SELECT AXIS 2: A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis

Sponsor

AbbVie (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04169373

Collaborator

(none)

734

Enrollment

212

Locations

Arms

67.2

Anticipated Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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 adult participants 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 adult participants with active axSpA including bDMARD-IR AS (Study 1) and with 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 with nr-axSpA who have completed the Double-Blind Period (Study 2).
To evaluate the maintenance of disease control after withdrawal of upadacitinib.

Condition or Disease	Intervention/Treatment	Phase
Spondyloarthritis	Drug: Upadacitinib Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

734 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 3 Randomized, Placebo-Controlled, Double-Blind Program to Evaluate Efficacy and Safety of Upadacitinib in Adult Subjects With Axial Spondyloarthritis Followed by a Remission-Withdrawal Period

Actual Study Start Date :

Nov 26, 2019

Actual Primary Completion Date :

Sep 2, 2021

Anticipated Study Completion Date :

Jul 3, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Study 1: Upadacitinib Participants will be administered upadacitinib 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).	Drug: Upadacitinib Upadacitinib is administered as oral tablet Other Names: ABT-494 RINVOQ
Experimental: Study 1: Placebo Participants will be administered placebo for 14 weeks followed by upadacitinib 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).	Drug: Upadacitinib Upadacitinib is administered as oral tablet Other Names: ABT-494 RINVOQ Drug: Placebo Placebo for upadacitinib is administered as oral tablet
Experimental: Study 2: Upadacitinib Participants will be administered upadacitinib 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).	Drug: Upadacitinib Upadacitinib is administered as oral tablet Other Names: ABT-494 RINVOQ
Experimental: Study 2: Placebo Participants will be administered placebo for 52 weeks followed by upadacitinib 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).	Drug: Upadacitinib Upadacitinib is administered as oral tablet Other Names: ABT-494 RINVOQ Drug: Placebo Placebo for upadacitinib is administered as oral tablet

Outcome Measures

Primary Outcome Measures

Study 1: Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) 40 Response [Week 14]
ASAS40 is defined as a >= 40% improvement and an absolute improvement of ≥ 2 units (on a scale of 0 to 10) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no worsening at all in the remaining domain.
Study 2: Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) 40 Response [Week 14]
ASAS40 is defined as a >= 40% improvement and an absolute improvement of ≥ 2 units (on a scale of 0 to 10; 0 = no pain and 10 = worst possible pain) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no worsening at all in the remaining domain.

Secondary Outcome Measures

Study 1: Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) [Baseline (Week 0) and Week 14]
The ASDAS is a composite index with proven validity and reliability to assess disease activity in AS patients. It combines the following 5 disease activity variables: back pain, duration of morning stiffness, patient's global assessment (PtGA), peripheral pain/swelling, and high-sensitivity C-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Study 1: Change From Baseline in Magnetic Resonance Imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) Score (Spine) [Baseline (Week 0) and Week 14]
SPARCC scores for spine are calculated by adding up the dichotomous outcomes from evaluations of the presence, depth, and intensity of bone marrow edema lesions of the spine.
Study 1: Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response [Baseline (Week 0) and Week 14]
BASDAI 50 response is defined as at least 50% improvement from Baseline in the BASDAI. The BASDAI is a commonly used measure to define disease activity levels in axSpA patients. It consists of 6 questions on a 0 through 10 numeric rating scale (NRS) (0 being no problem and 10 being the worst problem) pertaining to the 5 major symptoms of AS: Fatigue, Spinal pain, Joint pain/swelling, Areas of localized tenderness, Morning stiffness duration, and Morning stiffness severity.
Study 1: Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) 20 Response [Baseline (Week 0) and Week 14]
ASAS20 is defined as a >= 20% improvement and an absolute improvement of >= 1 units (on a scale of 0 to 10) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no deterioration in the remaining domain (where deterioration is defined as a worsening of >= 20% and a net worsening of >= 1 unit [on a scale of 0 to 10]).
Study 1: Percentage of Participants With ASDAS Inactive Disease [Baseline (Week 0) and Week 14]
ASDAS Inactive Disease is defined as ASDAS score <1.3.
Study 1: Change From Baseline in Patient's Assessment of Total Back Pain [Baseline (Week 0) and Week 14]
Pain will be measured using 0 - 10 numerical rating scale (NRS) items for Total Back Pain (0 = no pain and 10 = severe pain).
Study 1: Change From Baseline in Patient's Assessment of Nocturnal Back Pain [Baseline (Week 0) and Week 14]
Pain will be measured using 0 - 10 numerical rating scale (NRS) items for Nocturnal Back Pain NRS (0 = no pain and 10 = worst possible pain).
Study 1: Percentage of Participants With ASDAS Low Disease Activity [Baseline (Week 0) and Week 14]
ASDAS Low Disease Activity is defined as ASDAS score <2.1.
Study 1: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) [Baseline (Week 0) and Week 14]
The BASFI is a validated patient reported outcome (PRO) instrument for use in the AS patient population. It consists of 10 items measured on a 0 to 10 NRS, which assesses the ability to perform activities known to be problematic to AS patients such as dressing, bending, reaching, turning, and climbing steps.
Study 1: Percentage of Participants With ASAS Partial Remission (PR) [Baseline (Week 0) and Week 14]
ASAS PR is defined as an absolute score of <= 2 units (on a scale of 0 to 10) from Baseline for each of 4 domains (patient's global assessment, back pain, function and inflammation).
Study 1: Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) [Baseline (Week 0) and Week 14]
The ASQoL is an 18-item axSpA-specific Quality of Life (QoL) PRO measure validated in the AS patient population. Concepts measured include activities of daily life, emotional functioning, pain, fatigue, and sleep problems. Each item on ASQoL is given a score of "1" or "0," where a score of "1" is given when an item is affirmed indicating adverse QoL. Total scores can range from 0 (good QoL) to 18 (poor QoL).
Study 1: Change From Baseline in ASAS Health Index (HI) [Baseline (Week 0) and Week 14]
The ASAS HI is validated for patients with all forms of axSpA. It consists of 17 items measuring aspects of functioning and health that are typical and relevant for these patients. Items are scored dichotomously and assess pain, emotional function, sleep, sexual function, mobility, self-care, and community life. Total scores range from 0 (good health) to 17 (poor health), with lower scores indicating better health.
Study 1: Change From Baseline in Linear Bath Ankylosing Spondylitis Metrology Index (BASMIlin) [Baseline (Week 0) and Week 14]
The BASMIlin will be conducted at the visits specified to evaluate spinal mobility in a participant.
Study 1: Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) [Baseline (Week 0) and Week 14]
The MASES evaluation will be conducted by a qualified assessor at the visits specified to assess the presence or absence of enthesitis at 13 different sites noting the participant's responses.
Study 1: Change From Baseline in MRI SPARCC Score (SI Joints) [Baseline (Week 0) and Week 14]
SPARCC scores for sacroiliac (SI) joints are calculated by adding up the dichotomous outcomes from evaluations of the presence, depth, and intensity of bone marrow edema lesions of the SI joints.
Study 2: Change From Baseline in ASDAS [Baseline (Week 0) and Week 14]
The ASDAS is a composite index with proven validity and reliability to assess disease activity in AS patients. It combines the following 5 disease activity variables: back pain, duration of morning stiffness, patient's global assessment (PtGA), peripheral pain/swelling, and high-sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Study 2: Change From Baseline in MRI SPARCC Score (SI Joints) [Baseline (Week 0) and Week 14]
SPARCC scores for sacroiliac (SI) joints are calculated by adding up the dichotomous outcomes from evaluations of the presence, depth, and intensity of bone marrow edema lesions of the SI joints.
Study 2: Percentage of Participants With BASDAI 50 Response [Baseline (Week 0) and Week 14]
BASDAI 50 response is defined as at least 50% improvement from Baseline in the BASDAI. The BASDAI is a commonly used measure to define disease activity levels in axSpA patients. It consists of a 1 through 10 scale (1 being no problem and 10 being the worst problem) and is used to answer 6 questions pertaining to the 5 major symptoms of AS: Fatigue, Spinal pain, Joint pain/swelling, Areas of localized tenderness, Morning stiffness duration, and Morning stiffness severity.
Study 2: Percentage of Participants With ASDAS Inactive Disease [Baseline (Week 0) and Week 14]
ASDAS Inactive Disease is defined as ASDAS score <1.3.
Study 2: Change From Baseline in Patient's Assessment of Total Back Pain [Baseline (Week 0) and Week 14]
Pain will be measured using 0 - 10 numerical rating scale (NRS) items for Total Back Pain (0 = no pain and 10 = severe pain).
Study 2: Change From Baseline in Patient's Assessment of Nocturnal Back Pain [Baseline (Week 0) and Week 14]
Pain will be measured using 0 - 10 numerical rating scale (NRS) items for Nocturnal Back Pain NRS (0 = no pain and 10 = worst possible pain).
Study 2: Percentage of Participants With ASDAS Low Disease Activity [Baseline (Week 0) and Week 14]
ASDAS Low Disease Activity is defined as ASDAS score <2.1.
Study 2: Percentage of Participants With ASAS PR [Baseline (Week 0) and Week 14]
ASAS PR is defined as an absolute score of <= 2 units (on a scale of 0 to 10) from Baseline for each of 4 domains (patient's global assessment, pain, function and inflammation).
Study 2: Change From Baseline in BASFI [Baseline (Week 0) and Week 14]
The BASFI is a validated patient reported outcome (PRO) instrument for use in the AS patient population. It consists of 10 items measured on a 0 to 10 NRS, which assesses the ability to perform activities known to be problematic to AS patients such as dressing, bending, reaching, turning, and climbing steps. The total scores range from 0 to 10.
Study 2: Change From Baseline in ASQoL [Baseline (Week 0) and Week 14]
The ASQoL is an 18-item axSpA-specific Quality of Life (QoL) PRO measure validated in the AS patient population. Concepts measured include activities of daily life, emotional functioning, pain, fatigue, and sleep problems. Each item on ASQoL is given a score of "1" or "0," where a score of "1" is given when an item is affirmed indicating adverse QoL. Total scores can range from 0 (good QoL) to 18 (poor QoL).
Study 2: Change From Baseline in ASAS HI [Baseline (Week 0) and Week 14]
The ASAS HI is validated for patients with all forms of axSpA. It consists of 17 items measuring aspects of functioning and health. Items are scored dichotomously and assess pain, emotional function, sleep, sexual function, mobility, self-care, and community life. Total scores range from 0 (good health) to 17 (poor health), with lower scores indicating better health.
Study 2: Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) 20 Response [Baseline (Week 0) and Week 14]
ASAS20 is defined as a >= 20% improvement and an absolute improvement of >= 1 units (on a scale of 0 to 10) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no deterioration in the remaining domain (where deterioration is defined as a worsening of >= 20% and a net worsening of >= 1 unit [on a scale of 0 to 10]).
Study 2: Change From Baseline in BASMIlin [Baseline (Week 0) and Week 14]
The BASMIlin will be conducted at the visits specified to evaluate spinal mobility in a participant.
Study 2: Change From Baseline in MASES [Baseline (Week 0) and Week 14]
The MASES evaluation will be conducted by a qualified assessor at the visits specified to assess the presence or absence of enthesitis at 13 different sites noting the participant's responses.
Study 2: Change From Baseline in Magnetic Resonance Imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) Score (Spine) [Baseline (Week 0) and Week 14]
SPARCC scores for spine are calculated by adding up the dichotomous outcomes from evaluations of the presence, depth, and intensity of bone marrow edema lesions of the spine.
Study 2: Percentage of Participants Rescued Between Week 24 and Week 52 [Week 24 through Week 52]
Participants who do not achieve an ASAS20 response at any 2 consecutive scheduled visits will be rescued with standard of care as described in the protocol.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Study 1: Participant has the clinical diagnosis of ankylosing spondylitis (AS) who meet the modified New York Criteria for AS (Study 1); OR
Study 2: Participant has the clinical diagnosis of nr-axSpA fulfilling the 2009 ASAS classification criteria for axSpA but not meeting the radiologic criterion of the modified New York criteria for AS and have objective signs of active inflammation on magnetic resonance imaging (MRI) or based on high sensitivity C-reactive protein (CRP).
Study 1 and Study 2: Participant must have a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 and a Patient's Assessment of Total Back Pain score ≥ 4 based on a 0 - 10 numerical rating scale at the Screening and Baseline Visits.
Study 1: Participants must have had an inadequate response to biologic disease-modifying antirheumatic drug (bDMARD) therapy.
Study 2: Participant with prior treatment with bDMARD-therapy is allowed.

Exclusion Criteria:

Participant must not have been exposed to Janus Kinase (JAK) inhibitor.
Prior bDMARD therapy has to be washed out.
Participant must not have a history of an allergic reaction or significant sensitivity to constituents of the study drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Arthritis & Rheumatology Associates, P.C. /ID# 215282	Flagstaff	Arizona	United States	86001-6269
2	AZ Arthritis and Rheumotology Research, PLLC /ID# 215113	Phoenix	Arizona	United States	85032-9306
3	Arizona Arthritis & Rheumatology Research, PLLC /ID# 214731	Tucson	Arizona	United States	85704
4	Newport Huntington Medical Group /ID# 216281	Huntington Beach	California	United States	92648
5	Inland Rheum & Osteo Med Grp /ID# 215807	Upland	California	United States	91786
6	Denver Arthritis Clinic /ID# 215346	Denver	Colorado	United States	80230
7	Tekton Research /ID# 215054	Fort Collins	Colorado	United States	80528
8	Arthritis & Rheumatic Disease Specialties /ID# 215306	Aventura	Florida	United States	33180
9	Sweet Hope Research Specialty Inc /ID# 215931	Hialeah	Florida	United States	33016-1897
10	Innovation Medical Research Center /ID# 216068	Palmetto Bay	Florida	United States	33157-1737
11	Conquest Research /ID# 215804	Winter Park	Florida	United States	32789
12	Great Lakes Clinical Trials /ID# 215790	Chicago	Illinois	United States	60640
13	Greater Chicago Specialty Physicians /ID# 216213	Schaumburg	Illinois	United States	60195-3106
14	Clinic of Robert Hozman/Clinical Investigation Specialists /ID# 215055	Skokie	Illinois	United States	60076
15	Klein and Associates MD /ID# 214767	Hagerstown	Maryland	United States	21740
16	Tufts Medical Center /ID# 215925	Boston	Massachusetts	United States	02111-1552
17	Clinical Pharmacology Study Gr /ID# 215293	Worcester	Massachusetts	United States	01605
18	Wayne State University Health Center /ID# 215930	Detroit	Michigan	United States	48201-2153
19	Advanced Rheumatology, PC /ID# 214973	Lansing	Michigan	United States	48910
20	St. Paul Rheumatology /ID# 215537	Eagan	Minnesota	United States	55121
21	CenterPointe Institute of Research /ID# 215793	Saint Louis	Missouri	United States	63128-3841
22	Clinvest Research LLC /ID# 215785	Springfield	Missouri	United States	65810-2607
23	NYU Langone Orthopedic Center /ID# 215594	New York	New York	United States	10016-2772
24	St. Lawrence Health System /ID# 215844	Potsdam	New York	United States	13676
25	Cape Fear Arthritis Care /ID# 215927	Leland	North Carolina	United States	28451
26	Marietta Memorial Hospital /ID# 215929	Marietta	Ohio	United States	45750-1635
27	STAT Research, Inc. /ID# 215264	Springboro	Ohio	United States	45066
28	Health Research of Oklahoma /ID# 215117	Oklahoma City	Oklahoma	United States	73103-2400
29	Oregon Health and Science University /ID# 216446	Portland	Oregon	United States	97239
30	Altoona Ctr Clinical Res /ID# 214770	Duncansville	Pennsylvania	United States	16635
31	Tekton Research, Inc. /ID# 214923	Austin	Texas	United States	78745
32	Trinity Universal Research Associates - Carrollton /ID# 214948	Carrollton	Texas	United States	75007
33	Arth and Osteo Clin Brazo Valley /ID# 215805	College Station	Texas	United States	77845
34	JPS Health Network /ID# 215962	Fort Worth	Texas	United States	76104-4917
35	Memorial Rheumatology /ID# 216311	Houston	Texas	United States	77024-2420
36	Biopharma Informatic, LLC /ID# 215885	Houston	Texas	United States	77043
37	Biopharma Informatic - Park Row /ID# 215907	Houston	Texas	United States	77084
38	West Texas Clinical Research /ID# 215928	Lubbock	Texas	United States	79410-1198
39	Trinity Universal Research Associates, Inc /ID# 215189	Plano	Texas	United States	75024-5283
40	Rheumatology and Pulmonary Clinic /ID# 214946	Beckley	West Virginia	United States	25801
41	West Virginia Research Inst /ID# 214921	South Charleston	West Virginia	United States	25309
42	Organizacion Medica de Investigacion (OMI) /ID# 214557	Ciudad Autonoma de Buenos Aire	Ciuadad Autonoma De Buenos Aires	Argentina	1015
43	Centro de Enfermedades del Hígado y Aparato Digestivo /ID# 214556	Rosario	Santa Fe	Argentina	2000
44	Instituto CAICI /ID# 215242	Rosario	Santa Fe	Argentina	2000
45	Centro Medico Privado de Reumatologia /ID# 214559	San Miguel de Tucuman	Tucuman	Argentina	4000
46	Hospital Cordoba /ID# 215846	Cordoba		Argentina	5000
47	Instituto Medico Strusberg /ID# 215239	Cordoba		Argentina	5000
48	Cimer /Id# 215240	San Miguel de Tucuman		Argentina	4000
49	Emeritus Research Sydney /ID# 215507	Botany	New South Wales	Australia	2019
50	BJC Health /ID# 215510	Paramatta	New South Wales	Australia	2150
51	Emeritus Research /ID# 215506	Camberwell	Victoria	Australia	3124
52	Monash Medical Centre /ID# 215509	Clayton	Victoria	Australia	3168
53	Barwon Rheumatology Services /ID# 215508	Geelong	Victoria	Australia	3220
54	UZ Gent /ID# 215004	Gent	Oost-Vlaanderen	Belgium	9000
55	Universitair Ziekenhuis Leuven /ID# 215006	Leuven	Vlaams-Brabant	Belgium	3000
56	ReumaClinic /ID# 215005	Genk		Belgium	3600
57	CMiP - Centro Mineiro de Pesquisa Ltda - ME /ID# 215277	Juiz de Fora	Minas Gerais	Brazil	36010-570
58	EDUMED Educacao em Saude S/S L /ID# 215111	Curitiba	Parana	Brazil	80440-080
59	LMK Sevicos Medicos S/S /ID# 215112	Porto Alegre	Rio Grande Do Sul	Brazil	90480-000
60	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto /ID# 215176	Sao Jose Do Rio Preto	Sao Paulo	Brazil	15090-000
61	CPCLIN - Centro de Pesquisas Clínicas /ID# 215175	Sao Paulo		Brazil	01228-200
62	UMHAT Kaspela EOOD /ID# 214803	Plovdiv		Bulgaria	4001
63	Medical center Unimed /ID# 214816	Plovdiv		Bulgaria	4023
64	MHAT Plovdiv /ID# 214815	Plovdiv		Bulgaria	4027
65	Medical center Teodora /ID# 214813	Ruse		Bulgaria	7012
66	Medical center Excelsior /ID# 214805	Sofia		Bulgaria	1407
67	UMHAT Sveti Ivan Rilski /ID# 214804	Sofia		Bulgaria	1431
68	UMHAT Sveti Ivan Rilski /ID# 214806	Sofia		Bulgaria	1431
69	Diagnostic consultative center 17 Sofia /ID# 214808	Sofia		Bulgaria	1505
70	Percuro Clinical Research, Ltd /ID# 215302	Victoria	British Columbia	Canada	V8V 3M9
71	Toronto Western Hospital /ID# 215041	Toronto	Ontario	Canada	M5T 2S8
72	Applied Medical Informatics Research Inc. (AMIR) /ID# 215303	Montréal	Quebec	Canada	H4A 3T2
73	Centre de Recherche Musculo-Squelettique /ID# 215096	Trois-rivières	Quebec	Canada	G8Z 1Y2
74	Centre de recherche du CHUQ /ID# 215038	Quebec		Canada	G1R 3S2
75	The first affiliated hospital of bengbu medical college /ID# 216609	Bengbu	Anhui	China	233004
76	Anhui Provincial Hospital /ID# 216631	Hefei	Anhui	China	230001
77	Peking Union Medical College Hospital /ID# 216545	Beijing	Beijing	China	100730
78	Guangdong Provincial People's Hospital /ID# 216645	Guangzhou	Guangdong	China	510080
79	The First Affiliated Hospital of Shantou University Medical College /ID# 217883	Shantou	Guangdong	China	515041
80	Shenzhen People's Hospital /ID# 225438	Shenzhen	Guangdong	China	518020
81	Zhuzhou Central Hospital /ID# 216644	Zhuzhou	Hunan	China	412007
82	The First Affiliated Hospital of BaoTou Medical College, Inner Mongolia Universi /ID# 216612	Baotou	Inner Mongolia	China	014016
83	First Affiliated Hospital of Kunming Medical University /ID# 217945	Kunming		China	650032
84	Huashan Hospital of Fudan University /ID# 216646	Shanghai		China	200040
85	The First Affiliated Hospital of Soochow University /ID# 216607	Soochow		China	215006
86	REVMACLINIC s.r.o. /ID# 215153	Brno		Czechia	602 00
87	Revmacentrum MUDr. Mostera, s.r.o. /ID# 215161	Brno		Czechia	615 00
88	Revmatologie, s.r.o. /ID# 215309	Brno		Czechia	638 00
89	CCR Ostrava, s.r.o. /ID# 215226	Ostrava		Czechia	702 00
90	ARTHROHELP, s.r.o. /ID# 215224	Pardubice		Czechia	530 02
91	Revmatologicky ustav v Praze /ID# 215154	Praha		Czechia	128 00
92	PV MEDICAL Services s.r.o. /ID# 215119	Praha		Czechia	130 00
93	Revmatologicka ambulance - MUDr. Zuzana Urbanova /ID# 215652	Praha		Czechia	140 00
94	Thomayerova nemocnice /ID# 215118	Praha		Czechia	140 59
95	Fakultni Nemocnice v Motole /ID# 215160	Praha		Czechia	150 06
96	MEDICAL PLUS, s.r.o. /ID# 215324	Uherske Hradiste		Czechia	686 01
97	CHU Toulouse - Hôtel-Dieu Saint-Jacques /ID# 214780	Toulouse	Occitanie	France	31300
98	CHU Bordeaux - Hopital Pellegrin /ID# 214784	Bordeaux		France	33000
99	Hopital Ambroise Pare /ID# 214783	Boulogne Billancourt		France	92104
100	AP-HP - Hopital Cochin /ID# 214782	Paris		France	75014
101	Universitaetsklinikum Erlangen /ID# 214281	Erlangen	Bayern	Germany	91054
102	Rheumatologische Schwerpunktpraxis Brandt-Juergens /ID# 214282	Berlin		Germany	12161
103	Charite Universitaetsklinikum Berlin - Campus Benjamin Franklin /ID# 214211	Berlin		Germany	12203
104	Rheuma Research Lausitz, Dr. Mario Sutowicz /ID# 214218	Cottbus		Germany	30342
105	Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 214207	Dresden		Germany	01307
106	Praxisgemeinschaft Rheumatologie Nephrologie Erlangen /ID# 214212	Erlangen		Germany	91056
107	MVZ Rheumatologie und Autoimmunmedizin Hamburg GmbH /ID# 214208	Hamburg		Germany	20095
108	Medizinische Hochschule Hannover /ID# 214209	Hannover		Germany	30625
109	MVZ für Rheumatologie Dr. M. Welcker GmbH /ID# 214261	Planegg		Germany	82152
110	Debreceni Egyetem Klinikai Kozpont /ID# 215187	Debrecen	Hajdu-Bihar	Hungary	4032
111	Vital-Medicina Kft. /ID# 215182	Veszprém	Veszprem	Hungary	8200
112	Rehavita Egeszsegkozpont /ID# 215188	Kormend	Zala	Hungary	9900
113	Betegapolo Irgalmasrend Budai Irgalmasrendi Korhaz /ID# 215183	Budapest		Hungary	1023
114	Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz /ID# 215186	Gyula		Hungary	5700
115	Hevizgyogyfurdo es Szent Andras Reumakorhaz /ID# 215184	Heviz		Hungary	8380
116	Pest Megyei Flor Ferenc Korhaz /ID# 214501	Kistarcsa		Hungary	2143
117	CMED Rehabilitacios es Diagnosztikai Kozpont /ID# 215181	Szekesfehervar		Hungary	8000
118	The Chaim Sheba Medical Center /ID# 215854	Ramat Gan	Tel-Aviv	Israel	5265601
119	Tel Aviv Sourasky Medical Center /ID# 216956	Tel Aviv-Yafo	Tel-Aviv	Israel	6423906
120	Bnai Zion Medical Center /ID# 215856	Haifa		Israel	3339419
121	Meir Medical Center /ID# 217255	Kfar Saba		Israel	4428164
122	Daido Clinic /ID# 214735	Nagoya-shi	Aichi	Japan	457-8511
123	Matsuyama Red Cross Hospital /ID# 216021	Matsuyama-shi	Ehime	Japan	790-8524
124	National Hospital Organization Asahikawa Medical Center /ID# 214930	Asahikawa-shi	Hokkaido	Japan	070-8644
125	Hokkaido University Hospital /ID# 215221	Sapporo-shi	Hokkaido	Japan	060-8648
126	Kobe University Hospital /ID# 214598	Kobe-shi	Hyogo	Japan	650-0017
127	Hyogo College of Medicine College Hospital /Id# 215638	Nishinomiya-shi	Hyogo	Japan	663-8501
128	Kita-harima Medical Center /ID# 216069	Ono-shi	Hyogo	Japan	675-1327
129	Kuwana City Medical Center /ID# 215196	Kuwana-shi	Mie	Japan	511-0061
130	Nagasaki University Hospital /ID# 215947	Nagasaki-shi	Nagasaki	Japan	852-8501
131	Sasebo Chuo Hospital /ID# 214703	Sasebo-shi	Nagasaki	Japan	857-1195
132	Japanese Red Cross Okayama Hospital /ID# 214732	Okayama-shi	Okayama	Japan	700-8607
133	Okinawa Prefectural Chubu Hospital /ID# 215575	Uruma-shi	Okinawa	Japan	904-2293
134	National Hospital Organization Osaka Minami Medical Center /ID# 214205	Kawachinagano Shi	Osaka	Japan	586-8521
135	Osaka City General Hospital /ID# 215640	Osaka-shi	Osaka	Japan	534-0021
136	Juntendo University Hospital /ID# 214929	Bunkyo-ku	Tokyo	Japan	113-8431
137	St.Luke's International Hospital /ID# 215414	Chuo-ku	Tokyo	Japan	104-8560
138	Ajou University Hospital /ID# 214533	Suwon	Gyeonggido	Korea, Republic of	16499
139	Hanyang University Seoul Hospital /ID# 214297	Seoul	Seoul Teugbyeolsi	Korea, Republic of	04763
140	Gachon University Gil Medical Center /ID# 214534	Incheon		Korea, Republic of	21565
141	Seoul National University Hospital /ID# 214532	Seoul		Korea, Republic of	03080
142	Kyunghee University Hospital at Gangdong /ID# 214296	Seoul		Korea, Republic of	05278
143	Asan Medical Center /ID# 214294	Seoul		Korea, Republic of	05505
144	The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 214295	Seoul		Korea, Republic of	06591
145	CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 215217	Mexico City	Ciudad De Mexico	Mexico	11850
146	Middlemore Clinical Trials /ID# 215502	Papatoetoe	Auckland	New Zealand	2025
147	Waikato Hospital /ID# 215503	Hamilton	Waikato	New Zealand	3240
148	WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 215093	Wroclaw	Dolnoslaskie	Poland	51-685
149	Nasz Lekarz Przychodnie Medyczne /ID# 214352	Torun	Kujawsko-pomorskie	Poland	87-100
150	REUMED Sp.z o.o. Filia nr 1 /ID# 214353	Lublin	Lubelskie	Poland	20-607
151	Osteo-Medic S.C. /ID# 214351	Bialystok	Podlaskie	Poland	15-351
152	ETYKA-Osrodek Badan Klinicznych /ID# 215572	Olsztyn	Warminsko-mazurskie	Poland	10-117
153	AI Centrum Medyczne Sp. z o.o. sp.k. /ID# 214354	Poznan	Wielkopolskie	Poland	61-113
154	Chelyabinsk Regional Clinical Hospital /ID# 214463	Chelyabinsk	Chelyabinskaya Oblast	Russian Federation	454087
155	Immanuel Kant Baltic Federal University /ID# 218259	Kaliningrad	Kaliningradskaya Oblast	Russian Federation	236016
156	LLC Family Outpatient Clinic № /ID# 214455	Korolev	Moskva	Russian Federation	141060
157	Research Institute of Rheumatology named after V.A. Nasonova /ID# 214459	Moscow	Moskva	Russian Federation	115522
158	LLC Medical Center /ID# 214410	Novosibirsk	Novosibirskaya Oblast	Russian Federation	630099
159	Nort-Western State Medical University n.a. Mechnikov /ID# 214454	St. Petersburg	Sankt-Peterburg	Russian Federation	193015
160	LLC Novaya Klinika /ID# 214420	Pyatigorsk	Stavropol Skiy Kray	Russian Federation	357500
161	Family Clinic /ID# 214737	Yekaterinburg	Sverdlovskaya Oblast	Russian Federation	620109
162	Central City Hospital #7 /ID# 214741	Yekaterinburg	Sverdlovskaya Oblast	Russian Federation	620137
163	Kazan State Medical University /ID# 214421	Kazan	Tatarstan, Respublika	Russian Federation	420012
164	Alliance Biomedical Ural Group /ID# 214457	Izhevsk	Udmurtskaya Respublika	Russian Federation	426061
165	Olla-Med Clinic /ID# 214460	Moscow		Russian Federation	105554
166	City Clinical Hospital n.a. O.M. Filatov /ID# 214486	Moscow		Russian Federation	111539
167	Omsk Regional Clinic Hospital /ID# 214464	Omsk		Russian Federation	644111
168	Orenburg State Medical University /ID# 214408	Orenburg		Russian Federation	460000
169	Ryazan State Medical University named after academician I.P. Pavlov /ID# 214418	Ryazan		Russian Federation	390026
170	RZD-Medicine Saratov /ID# 214465	Saratov		Russian Federation	410004
171	Clinical Rheumatologic Hospital No 25 /ID# 214488	St. Petersburg		Russian Federation	190068
172	Ulyanovsk Regional Clinical Hospital /ID# 214458	Ulyanovsk		Russian Federation	432017
173	Univerzitna nemocnica Bratislava Nemocnica Stare Mesto /ID# 214675	Bratislava		Slovakia	813 69
174	Reum.hapi s.r.o. /ID# 224268	Nove Mesto nad Vahom		Slovakia	915 01
175	Narodny ustav reumatickych chorob /ID# 214674	Piestany		Slovakia	921 12
176	MUDr. Zuzana Cizmarikova s.r.o. /ID# 215220	Poprad		Slovakia	058 01
177	ALBAMED s.r.o. /ID# 215248	Zvolen		Slovakia	960 01
178	Hospital Marina Baixa /ID# 215970	Villajoyosa	Alicante	Spain	03570
179	Consorci Corporacio Sanitaria Parc Tauli Sabadell /ID# 214967	Sabadell	Barcelona	Spain	08208
180	Hospital Unversitario Marques de Valdecilla /ID# 214965	Santander	Cantabria	Spain	39008
181	Hospital Meixoeiro (CHUVI) /ID# 214969	Vigo	Pontevedra	Spain	36213
182	Hospital Universitario Reina Sofia /ID# 214968	Cordoba		Spain	14004
183	Hospital Universitario La Paz /ID# 216032	Madrid		Spain	28046
184	Hospital Universitario y Politecnico La Fe /ID# 214966	Valencia		Spain	46026
185	Kaohsiung Veterans General Hos /ID# 214332	Kaohsiung	Taichung	Taiwan	81362
186	Far Eastern Memorial Hospital /ID# 215384	New Taipei City		Taiwan	22060
187	China Medical University Hospital /ID# 214019	Taichung City		Taiwan	40447
188	Chung Shan Medical University Hospital /ID# 214018	Taichung		Taiwan	40201
189	Cathay General Hospital /ID# 214183	Taipei		Taiwan	10630
190	Hacettepe Universitesi Tip Fak /ID# 214898	Sihhiye	Ankara	Turkey	06100
191	Istanbul University Cerrahpasa Faculty of Medicine /ID# 214895	Cerrahpasa		Turkey	34098
192	Mugla Sitki Kocman University Medical Faculty /ID# 215358	Mugla		Turkey	48000
193	State Institution L. T. Malaya Therapy National Institution of NAMS of Ukraine /ID# 214155	Kharkiv	Kharkivska Oblast	Ukraine	61039
194	Scientific Research Institute of Invalid Rehabilitation /ID# 214148	Vinnytsia	Vinnytska Oblast	Ukraine	21029
195	MNPE Chernihiv Regional Hospital of the Chernihiv Region Council /ID# 214145	Chernihiv		Ukraine	14029
196	PNE City Multifunctional Hospital No.18 /ID# 214154	Kharkiv		Ukraine	61029
197	CNCE of Kharkiv Regional Council Regional Clinical Hospital /ID# 214158	Kharkiv		Ukraine	61058
198	Khmelnytskyi Regional Hospital /ID# 214153	Khmelnytskyi		Ukraine	29000
199	MI Kryvyi Rih City Clinical Hospital No.2 /ID# 214152	Kryvyi Rih		Ukraine	50056
200	Medical Center LLC Institute of Rheumatology /ID# 214146	Kyiv		Ukraine	02081
201	Kyiv Railway Clinical Hosp No.2 /ID# 214779	Kyiv		Ukraine	03049
202	Medical centre of CONSILIUM MEDICAL LLC /ID# 216234	Kyiv		Ukraine	04050
203	MNI KRC Kyiv Regional Clinical Hospital /ID# 214156	Kyiv		Ukraine	04107
204	Municipal Non-Commercial Enterprise Odesa Regional Clinical Hospital of the Od /ID# 214159	Odesa		Ukraine	65025
205	Multifield Medical Centre of ONMU /ID# 214149	Odesa		Ukraine	65026
206	PI "Poltava Regional Clinical Hospital n.a. M.V.Sklifosovsky" /ID# 214151	Poltava		Ukraine	36011
207	Ternopil University Hospital /ID# 214705	Ternopil		Ukraine	46002
208	MNPE Vinnytsia Regional Clinical Hospital n.a. M.I. Pyrohov /ID# 214147	Vinnytsia		Ukraine	21028
209	Norfolk and Norwich University Hospitals NHS Foundation Trust /ID# 214865	Norwich	Norfolk	United Kingdom	NR4 7UY
210	West Suffolk NHS Foundation Trust /ID# 215529	Bury St Edmunds	Suffolk	United Kingdom	IP33 2QZ
211	Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust /ID# 214971	Armthorpe Road		United Kingdom	DN2 5LT
212	Lancashire Teaching Hospitals NHS Foundation Trust /ID# 216226	Preston		United Kingdom	PR2 9HT