AVERT-2: Effects of Abatacept in Patients With Early Rheumatoid Arthritis

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02504268
• Collaborator: (none)
• Enrollment: 994
• Locations: 201
• Arms: 4
• Actual Duration (Months): 54.5
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if abatacept is effective in the treatment of early rheumatoid arthritis.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Abatacept; Drug: Methotrexate; Other: Abatacept Placebo; Other: Methotrexate Placebo	Phase 3

Detailed Description

Subcutaneous (SC)

Study Design

• Study Type: Interventional
• Actual Enrollment: 994 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3B, Randomized, Double-Blind Clinical Trial to Evaluate the Efficacy and Safety of Abatacept SC in Combination With Methotrexate Compared to Methotrexate Monotherapy in Achieving Clinical Remission in Adults With Early Rheumatoid Arthritis Who Are Methotrexate Naive
• Actual Study Start Date: Sep 3, 2015
• Actual Primary Completion Date: Jan 16, 2017
• Actual Study Completion Date: Mar 19, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Combination Therapy: Abatacept + Methotrexate Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Drug: Abatacept; Drug: Methotrexate
Active Comparator: Methotrexate treatment Methotrexate at least 15mg per week tablet or capsule orally	Drug: Methotrexate
Placebo Comparator: Abatacept Placebo Placebo for Abatacept subcutaneous injection once per week	Other: Abatacept Placebo
Placebo Comparator: Methotrexate Placebo Placebo to match Methotrexate capsule orally once per week	Other: Methotrexate Placebo

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants in Simple Disease Activity Index (SDAI) Remission at Week 24 [Week 24]

   Simple Disease Activity Index (SDAI) is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP (TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, MDGA = physician global assessment on a visual analog scale 0-10 cm, and CRP = c-reactive protein in mg/dL) SDAI Remission is defined as SDAI <= 3.3. Using a logistic regression model that includes treatment arm, randomization stratification factor, and baseline SDAI as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided. SDAI total score range: 0 to 86. SDAI <= 3.3 indicates disease remission and SDAI >26 = high disease activity.

Secondary Outcome Measures

1. Percentage of Participants in Disease Activity Score (DAS)28 - C-reactive Protein (CRP) Remission at Week 24 [Week 24]

   DAS28-CRP = Disease Activity Score 28 based on C-reactive protein DAS28-CRP Remission is defined as DAS28-CRP <= 2.6 Using a logistic regression model that includes treatment arm, stratification variable and baseline measure as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided.

2. Percentage of Participants in SDAI Remission at Week 52 [Week 52]

   Simple Disease Activity Index (SDAI) is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP (TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, MDGA = physician global assessment on a visual analog scale 0-10 cm, and CRP = c-reactive protein in mg/dL) SDAI Remission is defined as SDAI <= 3.3. Using a logistic regression model that includes treatment arm, randomization stratification factor, and baseline SDAI as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided. SDAI total score range: 0 to 86. SDAI <= 3.3 indicates disease remission and SDAI >26 = high disease activity.

3. Mean Change From Baseline in Radiographic Progression of Joint Damage as Measured by Modified Sharp/Van Der Heijide Total Sharp Scores (TSS) at Week 52 [Week 52]

   The Modified Total Sharp Score (mTSS) is calculated as the bilateral sum of erosion and Joint Space Narrowing (JSN) scores across all joints of the hands and feet.The score range for mTSS is 0-448. Higher scores indicate more joint damage. The mean change from baseline in TSS using modified Sharp/van der Heijide scores was assessed using a rank-based nonparametric ANCOVA model.

4. Percentage of Participants in Boolean Remission at Week 52 [Week 52]

   Boolean Remission is defined as Tender joint count less than 1, Swollen joint count less than 1, CRP less than 1 mg/dL, patient global assessment less than 1 (on 0 to 10 VAS scale). Logistic regression was used for this endpoint.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Rheumatoid arthritis (RA) diagnosis less than 6 months

• CRP > 3 mg/L or Erythrocyte Sedimentation Rate (ESR) ≥ 28 mm/h

• At least 3 swollen and 3 tender joints

• Anti-citrullinated protein antibodies (ACPA) positive

Exclusion Criteria:

• At risk for tuberculosis

• Have acute infection

• Have chronic or recurrent bacterial or serious latent viral infection

• History of malignancies in the last 5 years except squamous skin, basal skin or cervical carcinoma

