A Study of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Who Don't Have a Response to Anti-TNF-α Therapy (SCRIPT)

Sponsor

Genentech, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT00476996

Collaborator

Roche Pharma AG (Industry)

836

Enrollment

266

Locations

Arms

132

Actual Duration (Months)

3.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of ocrelizumab, compared with placebo, in patients with active rheumatoid arthritis who have an inadequate response to at least one anti-TNF-alpha therapy. Patients will be randomized to receive placebo, 200mg of intravenous ocrelizumab, or 500mg of i.v. ocrelizumab on days 1 and 15. A repeat course of i.v. treatment will be administered at weeks 24 and 26. All patients will receive stable doses of either concomitant methotrexate (7.5-25mg/week) or leflunomide (10-20mg po daily) and may receive additional DMARDs. The treatment period is planned for 48 weeks (until primary analysis) and then participants will enter the open label phase until the drug is commercialized. Target sample size is 1000.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Leflunomide Drug: Methotrexate Drug: Ocrelizumab Drug: Ocrelizumab Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

836 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Parallel Group, International Study to Evaluate the Safety and Efficacy of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to at Least One Anti-TNF-α Therapy

Actual Study Start Date :

May 15, 2007

Actual Primary Completion Date :

Jan 21, 2010

Actual Study Completion Date :

May 14, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ocrelizumab 200 mg x 2 IV + Non-Biologic DMARD Therapy Participants will receive 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Drug: Leflunomide Oral repeating dose Drug: Methotrexate Oral or parenteral repeating dose Drug: Ocrelizumab Intravenous repeating dose (200mg)
Experimental: Ocrelizumab 500 mg x 2 IV + Non-Biologic DMARD Therapy Participants will receive 2 IV infusions of 500 mg of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Drug: Leflunomide Oral repeating dose Drug: Methotrexate Oral or parenteral repeating dose Drug: Ocrelizumab Intravenous repeating dose (500mg)
Placebo Comparator: Placebo x 2 IV + Non-Biologic DMARD Therapy Participants will receive ocrelizumab matching placebo IV in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Drug: Leflunomide Oral repeating dose Drug: Methotrexate Oral or parenteral repeating dose Drug: Placebo Intravenous repeating dose

Arm

Intervention/Treatment

Experimental: Ocrelizumab 200 mg x 2 IV + Non-Biologic DMARD Therapy

Participants will receive 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD

Drug: Leflunomide

Oral repeating dose

Drug: Methotrexate

Oral or parenteral repeating dose

Drug: Ocrelizumab

Intravenous repeating dose (200mg)

Experimental: Ocrelizumab 500 mg x 2 IV + Non-Biologic DMARD Therapy

Participants will receive 2 IV infusions of 500 mg of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD

Drug: Leflunomide

Oral repeating dose

Drug: Methotrexate

Oral or parenteral repeating dose

Drug: Ocrelizumab

Intravenous repeating dose (500mg)

Placebo Comparator: Placebo x 2 IV + Non-Biologic DMARD Therapy

Participants will receive ocrelizumab matching placebo IV in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD

Drug: Leflunomide

Oral repeating dose

Drug: Methotrexate

Oral or parenteral repeating dose

Drug: Placebo

Intravenous repeating dose

Outcome Measures

Primary Outcome Measures

Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses [Weeks 24 and 48]
ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale [VAS]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.

Secondary Outcome Measures

Percentage of Participants With a Major Clinical Response [Week 48]
Major clinical response was defined as achieving an ACR70 response and maintaining this response for a consecutive period of at least 6 months.
Percentage of Participants Achieving Disease Activity Score (DAS28) Remission [Weeks 24 and 48]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.
Change in DAS28 From Baseline [Weeks 24 and 48]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.
Percentage of Participants With EULAR Response Rates of Good/ Moderate [Weeks 24 and 48]
The EULAR response rate was based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none.
Percentage of Participants Achieving an ACR50 Response [Weeks 24 and 48]
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, Health Assessment Questionnaire with Disability Index (HAQ-DI), and C-Reactive Protein (CRP).
Percentage of Participants Achieving an ACR70 Response [Weeks 24 and 48]
ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, HAQ-DI and CRP.
Percentage of Participants With a Reduction in the HAQ-DI Score [Weeks 24 and 48]
Health Assessment Questionnaire - Disability Index (HAQ-DI): The Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA. It consists of 20 questions referring to eight component. Reduction in the HAQ-DI score of 0.25 units from baseline to weeks 24 and 48 represented a minimal clinically relevant improvement.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients, ≥ 18 years of age
Rheumatoid arthritis for at least 3 months
Inadequate response to previous or current treatment with at least one anti-TNF-alpha agent
Receiving either leflunomide or methotrexate for ≥ 12 weeks, with a stable dose for the last 4 weeks
Swollen joint count (SJC) ≥ 4 (66 joint count) and tender joint count (TJC) ≥ 4 (68 joint count) at screening and baseline.
CRP ≥ 0.6 mg/dL using a high-sensitivity assay.
Positive rheumatoid factor or positive anti-CCP antibody or both.

Exclusion Criteria:

Rheumatic autoimmune disease or inflammatory joint disease, other than RA
Any surgical procedure in past 12 weeks,or planned within 48 weeks of baseline

