A Study to Compare Subcutaneous Versus Intravenous Administration of RoActemra/Actemra (Tocilizumab) in Participants With Moderate to Severe Active Rheumatoid Arthritis

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01194414

Collaborator

(none)

1,262

Enrollment

217

Locations

Arms

Duration (Months)

5.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized, double-blind, parallel group study compares the efficacy and safety of subcutaneous (sc) versus intravenous (iv) administration of tocilizumab in participants with moderate to severe active rheumatoid arthritis. Participants were randomized to receive either tocilizumab 162 mg sc weekly plus iv placebo every 4 weeks, or tocilizumab 8 mg/kg iv every 4 weeks plus sc placebo weekly during the double-blind period from baseline to Week 24. The double-blind period was followed by a 72-week open-label treatment with some switching of sc and iv administration. No placebo was administered in the open-label phase. Participants continued on their stable dose of disease-modifying antirheumatic drugs (DMARDs) throughout the study. Anticipated time on study treatment was 2 years.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: tocilizumab SC Drug: tocilizumab IV Drug: placebo to tocilizumab SC Drug: placebo to tocilizumab IV Drug: Disease-modifying antirheumatic drugs (DMARDs)	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

1262 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Parallel Group Study of the Safety and Effect on Clinical Outcome of Tocilizumab SC Versus Tocilizumab IV, in Combination With Traditional Disease Modifying Anti-rheumatic Drugs (DMARDs), in Patients With Moderate to Severe Active Rheumatoid Arthritis

Study Start Date :

Sep 1, 2010

Actual Primary Completion Date :

Jan 1, 2012

Actual Study Completion Date :

Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tocilizumab SC Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Drug: tocilizumab SC Tocilizumab supplied in a single-use pre-filled syringe, with a needle safety device, delivering 162 mg/0.9 mL solution for subcutaneous injection once a week. Other Names: RoActemra/Actemra Drug: placebo to tocilizumab IV Placebo to tocilizumab supplied as a solution in 10 mL vials containing polysorbate 80 and sucrose in water for infusion every 4 weeks for a total of 24 weeks in the double-blind period. Drug: Disease-modifying antirheumatic drugs (DMARDs) stable dose as prescribed
Experimental: Tocilizumab IV Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Drug: tocilizumab IV Tocilizumab supplied in vials as a sterile solution for 8 mg/kg intravenous infusion every 4 weeks. Other Names: RoActemra/Actemra Drug: placebo to tocilizumab SC Placebo tocilizumab supplied as a single-use pre-filled syringe with a needle safety device, delivering 0.9 mL sodium chloride for subcutaneous injection once a week for 24 weeks in the double-blind period. Drug: Disease-modifying antirheumatic drugs (DMARDs) stable dose as prescribed
Experimental: Tocilizumab SC Then Tocilizumab IV Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Drug: tocilizumab SC Tocilizumab supplied in a single-use pre-filled syringe, with a needle safety device, delivering 162 mg/0.9 mL solution for subcutaneous injection once a week. Other Names: RoActemra/Actemra Drug: tocilizumab IV Tocilizumab supplied in vials as a sterile solution for 8 mg/kg intravenous infusion every 4 weeks. Other Names: RoActemra/Actemra Drug: placebo to tocilizumab IV Placebo to tocilizumab supplied as a solution in 10 mL vials containing polysorbate 80 and sucrose in water for infusion every 4 weeks for a total of 24 weeks in the double-blind period. Drug: Disease-modifying antirheumatic drugs (DMARDs) stable dose as prescribed
Experimental: Tocilizumab IV Then Tocilizumab SC Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.	Drug: tocilizumab SC Tocilizumab supplied in a single-use pre-filled syringe, with a needle safety device, delivering 162 mg/0.9 mL solution for subcutaneous injection once a week. Other Names: RoActemra/Actemra Drug: tocilizumab IV Tocilizumab supplied in vials as a sterile solution for 8 mg/kg intravenous infusion every 4 weeks. Other Names: RoActemra/Actemra Drug: placebo to tocilizumab SC Placebo tocilizumab supplied as a single-use pre-filled syringe with a needle safety device, delivering 0.9 mL sodium chloride for subcutaneous injection once a week for 24 weeks in the double-blind period. Drug: Disease-modifying antirheumatic drugs (DMARDs) stable dose as prescribed

Outcome Measures

Primary Outcome Measures

Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR20) Response at Week 24 [Baseline, 24 weeks]
ACR20 response is defined as a ≥ 20% 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 five additional ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) where left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either C-reactive protein [CRP] or Erythrocyte Sedimentation Rate [ESR]).
Percentage of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Assessments [Baseline to up to 3 months after last dose of study drug (approximately up to 2 years)]