• Previous treatment with any conventional or biologic Disease-modifying anti rheumatic drugs (DMARD)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rheumatology Associates Of North Alabama, P.C.	Huntsville	Alabama	United States	35801
2	Arizona Arthritis & Rheumatology Research PLLC	Glendale	Arizona	United States	85306
3	Arizona Arthritis & Rheumatology Research PLLC	Mesa	Arizona	United States	85210
4	Arizona Arthritis & Rheumatology Research PLLC	Phoenix	Arizona	United States	85032
5	Arizona Arthritis & Rheumatology Research PLLC	Phoenix	Arizona	United States	85037
6	Arizona Arthritis & Rheumatology Research PLLC	Sun City	Arizona	United States	85351
7	CHI St. Vincent Medical Group Hot Springs	Hot Springs	Arkansas	United States	71913
8	Arkansas Primary Care Clinic	Little Rock	Arkansas	United States	72204
9	St. Joseph Heritage Medical Group	Fullerton	California	United States	92835
10	Healthcare Partners Medical Group	Huntington Beach	California	United States	92646
11	Valerius Medical Group and Research Center	Los Alamitos	California	United States	90720
12	Inland Rheumatology Clinical Trials Inc.	Upland	California	United States	91786
13	Joao Nascimento	Bridgeport	Connecticut	United States	06606
14	Rheumatology Associates Of Central Florida, P.A.	Orlando	Florida	United States	32806
15	Tampa Medical Group, Pa	Tampa	Florida	United States	33614
16	Coeur D'Alene Arthrit Clin	Coeur d'Alene	Idaho	United States	83814
17	Arthritis And Diabetes Clinic	Monroe	Louisiana	United States	71203
18	Klein And Associates, M.D., Pa	Hagerstown	Maryland	United States	21740
19	St. Paul Rheumatology, P.A.	Eagan	Minnesota	United States	55121
20	Arthritis Consultants	Saint Louis	Missouri	United States	63141
21	Physician Research Collaboration, Llc	Lincoln	Nebraska	United States	68516
22	Arthritis And Osteoporosis Associates, Pa	Freehold	New Jersey	United States	07728
23	Physicians Research Center, Llc	Toms River	New Jersey	United States	08755
24	Albuquerque Center For Rheumatology	Albuquerque	New Mexico	United States	87102
25	Albuquerque Clinical Trials	Albuquerque	New Mexico	United States	87102
26	Hospital For Special Surgery	New York	New York	United States	10021-4892
27	Local Institution	Hickory	North Carolina	United States	28601
28	Pmg Research Of Salisbury	Salisbury	North Carolina	United States	28144
29	Carolina Arthritis Associates	Wilmington	North Carolina	United States	28401
30	Pmg Research Of Wilmington Llc	Wilmington	North Carolina	United States	28401
31	Health Research Of Oklahoma	Oklahoma City	Oklahoma	United States	73103
32	Oklahoma Ctr For Arthritis Therapy And Research, Inc.	Tulsa	Oklahoma	United States	74104
33	Altoona Center For Clinical Research	Duncansville	Pennsylvania	United States	16635
34	The Arthritis Group	Philadelphia	Pennsylvania	United States	19152
35	Clinical Research Center Of Reading, Llp	Wyomissing	Pennsylvania	United States	19610
36	West Tennessee Research Institute	Jackson	Tennessee	United States	38305
37	Metroplex Clinical Research Center	Dallas	Texas	United States	75231
38	Houston Institute For Clinical Research	Houston	Texas	United States	77074
39	Arthritis Clinic Of Northern Virginia, P.C.	Arlington	Virginia	United States	22205
40	Spectrum Medical, Inc.	Danville	Virginia	United States	24541
41	Arthritis Northwest	Spokane	Washington	United States	99204
42	Rheumatic Disease Center	Glendale	Wisconsin	United States	53217
43	Organizacion Medica De Investigacion S.A. (Omi)	Capital Federal	Buenos Aires	Argentina	1015
44	Local Institution	Ciudad Autonoma Beunos Aires	Buenos Aires	Argentina	1431
45	Hospital General De Agudos J.M. Ramos Mejia	Ciudad Autonoma De Buenos Aire	Buenos Aires	Argentina	1221
46	Framingham Centro Medico	La Plata	Buenos Aires	Argentina	1902
47	Instituto de Asistencia Reumatologica Integral	San Fernando	Buenos Aires	Argentina	1646
48	Caici	Rosario	Santa FE	Argentina	2000
49	Instituto De Rehabilitacion Psicofisica	Buenos Aires		Argentina	1428
50	Centro Consultora Integral de Salud SRL	Cordoba		Argentina	5004
51	Hospital Privado-Centro Medico De Cordoba S.A.	Cordoba		Argentina	5016
52	Centro De Investigaciones Reumatologicas	Tucuman		Argentina	4000
53	Centro Medico Privado De Reumatologia	Tucuman		Argentina	4000
54	Local Institution	Maroochydore	Queensland	Australia	4558
55	Local Institution	Southport	Queensland	Australia	4215
56	Local Institution	Hobart	Tasmania	Australia	7000
57	Local Institution	Camberwell	Victoria	Australia	3124
58	Local Institution	Coffs Harbour		Australia	2450
59	Rheuma Zentrum Favoriten	Wien		Austria	1100
60	Local Institution	Juiz De Fora	Minas Gerais	Brazil	36010-570
61	Local Institution	Varginha	Minas Gerais	Brazil	37006-710
62	Local Institution	Curitiba	Parana	Brazil	80030-110
63	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil	90480-000
64	Local Institution	Santo Andre	SAO Paulo	Brazil	09060-870
65	Local Institution	Sao Paulo		Brazil	01228-200
66	Local Institution	Sao Paulo		Brazil	04032-060
67	Local Institution	Sao Paulo		Brazil	04266-010
68	Local Institution	Winnipeg	Manitoba	Canada	R3A 1M3
69	Local Institution	Montreal	Quebec	Canada	H2L 1S6
70	Centre De Recherche Musculo-Squelettique	Trois-rivieres	Quebec	Canada	G8Z 1Y2
71	Local Institution	Saskatchewan		Canada	S7K 0H6
72	Centro Medico de Reumatologia Limitada	Temuco	Araucania	Chile	4790928
73	Centro De Estudios Reumatologicos	Santiago De Chile	Metropolitana	Chile	7501126
74	Someal	Santiago	Metropolitana	Chile	7510586
75	Centro de Investigacion en Reumatologia y Especialidades Medicas S.A.S	Bogota		Colombia
76	Fundacion Instituto de Reumatologia Fernando Chalem	Bogota		Colombia
77	Clinica de Artritis Temprana	Cali		Colombia
78	Hospital Pablo Tobon Uribe	Medellin		Colombia	MEDELLIN
79	Oddeleni klinicke farmakologie	Plzen-Bory		Czechia	305 99
80	Revmatologicky ustav	Praha 2		Czechia	128 50
81	MEDICAL PLUS, s.r.o.	Uherske Hradiste		Czechia	686 01
82	PV Medical Services, s.r.o.	Zlin		Czechia	760 01
83	Local Institution	Hyvinkaa		Finland	05800
84	Local Institution	Kuopio		Finland	70110
85	Local Institution	Lyon Cedex 03		France	69437
86	Local Institution	Orleans cedex 2		France	45067
87	Local Institution	Poitiers		France	86021
