SELECT- SWITCH: Study to Assess Change in Disease Activity and Adverse Events of Oral Upadacitinib Compared to Subcutaneous Adalimumab in Adult Participants With Moderate to Severe Rheumatoid Arthritis

Sponsor

AbbVie (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05814627

Collaborator

(none)

480

Enrollment

191

Locations

Arms

38.4

Anticipated Duration (Months)

2.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Rheumatoid Arthritis (RA) is a chronic inflammatory disease causing pain, stiffness, swelling and loss of joint function. This study will assess how safe and effective upadacitinib is in treating RA when compared to adalimumab in adult participants with inadequate response or intolerance to one TNF-inhibitor who are on a stable dose of methotrexate (MTX). Adverse events and change in disease activity will be assessed.

Upadacitinib is an approved drug for the treatment of RA. This study is double-blinded means that neither the participants nor the study doctors will know who will be given upadacitinib and who will be given adalimumab. Study doctors put the participants in 1 of the 2 groups, called treatment arms randomly, to receive either upadacitinib or adalimumab. There is 1 in 2 chance that participants will receive adalimumab. Each group consists of 2 periods. Approximately 480 participants diagnosed with RA will be enrolled in approximately 250 sites across the world.

Participants will receive the oral upadacitinib once daily and matching adalimumab placebo every other week, or the subcutaneous adalimumab every other week and matching upadacitinib placebo once daily during Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1 and will be followed for 30 days and 70 days.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, checking for side effects and completing questionnaires.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Upadacitinib Drug: Adalimumab Drug: Upadacitinib Matching Placebo Drug: Adalimumab Matching Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

480 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Treatment

Official Title:

A Phase 3b/4 Randomized, Double-Blind, Double Dummy, Active Comparator-Controlled Study, Comparing the Efficacy and Safety of Upadacitinib Versus Adalimumab in Subjects With Moderate to Severe Rheumatoid Arthritis on a Stable Background of MTX and Who Had an Inadequate Response or Intolerance to a Single TNF Inhibitor (SELECT- SWITCH)

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Sep 23, 2025

Anticipated Study Completion Date :

Aug 12, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Upadacitinib+ Adalimumab matching Placebo Participants will receive upadacitinib once a day along with matching placebo for adalimumab at eow (every other week) in Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1.	Drug: Upadacitinib Oral Tablets Other Names: RINVOQ Drug: Adalimumab Matching Placebo Subcutaneous Injection
Experimental: Adalimumab + Upadacitinib matching Placebo Participants will receive adalimumab at eow (every other week) along with matching placebo for upadacitinib once a day in Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1.	Drug: Adalimumab Subcutaneous Injection Other Names: Humira Drug: Upadacitinib Matching Placebo Oral Tablets

Arm

Intervention/Treatment

Experimental: Upadacitinib+ Adalimumab matching Placebo

Participants will receive upadacitinib once a day along with matching placebo for adalimumab at eow (every other week) in Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1.

Drug: Upadacitinib

Oral Tablets

Other Names:

RINVOQ

Drug: Adalimumab Matching Placebo

Subcutaneous Injection

Experimental: Adalimumab + Upadacitinib matching Placebo

Participants will receive adalimumab at eow (every other week) along with matching placebo for upadacitinib once a day in Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1.

Drug: Adalimumab

Subcutaneous Injection

Other Names:

Humira

Drug: Upadacitinib Matching Placebo

Oral Tablets

Outcome Measures

Primary Outcome Measures

Percentage of Participants Achieving Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) <= 3.2 [Week 12]
The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (NRS), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Low Disease Activity (LDA) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than or equal to 3.2.