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Research Group; Llc, Central	Anniston	Alabama	United States	36207
2	Rheumatology Associates	Birmingham	Alabama	United States	35205
3	Rheumatology Associates of North Alabama	Huntsville	Alabama	United States	35801
4	Arizona Arthritis & Rheumatology Research, Pllc	Mesa	Arizona	United States	85202
5	Arthrocare, Arthritis Care and Research, P.C.	Mesa	Arizona	United States	85208
6	Catalina Pointe Clinical Research, Inc.	Tucson	Arizona	United States	85704
7	Uni of Arizona Health Science Center; Dept of Rheumatology/Immunology	Tucson	Arizona	United States	85724
8	CHI St. Vincent Medical Group Hot Springs	Hot Springs	Arkansas	United States	71913
9	Little Rock Diagnostic Clinic	Little Rock	Arkansas	United States	72205
10	Allergy & Rheumatology Centre	La Jolla	California	United States	92037
11	Private Practice	Long Beach	California	United States	90808
12	Valerius Medical Group & Research Ctr of Greater Long Beach	Los Alamitos	California	United States	90720
13	Uni of Southern California School of Medicine	Los Angeles	California	United States	90033
14	Pacific Arthritis Care Center	Los Angeles	California	United States	90045
15	Stanford Uni Medical Center; Divison of Rheumatology	Palo Alto	California	United States	94304
16	Ucsd, Dept of Medicine; Rheumatology	San Diego	California	United States	92093
17	San Diego Arthritis Med Clnc	San Diego	California	United States	92108
18	East Bay Rheumatology	San Leandro	California	United States	94578
19	Arthritis Treatment Center of South Bay	Torrance	California	United States	90505
20	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
21	Arthritis Assoc & Osteoporosis; Ctr of Colorado Springs	Colorado Springs	Colorado	United States	80920
22	Arthritis & Osteoporosis Center P.C.	Camden	Connecticut	United States	06510
23	New England Research Associates	Trumbull	Connecticut	United States	06611
24	Rheumatolgy Consultants of Deleware	Lewes	Delaware	United States	19958
25	Javed Rheumatology Associates, Inc.	Newark	Delaware	United States	19713
26	Arthritis & Rheumatism; Disease Specialities	Aventura	Florida	United States	33180
27	Jacksonville Center For Clinical Research	Jacksonville	Florida	United States	32216
28	Arthritis Center Palm Harbor	Palm Harbor	Florida	United States	34684
29	Arthritis Rsrch of Florida, Inc.	Palm Harbor	Florida	United States	34684
30	Sarasota Arthritis Center; Research Dept	Sarasota	Florida	United States	34239
31	Center For Arthritis; Research Dept	South Miami	Florida	United States	33143
32	SW Florida Clinical Research	Tampa	Florida	United States	33609
33	Tampa General Hospital; Rheumatology Research Dept	Tampa	Florida	United States	33612
34	Burnette & Silverfield, MDS	Tampa	Florida	United States	33614
35	Florida Medical Center	Zephyrhills	Florida	United States	33540
36	Atlanta Center For Clinical Research.	Atlanta	Georgia	United States	30342
37	Csi Research, Inc.	Cumming	Georgia	United States	30041
38	Marietta Rheumatology Associates, Pc	Marietta	Georgia	United States	30060
39	Intermountain Orthopaedics	Boise	Idaho	United States	83702
40	Coeur D'Alene Arthritis Clinic	Coeur d'Alene	Idaho	United States	83814
41	Idaho Arthritis Center	Meridian	Idaho	United States	83642
42	Uni of Chicago	Chicago	Illinois	United States	60637
43	Evanston Northwestern Healthcare; Rheumatology	Evanston	Illinois	United States	60201
44	Quad City Rheumatology, Sc	Moline	Illinois	United States	61265
45	Illinois Bone & Joint Inst.	Morton Grove	Illinois	United States	60053
46	Springfield Clinic	Springfield	Illinois	United States	62703
47	Iu Outpatient Clinical Research Facility	Indianapolis	Indiana	United States	46202-5149
48	Diagnostic Rheumatology & Research	Indianapolis	Indiana	United States	46227
49	Medical Specialists Clinical Research Center	Munster	Indiana	United States	46321
50	Physician'S Clinic of Iowa	Cedar Rapids	Iowa	United States	52401
51	Uni of Kansas Medical Center	Kansas City	Kansas	United States	66160
52	Center For Arthritis & Osteoporosis	Elizabethtown	Kentucky	United States	42701
53	Bluegrass Comm Research, Inc.	Lexington	Kentucky	United States	40515
54	Kentuckiana Center For Better Bone & Joint Healthx	Louisville	Kentucky	United States	40202
55	Baton Rouge Clinic, Amc	Baton Rouge	Louisiana	United States	70808
56	Johns Hopkins University; Department of Rheumatology	Baltimore	Maryland	United States	21224
57	Center For Rheumatology & Bone Research	Wheaton	Maryland	United States	20902
58	Clinical Pharmacology Study Group	Worcester	Massachusetts	United States	01610
59	Clinsite;Research Division of Integrated Health Associates	Ann Arbor	Michigan	United States	48106
60	Rheumatology, P.C.; Medical Arts Building	Kalamazoo	Michigan	United States	49009
61	Borgess Research Institute	Kalamazoo	Michigan	United States	49048
62	Fiechtner Research Inc	Lansing	Michigan	United States	48910
63	Office of Andrew Sulich, Md	Saint Clair Shores	Michigan	United States	48080
64	St Luke's Whiteside Research	Duluth	Minnesota	United States	55805
65	St. Mary'S Duluth Clinic Health System; Rheumatology Dept	Duluth	Minnesota	United States	55805
66	St. Paul Rheumatology	Eagan	Minnesota	United States	55121
67	Park Nicollet Inst. ; Rtrc	Minneapolis	Minnesota	United States	55416
68	Jackson Arthritis Clinic	Flowood	Mississippi	United States	39232
69	North Mississippi Medical Ctr; Internal Medicine Associates	Tupelo	Mississippi	United States	38802
70	David S Rosenberg	Florissant	Missouri	United States	63031
71	Clayton Medical Research	Saint Louis	Missouri	United States	63117
72	Physicians Group, LC DBA Rheumatology & Internal Medicine Associates	Saint Louis	Missouri	United States	63131
73	Arthritis Consultants	Saint Louis	Missouri	United States	63141
74	St. John'S Health System Inc.; St. John'S Medical Research	Springfield	Missouri	United States	65807
75	Westroads Medical Group	Omaha	Nebraska	United States	68114
76	Seacoast Arthritis and Osteoporosis Center	Dover	New Hampshire	United States	03820
77	Nashua Rheumatology - Foundation Medical Partners	Nashua	New Hampshire	United States	03060
78	Mark Fisher Md, Facr, Llc	Haddon Heights	New Jersey	United States	08035
79	Arthritis Rheumatic & Back Disease Associates	Voorhees	New Jersey	United States	08043
80	The Center of Rheumatology	Albany	New York	United States	12206
81	Arthritis & Osteoporosis Center	Brooklyn	New York	United States	11201
82	Southern Tier Arthritis & Rheumatism	Olean	New York	United States	14760
83	Aair Research Center	Rochester	New York	United States	14618
84	Andrew Porges Pc	Roslyn	New York	United States	11576
85	Rheumatology Associates of Long Island	Smithtown	New York	United States	11787
86	Asheville Arthritis & Osteoporosis Center, PA	Asheville	North Carolina	United States	28803
87	Arthritis Associates	Belmont	North Carolina	United States	28012
88	Metrolina Medical Research	Charlotte	North Carolina	United States	28209
89	Carolina Bone & Joint P.A.	Charlotte	North Carolina	United States	28210