88	Local Institution	Toulouse cedex 9		France	31059
89	Rheumapraxis Dr. Kurthen	Aachen		Germany	52064
90	Charite Campus Mitte	Berlin		Germany	10117
91	Rheumatologische Schwerpunktpraxis Dr. Zinke	Berlin		Germany	13055
92	Immanuel Krankenhaus Berlin/Rheumaklinik Berlin Buch	Berlin		Germany	13125
93	Schlosspark-Klinik	Berlin		Germany	14059
94	Schwerpunktpraxis fuer Rheumatologie an den Kreiskliniken	Burghausen		Germany	84489
95	Klinikum Der Albrecht-Ludwigs-Universitat	Freiburg		Germany	79106
96	MVZ Rheuma	Hamburg		Germany	20095
97	Hamburger Rheuma Forschungszentrum	Hamburg		Germany	22391
98	Gemeinschaftspraxis Drs. von Hinueber u Demary	Hildesheim		Germany	31134
99	Rheumatologie In Wuermtal	Planegg		Germany	82152
100	Praxis Dr. Walter	Rendsburg		Germany	24768
101	Local Institution	Budapest		Hungary	1027
102	Belgyogy. Int. Reuma. DEOEC	Debrecen		Hungary	4032
103	Vaszary Kolos Hospital	Esztergom		Hungary	2500
104	Reumatologiai Osztaly Flor F.	Kistarcsa		Hungary	2143
105	Reumatologiai Osztaly MAV	Szolnok		Hungary	5000
106	Vital Medical Center	Veszprem		Hungary	8200
107	Local Institution	Haifa		Israel	31096
108	Local Institution	Petach Tikva		Israel	4941492
109	Local Institution	Ramat-gan		Israel	52621
110	Local Institution	Tel Hashomer		Israel	52620
111	Local Institution	Zrifin		Israel
112	Ospedale Vittorio Emanuele	Catania		Italy	95123
113	Istituto Gaetano Pini	Milano		Italy	20122
114	Azienda Ospedaliera Luigi Sacco	Milano		Italy	20154
115	Local Institution	Pavia		Italy	27100
116	Local Institution	Roma		Italy	00168
117	Ospedale Borgo Roma	Verona		Italy	37134
118	Local Institution	Nagoya-shi	Aichi	Japan	4578511
119	Local Institution	Nagoya-shi	Aichi	Japan	4668560
120	Local Institution	Fukuoka-shi	Fukuoka	Japan	8108563
121	Local Institution	Kitakyushu-shi	Fukuoka	Japan	8078556
122	Local Institution	Hiroshima-Shi	Hiroshima	Japan	7348551
123	Local Institution	Sapporo-shi	Hokkaido	Japan	0608604
124	Local Institution	Sapporo-shi	Hokkaido	Japan	0608648
125	Local Institution	Sapporo-shi	Hokkaido	Japan	0630811
126	Local Institution	Kato-shi	Hyogo	Japan	6731462
127	Local Institution	Hitachinaka-shi	Ibaraki	Japan	3120057
128	Local Institution	Mito-shi	Ibaraki	Japan	3100015
129	Local Institution	Kagoshima-shi	Kagoshima	Japan	8900063
130	Local Institution	Sagamihara-shi	Kanagawa	Japan	2520392
131	Local Institution	Isahaya-shi	Nagasaki	Japan	8548501
132	Local Institution	Sasebo-shi	Nagasaki	Japan	8571195
133	Local Institution	Tomigusuku-shi	Okinawa	Japan	9010224
134	Local Institution	Izumisano-shi	Osaka	Japan	5988577
135	Local Institution	Kawachinagano	Osaka	Japan	5868521
136	Local Institution	Iruma-gun	Saitama	Japan	3500495
137	Local Institution	Kawagoe-shi	Saitama	Japan	3508550
138	Local Institution	Sayama-shi	Saitama	Japan	3501305
139	Local Institution	Hamamatsu-shi	Shizuoka	Japan	4308558
140	Local Institution	Chuo-ku	Tokyo	Japan	1048560
141	Local Institution	Itabashi-ku	Tokyo	Japan	1738610
142	Local Institution	Meguro-ku	Tokyo	Japan	1528902
143	Local Institution	Meguro-ku	Tokyo	Japan	1538515
144	Local Institution	Shinjuku-Ku	Tokyo	Japan	1608582
145	Local Institution	Anyang-si	Gyeonggi-do	Korea, Republic of	14068
146	Local Institution	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
147	Local Institution	Seoul		Korea, Republic of	04763
148	Local Institution	Mexicali	Baja California	Mexico
149	Local Institution	Mexico City	Distrito Fededral	Mexico	11850
150	Local Institution	León	Guanajuato	Mexico	37000
151	Local Institution	Guadalajara	Jalisco	Mexico	44280
152	Local Institution	Guadalajara	Jalisco	Mexico	44600
153	Local Institution	Guadalajara	Jalisco	Mexico
154	Local Institution	Guadalajara		Mexico
155	Local Institution	México D.F.		Mexico
156	Local Institution	San Luis Potosi		Mexico	78213
157	Local Institution	Monaco		Monaco	98012
158	Local Institution	Leiden		Netherlands	2333 ZA
159	Local Institution	Lima		Peru	27
160	Acq Medic Sac	Lima		Peru	LIMA 11
161	Clinica El Golf	Lima		Peru	Lima 27
162	Instituto De Ginecologia Y Reproduccion Inv. Clinical Sac	Lima		Peru	LIMA 33
163	Nszoz Unica Cr	Dabrowka		Poland	62-069
164	Nzoz Mak Med	Nadarzyn		Poland	05-830
165	SANUS Szpital Specjalistyczny Sp. z o.o.	Stalowa Wola		Poland	37-450
166	Local Institution	Staszow		Poland	28-200
167	Slaski Szpital Reumatologiczno - Rehabilitacyjny	Ustron		Poland	43-450
168	Instytut Reumatologii, I Klinika Reumatologii	Warszawa		Poland	02637
169	Centrum Medyczne AMED Sp. z o.o.	Warszawa		Poland	03-291
170	Local Institution	Doha		Qatar
171	Local Institution	Bucharest		Romania	011192
172	Local Institution	Bucuresti		Romania	020983
173	Local Institution	Cluj-napoca		Romania	400006
174	Local Institution	Ekaterinburg		Russian Federation	620102
175	Local Institution	Moscow		Russian Federation	119049
176	Local Institution	St Petersburg		Russian Federation	191124
177	Local Institution	St.petersburg		Russian Federation	197022
178	Local Institution	Yaroslavl		Russian Federation	150003
179	Local Institution	Singapore		Singapore	117549
180	Local Institution	Singapore		Singapore	169856
181	Local Institution	Port Elizabeth	Eastern CAPE	South Africa	6045
182	Local Institution	Soweto	Gauteng	South Africa	2013
183	Local Institution	Cape Town	Western CAPE	South Africa	7500
184	Local Institution	Pinelands, Cape Town	Western Cape	South Africa	7405
185	Local Institution	Stellenbosch	Western Cape	South Africa	7600
186	Local Institution	A Coruna		Spain	15006
187	Local Institution	Barcelona		Spain	08036
188	Local Institution	Madrid		Spain	28006
189	Local Institution	Madrid		Spain	28046
190	Local Institution	Santiago Compostela		Spain	15702
191	Local Institution	Goteborg		Sweden	413 45
192	Local Institution	Malmo		Sweden	205 02
193	Local Institution	Stockholm		Sweden	171 76
194	Local Institution	Uppsala		Sweden	751 85
195	Local Institution	Tainan		Taiwan	704
196	Local Institution	Taipei		Taiwan	100
197	Local Institution	Taipei		Taiwan	112
198	Local Institution	Taoyuan		Taiwan	333
199	Local Institution	Leeds	North Yorkshire	United Kingdom	LS7 4SA
200	Local Institution	Hull		United Kingdom	HU3 2JZ
201	Local Institution	Manchester		United Kingdom	M13 9WL

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02504268
• Other Study ID Numbers: IM101-550; 2015-001275-50
• First Posted: Jul 21, 2015
• Last Update Posted: Jun 28, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Methotrexate; Abatacept

Study Results

Participant Flow

Pre-assignment Detail	994 treated in the induction period (IP). 184 from IP randomized and treated in De-Escalation (DeE), 685 treated in the Open Label (OL) and 120 treated in the Open Label Extension (OLE) period. Participants in IP could move to the OL period after IP completion or through early IP escape. Participants from DeE could transfer to OL through early escape or to OLE after completing DeE.

Arm/Group Title	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP)	Placebo + Methotrexate (Cohort 1, IP)	Combination Therapy: Abatacept + Methotrexate (Cohort 2, IP)	Abatacept + Methotrexate (De-Escalation Period)	Abatacept (End of Week) + Methotrexate (De-Escalation Period)	Abatacept Monotherapy (De-Escalation Period)	Methotrexate Monotherapy (De-Escalation Period)	Abatacept + Methotrexate (Open Label Period)	Abatacept + Methotrexate (Open Label Extension Period)
Arm/Group Description	Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Placebo of Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Active abatacept SC (125 mg) weekly + methotrexate weekly	Active Abatacept SC (125 mg) weekly + MTX weekly	Active Abatacept SC (125 mg) alternating with placebo for abatacept every other week + MTX weekly	Active Abatacept SC (125 mg) weekly + placebo MTX weekly	Placebo Abatacept SC weekly + methotrexate weekly	weekly abatacept SC 125 mg + methotrexate	abatacept SC (125 mg) qw for 24 weeks
Period Title: Overall Study
STARTED	451	301	242	0	0	0	0	0	0
Induction to Open Label	289	196	147	0	0	0	0	0	0
Early Escaped to Open Label	10	21	8	0	0	0	0	0	0
Induction to De-Escalation	94	37	53	0	0	0	0	0	0
Randomized in De-Escalation Period	0	0	0	50	50	47	37	0	0
De-Escalation to Open Label Extension	0	0	0	36	30	32	22	0	0
Early Escaped De-Escalation to Open Label Period	0	0	0	2	5	4	3	0	0
Open Label and Open Label Extension Period	0	0	0	0	0	0	0	685	120
COMPLETED	388	233	201	0	0	0	0	0	0
NOT COMPLETED	63	68	41	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP)	Placebo + Methotrexate (Cohort 1, IP)	Combination Therapy: Abatacept + Methotrexate (Cohort 2, IP)	Total
Arm/Group Description	Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Placebo of Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Active abatacept SC (125 mg) weekly + methotrexate weekly	Total of all reporting groups
Overall Participants	451	301	242	994
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.9 (12.74)	48.8 (13.99)	50.0 (12.91)	49.1 (13.17)
Sex: Female, Male (Count of Participants)
Female	349 77.4%	243 80.7%	189 78.1%	781 78.6%
Male	102 22.6%	58 19.3%	53 21.9%	213 21.4%
Race/Ethnicity, Customized (Number) [Number]
WHITE	315 69.8%	209 69.4%	174 71.9%	698 70.2%
BLACK/AFRICAN AMERICAN	20 4.4%	16 5.3%	7 2.9%	43 4.3%
AMERICAN INDIAN/ALASKA NATIVE	0 0%	3 1%	1 0.4%	4 0.4%
ASIAN	77 17.1%	52 17.3%	11 4.5%	140 14.1%
RACE - OTHER/ NOT REPORTED	39 8.6%	21 7%	49 20.2%	109 11%
HISPANIC OR LATINO	8 1.8%	5 1.7%	9 3.7%	22 2.2%
NOT HISPANIC OR LATINO	43 9.5%	37 12.3%	32 13.2%	112 11.3%
ETHNICITY - NOT REPORTED	400 88.7%	259 86%	201 83.1%	860 86.5%
MODIFIED SHARP/VAN DER HEIJDE TOTAL SCORE (mTSS) (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	9.82 (16.342)	12.99 (19.769)	11.08 (17.839)
Tender Joints - 28 (Joint Count) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Joint Count]	13.2 (6.76)	13.7 (6.77)	13.4 (6.76)
Swollen Joints - 28 (Joint Count) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Joint Count]	10.0 (5.71)	10.7 (5.85)	10.3 (5.77)
Subject global assessment of disease activity (mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm]	65.7 (22.7)	62.7 (24.05)	64.5 (23.28)
Physician global assessment of disease activity (mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm]	65.1 (18.48)	66.1 (19.75)	65.5 (18.99)
C-Reactive Protein (CRP) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	1.998 (2.7062)	1.904 (2.1956)	1.960 (2.5129)
DAS28-CRP (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	5.56 (1.062)	5.61 (1.032)	5.58 (1.049)
SDAI (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	38.24 (14.084)	39.36 (13.770)	38.69 (13.961)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants in Simple Disease Activity Index (SDAI) Remission at Week 24
Description	Simple Disease Activity Index (SDAI) is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP (TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, MDGA = physician global assessment on a visual analog scale 0-10 cm, and CRP = c-reactive protein in mg/dL) SDAI Remission is defined as SDAI <= 3.3. Using a logistic regression model that includes treatment arm, randomization stratification factor, and baseline SDAI as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided. SDAI total score range: 0 to 86. SDAI <= 3.3 indicates disease remission and SDAI >26 = high disease activity.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Primary analysis population included the first 50 Japanese and 325 rest of world (ROW) randomized and treated subjects in cohort 1 in the Induction Period. Intention to treat analysis. Non-Responder imputation.

Arm/Group Title	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP)	Placebo + Methotrexate (Cohort 1, IP)	Combination Therapy: Abatacept + Methotrexate (Cohort 2, IP)	Abatacept + Methotrexate (De-Escalation Period)	Abatacept (End of Week) + Methotrexate (De-Escalation Period)	Abatacept Monotherapy (De-Escalation Period)	Methotrexate Monotherapy (De-Escalation Period)	Abatacept + Methotrexate (Open Label Period)	Abatacept + Methotrexate (Open Label Extension Period)
Arm/Group Description	Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Placebo of Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Active abatacept SC (125 mg) weekly + methotrexate weekly	Active Abatacept SC (125 mg) weekly + MTX weekly	Active Abatacept SC (125 mg) alternating with placebo for abatacept every other week + MTX weekly	Active Abatacept SC (125 mg) weekly + placebo MTX weekly	Placebo Abatacept SC weekly + methotrexate weekly	weekly abatacept SC 125 mg + methotrexate	abatacept SC (125 mg) qw for 24 weeks
Measure Participants	225	150	0	0	0	0	0	0	0
Number (95% Confidence Interval) [Percentage of participants]	21.3 4.7%	16.0 5.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP), Placebo + Methotrexate (Cohort 1, IP)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2359
	Comments
	Method	Regression, Logistic
	Comments

2. Secondary Outcome

Title	Percentage of Participants in Disease Activity Score (DAS)28 - C-reactive Protein (CRP) Remission at Week 24
Description	DAS28-CRP = Disease Activity Score 28 based on C-reactive protein DAS28-CRP Remission is defined as DAS28-CRP <= 2.6 Using a logistic regression model that includes treatment arm, stratification variable and baseline measure as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Primary analysis population included the first 50 Japanese and 325 rest of world (ROW) randomized and treated subjects in cohort 1 in the Induction Period. Intention to treat analysis. Non-Responder imputation.

Arm/Group Title	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP)	Placebo + Methotrexate (Cohort 1, IP)	Combination Therapy: Abatacept + Methotrexate (Cohort 2, IP)	Abatacept + Methotrexate (De-Escalation Period)	Abatacept (End of Week) + Methotrexate (De-Escalation Period)	Abatacept Monotherapy (De-Escalation Period)	Methotrexate Monotherapy (De-Escalation Period)	Abatacept + Methotrexate (Open Label Period)	Abatacept + Methotrexate (Open Label Extension Period)
Arm/Group Description	Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Placebo of Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Active abatacept SC (125 mg) weekly + methotrexate weekly	Active Abatacept SC (125 mg) weekly + MTX weekly	Active Abatacept SC (125 mg) alternating with placebo for abatacept every other week + MTX weekly	Active Abatacept SC (125 mg) weekly + placebo MTX weekly	Placebo Abatacept SC weekly + methotrexate weekly	weekly abatacept SC 125 mg + methotrexate	abatacept SC (125 mg) qw for 24 weeks
Measure Participants	225	150	0	0	0	0	0	0	0
Number (95% Confidence Interval) [Percentage of Participants]	38.7 8.6%	25.3 8.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP), Placebo + Methotrexate (Cohort 1, IP)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0112
	Comments
	Method	Regression, Logistic
	Comments

3. Secondary Outcome

Title	Percentage of Participants in SDAI Remission at Week 52
Description	Simple Disease Activity Index (SDAI) is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP (TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, MDGA = physician global assessment on a visual analog scale 0-10 cm, and CRP = c-reactive protein in mg/dL) SDAI Remission is defined as SDAI <= 3.3. Using a logistic regression model that includes treatment arm, randomization stratification factor, and baseline SDAI as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided. SDAI total score range: 0 to 86. SDAI <= 3.3 indicates disease remission and SDAI >26 = high disease activity.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Primary analysis population included the first 50 Japanese and 325 rest of world (ROW) randomized and treated subjects in cohort 1 in the Induction Period. Intention to treat analysis. Non-Responder imputation.

Arm/Group Title	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP)	Placebo + Methotrexate (Cohort 1, IP)	Combination Therapy: Abatacept + Methotrexate (Cohort 2, IP)	Abatacept + Methotrexate (De-Escalation Period)	Abatacept (End of Week) + Methotrexate (De-Escalation Period)	Abatacept Monotherapy (De-Escalation Period)	Methotrexate Monotherapy (De-Escalation Period)	Abatacept + Methotrexate (Open Label Period)	Abatacept + Methotrexate (Open Label Extension Period)
Arm/Group Description	Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Placebo of Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Active abatacept SC (125 mg) weekly + methotrexate weekly	Active Abatacept SC (125 mg) weekly + MTX weekly	Active Abatacept SC (125 mg) alternating with placebo for abatacept every other week + MTX weekly	Active Abatacept SC (125 mg) weekly + placebo MTX weekly	Placebo Abatacept SC weekly + methotrexate weekly	weekly abatacept SC 125 mg + methotrexate	abatacept SC (125 mg) qw for 24 weeks
Measure Participants	225	150	0	0	0	0	0	0	0
Number (95% Confidence Interval) [Percentage of participants]	29.8 6.6%	15.3 5.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP), Placebo + Methotrexate (Cohort 1, IP)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0021
	Comments
	Method	Regression, Logistic
	Comments

4. Secondary Outcome

Title	Mean Change From Baseline in Radiographic Progression of Joint Damage as Measured by Modified Sharp/Van Der Heijide Total Sharp Scores (TSS) at Week 52
Description	The Modified Total Sharp Score (mTSS) is calculated as the bilateral sum of erosion and Joint Space Narrowing (JSN) scores across all joints of the hands and feet.The score range for mTSS is 0-448. Higher scores indicate more joint damage. The mean change from baseline in TSS using modified Sharp/van der Heijide scores was assessed using a rank-based nonparametric ANCOVA model.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Cohort 1 analysis population included all randomized and treated subjects in the Induction Period. Intention to treat analysis. Linear extrapolation imputation.

Arm/Group Title	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP)	Placebo + Methotrexate (Cohort 1, IP)	Combination Therapy: Abatacept + Methotrexate (Cohort 2, IP)	Abatacept + Methotrexate (De-Escalation Period)	Abatacept (End of Week) + Methotrexate (De-Escalation Period)	Abatacept Monotherapy (De-Escalation Period)	Methotrexate Monotherapy (De-Escalation Period)	Abatacept + Methotrexate (Open Label Period)	Abatacept + Methotrexate (Open Label Extension Period)
Arm/Group Description	Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Placebo of Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Active abatacept SC (125 mg) weekly + methotrexate weekly	Active Abatacept SC (125 mg) weekly + MTX weekly	Active Abatacept SC (125 mg) alternating with placebo for abatacept every other week + MTX weekly	Active Abatacept SC (125 mg) weekly + placebo MTX weekly	Placebo Abatacept SC weekly + methotrexate weekly	weekly abatacept SC 125 mg + methotrexate	abatacept SC (125 mg) qw for 24 weeks
Measure Participants	401	249	0	0	0	0	0	0	0
Mean (Standard Deviation) [Total Sharp Score]	0.53 (2.279)	2.52 (6.205)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP), Placebo + Methotrexate (Cohort 1, IP)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	rank-based ANCOVA
	Comments

5. Secondary Outcome

Title	Percentage of Participants in Boolean Remission at Week 52
Description	Boolean Remission is defined as Tender joint count less than 1, Swollen joint count less than 1, CRP less than 1 mg/dL, patient global assessment less than 1 (on 0 to 10 VAS scale). Logistic regression was used for this endpoint.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Cohort 1 analysis population included all randomized and treated subjects in the Induction Period. Intention to treat analysis. Non-Responder imputation.

Arm/Group Title	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP)	Placebo + Methotrexate (Cohort 1, IP)	Combination Therapy: Abatacept + Methotrexate (Cohort 2, IP)	Abatacept + Methotrexate (De-Escalation Period)	Abatacept (End of Week) + Methotrexate (De-Escalation Period)	Abatacept Monotherapy (De-Escalation Period)	Methotrexate Monotherapy (De-Escalation Period)	Abatacept + Methotrexate (Open Label Period)	Abatacept + Methotrexate (Open Label Extension Period)
Arm/Group Description	Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Placebo of Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week	Active abatacept SC (125 mg) weekly + methotrexate weekly	Active Abatacept SC (125 mg) weekly + MTX weekly	Active Abatacept SC (125 mg) alternating with placebo for abatacept every other week + MTX weekly	Active Abatacept SC (125 mg) weekly + placebo MTX weekly	Placebo Abatacept SC weekly + methotrexate weekly	weekly abatacept SC 125 mg + methotrexate	abatacept SC (125 mg) qw for 24 weeks
Measure Participants	451	301	0	0	0	0	0	0	0
Number (95% Confidence Interval) [Percentage of participants]	21.5 4.8%	11.6 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP), Placebo + Methotrexate (Cohort 1, IP)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Regression, Logistic
	Comments

Adverse Events

Time Frame	approximately 54 months
Adverse Event Reporting Description	Participants from the Induction period (IP) cohorts randomized to the De-Escalation period. Participants from the induction period also entered the Open Label period. Participants from the De-Escalation period entered 1 of 2 the open label period or the open label extension period.
Arm/Group Title	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP)		Placebo + Methotrexate (Cohort 1, IP)		Combination Therapy: Abatacept + Methotrexate (Cohort 2, IP)		Abatacept + Methotrexate (De-Escalation Period)		Abatacept (End of Week) + Methotrexate (De-Escalation Period)		Abatacept Monotherapy (De-Escalation Period)		Methotrexate Monotherapy (De-Escalation Period)		Abatacept + Methotrexate (Open Label Period)		Abatacept + Methotrexate (Open Label Extension Period)
Arm/Group Description	Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week		Placebo of Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week		Active abatacept SC (125 mg) weekly + methotrexate weekly		Active Abatacept SC (125 mg) weekly + MTX weekly		Active Abatacept SC (125 mg) alternating with placebo for abatacept every other week + MTX weekly		Active Abatacept SC (125 mg) weekly + placebo MTX weekly		Placebo Abatacept SC weekly + methotrexate weekly		weekly abatacept SC 125 mg + methotrexate		abatacept SC (125 mg) qw for 24 weeks
All Cause Mortality
	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP)		Placebo + Methotrexate (Cohort 1, IP)		Combination Therapy: Abatacept + Methotrexate (Cohort 2, IP)		Abatacept + Methotrexate (De-Escalation Period)		Abatacept (End of Week) + Methotrexate (De-Escalation Period)		Abatacept Monotherapy (De-Escalation Period)		Methotrexate Monotherapy (De-Escalation Period)		Abatacept + Methotrexate (Open Label Period)		Abatacept + Methotrexate (Open Label Extension Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/451 (0.2%)		1/301 (0.3%)		0/242 (0%)		0/50 (0%)		1/50 (2%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Serious Adverse Events
	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP)		Placebo + Methotrexate (Cohort 1, IP)		Combination Therapy: Abatacept + Methotrexate (Cohort 2, IP)		Abatacept + Methotrexate (De-Escalation Period)		Abatacept (End of Week) + Methotrexate (De-Escalation Period)		Abatacept Monotherapy (De-Escalation Period)		Methotrexate Monotherapy (De-Escalation Period)		Abatacept + Methotrexate (Open Label Period)		Abatacept + Methotrexate (Open Label Extension Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/451 (7.1%)		9/301 (3%)		23/242 (9.5%)		3/50 (6%)		3/50 (6%)		0/47 (0%)		0/37 (0%)		40/685 (5.8%)		0/120 (0%)
Blood and lymphatic system disorders
Anaemia	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Cardiac disorders
Acute myocardial infarction	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Angina pectoris	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Angina unstable	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Atrial fibrillation	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Cardiac arrest	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Cardiac failure congestive	0/451 (0%)		1/301 (0.3%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Coronary artery occlusion	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Myocardial ischaemia	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Pericarditis	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Ear and labyrinth disorders
Vertigo	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		2/685 (0.3%)		0/120 (0%)
Endocrine disorders
Goitre	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Eye disorders
Cataract	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Macular degeneration	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Macular hole	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Gastrointestinal disorders
Gastritis erosive	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Gastrooesophageal reflux disease	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Intestinal ischaemia	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Malocclusion	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Melaena	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Pancreatitis	1/451 (0.2%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Pancreatitis acute	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		1/50 (2%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
General disorders
Pyrexia	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		1/50 (2%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Hepatobiliary disorders
Cholecystitis acute	1/451 (0.2%)		0/301 (0%)		2/242 (0.8%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Cholecystitis chronic	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Cholelithiasis	0/451 (0%)		0/301 (0%)		0/242 (0%)		1/50 (2%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Immune system disorders
Anaphylactic reaction	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Infections and infestations
Abscess intestinal	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Appendicitis	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Cellulitis	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Diverticulitis	0/451 (0%)		1/301 (0.3%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Gastroenteritis	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Haemophilus infection	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Infectious mononucleosis	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		1/50 (2%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Peritonsillar abscess	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Pneumocystis jirovecii pneumonia	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Pneumonia	2/451 (0.4%)		2/301 (0.7%)		1/242 (0.4%)		0/50 (0%)		1/50 (2%)		0/47 (0%)		0/37 (0%)		2/685 (0.3%)		0/120 (0%)
Pyelonephritis	0/451 (0%)		1/301 (0.3%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Pyelonephritis acute	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Sepsis	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Tuberculosis	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Urinary tract infection	2/451 (0.4%)		1/301 (0.3%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Injury, poisoning and procedural complications
Femur fracture	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Fracture displacement	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Humerus fracture	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Meniscus injury	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Overdose	2/451 (0.4%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Pneumoconiosis	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Radius fracture	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Skin laceration	1/451 (0.2%)		1/301 (0.3%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Subdural haematoma	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Investigations
Oxygen saturation decreased	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Weight decreased	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Hyperkalaemia	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Exostosis	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Intervertebral disc protrusion	2/451 (0.4%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Osteoarthritis	1/451 (0.2%)		1/301 (0.3%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Rheumatoid arthritis	0/451 (0%)		1/301 (0.3%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Spinal pain	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Spondylolisthesis	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Synovial cyst	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Benign ovarian tumour	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Carcinoid tumour of the gastrointestinal tract	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Cervix carcinoma	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Intraductal proliferative breast lesion	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Invasive ductal breast carcinoma	0/451 (0%)		1/301 (0.3%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Metastases to lung	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Pancreatic carcinoma	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Prostate cancer	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Renal cancer	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Squamous cell carcinoma	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Squamous cell carcinoma of skin	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Superficial spreading melanoma stage unspecified	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Uterine leiomyoma	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Nervous system disorders
Cerebrovascular accident	1/451 (0.2%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Dysarthria	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Encephalopathy	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Epilepsy	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Hypoxic-ischaemic encephalopathy	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Lacunar infarction	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Lacunar stroke	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Seizure	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Subarachnoid haemorrhage	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Syncope	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Psychiatric disorders
Bipolar disorder	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Renal and urinary disorders
Bladder prolapse	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Reproductive system and breast disorders
Adenomyosis	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Benign prostatic hyperplasia	0/451 (0%)		0/301 (0%)		0/242 (0%)		1/50 (2%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Hydrometra	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Metrorrhagia	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Ovarian cyst	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Vaginal polyp	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Bronchiectasis	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Pneumonia aspiration	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Pneumothorax	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		1/50 (2%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Pulmonary congestion	0/451 (0%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Pulmonary embolism	0/451 (0%)		0/301 (0%)		1/242 (0.4%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		1/685 (0.1%)		0/120 (0%)
Surgical and medical procedures
Knee operation	0/451 (0%)		0/301 (0%)		0/242 (0%)		1/50 (2%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Vascular disorders
Hypotension	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		0/685 (0%)		0/120 (0%)
Other (Not Including Serious) Adverse Events
	Combination Therapy: Abatacept + Methotrexate (Cohort 1, IP)		Placebo + Methotrexate (Cohort 1, IP)		Combination Therapy: Abatacept + Methotrexate (Cohort 2, IP)		Abatacept + Methotrexate (De-Escalation Period)		Abatacept (End of Week) + Methotrexate (De-Escalation Period)		Abatacept Monotherapy (De-Escalation Period)		Methotrexate Monotherapy (De-Escalation Period)		Abatacept + Methotrexate (Open Label Period)		Abatacept + Methotrexate (Open Label Extension Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	237/451 (52.5%)		152/301 (50.5%)		123/242 (50.8%)		12/50 (24%)		22/50 (44%)		10/47 (21.3%)		16/37 (43.2%)		230/685 (33.6%)		15/120 (12.5%)
Blood and lymphatic system disorders
Anaemia	12/451 (2.7%)		18/301 (6%)		4/242 (1.7%)		1/50 (2%)		1/50 (2%)		0/47 (0%)		1/37 (2.7%)		10/685 (1.5%)		1/120 (0.8%)
Gastrointestinal disorders
Abdominal pain upper	12/451 (2.7%)		5/301 (1.7%)		14/242 (5.8%)		1/50 (2%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		8/685 (1.2%)		1/120 (0.8%)
Diarrhoea	17/451 (3.8%)		12/301 (4%)		13/242 (5.4%)		1/50 (2%)		0/50 (0%)		0/47 (0%)		1/37 (2.7%)		13/685 (1.9%)		1/120 (0.8%)
Nausea	42/451 (9.3%)		24/301 (8%)		22/242 (9.1%)		1/50 (2%)		2/50 (4%)		0/47 (0%)		1/37 (2.7%)		23/685 (3.4%)		0/120 (0%)
Stomatitis	27/451 (6%)		8/301 (2.7%)		1/242 (0.4%)		0/50 (0%)		1/50 (2%)		2/47 (4.3%)		2/37 (5.4%)		21/685 (3.1%)		2/120 (1.7%)
General disorders
Drug intolerance	7/451 (1.6%)		4/301 (1.3%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		0/47 (0%)		2/37 (5.4%)		4/685 (0.6%)		0/120 (0%)
Infections and infestations
Bronchitis	19/451 (4.2%)		12/301 (4%)		16/242 (6.6%)		3/50 (6%)		6/50 (12%)		1/47 (2.1%)		0/37 (0%)		24/685 (3.5%)		1/120 (0.8%)
Gastroenteritis	13/451 (2.9%)		9/301 (3%)		10/242 (4.1%)		0/50 (0%)		3/50 (6%)		1/47 (2.1%)		2/37 (5.4%)		13/685 (1.9%)		1/120 (0.8%)
Herpes zoster	3/451 (0.7%)		2/301 (0.7%)		1/242 (0.4%)		1/50 (2%)		0/50 (0%)		0/47 (0%)		2/37 (5.4%)		7/685 (1%)		0/120 (0%)
Nasopharyngitis	63/451 (14%)		43/301 (14.3%)		36/242 (14.9%)		2/50 (4%)		6/50 (12%)		4/47 (8.5%)		5/37 (13.5%)		59/685 (8.6%)		6/120 (5%)
Pharyngitis	22/451 (4.9%)		17/301 (5.6%)		14/242 (5.8%)		0/50 (0%)		1/50 (2%)		1/47 (2.1%)		2/37 (5.4%)		18/685 (2.6%)		0/120 (0%)
Upper respiratory tract infection	24/451 (5.3%)		16/301 (5.3%)		18/242 (7.4%)		1/50 (2%)		2/50 (4%)		1/47 (2.1%)		3/37 (8.1%)		28/685 (4.1%)		3/120 (2.5%)
Urinary tract infection	17/451 (3.8%)		9/301 (3%)		13/242 (5.4%)		2/50 (4%)		1/50 (2%)		1/47 (2.1%)		0/37 (0%)		26/685 (3.8%)		0/120 (0%)
Investigations
Alanine aminotransferase increased	24/451 (5.3%)		15/301 (5%)		10/242 (4.1%)		2/50 (4%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		20/685 (2.9%)		0/120 (0%)
Aspartate aminotransferase increased	14/451 (3.1%)		10/301 (3.3%)		9/242 (3.7%)		3/50 (6%)		0/50 (0%)		0/47 (0%)		0/37 (0%)		11/685 (1.6%)		0/120 (0%)
Influenza A virus test positive	1/451 (0.2%)		0/301 (0%)		0/242 (0%)		0/50 (0%)		0/50 (0%)		1/47 (2.1%)		2/37 (5.4%)		1/685 (0.1%)		0/120 (0%)
Nervous system disorders
Headache	31/451 (6.9%)		21/301 (7%)		8/242 (3.3%)		0/50 (0%)		1/50 (2%)		1/47 (2.1%)		1/37 (2.7%)		20/685 (2.9%)		0/120 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	15/451 (3.3%)		16/301 (5.3%)		13/242 (5.4%)		1/50 (2%)		0/50 (0%)		0/47 (0%)		1/37 (2.7%)		11/685 (1.6%)		1/120 (0.8%)
Vascular disorders
Hypertension	11/451 (2.4%)		8/301 (2.7%)		5/242 (2.1%)		0/50 (0%)		3/50 (6%)		0/47 (0%)		0/37 (0%)		4/685 (0.6%)		0/120 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.