Secondary Outcome Measures

Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR50) Response at Week 24 [Baseline, 24 weeks]
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 five additional ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) where left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either C-reactive protein or Erythrocyte Sedimentation Rate).
Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR70) Response at Week 24 [Baseline, 24 weeks]
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 five additional ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) where left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either C-reactive protein or Erythrocyte Sedimentation Rate).
Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 24 [Week 24]
The DAS28 (ESR) score is a measure of the subject's disease activity. It is calculated using the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity VAS where left side of the line 0=no disease activity to right side of the line 100=extreme disease activity and ESR. DAS28-(ESR) total scores range from 0 - 10. Remission is defined as achieving a DAS28-ESR score of less than 2.6.
Percentage of Participants Achieving a Decrease of ≥ 0.3 in the Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 24 [Baseline, 24 Weeks]
The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a participant completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A decrease indicates improvement.
Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 24 [24 Weeks]
The percentage of participants who withdrew from the study because they were not responding to treatment with the study drug.
Percentage of Participants With American College of Rheumatology Criteria (ACR20, ACR50, ACR70) at Week 97 [Week 97]
ACR20, ACR50 and ACR70: ≥20%, ≥50% and ≥70% reduction from baseline for both TJC68 and SJC66, as well as for 3 of 5 additional ACR variables: Patient's Assessment of Pain in last 24 hours using a Visual Analog Scale (VAS) (0=no pain and 100=unbearable pain); Patient's and Physician's Global Assessment of Disease Activity in last 24 hours using a VAS (0=no disease activity and100=maximum disease activity); Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either CRP or ESR). CRP was used for calculation of ACR. If missing, ESR was used. LOCF was used for missing joint counts, no imputation for other ACR components.
Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 97 [Week 97]
The DAS28 (ESR) score is a measure of the subject's disease activity. It is calculated using the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity VAS where left side of the line 0=no disease activity to right side of the line 100=extreme disease activity and ESR. DAS28-(ESR) total scores range from 0 - 10. Remission is defined as achieving a DAS28-ESR score of less than 2.6. LOCF used for tender and swollen joint counts, no imputation used for ESR and Patient's Global Assessment of Disease Activity VAS.
Percentage of Participants Achieving a Decrease of ≥0.3 in the Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 97 [Baseline, Week 97]
The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A decrease indicates improvement. No imputation of missing scores was made other than for missing baseline scores, for which last score prior to baseline will be carried forward. For participants who prematurely withdrew, data collected at withdrawal visit was used and data thereafter is missing.
Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 97 [Week 97]
The percentage of participants who withdrew from the study because they were not responding to treatment with the study drug.
Area Under the Serum Concentration Curve of Tocilizumab After First SC Injection or IV Infusion [Week 0: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after first dose]
Area Under the Serum Concentration Curve of Tocilizumab at Steady State for SC and IV Treatment [Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose.]
Minimum Serum Concentration (Cmin) of Tocilizumab [Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose]
Maximum Serum Concentration (Cmax) of Tocilizumab [Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose]
Time to Maximum Serum Concentration (Tmax) of Tocilizumab [Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose]
Change From Baseline in Serum Interleukin-6 (IL-6) Concentration at Week 25 [Baseline, Week 25]
Change From Baseline in Serum Soluble Interleukin-6 Receptor (sIL-6R) Concentration at Week 97 [Baseline, Week 97]
Percentage of Participants Who Developed Antibodies To Tocilizumab at Week 97 [Week 97]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult participants, ≥ 18 years of age
Rheumatoid arthritis of ≥ 6 months duration, according to American College of Rheumatology (ACR) criteria
Swollen joint count (SJC) ≥ 4 (66 joint count), tender joint count (TJC) ≥ 4 (68 joint count) at screening and baseline
Inadequate response to current DMARD therapy
Permitted DMARDs must be at stable dose for ≥ 8 weeks prior to baseline
Oral corticosteroids (≤ 10 mg/day prednisone or equivalent) and NSAIDs (up to maximum recommended dose) must be at stable dose for ≥ 4 weeks prior to baseline

Exclusion Criteria:

Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization
Rheumatic autoimmune disease other than RA
Functional class IV (ACR classification)
Diagnosis of juvenile idiopathic arthritis (JIA) or juvenile rheumatoid arthritis (JRA) and/or RA before the age of 16
Prior history of or current inflammatory joint disease other than RA
Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
Previous treatment with tocilizumab
Active current or history of recurrent infection