90	Physicians East Pa	Greenville	North Carolina	United States	27834
91	St. Alexius Medical Center; Arthritis Clinic	Bismarck	North Dakota	United States	58501
92	Deaconess Arthritis Center; Rheumatic Disease Study Group	Cincinnati	Ohio	United States	45219
93	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
94	Stat Research, Inc	Dayton	Ohio	United States	45402
95	David Mandel Inc	Mayfield	Ohio	United States	44143
96	Paramount Medical Research	Middleburg Heights	Ohio	United States	44130
97	Health Research of Oklahoma, Llc	Oklahoma City	Oklahoma	United States	73103
98	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma	United States	73104
99	Oklahoma Center For Arthritis Therapy & Research	Tulsa	Oklahoma	United States	74104
100	Healthcare Research Consultants	Tulsa	Oklahoma	United States	74135
101	Bend Memorial Clinic	Bend	Oregon	United States	97701
102	Pro Research	Eugene	Oregon	United States	97401
103	Portland Rheumatology Clinic Llc	Lake Oswego	Oregon	United States	97035
104	Providence Arthritis Center	Portland	Oregon	United States	97213
105	East Penn Rheumatology Associates, Pc	Bethlehem	Pennsylvania	United States	18015
106	Arthritis Associates	Erie	Pennsylvania	United States	16508
107	Rheumatology Associates of NW Pa	Erie	Pennsylvania	United States	16508
108	Arthritis Group	Philadelphia	Pennsylvania	United States	19152
109	Advanced Rheumatology & Arthritis Research Center	Wexford	Pennsylvania	United States	15090
110	Clinical Research Center of Reading	Wyomissing	Pennsylvania	United States	19610
111	Low Country Research Center	Charleston	South Carolina	United States	29406
112	Palmetto Clinical Trial Services, LLC	Fountain Inn	South Carolina	United States	29644
113	Unifour Medical Research Associates	Hickory Grove	South Carolina	United States	28602
114	Medical Uni of South Carolina	North Charleston	South Carolina	United States	29425
115	Spartanburg Medical Research	Spartanburg	South Carolina	United States	29303
116	West Tennessee Research Institute	Jackson	Tennessee	United States	38305
117	Rheumatology Consultants	Knoxville	Tennessee	United States	37909
118	Arthritis Group	Memphis	Tennessee	United States	38104
119	Ramesh Gupta - PP	Memphis	Tennessee	United States	38119
120	Aamr Research Clinic	Amarillo	Texas	United States	79106
121	Amarillo Center For Clinical Research	Amarillo	Texas	United States	79124
122	Austin Rheumatology Research	Austin	Texas	United States	78705
123	Walter F. Chase, Md, Pa	Austin	Texas	United States	78705
124	Arthritis Care & Diagnostic Center	Dallas	Texas	United States	75231-4406
125	Arthritis Care and Research Centre	Dallas	Texas	United States	75231
126	Metroplex Clinical Research	Dallas	Texas	United States	75231
127	Arthritis Centers of Texas	Dallas	Texas	United States	75246
128	Uni of Texas Southwestern Medical Center; Internal Medicine	Dallas	Texas	United States	75390
129	Arthritis & Osteoporosis Associates, LLP	Lubbock	Texas	United States	79424
130	Southwest Rheumatology	Mesquite	Texas	United States	75150
131	Radiant Research	San Antonio	Texas	United States	78217
132	Texas Arthritis Research Center; Center for Arthritis & Rheumatic Diseases	San Antonio	Texas	United States	78217
133	Texas Research Center	Sugar Land	Texas	United States	77479
134	Uni of Utah Medical Center	Salt Lake City	Utah	United States	84132
135	Arthritis Clinic of Northern Virginia	Arlington	Virginia	United States	22205
136	Sentara Medical Group	Norfolk	Virginia	United States	23507
137	Seattle Rheumatology Associates	Seattle	Washington	United States	98104
138	Arthritis Northwest, Spokane	Spokane	Washington	United States	99204
139	Office of George Krick, Md	Tacoma	Washington	United States	98405
140	Tacoma Center For Arthritis Research	Tacoma	Washington	United States	98405
141	Vancouver Clinic; Research Dept	Vancouver	Washington	United States	98664
142	Clinical Trials Northwest	Yakima	Washington	United States	98902
143	Rheumatic Disease Center	Glendale	Wisconsin	United States	53217
144	Gundersen Clinic Ltd;Sec. Rheumatology/Dept. of Internal Med	Onalaska	Wisconsin	United States	54605
145	Organizacion Medica de Investigacion	Buenos Aires		Argentina	C1015ABO
146	Inst. de Rehabilitacion Psicofisica; Reumathology	Buenos Aires		Argentina	C1428DQG
147	CER Instituto Médico; REUMATOLOGÍA	Florencio Varela		Argentina	B1878DVB
148	Sunshine Coast Rheumatology Research Unit	Maroochydore	Queensland	Australia	4558
149	Princess Alexandra Hospital; Rheumatology	Woolloongabba	Queensland	Australia	4102
150	Royal Perth Hospital; Rheumatology	Shenton Park	Western Australia	Australia	6008
151	AZ Sint Jan	Brugge		Belgium	8000
152	CHU Brugmann (Victor Horta)	Bruxelles		Belgium	1020
153	CHU de Charleroi	Charleroi		Belgium	6000
154	UZ Gent	Gent		Belgium	9000
155	GHdC Site Saint-Joseph	Gilly (Charleroi)		Belgium	6000
156	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
157	ZNA Jan Palfijn	Merksem		Belgium	2170
158	Centro Internacional de Pesquisa; Reumatologia	Goiania	GO	Brazil	74110010
159	Centro de Estudos em Terapias Inovadoras - CETI	Curtiba	PR	Brazil	80030-110
160	Hospital Universitario Clementino Fraga Filho - UFRJ; Reumatologia	Rio de Janeiro	RJ	Brazil	21941-590
161	Hospital das Clinicas - UNICAMP	Campinas	SP	Brazil	13083-888
162	Hospital Abreu Sodre - AACD;Pesquisa Clinica	Sao Paulo	SP	Brazil	04027-000
163	The Governors of the Uni of Alberta; Heritage Medical Research Centre	Edmonton	Alberta	Canada	T6G 2S2
164	Arthritis Research Centre	Vancouver	British Columbia	Canada	V5Z 1L7
165	Manitoba Clinic	Winnipeg	Manitoba	Canada	R3A 1M3
166	Wharton Medical Clinic; Burlington	Burlington	Ontario	Canada	L7R 1E2
167	Mac Research Inc.	Hamilton	Ontario	Canada	L8N 2B6
168	K-W Musculoskeletal Research	Kitchener	Ontario	Canada	N2M 5N6
169	St. Joseph'S Health Care Centre; Rheumatology	London	Ontario	Canada	N6A 4V2
170	Credit Valley, Rheumatology	Mississauga	Ontario	Canada	L5M 2V8
171	The Ottawa Hospital - Riverside Campus; the Arthritis Centre	Ottawa	Ontario	Canada	K1H 7W9
172	University Health Network; Toronto Western Hospital	Toronto	Ontario	Canada	M5T 2S8
173	Hopital Maisonneuve- Rosemont; Rheumatology	Montreal	Quebec	Canada	H1T 2M4
174	Institut de Rhumatologie de Montreal	Montreal	Quebec	Canada	H2L 1S6
175	Montreal Rheumatic Disease Centre	Montreal	Quebec	Canada	H3Z 2Z3
176	Groupe de Recherche En Rhumatologie Et Maladies Osseuses	Quebec City	Quebec	Canada	G1V 3M7
177	Clin. de Rhumatologie	Trois-rivieres	Quebec	Canada	G8Z 1Y2
178	Royal Uni Hospital; Medicine Dept	Saskatoon	Saskatchewan	Canada	S7N 0W8
179	Revmatologicky Ustav	Prague		Czechia	128500
180	Hopital De Bois Guillaume; Rhumatologie	Bois Guillaume		France	76233
181	CH Jean Rougier; Rhumato Reed Fonctionnelle	Cahors		France	46005
182	Hopital Louis Pasteur; Service De Medecine Interne et de Rhumatologie	Colmar		France	68024
183	CH Du Mans; Rhumatologie	Le Mans		France	72037
184	Hopital B Roger Salengro; Rhumatologie	Lille		France	59037
185	Fondation Hopital Saint Joseph; Rhumatologie	Marseille		France	13285
186	Hopital Lapeyronie; Immunologie Rhumatologie	Montpellier		France	34295
187	Hopital de L'Archet; Rhumatologie	Nice		France	06202
188	Hopital Cochin; Rhumatologie A	Paris		France	75679
189	Hopital Cochin; Rhumatologie B	Paris		France	75679
190	Praxis Dr. med. Reiner Kurthen	Aachen		Germany	52064
191	Schlosspark Klinik; Abt. Rheumatologie	Berlin		Germany	14059
192	Klinik Duisburg; Klinik Für Rheumatologie	Duisburg		Germany	47055
193	Endokrinologikum Frankfurt; Rheumatologie & Gynäkologie	Frankfurt		Germany	60596
194	Universitätsklinikum Freiburg; Medizinische UNI-Klinik; Abt. Innere Medizin - VI Rheumatologie	Freiburg		Germany	79106
195	Internistisches Praxiszentrum Am Krankenhaus Balserische Stiftung; Innere Medizin / Rheumatologie	Giessen		Germany	35392
196	Evangelisches Krankenhaus Hagen-Haspe Rheumaklinik	Hagen		Germany	58135
197	Medizinische Hochschule Zentrum Innere Medizin Abt.Klinische Immunologie und Rheumatologie	Hannover		Germany	30625
198	Rheumapraxis PD Dr.med. Bernhard Heilig	Heidelberg		Germany	69120
199	UNI-Klinikum Heidelberg Medizinische Klinik Innere Medizin V	Heidelberg		Germany	69120
200	Fachärzte für Innere Medizin - Rheumatologie - Dr. med. Ino Gao und Dr. med. Maria Anna Meier	Heidelberg		Germany	69121
201	Klinik der Uni zu Köln; Klinik für Innere Medizin	Köln		Germany	50924
202	Uniklinik Mainz; I. Medizinische Klinik	Mainz		Germany	55131
203	Klinikum der Universitat Munchen; Bereich Pettenkoferstr; Rheumaeinheit der medizinischen Klinik IV	München		Germany	80336
204	Rheumapraxis an der Hase	Osnabrück		Germany	49074
205	Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Hämatologie / Onkologie	Würzburg		Germany	97080
206	Orszagos Reumatologiai Es Fizioterapias Intezet	Budapest		Hungary	1023
207	Budai Irgalmasrendi Kórház KHT. II. Reumatológia	Budapest		Hungary	1027
208	Debreceni Egyetem Orvos- és Egészségtudományi Centrum; Belgyógyászati Intézet, Reumatológiai Tanszék	Debrecen		Hungary	4032
209	Vas Megye Es Szombathely M.J.V. Markusovszky Korhaza	Szombathely		Hungary	9700
210	Soroka Medical Center; Reumatology	Beer Sheva		Israel	8410101
211	Assaf Harofe; Dept of Medicine B	Beer Yaakov		Israel	6093000
212	Meir Medical Center; Heamatology Dept	Kfar Saba		Israel	4428164
213	Beilinson Medical Center; Rheumatology	Petach Tikva		Israel	4941492
214	Sourasky / Ichilov Hospital; Rheumatology	Tel Aviv		Israel	6423906
215	Arcispedale Santa Maria Nuova; Reumatologia	Reggio Emilia	Emilia-Romagna	Italy	42100
216	Università Degli Studi Di Genova - Dimi; Reumatologia	Genova	Liguria	Italy	16132
217	Irccs Policlinico San Matteo; Reumatologia Adulti	Pavia	Lombardia	Italy	27100
218	Az. Osp. Pisana Ospedale S. Chiara; U.O. Di Reumatologia	Pisa	Toscana	Italy	56100
219	Seihoku Chuoh Hospital; Department Of Rheumatology	Aomori		Japan	037-0053
220	Univ. of Occupational and Environmental Health; Rheumatology, Clinical Immunology and Medicine	Fukuoka		Japan	807-8555
221	National Hospital Organization Kyushu Medical Center; Rheumatology and Internal Medicine	Fukuoka		Japan	810-8563
222	Higashihiroshima Memorial Hospital; Rheumatology, Internal Medicine	Hiroshima		Japan	739-0002
223	Hokkaido Uni Hospital; Second Department of Internal Medicine	Hokkaido		Japan	060-8648
224	Matsubara Mayflower Hospital; Rheumatology	Hyogo		Japan	673-1462
225	Sasebo Chuo Hospital ; Internal Medicine	Nagasaki		Japan	857-1195
226	Osaka Minami Medical Center; Rheumatoid Arthritis	Osaka		Japan	586-8521
227	Saitama Medical University Hospital ; Rheumatology and Applied Immunology	Saitama		Japan	350-0495
228	Saitama Medical Center/School; Rheumatology, Clinical immunology	Saitama		Japan	350-0844
229	Seirei Hamamatsu General Hospital; Rheumatology	Shizuoka		Japan	430-8558
230	Jichi Medical School Hospital; Rheumatology and Clinical Immunology	Tochigi		Japan	329-0498
231	Tokyo Medical & Dental University; Medicine & Rheumatology	Tokyo		Japan	113-8519
232	Tokyo Women's Medical University	Tokyo		Japan	162-0054
233	Consultorio Privado Dr. Javier Orozco	Guadalajara		Mexico	44650
234	Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel	Mexicali		Mexico	21100
235	Unidad De Enfermedades; Cronico Degenerativas, SC.	Mexico		Mexico	44620
236	Clinica San Jose Obregon; Rheumatology	Obregon		Mexico	85000
237	Academisch Medisch Centrum; Division of Clinical Immunology & Rheumatology	Amsterdam		Netherlands	1105 AZ
238	Maxima Medisch Centrum; Rheumatology	Eindhoven		Netherlands	5631 BM
239	Timaru Hospital	Timaru		New Zealand	7910
240	Centro de Infusion Marbella; Consultorios Royal Center Num 214	Panama City		Panama	32400
241	Hospital Alberto Sabogal Sologuren; Remautology	Callao		Peru
242	Clinica San Felipe; Consultorio de Reumatología	Lima		Peru	11
243	Hospital Nacional Edgardo Rebagliati Martins; Servicio de Reumatología	Lima		Peru	11
244	Szpital Uniwersytecki; nr 2 im. Dr J. Biziela	Bydgoszcz		Poland	85-168
245	Wojewodzki Szpital Zespolony; Oddzial Reumatologii	Elblag		Poland	82-300
246	Klinika Reumatologii I Chorób Wewn. Pum W Szczecinie; Samodzielny Publiczny Szpital Kliniczny Nr 1	Szczecin		Poland	71-252
247	Narodny Ustav Reumatickych Chorob - 34479; Rheumatology	Piestany		Slovakia	921 01
248	Bolnica dr. Petra Drzaja, Klinicni center Ljubljana; Klinicni oddelek za revmatologijo	Ljubljana		Slovenia	1000
249	Hospital Univ. Central de Asturias; Servicio de Reumatologia	Oviedo	Asturias	Spain	33006
250	Corporacio Sanitaria Parc Tauli; Servicio de Reumatologia	Sabadell	Barcelona	Spain	08208
251	Hospital de Jerez de la Frontera; Servicio de Reumatologia	Jerez de La Frontera	Cadiz	Spain	11407
252	Hospital Sierrallana; Servicio de Reumatologia	Torrelavega	Cantabria	Spain	39300
253	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Reumatologia	La Coruna	LA Coruña	Spain	15006
254	Hospital de Basurto; Servicio de Reumatologia	Bilbao	Vizcaya	Spain	48013
255	Hospital Universitario Infanta Cristina; Servicio de Reumatologia	Badajoz		Spain	06080
256	Hospital Clinic i Provincial; Servicio de Reumatologia	Barcelona		Spain	08036
257	Hospital Universitari de Bellvitge; Servicio de Reumatologia	Barcelona		Spain	08907
258	Complejo Asistencial Universitario de Burgos; Servicio de Reumatología	Burgos		Spain	06006
259	Hospital General Universitario de Guadalajara; Servicio de Reumatologia	Guadalajara		Spain	19002
260	Hospital Universitario 12 de Octubre; Servicio de Reumatologia	Madrid		Spain	28041
261	Hospital Clinico Universitario de Salamanca; Servicio de Reumatologia	Salamanca		Spain	37007
262	Uni Hospital Linkoeping; Dept. of Rheumatology	Linkoeping		Sweden	58185
263	Akademiska sjukhuset, Reumatologkliniken	Uppsala		Sweden	75185
264	CHUV; Hôpital orthopédique, Rhumatologie	Lausanne		Switzerland	1011
265	Universitätsspital Zürich; Klinik für Rheumatologie	Zürich		Switzerland	8091
266	Chang Gung Medical Foundation - Kaohsiung; Rheumatology	Kaohsiung		Taiwan	00833

Sponsors and Collaborators

Genentech, Inc.
Roche Pharma AG

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Genentech, Inc.

ClinicalTrials.gov Identifier:

NCT00476996

Other Study ID Numbers:

ACT3986g
WA20495
2006-005330-20

First Posted:

May 22, 2007

Last Update Posted:

Aug 12, 2019

Last Verified:

Aug 1, 2019

Keywords provided by Genentech, Inc.

SCRIPT

anti-CD20

CD20

Additional relevant MeSH terms:

Arthritis

Arthritis, Rheumatoid

Methotrexate

Leflunomide

Ocrelizumab

Study Results

Participant Flow

Recruitment Details	Participants were recruited across 25 countries.
Pre-assignment Detail	The study population comprised of adult participants with active RA of >/= 3 months duration who had an inadequate clinical response due to toxicity or inadequate efficacy to previous or current treatment with one or more anti-TNF-alpha therapies.

Arm/Group Title	Placebo x 2 IV + Non-Biologic DMARD	Ocrelizumab 200 mg x 2 + Non-Biologic DMARD	Ocrelizumab 500 mg x 2 + Non-Biologic DMARD	Ocrelizumab 500 mg x 2 IV + Non-biologic DMARD (OLE)
Arm/Group Description	Participants received Ocrelizumab matching placebo intravenously (IV) in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab (total 400 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 500 milligram (mg) of ocrelizumab (total 1000 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	At the discretion of the investigator, eligible participants received 500 mg Ocrelizumab IV in two infusions separated by 14 days
Period Title: Blinded Treatment Phase (up to Week 48)
STARTED	277	277	282	0
COMPLETED	205	222	237	0
NOT COMPLETED	72	55	45	0
Period Title: Blinded Treatment Phase (up to Week 48)
STARTED	0	0	0	664
COMPLETED	0	0	0	0
NOT COMPLETED	0	0	0	664

Baseline Characteristics

Arm/Group Title	Placebo x 2 IV + Non-Biologic DMARD	Ocrelizumab 200 mg x 2 + Non-Biologic DMARD	Ocrelizumab 500 mg x 2 + Non-Biologic DMARD	Total
Arm/Group Description	Participants received Ocrelizumab matching placebo intravenously (IV) in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab (total 400 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 500 milligram (mg) of ocrelizumab (total 1000 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Total of all reporting groups
Overall Participants	277	277	282	836
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.1 (11.3)	54.5 (11.2)	53.8 (11.6)	54.2 (11.3)
Sex: Female, Male (Count of Participants)
Female	215 77.6%	214 77.3%	236 83.7%	665 79.5%
Male	62 22.4%	63 22.7%	46 16.3%	171 20.5%
Race/Ethnicity, Customized (Number) [Number]
American indian or Alaska native	9 3.2%	8 2.9%	9 3.2%	26 3.1%
Asian (Indian Subcontinent)	1 0.4%	0 0%	0 0%	1 0.1%
Asian (Other than Indian subcontinent)	39 14.1%	38 13.7%	38 13.5%	115 13.8%
Black	16 5.8%	18 6.5%	12 4.3%	46 5.5%
Native Hawaiian or other Pacific Islander	0 0%	1 0.4%	2 0.7%	3 0.4%
Other	6 2.2%	11 4%	14 5%	31 3.7%
White	206 74.4%	201 72.6%	207 73.4%	614 73.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses
Description	ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale [VAS]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.

Arm/Group Title	Placebo x 2 IV + Non-Biologic DMARD	Ocrelizumab 200 mg x 2 + Non-Biologic DMARD	Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
Arm/Group Description	Participants received Ocrelizumab matching placebo intravenously (IV) in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab (total 400 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 500 milligram (mg) of ocrelizumab (total 1000 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Measure Participants	277	277	282
Percentage of Responders at Week 24	22	42.2	47.9
Percentage of Responders at Week 48	19.5	48.7	50.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	At Week 24, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	20.4
	Confidence Interval	(2-Sided) 95% 12.8 to 27.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	At Week 24, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	25.2
	Confidence Interval	(2-Sided) 95% 17.7 to 32.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	At Week 48, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	29.1
	Confidence Interval	(2-Sided) 95% 21.6 to 36.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	At Week 48, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	30.3
	Confidence Interval	(2-Sided) 95% 22.8 to 37.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With a Major Clinical Response
Description	Major clinical response was defined as achieving an ACR70 response and maintaining this response for a consecutive period of at least 6 months.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.

Arm/Group Title	Placebo x 2 IV + Non-Biologic DMARD	Ocrelizumab 200 mg x 2 + Non-Biologic DMARD	Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
Arm/Group Description	Participants received Ocrelizumab matching placebo intravenously (IV) in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab (total 400 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 500 milligram (mg) of ocrelizumab (total 1000 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Measure Participants	277	277	282
Number (95% Confidence Interval) [Percentage]	1.8	4.0	5.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	Analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1885
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95% -1.0 to 5.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	Analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0330
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95% 0.3 to 6.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants Achieving Disease Activity Score (DAS28) Remission
Description	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.

Arm/Group Title	Placebo x 2 IV + Non-Biologic DMARD	Ocrelizumab 200 mg x 2 + Non-Biologic DMARD	Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
Arm/Group Description	Participants received Ocrelizumab matching placebo intravenously (IV) in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab (total 400 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 500 milligram (mg) of ocrelizumab (total 1000 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Measure Participants	277	277	282
Percentage of Participants at Week 24	1.8	5.8	6.0
Percentage of Participants at Week 48	1.4	11.9	12.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	At Week 24, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0175
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	4.2
	Confidence Interval	(2-Sided) 95% 0.7 to 7.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	At Week 24, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0134
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 95% 0.9 to 7.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	At Week 48, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	10.5
	Confidence Interval	(2-Sided) 95% 6.2 to 14.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	At Week 48, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	10.5
	Confidence Interval	(2-Sided) 95% 6.2 to 14.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change in DAS28 From Baseline
Description	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis Number of participants for whom data were collected is indicated for each time point.

Arm/Group Title	Placebo x 2 IV + Non-Biologic DMARD	Ocrelizumab 200 mg x 2 + Non-Biologic DMARD	Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
Arm/Group Description	Participants received Ocrelizumab matching placebo intravenously (IV) in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab (total 400 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 500 milligram (mg) of ocrelizumab (total 1000 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Measure Participants	277	277	282
Baseline	6.50 (1.014)	6.47 (1.217)	6.44 (1.039)
Week 24	-0.99 (1.166)	-1.60 (1.307)	-1.91 (1.349)
Week 48	-1.13 (1.404)	-2.11 (1.348)	-2.38 (1.496)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	Week 24 analysis using adjusted mean difference. Model contains region, baseline DMARD therapy, baseline DAS28 score and treatment
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Analysis of Variance
	Comments

Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95% -0.8 to -0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	Week 24 analysis using adjusted mean difference. Model contains region, baseline DMARD therapy, baseline DAS28 score and treatment
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Analysis of Variance
	Comments

Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95% -1.1 to -0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	Week 48 analysis using adjusted mean difference. Model contains region, baseline DMARD therapy, baseline DAS28 score and treatment
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Analysis of Variance
	Comments

Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95% -1.2 to -0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	Week 48 analysis using adjusted mean difference. Model contains region, baseline DMARD therapy, baseline DAS28 score and treatment
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Analysis of Variance
	Comments

Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95% -1.5 to -0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With EULAR Response Rates of Good/ Moderate
Description	The EULAR response rate was based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.

Arm/Group Title	Placebo x 2 IV + Non-Biologic DMARD	Ocrelizumab 200 mg x 2 + Non-Biologic DMARD	Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
Arm/Group Description	Participants received Ocrelizumab matching placebo intravenously (IV) in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab (total 400 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 500 milligram (mg) of ocrelizumab (total 1000 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Measure Participants	277	277	282
Week 24	31.4	54.2	61.0
Week 48	24.9	58.8	60.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	At Week 24, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Proportional Odds Analysis
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.60
	Confidence Interval	(2-Sided) 95% 1.85 to 3.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	At Week 24, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Proportional Odds Analysis
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.49
	Confidence Interval	(2-Sided) 95% 2.49 to 4.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	At Week 48, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Proportional Odds Analysis
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.18
	Confidence Interval	(2-Sided) 95% 2.93 to 5.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	At Week 48, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Proportional Odds Analysis
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.04
	Confidence Interval	(2-Sided) 95% 3.54 to 7.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants Achieving an ACR50 Response
Description	ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, Health Assessment Questionnaire with Disability Index (HAQ-DI), and C-Reactive Protein (CRP).
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.

Arm/Group Title	Placebo x 2 IV + Non-Biologic DMARD	Ocrelizumab 200 mg x 2 + Non-Biologic DMARD	Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
Arm/Group Description	Participants received Ocrelizumab matching placebo intravenously (IV) in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab (total 400 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 500 milligram (mg) of ocrelizumab (total 1000 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Measure Participants	277	277	282
Percentage of Participants at Week 24	7.9	21.3	24.8
Percentage of Participants at Week 48	9	28.5	30.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	At Week 24, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	13.2
	Confidence Interval	(2-Sided) 95% 7.4 to 19.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	At Week 24, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	16.2
	Confidence Interval	(2-Sided) 95% 10.2 to 22.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	At Week 48, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	19.3
	Confidence Interval	(2-Sided) 95% 12.9 to 25.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	At Week 48, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	20.8
	Confidence Interval	(2-Sided) 95% 14.5 to 27.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants Achieving an ACR70 Response
Description	ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, HAQ-DI and CRP.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.

Arm/Group Title	Placebo x 2 IV + Non-Biologic DMARD	Ocrelizumab 200 mg x 2 + Non-Biologic DMARD	Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
Arm/Group Description	Participants received Ocrelizumab matching placebo intravenously (IV) in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab (total 400 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 500 milligram (mg) of ocrelizumab (total 1000 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Measure Participants	277	277	282
Percentage of Participants at Week 24	2.9	7.6	9.9
Percentage of Participants at Week 48	4.3	11.2	18.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	At Week 24, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0203
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	4.6
	Confidence Interval	(2-Sided) 95% 0.7 to 8.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	At Week 24, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0014
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	6.7
	Confidence Interval	(2-Sided) 95% 2.6 to 10.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	At Week 48, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0042
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	6.6
	Confidence Interval	(2-Sided) 95% 2.1 to 11.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	At Week 48, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	13.4
	Confidence Interval	(2-Sided) 95% 8.2 to 18.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With a Reduction in the HAQ-DI Score
Description	Health Assessment Questionnaire - Disability Index (HAQ-DI): The Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA. It consists of 20 questions referring to eight component. Reduction in the HAQ-DI score of 0.25 units from baseline to weeks 24 and 48 represented a minimal clinically relevant improvement.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.

Arm/Group Title	Placebo x 2 IV + Non-Biologic DMARD	Ocrelizumab 200 mg x 2 + Non-Biologic DMARD	Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
Arm/Group Description	Participants received Ocrelizumab matching placebo intravenously (IV) in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab (total 400 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD	Participants received 2 intravenous (IV) infusions of 500 milligram (mg) of ocrelizumab (total 1000 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Measure Participants	277	277	282
Percentage of Participants at Week 24	32.9	52.3	58.5
Percentage of Participants at Week 48	23.1	50.5	51.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	At Week 24, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	19.4
	Confidence Interval	(2-Sided) 95% 11.3 to 27.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	At Week 24, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	24.7
	Confidence Interval	(2-Sided) 95% 16.8 to 32.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 200 mg x 2 + Non-Biologic DMARD
	Comments	At Week 48, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	27.2
	Confidence Interval	(2-Sided) 95% 19.5 to 34.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo x 2 IV + Non-Biologic DMARD, Ocrelizumab 500 mg x 2 + Non-Biologic DMARD
	Comments	At Week 48, analysis was stratified by region and baseline DMARD therapy
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Weighted Difference
	Estimated Value	27.6
	Confidence Interval	(2-Sided) 95% 20.0 to 35.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

	Placebo x 2 IV + Non-Biologic DMARD		Ocrelizumab 200 mg x 2 + Non-Biologic DMARD		Ocrelizumab 500 mg x 2 + Non-Biologic DMARD		Ocrelizumab 500 mg x 2 IV + Non-biologic DMARD (OLE)
Time Frame	From Day 1 to Week 48 and Week 96
Adverse Event Reporting Description	The safety population included all participants who received at least one treatment with study medication. In the safety population patients are categorized as treated, the ITT population as randomized. One patient randomized to Placebo and one patient randomized to the OCR 200 mg group, received at least one dose of OCR 500 mg.

Arm/Group Title	Placebo x 2 IV + Non-Biologic DMARD		Ocrelizumab 200 mg x 2 + Non-Biologic DMARD		Ocrelizumab 500 mg x 2 + Non-Biologic DMARD		Ocrelizumab 500 mg x 2 IV + Non-biologic DMARD (OLE)
Arm/Group Description	Participants received Ocrelizumab matching placebo intravenously (IV) in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD		Participants received 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab (total 400 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD		Participants received 2 intravenous (IV) infusions of 500 milligram (mg) of ocrelizumab (total 1000 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD		At the discretion of the investigator, eligible participants received 500 mg Ocrelizumab IV in two infusions separated by 14 days
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/276 (1.8%)		2/276 (0.7%)		4/284 (1.4%)		11/664 (1.7%)
Serious Adverse Events
	Placebo x 2 IV + Non-Biologic DMARD		Ocrelizumab 200 mg x 2 + Non-Biologic DMARD		Ocrelizumab 500 mg x 2 + Non-Biologic DMARD		Ocrelizumab 500 mg x 2 IV + Non-biologic DMARD (OLE)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/276 (14.9%)		46/276 (16.7%)		40/284 (14.1%)		138/664 (20.8%)
Blood and lymphatic system disorders
Anaemia	2/276 (0.7%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Iron deficiency anaemia	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		2/664 (0.3%)
Granulocytopenia	0/276 (0%)		1/276 (0.4%)		1/284 (0.4%)		0/664 (0%)
Disseminated intravascular coagulation	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Leukopenia	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Neutropenia	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Cardiac disorders
Acute myocardial infarction	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Angina pectoris	1/276 (0.4%)		2/276 (0.7%)		1/284 (0.4%)		1/664 (0.2%)
Arteriosclerosis coronary artery	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Atrial fibrillation	1/276 (0.4%)		1/276 (0.4%)		1/284 (0.4%)		2/664 (0.3%)
Cardiac failure congestive	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Cardiomyopathy	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Coronary artery disease	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		2/664 (0.3%)
Coronary artery occlusion	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Myocardial infarction	1/276 (0.4%)		2/276 (0.7%)		1/284 (0.4%)		6/664 (0.9%)
Pericardial effusion	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Supraventricular extrasystoles	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Acute coronary syndrome	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Atrioventricular block complete	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Sinus bradycardia	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Supraventricular tachycardia	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Ventricular extrasystoles	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Aortic valve incompetence	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		0/664 (0%)
Congenital, familial and genetic disorders
Hydrocele	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Endocrine disorders
Basedow's disease	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		0/664 (0%)
Eye disorders
Cataract	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		1/664 (0.2%)
Uveitis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Glaucoma	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Gastrointestinal disorders
Colitis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Colitis ischaemic	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Diarrhoea	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Diverticular perforation	0/276 (0%)		0/276 (0%)		0/284 (0%)		2/664 (0.3%)
Duodenal ulcer	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Duodenal ulcer haemorrhage	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Enterovesical fistula	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Gastric ulcer	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Gastroduodenal ulcer	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Gastrointestinal haemorrhage	0/276 (0%)		1/276 (0.4%)		1/284 (0.4%)		2/664 (0.3%)
Gastrointestinal perforation	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Hiatus hernia	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		1/664 (0.2%)
Inguinal hernia	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		2/664 (0.3%)
Large intestinal obstruction	0/276 (0%)		0/276 (0%)		0/284 (0%)		2/664 (0.3%)
Peptic ulcer haemorrhage	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		1/664 (0.2%)
Upper gastrointestinal haemorrhage	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Gastric ulcer perforation	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		0/664 (0%)
Gastric ulcer haemorrhage	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Gastrooesophageal reflux disease	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Large intestine perforation	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Mesenteric vein thrombosis	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		0/664 (0%)
Nausea	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Small intestinal obstruction	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Subileus	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
General disorders
Chest pain	0/276 (0%)		0/276 (0%)		0/284 (0%)		4/664 (0.6%)
Death	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		1/664 (0.2%)
Device dislocation	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Lead dislodgement	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Multi-organ failure	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Non-cardiac chest pain	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Pyrexia	0/276 (0%)		0/276 (0%)		0/284 (0%)		2/664 (0.3%)
Sudden death	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Systemic inflammatory response syndrome	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Surgical failure	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Hepatobiliary disorders
Cholecystitis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Cholelithiasis	0/276 (0%)		0/276 (0%)		2/284 (0.7%)		0/664 (0%)
Hepatitis toxic	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Infections and infestations
Appendicitis	1/276 (0.4%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Arthritis bacterial	1/276 (0.4%)		0/276 (0%)		1/284 (0.4%)		1/664 (0.2%)
Atypical pneumonia	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Bronchitis	2/276 (0.7%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Bronchopneumonia	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		1/664 (0.2%)
Bronchitis pneumococcal	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Bacterial infection	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Candida infection	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Bursitis infective	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Cellulitis	3/276 (1.1%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Conjunctivitis	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Clostridium difficile infection	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Diverticulitis	0/276 (0%)		0/276 (0%)		0/284 (0%)		2/664 (0.3%)
Escherichia pyelonephritis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Extradural abscess	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Enterocolitis viral	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Enteritis infectious	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		0/664 (0%)
Gastroenteritis	0/276 (0%)		1/276 (0.4%)		1/284 (0.4%)		2/664 (0.3%)
Genitourinary tract infection	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Gastroenteritis salmonella	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Hepatitis B	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Herpes zoster	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Implant site infection	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		0/664 (0%)
Incision site cellulitis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Infectious colitis	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Influenza	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Kidney infection	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		1/664 (0.2%)
Lower respiratory tract infection	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Osteomyelitis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Parotitis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Peritonitis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Pharyngitis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Pilonidal cyst	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Paronychia	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		0/664 (0%)
Pneumonia	5/276 (1.8%)		5/276 (1.8%)		1/284 (0.4%)		11/664 (1.7%)
Pneumonia bacterial	0/276 (0%)		0/276 (0%)		2/284 (0.7%)		1/664 (0.2%)
Pneumonia pneumococcal	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Pneumonia streptococcal	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Pulmonary sepsis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Pyelonephritis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Pneumocystis jirovecii pneumonia	0/276 (0%)		1/276 (0.4%)		1/284 (0.4%)		0/664 (0%)
Pyelonephritis acute	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Pseudomembranous colitis	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Pulmonary tuberculosis	0/276 (0%)		2/276 (0.7%)		0/284 (0%)		0/664 (0%)
Sepsis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Septic shock	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		1/664 (0.2%)
Subcutaneous abscess	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Sinusitis	0/276 (0%)		1/276 (0.4%)		1/284 (0.4%)		0/664 (0%)
Streptococcal infection	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Sycosis barbae	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Serratia infection	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		0/664 (0%)
Urethritis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Urinary tract infection	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		2/664 (0.3%)
Urosepsis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Injury, poisoning and procedural complications
Acetabulum fracture	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Ankle fracture	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		0/664 (0%)
Comminuted fracture	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Contusion	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		1/664 (0.2%)
Coronary artery restenosis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Dislocation of vertebra	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Fall	0/276 (0%)		0/276 (0%)		0/284 (0%)		2/664 (0.3%)
Femoral neck fracture	0/276 (0%)		0/276 (0%)		0/284 (0%)		2/664 (0.3%)
Femur fracture	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Foreign body	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Hip fracture	1/276 (0.4%)		1/276 (0.4%)		0/284 (0%)		1/664 (0.2%)
Limb crushing injury	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Multiple fractures	0/276 (0%)		0/276 (0%)		0/284 (0%)		3/664 (0.5%)
Overdose	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Postoperative fever	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Rib fracture	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		0/664 (0%)
Subdural haematoma	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Spinal compression fracture	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		0/664 (0%)
Tendon rupture	2/276 (0.7%)		0/276 (0%)		1/284 (0.4%)		1/664 (0.2%)
Thermal burn	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Upper limb fracture	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Vascular graft occlusion	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Wound dehiscence	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Wrist fracture	0/276 (0%)		0/276 (0%)		0/284 (0%)		2/664 (0.3%)
Metabolism and nutrition disorders
Dehydration	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Diabetes mellitus	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Diabetic ketoacidosis	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Hyperglycaemia	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Hypoglycaemia	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/276 (0.4%)		1/276 (0.4%)		0/284 (0%)		1/664 (0.2%)
Arthropathy	1/276 (0.4%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Arthritis	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		0/664 (0%)
Back pain	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Foot deformity	0/276 (0%)		0/276 (0%)		0/284 (0%)		3/664 (0.5%)
Joint destruction	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Joint range of motion decreased	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		0/664 (0%)
Intervertebral disc protrusion	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		2/664 (0.3%)
Intervertebral disc degeneration	0/276 (0%)		0/276 (0%)		0/284 (0%)		2/664 (0.3%)
Muscular weakness	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Osteoarthritis	2/276 (0.7%)		2/276 (0.7%)		1/284 (0.4%)		2/664 (0.3%)
Osteoporotic fracture	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		1/664 (0.2%)
Osteochondroitis	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Osteonecrosis	1/276 (0.4%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Rheumatoid arthritis	7/276 (2.5%)		4/276 (1.4%)		4/284 (1.4%)		7/664 (1.1%)
Rotator cuff syndrome	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Spinal column stenosis	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		2/664 (0.3%)
Spondylolisthesis	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Tenosynovitis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Wrist deformity	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/276 (0.4%)		0/276 (0%)		1/284 (0.4%)		1/664 (0.2%)
Breast cancer	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Benign ovarian tumour	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Colon cancer	0/276 (0%)		0/276 (0%)		0/284 (0%)		2/664 (0.3%)
Diffuse large B-cell lymphoma	1/276 (0.4%)		1/276 (0.4%)		0/284 (0%)		1/664 (0.2%)
Gastric cancer	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Lung neoplasm malignant	1/276 (0.4%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Lung adenocarcinoma metastatic	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Lymphoma	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Malignant melanoma	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Meningioma	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Prostate cancer	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Rectal cancer	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Squamous cell carcinoma	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Squamous cell carcinoma of lung	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Uterine leiomyoma	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		2/664 (0.3%)
Nervous system disorders
Carotid artery stenosis	0/276 (0%)		0/276 (0%)		0/284 (0%)		2/664 (0.3%)
Radiculitis lumbosacral	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Dementia	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		1/664 (0.2%)
Somnolence	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
VIIth nerve paralysis	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		1/664 (0.2%)
Cerebrovascular accident	0/276 (0%)		0/276 (0%)		0/284 (0%)		3/664 (0.5%)
Cervical myelopathy	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Dizziness	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Hydrocephalus	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Hypoxic-ischaemic encephalopathy	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Loss of consciousness	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Nervous system disorder	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Syncope	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Transient ischaemic attack	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Pregnancy	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Psychiatric disorders
Bipolar I disorder	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Depression	1/276 (0.4%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Renal and urinary disorders
Acute kidney injury	0/276 (0%)		0/276 (0%)		0/284 (0%)		2/664 (0.3%)
Cystitis haemorrhagic	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Focal segmental glomerulosclerosis	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		0/664 (0%)
Nephrolithiasis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Urinary incontinence	0/276 (0%)		0/276 (0%)		0/284 (0%)		2/664 (0.3%)
Reproductive system and breast disorders
Female genital tract fistula	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Ovarian cyst	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Asthma	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Chronic obstructive pulmonary disease	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		3/664 (0.5%)
Epistaxis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Interstitial lung disease	1/276 (0.4%)		0/276 (0%)		1/284 (0.4%)		1/664 (0.2%)
Pleura effusion	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Pleurisy	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		1/664 (0.2%)
Pneumonitis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Pneumothorax	0/276 (0%)		0/276 (0%)		1/284 (0.4%)		2/664 (0.3%)
Pulmonary embolism	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Pulmonary haemorrhage	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Pulmonary hypertension	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Organising pneumonia	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Respiratory failure	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Sinus polyp	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Sleep apnoea syndrome	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Upper respiratory tract inflammation	0/275 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Skin and subcutaneous tissue disorders
Hyperkeratosis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Skin ulcer	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Social circumstances
Physical assault	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Surgical and medical procedures
Hip arthroplasty	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Hernia repair	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		0/664 (0%)
Vascular disorders
Arteritis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Deep vein thrombosis	0/276 (0%)		0/276 (0%)		2/284 (0.7%)		3/664 (0.5%)
Hypotension	0/276 (0%)		1/276 (0.4%)		0/284 (0%)		1/664 (0.2%)
Peripheral artery stenosis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Peripheral vascular disorder	1/276 (0.4%)		1/276 (0.4%)		0/284 (0%)		1/664 (0.2%)
Peripheral venous disease	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Vasculitis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Venous thrombosis	0/276 (0%)		0/276 (0%)		0/284 (0%)		1/664 (0.2%)
Other (Not Including Serious) Adverse Events
	Placebo x 2 IV + Non-Biologic DMARD		Ocrelizumab 200 mg x 2 + Non-Biologic DMARD		Ocrelizumab 500 mg x 2 + Non-Biologic DMARD		Ocrelizumab 500 mg x 2 IV + Non-biologic DMARD (OLE)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	152/276 (55.1%)		153/276 (55.4%)		158/284 (55.6%)		361/664 (54.4%)
Gastrointestinal disorders
Darrhoea	10/276 (3.6%)		15/276 (5.4%)		15/284 (5.3%)		0/664 (0%)
Nausea	15/276 (5.4%)		11/276 (4%)		10/284 (3.5%)		0/664 (0%)
Infections and infestations
Bronchitis	19/276 (6.9%)		28/276 (10.1%)		22/284 (7.7%)		64/664 (9.6%)
Influenza	9/276 (3.3%)		7/276 (2.5%)		15/284 (5.3%)		0/664 (0%)
Nasopharyngitis	31/276 (11.2%)		28/276 (10.1%)		22/284 (7.7%)		69/664 (10.4%)
Sinusitis	14/276 (5.1%)		13/276 (4.7%)		13/284 (4.6%)		53/664 (8%)
Upper respiratory tract infection	36/276 (13%)		37/276 (13.4%)		45/284 (15.8%)		96/664 (14.5%)
Urinary tract infection	23/276 (8.3%)		19/276 (6.9%)		24/284 (8.5%)		78/664 (11.7%)
Injury, poisoning and procedural complications
Infusion related reaction	25/276 (9.1%)		41/276 (14.9%)		41/284 (14.4%)		128/664 (19.3%)
Nervous system disorders
Headache	15/276 (5.4%)		12/276 (4.3%)		15/284 (5.3%)		0/664 (0%)
Psychiatric disorders
Insomnia	12/276 (4.3%)		9/276 (3.3%)		16/284 (5.6%)		0/664 (0%)
Vascular disorders
Hypertension	21/276 (7.6%)		18/276 (6.5%)		19/284 (6.7%)		44/664 (6.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

Name/Title	Medical Communications
Organization	Hoffmann-La Roche
Phone	800 821-8590
Email	genentech@druginfo.com

Responsible Party:

Genentech, Inc.

ClinicalTrials.gov Identifier:

NCT00476996

Other Study ID Numbers:

ACT3986g
WA20495
2006-005330-20

First Posted:

May 22, 2007

Last Update Posted:

Aug 12, 2019

Last Verified:

Aug 1, 2019

A Study of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Who Don't Have a Response to Anti-TNF-α Therapy (SCRIPT)

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact