkuk University Hospital
🇰🇷
Seoul, Korea, Republic of
Gangnam Severance Hospital
🇰🇷
Seoul, Korea, Republic of
Centro de Salud Mental Parc Tauli
🇪🇸
Sabadell, Barcelona, Spain
Chang Gung Memorial Hospital - Kaohsiung
🇨🇳
Kaohsiung, Taiwan
Univ of Texas Health Science Center - Houston
🇺🇸
Houston, Texas, United States
Arthritis Assoc. & Osteoporosis Ctr of Colorado Springs, LLC
🇺🇸
Colorado Springs, Colorado, United States
Desert Medical Advances
🇺🇸
Palm Desert, California, United States
Marietta Rheumatology
🇺🇸
Marietta, Georgia, United States
Center for Arthritis & Osteoporosis
🇺🇸
Elizabethtown, Kentucky, United States
Arthritis Consultants Inc.
🇺🇸
Saint Louis, Missouri, United States
Altoona Center for Clinical Research
🇺🇸
Duncansville, Pennsylvania, United States
CER Instituto Medico
🇦🇷
Quilmes, Buenos Aires, Argentina
Interni a revmatologicka ambulance, Inrea s.r.o.
🇨🇿
Ostrava, Czechia
Nouvel Hôpital Orléans La Source
🇫🇷
Orleans CEDEX 2, France
Rheumazentrum Ruhrgebiet
🇩🇪
Herne, Nordrhein-Westfalen, Germany
Barzilai Medical Center
🇮🇱
Ashkelon, Israel
Hokkaido University Hospital
🇯🇵
Sapporo, Hokkaido, Japan
Osaka City General Hospital
🇯🇵
Osaka, Japan
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Kyunghee University Hospital at Gangdong
🇰🇷
Seoul, Korea, Republic of
Seoul Municipal Boramae Hospital
🇰🇷
Seoul, Korea, Republic of
NZOZ ZDROWIE Osteo-Medic
🇵🇱
Bialystok, Poland
Centrum Kliniczno-Badawcze
🇵🇱
Elblag, Poland
GCM Medical Group PSC
🇵🇷
San Juan, Puerto Rico
Hospital Infanta Luisa
🇪🇸
Sevilla, Spain
China Medical University Hospital
🇨🇳
Taichung, Taiwan
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
Chung Shan Medical University Hospital
🇨🇳
Taichung City, Taiwan
Chi-Mei Medical Center
🇨🇳
Yongkang City, Taiwan
Norfolk and Norwich Hospital
🇬🇧
Norwich, Norfolk, United Kingdom
Haywood Hospital
🇬🇧
Stoke on Trent, Staffordshire, United Kingdom
New Cross Hospital
🇬🇧
Wolverhampton, West Midlands, United Kingdom
LMK Serviços Médicos S/S
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
Wythenshawe Hospital
🇬🇧
Wythenshawe, Manchester, United Kingdom
CMIP - Centro Mineiro de Pesquisa
🇧🇷
Juiz de Fora, Minas Gerais, Brazil
Institute of Arthritis Research
🇺🇸
Idaho Falls, Idaho, United States
Glacier View Research Institute
🇺🇸
Kalispell, Montana, United States
Articularis Healthcare Group, INC dba Columbia Arthritis Ctr
🇺🇸
Columbia, South Carolina, United States
Sasebo Chuo Hospital
🇯🇵
Sasebo, Nagasaki, Japan
Osaka University Hospital
🇯🇵
Suita-shi, Osaka, Japan
Szpital Uniwersytecki nr 2 im. dr J. Biziela
🇵🇱
Bydgoszcz, Poland
Ryazan Regional Clinincal Cardiology Dispensary
🇷🇺
Ryazan, Russian Federation
Centro de Enfermedades del Higado y Aparato Digestivo
🇦🇷
Rosario, Santa Fe, Argentina
Ctro Inv en Artritis y Osteoporosis SC
🇲🇽
Mexicali, Baja California, Mexico
Kiljava Medical Research
🇫🇮
Hyvinkaa, Finland
Rabin Medical Center
🇮🇱
Petach Tikva, Israel
Tel Aviv Sourasky Medical Center
🇮🇱
Tel Aviv, Israel
Kagawa University Hospital
🇯🇵
Kita-gun, Kagawa, Japan
Kochi Medical School Hospital
🇯🇵
Nankoku, Kochi, Japan
Osaka City University Hospital
🇯🇵
Osaka, Japan
Yamagata University Hospital
🇯🇵
Yamagata, Japan
Centro de Alta Especialidad Reumatologia Inv del Potosi SC
🇲🇽
San Luis Potosi, SLP, Mexico
Clinical Research Center of CT/NY
🇺🇸
Danbury, Connecticut, United States
Centre de Recherche Musculo-Squelettique
🇨🇦
Trois-Rivieres, Quebec, Canada
CIR Centro de Investigacions Reumatologicas
🇦🇷
San Miguel de Tucuman, Argentina
Terveystalo Kamppi
🇫🇮
Helsinki, Finland
Hospital Universitario de Monterrey
🇲🇽
Monterrey, Nuevo Leon, Mexico
Lecznica MAK-MED, NZOZ
🇵🇱
Nadarzyn, Poland
Lubelskie Centrum Diagnostyczne
🇵🇱
Swidnik, Poland
Reumatika Centrum Reumatologii
🇵🇱
Warszawa, Poland
Saratov State Medical University
🇷🇺
Saratov, Russian Federation
Clinical Hospital for Emergency Care
🇷🇺
Yaroslavl, Russian Federation
Cpclin Centro de Pesquisas Clinicas
🇧🇷
Sao Paulo, São Paulo, Brazil
City Clinical Hospital N1
🇷🇺
Moscow, Russian Federation
Articularis Healthcare d/b/a/ Low Country Rheumatology, PA
🇺🇸
Summerville, South Carolina, United States
Clinica Adventista de Belgrano
🇦🇷
Ciudad de Buenos Aires, Buenos Aires, Argentina
Vital Medical Center
🇭🇺
Veszprem, Hungary
Kuwana City Medical Center
🇯🇵
Kuwana, Mie, Japan
Juntendo University Hospital
🇯🇵
Bunkyo-ku, Tokyo, Japan
Academisch Medisch Centrum
🇳🇱
Amsterdam, Netherlands
Prywatna Praktyka Lekarska P. Hrycaj
🇵🇱
Poznan, Poland
Sp Clinic Judetean de Urgenta Sf.Apostol Andrei Constanta
🇷🇴
Constanta, Romania
Clinica en Investigación en Reumatologia y Obesidad S.C.
🇲🇽
Guadalajara, Jalisco, Mexico
EDUMED - Educação em Saúde Ltda.
🇧🇷
Curitiba, Paraná, Brazil
Rheumazentrum Prof. Neeck
🇩🇪
Bad Doberan, Mecklenburg-Vorpommern, Germany
Revita Reumatologiai Kft.
🇭🇺
Budapest, Hungary
V.A. Nasonova Research Institute of Rheumatology
🇷🇺
Moscow, Russian Federation
Centro Medico Privado de Reumatologia
🇦🇷
San Miguel de Tucuman, Tucuman, Argentina
KH der Barmherzigen Schwestern Wien BetriebsGesmbH
🇦🇹
Wien, Austria
Medical Care and Research, S.A. de C.V.
🇲🇽
Merida, Yucatan, Mexico
Centrum Leczenia Osteoporozy Klinika Zdrowej Kosci
🇵🇱
Lodz, Poland
St. Clare's Mercy Hospital
🇨🇦
St. John's, Newfoundland and Labrador, Canada
Latin Clinical Trial Center
🇵🇷
San Juan, Puerto Rico
Mindful Medical Research
🇵🇷
San Juan, Puerto Rico
Spitalul Clinic Sf Maria Bucuresti
🇷🇴
Bucuresti, Romania
Clinical Rheumatology Hospital # 25
🇷🇺
St. Petersburg, Russian Federation
Solihull Hospital
🇬🇧
Solihull, West Midland, United Kingdom
Arizona Arthritis & Rheumatology Research
🇺🇸
Phoenix, Arizona, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Hospital de Clinicas de Porto Alegre
🇧🇷
Porto Alegre, RS, Brazil
Unidad de Investigacion en Enfermedades Cronico Degenerative
🇲🇽
Guadalajara, Jalisco, Mexico