Secondary Outcome Measures

Percentage of Participants Achieving American College of Rheumatology 50 % (ACR50) Response [Week 12]
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria: 50% improvement in tender joint count (TJC68); 50% improvement in swollen joint count (SJC66); and 50% improvement in at least 3 of the 5 following parameters: Physician's Global Assessment of Disease Activity measured on a Numerical Rating Scale of 0 to 10 (NRS) Patient's Global Assessment of Disease Activity (NRS) Patient's Assessment of Pain (NRS) Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP).
Percentage of Participants Achieving Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) < 2.6 [Week 12]
The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (NRS), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Clinical remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6.
Change from Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) [Week 12]
The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (NRS), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity.
Change from Baseline in Participants Assessment of Pain [Week 12]
Participants indicated their level of pain over the last 7 days using the Patient's Global Assessment Pain NRS. The range is 0 to 10 with no activity being indicated by 0 and severe activity by 10.
Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score [Week 12]
The HAQ-DI assesses physical function in RA. The HAQ-DI score is the average of the highest score in each of eight categories. The total score is between 0-3.0, in 0.125 increments. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of Rheumatoid Arthritis (RA) for >= 3 months based on the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for RA.
Treated for >= 3 consecutive months prior to screening with 1 tumor necrosis factor inhibitor (TNFi) (originator or biosimilar) for RA (except adalimumab [originator or biosimilar]), but continue to exhibit active RA, or had to discontinue due to intolerability, irrespective of treatment duration. Up to 15% of participants who were intolerant to 1 TNFi will be allowed to enroll.
On oral or parenteral methotrexate (MTX) therapy >= 3 months and on a stable prescription of 15 to 25 mg/week (or >= 10 mg/week in participants intolerant of MTX at doses >= 15 mg/week) for >= 4 weeks prior to the first dose of study drug. In addition, all participants should take a dietary supplement of folic acid or folinic acid throughout the study participation.
For participants in China, Japan, Korea, or Taiwan, a stable dose of MTX >= 7.5 mg/week is acceptable.
Additional local requirements for MTX may apply.
Meets both of the following disease activity criteria:
= 6 swollen joint (based on 66 joint counts) and >= 6 tender joints (based on 68 joint counts) at screening and baseline;
High-sensitivity C-reactive protein (hsCRP) >= 3 mg/L (central lab, upper limit of normal [ULN] 2.87 mg/L) at screening.

Exclusion Criteria:

History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than Rheumatoid Arthritis (RA).
Prior exposure to any janus kinase (JAK) inhibitor.
Prior exposure to adalimumab (original or biosimilar).
Prior exposure to a non-TNFi biologic disease modifying anti-rheumatic drug (bDMARD).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Arthritis & Rheumatology Associates, P.C. /ID# 253431	Flagstaff	Arizona	United States	86001-6269
2	Sun Valley Arthritis Center Ltd. /ID# 254654	Peoria	Arizona	United States	85381
3	AZ Arthritis and Rheumotology Research, PLLC /ID# 253432	Phoenix	Arizona	United States	85032-9306
4	Arizona Arthritis & Rheumatology Associates - Tucson /ID# 255017	Tucson	Arizona	United States	85704
5	Arthritis and Rheumatism Associates /ID# 254013	Jonesboro	Arkansas	United States	72401-6251
6	Providence Medical Foundation /ID# 252690	Fullerton	California	United States	92835
7	Newport Huntington Medical Group /ID# 252687	Huntington Beach	California	United States	92648-5994
8	Purushotham & Akther Kotha MD, Inc /ID# 252704	La Mesa	California	United States	91942
9	Valerius Medical Group & Research Center /ID# 252692	Los Alamitos	California	United States	90720-5402
10	Millennium Clinical Trials /ID# 252689	Thousand Oaks	California	United States	91360-3951
11	The Lundquist Institute at Harbor-UCLA Medical Center /ID# 252691	Torrance	California	United States	90502
12	Comprehensive Rheumatology Center /ID# 252688	Woodland Hills	California	United States	91364
13	Denver Arthritis Clinic /ID# 254058	Denver	Colorado	United States	80230
14	Rheumatology Associates of South Florida (RASF) - Clinical Research /ID# 253733	Boca Raton	Florida	United States	33486
15	Bay Area Arthritis and Osteo /ID# 254046	Brandon	Florida	United States	33511
16	Clinical Research of West Florida, Inc /ID# 254649	Clearwater	Florida	United States	33765
17	International Medical Research - Daytona /ID# 254651	Daytona Beach	Florida	United States	32117
18	Omega Research Debary, LLC /ID# 253735	DeBary	Florida	United States	32713-2260
19	Sweet Hope Research Specialty Inc /ID# 254622	Hialeah	Florida	United States	33016-1897
20	HMD Research LLC /ID# 253732	Orlando	Florida	United States	32819
21	BayCare Medical Group /ID# 253799	Saint Petersburg	Florida	United States	33705
22	University of South Florida /ID# 253745	Tampa	Florida	United States	33612
23	Atlanta Research Center for Rheumatology /ID# 254623	Marietta	Georgia	United States	20060
24	OrthoIllinois /ID# 254057	Rockford	Illinois	United States	61114-4937
25	Greater Chicago Specialty Physicians /ID# 254000	Schaumburg	Illinois	United States	60195-3106
26	Clinic of Robert Hozman/Clinical Investigation Specialists /ID# 253999	Skokie	Illinois	United States	60076
27	Springfield Clinic /ID# 253996	Springfield	Illinois	United States	62702-3749
28	Deerbrook Medical Associates /ID# 254008	Vernon Hills	Illinois	United States	60061
29	Qualmedica Research, LLC /ID# 254005	Evansville	Indiana	United States	47714-0805
30	Bluegrass Community Research /ID# 254653	Lexington	Kentucky	United States	40504
31	Ochsner Clinic Foundation /ID# 254059	Baton Rouge	Louisiana	United States	70836-6455
32	The Arthritis & Diabetes Clinic, Inc. /ID# 254014	Monroe	Louisiana	United States	71203
33	AA Medical Research Center - Grand Blanc /ID# 254007	Grand Blanc	Michigan	United States	48439
34	Arthritis Associates /ID# 253992	Hattiesburg	Mississippi	United States	39402
35	Clinvest Research LLC /ID# 254054	Springfield	Missouri	United States	65807
36	Logan Health Research /ID# 253738	Kalispell	Montana	United States	59901
37	Physician Research Collaboration, LLC /ID# 254012	Lincoln	Nebraska	United States	68516
38	Dartmouth-Hitchcock Medical Center /ID# 253798	Lebanon	New Hampshire	United States	03756
39	Arthritis and Osteo Assoc /ID# 252684	Las Cruces	New Mexico	United States	88011
40	NYU Langone Ambulatory Care Brooklyn Heights /ID# 254621	Brooklyn	New York	United States	11201
41	Paramount Medical Research Con /ID# 254048	Middleburg Heights	Ohio	United States	44130
42	Rheumatology Associates of Oklahoma /ID# 253994	Oklahoma City	Oklahoma	United States	73116-7226
43	West Tennessee Research Institute /ID# 254620	Jackson	Tennessee	United States	38305
44	Arthritis and Rheumatology Research Institute, PLLC /ID# 254045	Allen	Texas	United States	75013-6147
45	Tekton Research, Inc. /ID# 254004	Austin	Texas	United States	78745
46	Adriana Pop-Moody MD Clinic PA /ID# 255030	Corpus Christi	Texas	United States	78404
47	Biopharma Informatic, LLC /ID# 254053	Houston	Texas	United States	77043
48	Accurate Clinical Research /ID# 254647	Houston	Texas	United States	77089
49	West Texas Clinical Research /ID# 253736	Lubbock	Texas	United States	79424
50	Trinity Universal Research Associates, Inc /ID# 253995	Plano	Texas	United States	75024-5283
51	Advanced Rheumatology of Houston /ID# 254003	The Woodlands	Texas	United States	77382
52	DM Clinical Research - Tomball /ID# 254001	Tomball	Texas	United States	77375
53	Rheumatology Clinic of Houston /ID# 254002	Tomball	Texas	United States	77377
54	Aurora Rheumatology and Immunotherapy Center /ID# 254049	Franklin	Wisconsin	United States	53132
55	Rheumatic Disease Center, LLP /ID# 254015	Glendale	Wisconsin	United States	53217
56	Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich /ID# 253255	Ciudad Autonoma Buenos Aires	Buenos Aires	Argentina	1426
57	DIM Clinica Privada /ID# 253299	Ramos Mejía	Buenos Aires	Argentina	1704
58	Organizacion Medica de Investigacion (OMI) /ID# 253253	Ciudad Autonoma de Buenos Aire	Ciuadad Autonoma De Buenos Aires	Argentina	1015
59	Aprillus Asistencia e Investigacion /ID# 253258	Ciudad Autonoma de Buenos Aire	Ciuadad Autonoma De Buenos Aires	Argentina	1046
60	Mautalen Salud e Investigacion /ID# 253257	Ciudad Autonoma de Buenos Aire	Ciuadad Autonoma De Buenos Aires	Argentina	1128
61	Consultorios Reumatologicos Pampa /ID# 254095	Ciudad Autonoma de Buenos Aire	Ciuadad Autonoma De Buenos Aires	Argentina	1428
62	Instituto CAICI S.R.L /ID# 253254	Rosario	Santa Fe	Argentina	2000
63	Centro de Investigaciones Medicas Tucuman /ID# 253297	San Miguel de Tucuman	Tucuman	Argentina	4000
64	Centro Integral de Reumatologi /ID# 253298	San Miguel de Tucuman	Tucuman	Argentina	4000
65	Instituto Medico Privado DAMIC /ID# 253296	Cordoba		Argentina	5003
66	Instituto Medico de Alta Complejidad San Isidro S.A. /ID# 254319	San Isidro		Argentina	1643
67	UCL Saint-Luc /ID# 252276	Woluwe-Saint-Lambert	Bruxelles-Capitale	Belgium	1200
68	UZ Gent /ID# 252306	Gent	Oost-Vlaanderen	Belgium	9000
69	AZ Sint-Jan Brugge /ID# 252278	Brugge		Belgium	8000
70	ReumaClinic /ID# 252277	Genk		Belgium	3600
71	CHU de Liege /ID# 252309	Liege		Belgium	4000
72	CMiP - Centro Mineiro de Pesquisa Ltda - ME /ID# 254203	Juiz de Fora	Minas Gerais	Brazil	36010-570
73	CETI - Centro de Estudos em Terapias Inovadoras /ID# 254201	Curitiba	Parana	Brazil	80030-110
74	Hospital de Clinicas de Porto Alegre /ID# 254916	Porto Alegre	Rio Grande Do Sul	Brazil	90035-903
75	LMK Sevicos Medicos S/S /ID# 254202	Porto Alegre	Rio Grande Do Sul	Brazil	90480-000
76	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto /ID# 254917	Sao Jose Do Rio Preto	Sao Paulo	Brazil	15090-000
77	CEPIC - Centro Paulista de Investigação Clinica /ID# 254200	São Paulo	Sao Paulo	Brazil	04266-010
78	Medical Center Academy /ID# 253275	Sofiya	Sofia	Bulgaria	1612
79	UMHAT Kaspela EOOD /ID# 252343	Plovdiv		Bulgaria	4001
80	Medical center Unimed /ID# 252344	Plovdiv		Bulgaria	4023
81	MHAT Plovdiv /ID# 252342	Plovdiv		Bulgaria	4027
82	Diagnostic consultative center Focus-5 /ID# 252354	Sofia		Bulgaria	1463
83	Diagnostic consultative center Focus-5 /ID# 252555	Sofia		Bulgaria	1463
84	Diagnostic consultative center 17 Sofia /ID# 252341	Sofia		Bulgaria	1505
85	Military Medical Academy Multiprofile Hospital /ID# 252355	Sofia		Bulgaria	1606
86	Manitoba Clinic /ID# 254019	Winnipeg	Manitoba	Canada	R3A 1M3
87	The Waterside Clinic /ID# 254020	Barrie	Ontario	Canada	L4M 6L2
88	CISSSBSL -Hopital regional de Rimouski /ID# 253407	Rimouski	Quebec	Canada	G5L 5T1
89	Groupe de Recherche en Maladies Osseuses Inc /ID# 253409	Sainte-foy	Quebec	Canada	G1V 3M7
90	Dr. Latha Naik /ID# 254018	Saskatoon	Saskatchewan	Canada	S7K 3H3
91	Corporacion de Beneficiencia Osorno /ID# 252556	Osorno	Los Lagos	Chile	1710216
92	Complejo Asistencial Dr. Sotero del Rio /ID# 252559	Santiago	Region Metropolitana Santiago	Chile	8207257
93	Clinica DermaCross /ID# 252560	Santiago		Chile	7640881
94	Centro Internacional de Estudios Clinicos /ID# 252561	Santiago		Chile	8420383
95	The first affiliated hospital of bengbu medical college /ID# 252612	Bengbu	Anhui	China	233004
96	Peking University First Hospital /ID# 252392	Beijing	Beijing	China	100034
97	Peking University Third Hospital /ID# 252393	Beijing	Beijing	China	100191
98	The Third Affiliated Hospital Of Sun Yat-Sen University /ID# 252394	Guangzhou	Guangdong	China	510630
99	Zhuzhou Central Hospital /ID# 252390	Zhuzhou	Hunan	China	412007
100	Nanjing Drum Tower Hospital /ID# 252613	Nanjing	Jiangsu	China	210008
101	Jiangxi Pingxiang People's Hospital /ID# 252381	Pingxiang	Jiangxi	China	337055
102	West China Hospital, Sichuan University /ID# 252364	Chengdu	Sichuan	China	610041
103	Hospital Pablo Tobon Uribe /ID# 253371	Medellín	Antioquia	Colombia	50034
104	Centro Integral de Reumatologia del Caribe Circaribe SAS /ID# 252587	Barranquilla	Atlantico	Colombia	80002
105	Centro de Investigacion en Reumatologia y Especialidades Medicas- CIREEM SAS /ID# 252586	Bogota	Cundinamarca	Colombia	110221
106	Healthy Medical Center SAS /ID# 252585	Zipaquira	Cundinamarca	Colombia	250252
107	Fundacion Oftalmologica de Santander - FOSCAL /ID# 252589	Floridablanca	Santander	Colombia	681004
108	Poliklinika Repromed /ID# 252451	Zagreb	Grad Zagreb	Croatia	10000
109	Poliklinika Solmed /ID# 252453	Grad Zagreb		Croatia	10000
110	Specijalna bolnica za medicinsku rehabilitaciju Krapinske Toplice /ID# 252455	Krapinske Toplice		Croatia	49127
111	Medical Center Kuna-Peric /ID# 252452	Zagreb		Croatia	10000
112	Poliklinika Bonifarm /ID# 252741	Zagreb		Croatia	10000
113	CHU Toulouse - Hopital Purpan /ID# 252402	TOULOUSE Cedex 9	Haute-Garonne	France	31059
114	CHU Montpellier - Hôpital Saint Eloi /ID# 252386	Montpellier Cedex 5	Herault	France	34295
115	CHR Orleans - Hopital de la Source /ID# 252385	Orleans CEDEX 2	Loiret	France	45067
116	CHU Nice -Hopital Pasteur /ID# 254224	Nice CEDEX 1	Provence-Alpes-Cote-d Azur	France	06002
117	CHU Amiens-Picardie Site Sud /ID# 252384	Amiens CEDEX 1	Somme	France	80054
118	Hôpital Charles-Nicolle /ID# 252908	Rouen		France	76000
119	Rheumatologische-Immunologische Praxis Templin /ID# 252863	Templin	Brandenburg	Germany	17268
120	Rheumazentrum Ruhrgebiet /ID# 252670	Herne	Nordrhein-Westfalen	Germany	44649
121	MVZ für Rheumatologie Dr. M. Welcker GmbH /ID# 254221	Planegg		Germany	82152
122	Rheumazentrum Ratingen /ID# 252669	Ratingen		Germany	40882
123	General Hospital of Athens Laiko /ID# 252258	Athens	Attiki	Greece	11527
124	University General Hospital Attikon /ID# 254751	Athens	Attiki	Greece	12462
125	University General Hospital of Heraklion PA.G.N.I /ID# 252261	Heraklion	Kriti	Greece	71500
126	Vital Medical Center Orvosi es Fogaszati Kozpont /ID# 252399	Veszprém	Veszprem	Hungary	8200
127	Betegapolo Irgalmasrend Budai Irgalmasrendi Korhaz /ID# 253311	Budapest		Hungary	1023
128	CMED Rehabilitacios es Diagnosztikai Kozpont /ID# 252400	Szekesfehervar		Hungary	8000
129	MAV Korhaz ess Rendelointezet /ID# 252628	Szolnok		Hungary	5000
130	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona /ID# 252459	Ancona		Italy	60126
131	Azienda Ospedaliero Universitaria Careggi /ID# 252460	Florence		Italy	50134
132	ASST Gaetano Pini/Presidio Ospedaliero Pini /ID# 252461	Milan		Italy	20122
133	Japan Organization of Occupational Health and Safety Chubu Rosai Hospital /ID# 252836	Nagoya-shi	Aichi	Japan	455-8530
134	Daido Clinic /ID# 253058	Nagoya-shi	Aichi	Japan	457-8511
135	Sugimoto rheumatology and internal medicine clinic /ID# 252774	Fukui-shi	Fukui	Japan	910-0068
136	Hamanomachi Hospital /ID# 253168	Fukuoka-shi	Fukuoka	Japan	810-8539
137	Shono Rheumatism Clinic /ID# 252591	Fukuoka-shi	Fukuoka	Japan	814-0002
138	Katayama Orthopedic Rheumatology Clinic /ID# 252746	Asahikawa-shi	Hokkaido	Japan	078-8243
139	Sagawa Akira Rheumatology Clin /ID# 252773	Sapporo-shi	Hokkaido	Japan	060-0001
140	Matsubara Mayflower Hospital /ID# 252834	Kato-shi	Hyogo	Japan	673-1462
141	Sanuki Municipal Hospital /ID# 252747	Sanuki-shi	Kagawa	Japan	769-2393
142	Bay Side Misato Medical Center /ID# 252661	Kochi-shi	Kochi	Japan	781-0112
143	Kumamoto Orthopaedic Hospital /ID# 253167	Kumamoto shi	Kumamoto	Japan	8620975
144	Medical Corporation Keiai Kai Clinic /ID# 252750	Miyazaki-shi	Miyazaki	Japan	880-0053
145	Sasebo Chuo Hospital /ID# 252662	Sasebo-shi	Nagasaki	Japan	857-1195
146	St.Luke's International Hospital /ID# 253131	Chuo-ku	Tokyo	Japan	104-8560
147	Keio University Hospital /ID# 253205	Shinjuku-ku	Tokyo	Japan	160-8582
148	Tokito Clinic Rheumatology and Orthopaedics Surgery /ID# 253057	Shimonoseki-shi	Yamaguchi	Japan	752-0976
149	Chonnam National University Bitgoeul Hospital /Id# 254802	Gwangju-Gwangyeoksi	Gwangju Gwang Yeogsi	Korea, Republic of	61748
150	Hanyang University Seoul Hospital /ID# 252161	Seoul	Seoul Teugbyeolsi	Korea, Republic of	04763
151	Chungnam National University Hospital /ID# 252159	Daejeon		Korea, Republic of	35015
152	Seoul National University Hospital /ID# 252160	Seoul		Korea, Republic of	03080
153	CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 252873	Mexico City	Ciudad De Mexico	Mexico	11850
154	Centro Integral en Reumatologia S.A de C.V /ID# 252872	Guadalajara	Jalisco	Mexico	44160
155	Clinica de Investigacion en Reumatologia y Obesidad S.C. /ID# 253480	Guadalajara	Jalisco	Mexico	44650
156	Investigacion y Biomedicina de Chihuahua /ID# 253115	Chihuahua		Mexico	31000
157	Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 253114	Mexico City		Mexico	06090
158	Unidade Local de Saúde do Alto Minho, EPE - Hospital Conde de Bertiandos /ID# 252489	Ponte de Lima	Viana Do Castelo	Portugal	4990-041
159	Hospital Garcia de Orta, EPE /ID# 252491	Almada		Portugal	2805-267
160	Centro Hospitalar Universitario de Lisboa Norte, EPE - Hospital de Santa Maria /ID# 252492	Lisboa		Portugal	1649-035
161	GCM Medical Group PSC /ID# 252700	San Juan		Puerto Rico	00917-3104
162	Mindful Medical Research /ID# 252693	San Juan		Puerto Rico	00918-3756
163	Spitalul Clinic Dr. I. Cantacuzino /ID# 252761	Bucharest	Bucuresti	Romania	030167
164	Cabinet Medical Dr. Avram S.R.L /ID# 254133	Timisoara	Timis	Romania	300134
165	Banat Carina Med SRL /ID# 252757	Timisoara	Timis	Romania	300766
166	Spitalul Judetean de Urgenta Bacau /ID# 252860	Bacau		Romania	600114
167	Spitalul Clinic Sf. Maria /ID# 252759	Bucuresti		Romania	011172
168	Spitalul Clinic Sf. Maria /ID# 253334	Bucuresti		Romania	011172
169	Institute for Rheumatology /ID# 252333	Belgrade	Beograd	Serbia	11000
170	Institute for Rheumatology /ID# 252334	Belgrade	Beograd	Serbia	11000
171	Institute for Rheumatology /ID# 252335	Belgrade	Beograd	Serbia	11000
172	Institute for Rheumatology /ID# 252338	Belgrade	Beograd	Serbia	11000
173	Special Hospital for Rheuma /ID# 252336	Novi Sad	Vojvodina	Serbia	21000
174	Special Hospital for Rheuma /ID# 252339	Novi Sad	Vojvodina	Serbia	21000
175	Wits Clinical Research Site /ID# 252928	Johannesburg	Gauteng	South Africa	2193
176	University of Pretoria /ID# 252368	Pretoria	Gauteng	South Africa	0001
177	Dr Elsa van Duuren /ID# 252387	Pretoria	Gauteng	South Africa	0002
178	Emmed Research cc /ID# 254317	Pretoria	Gauteng	South Africa	0002
179	Dr Asokan Naidoo /ID# 252894	Umhlanga	Kwazulu-Natal	South Africa	4319
180	Winelands Medical Research - Somerset West /ID# 252745	Cape Town	Western Cape	South Africa	7130
181	Arthritis Clinical Research Trials /ID# 252370	Cape Town	Western Cape	South Africa	7405
182	Winelands Medical Research Centre /ID# 252369	Stellenbosch	Western Cape	South Africa	7600
183	Hospital Clínico Universitario de Santiago-CHUS /ID# 252430	Santiago de Compostela	A Coruna	Spain	15706
184	Hospital Marina Baixa /ID# 254141	Villajoyosa	Alicante	Spain	03570
185	Hospital Universitario Germans Trias i Pujol /ID# 254144	Badalona	Barcelona	Spain	08916
186	Consorci Corporacio Sanitaria Parc Tauli Sabadell /ID# 252425	Sabadell	Barcelona	Spain	08208
187	Hospital Universitario y Politecnico La Fe /ID# 254143	Valencia		Spain	46026
188	The Royal Free London NHS Foundation Trust /ID# 252297	London	London, City Of	United Kingdom	NW3 2QG
189	The Queen Elizabeth Hospital, Kings Lynn NHS Foundation Trust /ID# 252301	Kings Lynn	Norfolk	United Kingdom	PE30 4ET
190	Queen Mary University of London /ID# 252671	London		United Kingdom	EC1M 6BQ
191	Portsmouth Hospitals University NHS Trust /ID# 252772	Portsmouth		United Kingdom	PO6 3LY