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Huntsville	Alabama	United States	35801
2	Tuscaloosa	Alabama	United States	35406
3	Tucson	Arizona	United States	85704
4	Tucson	Arizona	United States	85712
5	Long Beach	California	United States	90806
6	Los Angeles	California	United States	90048
7	Upland	California	United States	91786
8	Van Nuys	California	United States	91405
9	Denver	Colorado	United States	80230-7127
10	Bridgeport	Connecticut	United States	06606
11	Delray Beach	Florida	United States	33484
12	Miami	Florida	United States	33133
13	Ocala	Florida	United States	34474
14	Orlando	Florida	United States	32806
15	Palm Harbor	Florida	United States	34684
16	Pinellas Park	Florida	United States	33782
17	South Miami	Florida	United States	33143
18	Tampa	Florida	United States	33614
19	Coeur D'alene	Idaho	United States	83814
20	Morton Grove	Illinois	United States	60053
21	Wichita	Kansas	United States	67208
22	Monroe	Louisiana	United States	71203
23	Petoskey	Michigan	United States	49770
24	St. Claire Shores	Michigan	United States	48081
25	Eagan	Minnesota	United States	55121
26	Florissant	Missouri	United States	63031
27	Saint Louis	Missouri	United States	63117
28	Saint Louis	Missouri	United States	63131
29	Lebanon	New Hampshire	United States	03756
30	Clifton	New Jersey	United States	07012
31	Manalapan	New Jersey	United States	07726
32	Voorhees	New Jersey	United States	08043
33	Albuquerque	New Mexico	United States	87102
34	Albany	New York	United States	12206
35	Binghamton	New York	United States	13905
36	Orchard Park	New York	United States	14127
37	Asheville	North Carolina	United States	28803
38	Raleigh	North Carolina	United States	27609
39	Wilmington	North Carolina	United States	28401
40	Cincinnati	Ohio	United States	45219
41	Toledo	Ohio	United States	43623
42	Oklahoma City	Oklahoma	United States	73103
43	Tulsa	Oklahoma	United States	74135
44	Bethlehem	Pennsylvania	United States	18015
45	Charleston	South Carolina	United States	29406
46	Charleston	South Carolina	United States	29407
47	Knoxville	Tennessee	United States	37909
48	Memphis	Tennessee	United States	38119
49	Houston	Texas	United States	77004
50	San Antonio	Texas	United States	78217
51	Olympia	Washington	United States	98502
52	Seattle	Washington	United States	98122
53	Spokane	Washington	United States	99204
54	Wenatchee	Washington	United States	98801
55	Buenos Aires		Argentina	B1878DVB
56	Buenos Aires		Argentina	C1015ABO
57	Buenos Aires		Argentina	C1428DQG
58	Rosario		Argentina	S2000PBJ
59	Adelaide		Australia	5011
60	Adelaide		Australia	5041
61	Clayton		Australia	3168
62	Geelong		Australia	3220
63	Hobart		Australia	7000
64	Malvern East		Australia	3145
65	Maroochydore		Australia	4558
66	New Lambton		Australia	2305
67	Curitiba		Brazil	80060-240
68	Goiania		Brazil	74110010
69	Juiz de Fora		Brazil	36010-570
70	Porto Alegre		Brazil	90035-903
71	Porto Alegre		Brazil	90610-000
72	Sao Paulo		Brazil	04039-000
73	Sao Paulo		Brazil	4037003
74	São Paulo		Brazil	05403-000
75	Sofia		Bulgaria	1606
76	Sofia		Bulgaria	1612
77	Sofia		Bulgaria	1784
78	Edmonton	Alberta	Canada	T5H 3V9
79	Kelowna	British Columbia	Canada	V1Y 3G8
80	Vancouver	British Columbia	Canada	V5Z 1L7
81	St John's	Newfoundland and Labrador	Canada	A1A 5E8
82	St John's	Newfoundland and Labrador	Canada	A1C 5B8
83	Hamilton	Ontario	Canada	L8N 1Y2
84	Hamilton	Ontario	Canada	L8N 2B6
85	Kitchener	Ontario	Canada	N2M 5N6
86	Ottawa	Ontario	Canada	K1Y 4G2
87	St. Catharines	Ontario	Canada	L2N 7E4
88	Windsor	Ontario	Canada	N8X 5A6
89	Montreal	Quebec	Canada	H2L 1S6
90	Quebec City	Quebec	Canada	G1V 3M7
91	Rimouski	Quebec	Canada	G5L 3W1
92	Sainte-foy	Quebec	Canada	G1W 4R4
93	Trois-rivieres	Quebec	Canada	G8Z 1Y2
94	Saskatoon	Saskatchewan	Canada	S7K 0H6
95	Barranquilla		Colombia
96	Bogota		Colombia
97	Bogotá		Colombia
98	Bordeaux		France	33076
99	Le Mans		France	72037
100	Marseille		France	13285
101	Montpellier		France	34295
102	Nantes		France	44035
103	Paris		France	75679
104	Strasbourg		France	67098
105	Toulouse		France	31059
106	Bad Bramstedt		Germany	24576
107	Berlin		Germany	10117
108	Berlin		Germany	14059
109	Dresden		Germany	01067
110	Essen		Germany	45239
111	Freiburg		Germany	79106
112	Gommern		Germany	39245
113	Heidelberg		Germany	69120
114	Herne		Germany	44652
115	Hildesheim		Germany	31134
116	Köln		Germany	50924
117	Ludwigshafen		Germany	67063
118	Osnabrück		Germany	49074
119	Ratingen		Germany	40882
120	Rostock		Germany	18059
121	Würzburg		Germany	97080
122	Guatemala City		Guatemala	01010
123	Guatemala City		Guatemala	01015
124	Hong Kong		Hong Kong	852
125	Hong Kong		Hong Kong
126	Arenzano		Italy	16011
127	Bergamo		Italy	24128
128	Catania		Italy	95124
129	Cona (ferrara)		Italy	44124
130	Genova		Italy	16132
131	Napoli		Italy	80131
132	Pavia		Italy	27100
133	Pisa		Italy	56100
134	Potenza		Italy	85100
135	Reggio Emilia		Italy	42100
136	Udine		Italy	33100
137	Varese		Italy	21100
138	Klaipeda		Lithuania	92288
139	Siauliai		Lithuania	76231
140	Vilnius		Lithuania	LT-08661
141	Culiacan		Mexico	80000
142	Guadalajara		Mexico	44629
143	Guadalajara		Mexico	44690
144	Leon		Mexico	37000
145	Merida		Mexico	97000
146	Mexico Ctiy		Mexico	07760
147	Miexico City		Mexico	06700
148	Morelia		Mexico	58070
149	Obregon		Mexico	85000
150	Queretaro		Mexico	76178
151	Saltillo		Mexico	25000
152	Torreon		Mexico	27000
153	Auckland		New Zealand	2025
154	Hamilton		New Zealand	3240
155	Tauranga		New Zealand	3112
156	Wellington		New Zealand	6035
157	Lima 01		Peru	01
158	Lima		Peru	LIMA 14
159	Lima		Peru	Lima 41
160	Cebu		Philippines	6000
161	Manila		Philippines	1000
162	Quezon		Philippines	1102
163	Bialystok		Poland	15-351
164	Lublin		Poland	20-954
165	Poznan		Poland	60-218
166	Warszawa		Poland	01-157
167	Ponce		Puerto Rico	00716
168	Bucharest		Romania	011172
169	Bucharest		Romania	020475
170	Bucuresti		Romania	020983
171	Iasi		Romania	700661
172	Moscow		Russian Federation	115522
173	Moscow		Russian Federation	119991
174	Novosibirsk		Russian Federation	630099
175	Novosibirsk		Russian Federation	630117
176	Ryazan		Russian Federation	390026
177	St Petersburg		Russian Federation	190068
178	Ulyanovsk		Russian Federation	432600
179	Yaroslavl		Russian Federation	150030
180	Yaroslavl		Russian Federation	150062
181	Singapore		Singapore	119074
182	Cape Town		South Africa	7500
183	Durban		South Africa	4001
184	Parktown		South Africa	2000
185	Port Elizabeth		South Africa	6045
186	Stellenbosch		South Africa	7600
187	Barakaldo		Spain	48903
188	Bilbao		Spain	48013
189	La Coruna		Spain	15006
190	La Laguna		Spain	38320
191	Madrid		Spain	28007
192	Madrid		Spain	28046
193	Malaga		Spain	29010
194	Merida		Spain	97500
195	Santander		Spain	39008
196	Santiago de Compostela		Spain	15706
197	Sevilla		Spain	41009
198	Torrelavega		Spain	39300
199	Valencia		Spain	46009
200	Bangkok		Thailand	10400
201	Bangkok		Thailand	10700
202	Chiang Mai		Thailand	50200
203	Khon Kaen		Thailand	40002
204	Cambridge		United Kingdom	CB2 2QQ
205	Cannock		United Kingdom	WS11 5XY
206	Coventry		United Kingdom	CV2 2DX
207	Eastbourne		United Kingdom	BN21 2UD
208	Exeter		United Kingdom	EX2 5DW
209	Harrogate		United Kingdom	HG2 7SX
210	Ipswich		United Kingdom	IP4 5PD
211	London		United Kingdom	E11 1NR
212	Middlesborough		United Kingdom	TS4 3BW
213	Newcastle Upon Tyne		United Kingdom	NE7 7DN
214	Northampton		United Kingdom	NN1 5BD
215	Nottingham		United Kingdom	NG7 2UH
216	Westcliffe-on-sea		United Kingdom	SS0 0RY
217	Wirral		United Kingdom	CH49 5PE

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01194414

Other Study ID Numbers:

WA22762
2010-018375-22

First Posted:

Sep 3, 2010

Last Update Posted:

Jun 20, 2016

Last Verified:

Sep 1, 2013

Additional relevant MeSH terms:

Arthritis

Arthritis, Rheumatoid

Antirheumatic Agents

Study Results

Participant Flow

Recruitment Details	A total of 1262 participants at 209 centers in 25 countries were randomized into the study.
Pre-assignment Detail

Arm/Group Title	Tocilizumab SC	Tocilizumab IV	Tocilizumab SC Then Tocilizumab IV	Tocilizumab IV Then Tocilizumab SC
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection once a week in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
Period Title: 24 Weeks Double Blind Period
STARTED	631	631	0	0
Per Protocol Population	558	537	0	0
COMPLETED	572	564	0	0
NOT COMPLETED	59	67	0	0
Period Title: 24 Weeks Double Blind Period
STARTED	524	377	48	186
COMPLETED	445	311	40	160
NOT COMPLETED	79	66	8	26

Baseline Characteristics

Arm/Group Title	Tocilizumab SC	Tocilizumab IV	Total
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Total of all reporting groups
Overall Participants	631	631	1262
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.7 (12.35)	52.8 (12.53)	52.7 (12.44)
Sex: Female, Male (Count of Participants)
Female	520 82.4%	521 82.6%	1041 82.5%
Male	111 17.6%	110 17.4%	221 17.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR20) Response at Week 24
Description	ACR20 response is defined as a ≥ 20% 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 five additional ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) where left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either C-reactive protein [CRP] or Erythrocyte Sedimentation Rate [ESR]).
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description
Per Protocol Population included all randomized participants who received study drug and had no major protocol violations. Last Observation Carried Forward was used for missing joint counts, no imputation for other ACR components. CRP will be used primarily for calculation of the ACR response. If missing, the ESR will be used for that participant.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.
Measure Participants	558	537
Number (95% Confidence Interval) [Percentage of participants]	69.4 11%	73.4 11.6%

2. Primary Outcome

Title	Percentage of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Assessments
Description
Time Frame	Baseline to up to 3 months after last dose of study drug (approximately up to 2 years)

Outcome Measure Data

Analysis Population Description
The safety population includes all participants who received at least one dose of study drug, whether re-randomized or not, and who had at least one post-dose safety assessment. Data are included from double blind and open label (OL) periods in the SC and IV arms but only from the OL period in IV-SC and SC-IV switch arms.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV	Tocilizumab SC Then Tocilizumab IV	Tocilizumab IV Then Tocilizumab SC
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection once a week in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
Measure Participants	631	631	48	186
Adverse Events (AEs)	91.6 14.5%	87.8 13.9%	81.3 6.4%	86.6 NaN
Serious Adverse Events (SAEs)	13.9 2.2%	12.7 2%	12.5 1%	11.3 NaN
Clinically Significant Laboratory Assessments	37.7 6%	28.2 4.5%	25.0 2%	19.4 NaN

3. Secondary Outcome

Title	Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR50) Response at Week 24
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 five additional ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) where left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either C-reactive protein or Erythrocyte Sedimentation Rate).
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description
Per Protocol Population included all randomized participants who received study drug and had no major protocol violations. Last Observation Carried Forward was used for missing joint counts, no imputation for other ACR components. CRP will be used primarily for calculation of the ACR response. If missing, the ESR will be used for that participant.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.
Measure Participants	558	537
Number [Percentage of participants]	47.0 7.4%	48.6 7.7%

4. Secondary Outcome

Title	Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR70) Response at Week 24
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 five additional ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) where left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either C-reactive protein or Erythrocyte Sedimentation Rate).
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description
Per Protocol Population included all randomized participants who received study drug and had no major protocol violations. Last Observation Carried Forward was used for missing joint counts, no imputation for other ACR components. CRP will be used primarily for calculation of the ACR response. If missing, the ESR will be used for that participant.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.
Measure Participants	558	537
Number [Percentage of participants]	24.0 3.8%	27.9 4.4%

5. Secondary Outcome

Title	Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 24
Description	The DAS28 (ESR) score is a measure of the subject's disease activity. It is calculated using the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity VAS where left side of the line 0=no disease activity to right side of the line 100=extreme disease activity and ESR. DAS28-(ESR) total scores range from 0 - 10. Remission is defined as achieving a DAS28-ESR score of less than 2.6.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Per Protocol Population (randomized participants who received study drug and had no major protocol violations) with data available for analysis. Missing SJC and TJC will be imputed using the last post-baseline value for the patient (LOCF). No imputation for missing ESR or patient's global assessment of disease activity.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.
Measure Participants	516	498
Number [Percentage of participants]	38.4 6.1%	36.9 5.8%

6. Secondary Outcome

Title	Percentage of Participants Achieving a Decrease of ≥ 0.3 in the Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 24
Description	The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a participant completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A decrease indicates improvement.
Time Frame	Baseline, 24 Weeks

Outcome Measure Data

Analysis Population Description
Participants from the Per Protocol Population (all randomized participants who received study drug and had no major protocol violations) with data available for analysis. No imputation of missing scores will be made other than for missing baseline scores, for which last score prior to defined protocol baseline time window will be carried forward.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.
Measure Participants	515	500
Number [Percentage of participants]	65.2 10.3%	67.4 10.7%

7. Secondary Outcome

Title	Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 24
Description	The percentage of participants who withdrew from the study because they were not responding to treatment with the study drug.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description
Per Protocol Population included all randomized participants who received study drug and had no major protocol violations.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.
Measure Participants	558	537
Number [Percentage of participants]	1.8 0.3%	0.9 0.1%

8. Secondary Outcome

Title	Percentage of Participants With American College of Rheumatology Criteria (ACR20, ACR50, ACR70) at Week 97
Description	ACR20, ACR50 and ACR70: ≥20%, ≥50% and ≥70% reduction from baseline for both TJC68 and SJC66, as well as for 3 of 5 additional ACR variables: Patient's Assessment of Pain in last 24 hours using a Visual Analog Scale (VAS) (0=no pain and 100=unbearable pain); Patient's and Physician's Global Assessment of Disease Activity in last 24 hours using a VAS (0=no disease activity and100=maximum disease activity); Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either CRP or ESR). CRP was used for calculation of ACR. If missing, ESR was used. LOCF was used for missing joint counts, no imputation for other ACR components.
Time Frame	Week 97

Outcome Measure Data

Analysis Population Description
Re-Randomized Intent-to-Treat Population (ITT Population) included all participants who completed double blind period and were re-randomized at Week 24, received at least 1 dose of study drug. Here, number of participants analyzed is the participants for whom parameter was collected.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV	Tocilizumab SC Then Tocilizumab IV	Tocilizumab IV Then Tocilizumab SC
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection once a week in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
Measure Participants	451	317	40	165
ACR20	83.6 13.2%	83.3 13.2%	82.5 6.5%	88.5 NaN
ACR50	65.4 10.4%	62.5 9.9%	57.5 4.6%	67.3 NaN
ACR70	44.8 7.1%	42.0 6.7%	37.5 3%	47.3 NaN

9. Secondary Outcome

Title	Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 97
Description	The DAS28 (ESR) score is a measure of the subject's disease activity. It is calculated using the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity VAS where left side of the line 0=no disease activity to right side of the line 100=extreme disease activity and ESR. DAS28-(ESR) total scores range from 0 - 10. Remission is defined as achieving a DAS28-ESR score of less than 2.6. LOCF used for tender and swollen joint counts, no imputation used for ESR and Patient's Global Assessment of Disease Activity VAS.
Time Frame	Week 97

Outcome Measure Data

Analysis Population Description
ITT Population included all participants who completed double blind period and were re-randomized at Week 24 and received at least one dose of study drug. If ESR=0 then ESR=1 is substituted into the DAS28 calculation to enable a non-missing DAS28 score. Here, number of participants analyzed is the participants for whom parameter was collected.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV	Tocilizumab SC Then Tocilizumab IV	Tocilizumab IV Then Tocilizumab SC
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection once a week in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
Measure Participants	446	306	40	162
Number [percentage of participants]	53.4 8.5%	46.4 7.4%	50.0 4%	55.6 NaN

10. Secondary Outcome

Title	Percentage of Participants Achieving a Decrease of ≥0.3 in the Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 97
Description	The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A decrease indicates improvement. No imputation of missing scores was made other than for missing baseline scores, for which last score prior to baseline will be carried forward. For participants who prematurely withdrew, data collected at withdrawal visit was used and data thereafter is missing.
Time Frame	Baseline, Week 97

Outcome Measure Data

Analysis Population Description
ITT Population included all participants who completed double blind period and were re-randomized at Week 24 and received at least one dose of study drug. Here, number of participants analyzed is the participants for whom parameter was collected.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV	Tocilizumab SC Then Tocilizumab IV	Tocilizumab IV Then Tocilizumab SC
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection once a week in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
Measure Participants	445	317	39	162
Number [percentage of participants]	72.4 11.5%	69.1 11%	56.4 4.5%	71.0 NaN

11. Secondary Outcome

Title	Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 97
Description	The percentage of participants who withdrew from the study because they were not responding to treatment with the study drug.
Time Frame	Week 97

Outcome Measure Data

Analysis Population Description
ITT Population included all participants who completed double blind period and were re-randomized at Week 24 and received at least one dose of study drug.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV	Tocilizumab SC Then Tocilizumab IV	Tocilizumab IV Then Tocilizumab SC
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection once a week in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
Measure Participants	521	372	48	186
Number [percentage of participants]	1.7 0.3%	3.0 0.5%	4.2 0.3%	1.6 NaN

12. Secondary Outcome

Title	Area Under the Serum Concentration Curve of Tocilizumab After First SC Injection or IV Infusion
Description
Time Frame	Week 0: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after first dose

Outcome Measure Data

Analysis Population Description
Pharmacokinetic-Evaluable Population included all participants who provided at least one evaluable PK sample were included in the pharmacokinetic analysis (PK) analysis. Here, number of participants analyzed who were evaluable for this outcome measure.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.
Measure Participants	17	16
Mean (Standard Deviation) [microgramhour/milliliter (mcghr/mL)]	1444 (839)	30988 (9114)

13. Secondary Outcome

Title	Area Under the Serum Concentration Curve of Tocilizumab at Steady State for SC and IV Treatment
Description
Time Frame	Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose.

Outcome Measure Data

Analysis Population Description
Pharmacokinetic-Evaluable Population included all participants who provided at least one evaluable PK sample were included in the pharmacokinetic analysis (PK) analysis. Here, number of participants analyzed who were evaluable for this outcome measure.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.
Measure Participants	13	13
Mean (Standard Deviation) [μg*hr/mL]	7542 (3989)	41304 (15104)

14. Secondary Outcome

Title	Minimum Serum Concentration (Cmin) of Tocilizumab
Description
Time Frame	Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose

Outcome Measure Data

Analysis Population Description
Pharmacokinetic-Evaluable Population included all participants who provided at least one evaluable PK sample were included in the PK analysis. Here, number of participants analyzed who were evaluable for this outcome measure and 'n' indicates number of participants who were evaluated at specified time point.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.
Measure Participants	17	16
Week 0 (after first dose) (n=17, 16)	7.48 (4.91)	6.65 (6.05)
Week 20 (n=13, 13)	35.7 (16.2)	16.0 (10.3)

15. Secondary Outcome

Title	Maximum Serum Concentration (Cmax) of Tocilizumab
Description
Time Frame	Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose

Outcome Measure Data

Analysis Population Description
Pharmacokinetic-Evaluable Population included all participants who provided at least one evaluable PK sample were included in the PK analysis. Here, number of participants analyzed who were evaluable for this outcome measure and 'n' indicates number of participants who were evaluated at specified time point.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.
Measure Participants	17	16
Week 0 (after first dose) (n=17, 16)	14.7 (8.74)	180 (40.1)
Week 20 (n=13, 13)	52.7 (27.3)	233 (117)

16. Secondary Outcome

Title	Time to Maximum Serum Concentration (Tmax) of Tocilizumab
Description
Time Frame	Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose

Outcome Measure Data

Analysis Population Description
Pharmacokinetic-Evaluable Population included all participants who provided at least one evaluable PK sample were included in the PK analysis. Here, number of participants analyzed who were evaluable for this outcome measure and 'n' indicates number of participants who were evaluated at specified time point.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.
Measure Participants	17	16
Week 0 (after first dose) (n=17, 16)	74	6
Week 20 (n=13, 13)	70	6

17. Secondary Outcome

Title	Change From Baseline in Serum Interleukin-6 (IL-6) Concentration at Week 25
Description
Time Frame	Baseline, Week 25

Outcome Measure Data

Analysis Population Description
The ITT-PK population includes all participants who were eligible for the ITT population and provided at least 1 evaluable PK sample in the double blind or open label periods. Here, number of participants analyzed who were evaluable for this outcome measure and 'n' indicates number of participants who were evaluated at specified time point.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV	Tocilizumab SC Then Tocilizumab IV	Tocilizumab IV Then Tocilizumab SC
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection once a week in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
Measure Participants	493	359	46	186
Baseline (n=493, 359, 46, 186)	39.04 (55.456)	52.48 (240.964)	62.18 (125.081)	50.07 (161.045)
Change at Week 25 (n=385, 280, 33, 149)	34.42 (110.842)	52.61 (507.157)	37.54 (93.464)	44.12 (136.955)

18. Secondary Outcome

Title	Change From Baseline in Serum Soluble Interleukin-6 Receptor (sIL-6R) Concentration at Week 97
Description
Time Frame	Baseline, Week 97

Outcome Measure Data

Analysis Population Description
The ITT-PK population includes all participants who were eligible for the ITT population and provided at least 1 evaluable PK sample in the double blind or open label periods. Here, number of participants analyzed who were evaluable for this outcome measure and 'n' indicates number of participants who were evaluated at specified time point.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV	Tocilizumab SC Then Tocilizumab IV	Tocilizumab IV Then Tocilizumab SC
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection once a week in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
Measure Participants	504	366	46	186
Baseline (n=504, 366, 46, 186)	44.53 (35.470)	45.72 (40.219)	44.71 (13.068)	43.28 (16.197)
Change at Week 97 (n=416, 296, 37,157)	601.52 (222.141)	575.75 (244.398)	569.60 (213.588)	586.50 (226.915)

19. Secondary Outcome

Title	Percentage of Participants Who Developed Antibodies To Tocilizumab at Week 97
Description
Time Frame	Week 97

Outcome Measure Data

Analysis Population Description
The safety population includes all participants who received at least one dose of study drug, whether re-randomized or not, and who had at least one post-dose safety assessment. Here, 'n' indicates number of subjects in the safety population tested by screening assay at any time point.

Arm/Group Title	Tocilizumab SC	Tocilizumab IV	Tocilizumab SC Then Tocilizumab IV	Tocilizumab IV Then Tocilizumab SC
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.	Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection once a week in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
Measure Participants	629	629	46	184
Number [percentage of participants]	1.3 0.2%	1.0 0.2%	0.0 0%	0.5 NaN

Adverse Events

	Tocilizumab SC		Tocilizumab IV		Tocilizumab SC Then Tocilizumab IV		Tocilizumab IV Then Tocilizumab SC
Time Frame	Baseline to up to 3 months after last dose of study drug (approximately up to 2 years)
Adverse Event Reporting Description	The safety population includes all participants who received at least one dose of study drug, whether re-randomized or not, and who had at least one post-dose safety assessment. Data are included from double blind and open label (OL) periods in the SC and IV arms but only from the OL period in IV-SC and SC-IV switch arms.

Arm/Group Title	Tocilizumab SC		Tocilizumab IV		Tocilizumab SC Then Tocilizumab IV		Tocilizumab IV Then Tocilizumab SC
Arm/Group Description	Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.		Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.		Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.		Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Tocilizumab SC		Tocilizumab IV		Tocilizumab SC Then Tocilizumab IV		Tocilizumab IV Then Tocilizumab SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	88/631 (13.9%)		80/631 (12.7%)		6/48 (12.5%)		21/186 (11.3%)
Blood and lymphatic system disorders
Anaemia	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Haemolytic anaemia	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Lymphadenopathy	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Neutropenia	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Cardiac disorders
Angina unstable	2/631 (0.3%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Atrial fibrillation	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Cardiac failure congestive	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Coronary artery disease	2/631 (0.3%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Myocardial infarction	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Acute myocardial infarction	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Angina pectoris	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Atrial tachycardia	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Atrioventricular block first degree	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Cardiac arrest	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Cardiac valve disease	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Mitral valve incompetence	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Myocardial ischaemia	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Congenital, familial and genetic disorders
Hydrocele	0/631 (0%)		2/631 (0.3%)		0/48 (0%)		0/186 (0%)
Ear and labyrinth disorders
Vertigo	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Eye disorders
Amaurosis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Retinal artery occlusion	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Gastrointestinal disorders
Colitis	2/631 (0.3%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Diverticular perforation	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Abdominal pain	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Colitis ischaemic	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Colitis ulcerative	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Diverticulum intestinal haemorrhagic	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Gastric ulcer haemorrhage	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Gastritis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Gastrooesophageal reflux disease	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Haemorrhoidal haemorrhage	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Ileus	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Impaired gastric emptying	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Inguinal hernia	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Lumbar hernia	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Megacolon	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Oesophageal ulcer	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Rectal haemorrhage	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Small intestinal perforation	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Umbilical hernia	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
General disorders
Device dislocation	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Death	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Ischaemic ulcer	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Non-cardiac chest pain	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Hepatobiliary disorders
Cholelithiasis	3/631 (0.5%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Cholecystitis chronic	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Bile duct stone	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Cholangitis acute	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Cholecystitis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Hepatic steatosis	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Sphincter of oddi dysfunction	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Immune system disorders
Hypersensitivity	3/631 (0.5%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Amyloidosis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Anaphylactic reaction	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Infections and infestations
Pneumonia	4/631 (0.6%)		6/631 (1%)		0/48 (0%)		4/186 (2.2%)
Cellulitis	8/631 (1.3%)		1/631 (0.2%)		0/48 (0%)		2/186 (1.1%)
Gastroenteritis	2/631 (0.3%)		2/631 (0.3%)		0/48 (0%)		0/186 (0%)
Septic Shock	3/631 (0.5%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Urinary tract infection	3/631 (0.5%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Peritonitis	2/631 (0.3%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Wound infection	0/631 (0%)		3/631 (0.5%)		0/48 (0%)		0/186 (0%)
Arthritis bacterial	0/631 (0%)		2/631 (0.3%)		0/48 (0%)		0/186 (0%)
Arthritis infective	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Bursitis infective	0/631 (0%)		2/631 (0.3%)		0/48 (0%)		0/186 (0%)
Pelvic abscess	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Sepsis	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		1/186 (0.5%)
Subcutaneous abscess	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Abscess	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Abscess limb	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Atypical pneumonia	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Bone tuberculosis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Bronchitis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Bronchopneumonia	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Bronchopulmonary aspergillosis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Burkholderia pseudomallei infection	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Dacryocystitis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Device related infection	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Diverticulitis	0/631 (0%)		0/631 (0%)		1/48 (2.1%)		0/186 (0%)
Empyema	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Endocarditis	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Groin abscess	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Infectious pleural effusion	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Intervertebral discitis	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Laryngitis	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Lobar pneumonia	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Localised infection	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Muscle abscess	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Osteomyelitis	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Pericolic abscess	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Pharyngeal abscess	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Post procedural infection	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Postoperative wound infection	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Pseudomonal sepsis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Pyelonephritis chronic	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Renal abscess	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Retroperitoneal abscess	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Tooth infection	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Tracheitis	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Tracheobronchitis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Urosepsis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Whipple's disease	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Injury, poisoning and procedural complications
Ankle fracture	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Humerus fracture	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Road traffic accident	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Adrenal gland injury	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Anastomotic ulcer haemorrhage	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Arthropod sting	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Cervical vertebral fracture	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Chillblains	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Comminuted fracture	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Facial bones fracture	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Femoral neck fracture	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Hepatic haematoma	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Hip fracture	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Jaw fracture	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Joint dislocation	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Laceration	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Lower limb fracture	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Post procedural haemorrhage	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Pubis fracture	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Pulmonary contusion	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Rib fracture	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Sternal fracture	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Synovial rupture	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Thoracic vertebral fracture	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Upper limb fracture	0/631 (0%)		0/631 (0%)		1/48 (2.1%)		0/186 (0%)
Fall	3/631 (0.5%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Femur fracture	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Investigations
Lipase increased	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Metabolism and nutrition disorders
Acidosis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Diabetes mellitus	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Diabetic ketoacidosis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	3/631 (0.5%)		5/631 (0.8%)		1/48 (2.1%)		0/186 (0%)
Intervertebral disc protrusion	2/631 (0.3%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Rheumatoid arthritis	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		1/186 (0.5%)
Bursitis	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Musculoskeletal chest pain	0/631 (0%)		2/631 (0.3%)		0/48 (0%)		0/186 (0%)
Osteonecrosis	2/631 (0.3%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Spinal osteoarthritis	0/631 (0%)		2/631 (0.3%)		0/48 (0%)		0/186 (0%)
Compartment syndrome	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Costochondritis	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Intervertebral disc degeneration	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Intervertebral disc disorder	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Myalgia	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Spinal column stenosis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Spondylolisthesis	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	2/631 (0.3%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Squamous cell carcinoma	0/631 (0%)		1/631 (0.2%)		1/48 (2.1%)		0/186 (0%)
Uterine leiomyoma	0/631 (0%)		0/631 (0%)		0/48 (0%)		2/186 (1.1%)
Basal cell carcinoma	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Brain neoplasm malignant	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Cervix carcinoma stage 0	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Endometrial adenoma	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Fibroadenoma of breast	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Gastrointestinal tract adenoma	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Intraductal proliferative breast lesion	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Invasive ductal breast carcinoma	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Leiomyoma	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Lentigo maligna	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Morton's neuroma	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Parathyroid tumour benign	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Renal cell carcinoma	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Schwannoma	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Small cell lung cancer	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Nervous system disorders
Sciatica	2/631 (0.3%)		2/631 (0.3%)		0/48 (0%)		0/186 (0%)
Transient ischaemic attack	0/631 (0%)		3/631 (0.5%)		0/48 (0%)		0/186 (0%)
Cerebral infarction	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Encephalopathy	2/631 (0.3%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Ischaemic stroke	0/631 (0%)		2/631 (0.3%)		0/48 (0%)		0/186 (0%)
Carotid artery thrombosis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Cerebellar ischaemia	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Cerebral haemorrhage	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Cerebral ischaemia	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Cerebrovascular insufficiency	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Dysarthria	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Grand mal convulsion	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Haemorrhagic stroke	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Headache	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Hemiparesis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Hepatic encephalopathy	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Ischaemic cerebral infarction	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Lumbar radiculopathy	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Migraine	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Syncope	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Transient global amnesia	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	2/631 (0.3%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Imminent abortion	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Renal and urinary disorders
Renal failure acute	2/631 (0.3%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Haematuria	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Renal colic	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Reproductive system and breast disorders
Cervical dysplasia	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Ovarian cyst ruptured	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Pelvic floor muscle weakness	0/631 (0%)		0/631 (0%)		1/48 (2.1%)		0/186 (0%)
Pelvic pain	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Uterine polyp	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/631 (0.2%)		2/631 (0.3%)		0/48 (0%)		1/186 (0.5%)
Pneumothorax	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		2/186 (1.1%)
Acute respiratory failure	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Chronic obstructive pulmonary disease	2/631 (0.3%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Respiratory failure	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		1/186 (0.5%)
Acute respiratory distress syndrome	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Idiopathic pulmonary fibrosis	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Pleurisy	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Pulmonary embolism	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Pulmonary hypertension	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Surgical and medical procedures
Abortion induced	0/631 (0%)		1/631 (0.2%)		1/48 (2.1%)		0/186 (0%)
Vascular disorders
Deep vein thrombosis	1/631 (0.2%)		2/631 (0.3%)		0/48 (0%)		1/186 (0.5%)
Haematoma	1/631 (0.2%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Peripheral ischaemia	0/631 (0%)		1/631 (0.2%)		0/48 (0%)		0/186 (0%)
Shock	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Thrombosis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Venous thrombosis	1/631 (0.2%)		0/631 (0%)		0/48 (0%)		0/186 (0%)
Venous thrombosis limb	0/631 (0%)		0/631 (0%)		0/48 (0%)		1/186 (0.5%)
Other (Not Including Serious) Adverse Events
	Tocilizumab SC		Tocilizumab IV		Tocilizumab SC Then Tocilizumab IV		Tocilizumab IV Then Tocilizumab SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	488/631 (77.3%)		430/631 (68.1%)		29/48 (60.4%)		118/186 (63.4%)
Blood and lymphatic system disorders
Neutropenia	62/631 (9.8%)		50/631 (7.9%)		2/48 (4.2%)		13/186 (7%)
Gastrointestinal disorders
Diarrhoea	55/631 (8.7%)		39/631 (6.2%)		1/48 (2.1%)		14/186 (7.5%)
Nausea	35/631 (5.5%)		40/631 (6.3%)		2/48 (4.2%)		4/186 (2.2%)
General disorders
Injection site erythema	33/631 (5.2%)		5/631 (0.8%)		1/48 (2.1%)		9/186 (4.8%)
Infections and infestations
Upper respiratory tract infection	122/631 (19.3%)		130/631 (20.6%)		8/48 (16.7%)		33/186 (17.7%)
Nasopharyngitis	88/631 (13.9%)		68/631 (10.8%)		7/48 (14.6%)		26/186 (14%)
Urinary tract infection	67/631 (10.6%)		53/631 (8.4%)		4/48 (8.3%)		15/186 (8.1%)
Bronchitis	44/631 (7%)		35/631 (5.5%)		2/48 (4.2%)		6/186 (3.2%)
Gastroenteritis	41/631 (6.5%)		26/631 (4.1%)		3/48 (6.3%)		6/186 (3.2%)
Pharyngitis	23/631 (3.6%)		39/631 (6.2%)		2/48 (4.2%)		4/186 (2.2%)
Sinusitis	33/631 (5.2%)		19/631 (3%)		0/48 (0%)		6/186 (3.2%)
Injury, poisoning and procedural complications
Fall	33/631 (5.2%)		25/631 (4%)		1/48 (2.1%)		7/186 (3.8%)
Investigations
Alanine aminotransferase increased	188/631 (29.8%)		140/631 (22.2%)		7/48 (14.6%)		29/186 (15.6%)
Aspartate aminotransferase increased	135/631 (21.4%)		96/631 (15.2%)		3/48 (6.3%)		14/186 (7.5%)
Musculoskeletal and connective tissue disorders
Back pain	33/631 (5.2%)		34/631 (5.4%)		2/48 (4.2%)		9/186 (4.8%)
Rheumatoid arthritis	29/631 (4.6%)		26/631 (4.1%)		3/48 (6.3%)		11/186 (5.9%)
Arthralgia	24/631 (3.8%)		28/631 (4.4%)		3/48 (6.3%)		6/186 (3.2%)
Osteoarthritis	21/631 (3.3%)		11/631 (1.7%)		3/48 (6.3%)		1/186 (0.5%)
Nervous system disorders
Headache	46/631 (7.3%)		41/631 (6.5%)		3/48 (6.3%)		9/186 (4.8%)
Skin and subcutaneous tissue disorders
Rash	32/631 (5.1%)		27/631 (4.3%)		1/48 (2.1%)		2/186 (1.1%)
Vascular disorders
Hypertension	49/631 (7.8%)		65/631 (10.3%)		4/48 (8.3%)		8/186 (4.3%)

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	Hoffman-LaRoche
Phone	800-821-8590
Email

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01194414

Other Study ID Numbers:

WA22762
2010-018375-22

First Posted:

Sep 3, 2010

Last Update Posted:

Jun 20, 2016

Last Verified:

Sep 1, 2013

A Study to Compare Subcutaneous Versus Intravenous Administration of RoActemra/Actemra (Tocilizumab) in Participants With Moderate to Severe Active Rheumatoid Arthritis

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

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact