A Study of RoActemra/Actemra (Tocilizumab) Versus Adalimumab in Combination With Methotrexate (MTX) in Patients With Moderate to Severe Active Rheumatoid Arthritis And an Inadequate Response to Treatment With Only One Tumor Necrosis Factor (TNF)-Inhibitor

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01283971
• Collaborator: (none)
• Enrollment: 96
• Locations: 170
• Arms: 2
• Duration (Months): 15
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized, parallel-group study will assess the efficacy and safety of RoActemra/Actemra (tocilizumab) versus adalimumab, both in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis. Patients, already treated with MTX at stable doses, will be randomized to receive either RoActemra/Actemra 8 mg/kg intravenously (IV) every 4 weeks or adalimumab 40 mg subcutaneous (SC) every 2 weeks. All patients will receive methotrexate (10-25 mg weekly) and folate (at least 5 mg weekly). The anticipated time on study treatment is 24 weeks.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: tocilizumab [RoActemra/Actemra]; Drug: adalimumab; Drug: placebo to tocilizumab; Drug: placebo to adalimumab; Drug: methotrexate; Drug: folate	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label, Parallel-group Study of the Reduction of Signs and Symptoms During Treatment With Tocilizumab Versus Adalimumab, Both in Combination With MTX, in Patients With Moderate to Severe Active Rheumatoid Arthritis and an Inadequate Response to Treatment With Only One TNF Inhibitor
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tocilizumab + Methotrexate Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Drug: tocilizumab [RoActemra/Actemra]; Tocilizumab 8 mg/kg IV every 4 weeks for 24 weeks.; Other Names: RoActemra/Actemra ; Drug: placebo to adalimumab; Placebo to adalimumab SC every 2 weeks for 24 weeks.; Drug: methotrexate; Methotrexate 10-25 mg weekly.; Drug: folate; Folate at least 5 mg weekly.
Active Comparator: Adalimumab + Methotrexate Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Drug: adalimumab; Adalimumab 40 mg SC every 2 weeks.; Drug: placebo to tocilizumab; Placebo to tocilizumab IV every 4 weeks for 24 weeks.; Drug: methotrexate; Methotrexate 10-25 mg weekly.; Drug: folate; Folate at least 5 mg weekly.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Disease Activity Score 28 Joints (DAS28) Remission at Week 24 [Week 24]

   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 2 to 10. DAS28 Remission is defined as a DAS28 score <2.6.

Secondary Outcome Measures

1. Percentage of Participants With American College of Rheumatology (ACR20) Response at Week 24 [Baseline, Week 24]

   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 additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) 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, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.

2. Percentage of Participants With ACR50 Response at Week 24 [Baseline, Week 24]

   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: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) 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, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.

3. Percentage of Participants With ACR70 Response at Week 24 [Baseline, Week 24]

   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: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) 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, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.

4. Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) DAS28 Responses at Week 24 [Baseline, Week 24]

   The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28 total score ranges from 0 (best) to 10 (worst). A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 or a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.

5. Percentage of Participants With DAS28 Low Disease Activity (LDAS) at Week 24 [Week 24]

   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 2 to 10. LDAS is defined as DAS28 ≤3.2.

6. Change From Baseline in DAS28 Score at Week 24 [Baseline, Week 24]

   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 2 to 10. A higher value indicated higher disease activity. A negative change from Baseline indicated improvement.

7. Change From Baseline in Swollen Joint Count (SJC) at Week 24 [Baseline, Week 24]

   66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement.

8. Change From Baseline in Tender Joint Count (TJC) at Week 24 [Baseline, Week 24]

   68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement.

9. Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS) at Week 24 [Baseline, Week 24]

   The patient assessed their pain using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.

10. Change From Baseline in the Patient Global Assessment of Disease Activity VAS at Week 24 [Baseline, Week 24]

    The patient's global assessment of disease activity is assessed on a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

11. Change From Baseline in the Physician Global Assessment of Disease Activity VAS at Week 24 [Baseline, Week 24]

    The physician global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

12. Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) at Week 24 [Baseline, Week 24]

    Blood was collected for C-Reactive Protein (CRP) (a test for analysis of inflammatory and infectious disorders) and was analyzed at a central laboratory. The concentration of CRP was measured in milligram/liter (mg/L). A reduction in the level is considered an improvement

13. Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24 [Baseline, Week 24]

    Blood was collected for Erythrocyte Sedimentation Rate (ESR) (a test that assesses tissue inflammation) and was analyzed at a local laboratory. ESR was measured in millimeter/hour (mm/hr). A reduction in the level is considered an improvement.

14. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 [Baseline, Week 24]

    The Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis, consisting of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. There are 4 possible responses for each question: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. The score for each of the domains is the highest (worst) score in each domain. A patient must have a domain score for at least 6 of 8 domains to calculate a valid HAQ-DI score which is the sum of domain scores, divided by the number of domains that have a score for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.

15. Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue) Score at Week 24 [Baseline, Week 24]

    FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status. A positive change from Baseline indicates improvement.

16. Change From Baseline in Quality of Life Short Form (SF-36) Score at Week 24 [Baseline, Week 24]

    The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.

17. Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Score at Week 24 [Baseline, Week 24]

    RAPID3 is a patient self reported assessment that combines the HAQ-DI [20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions answered on a 4-point scale where 0=without any difficulty to 3=unable to do} converted to a score of 0-10, the Patients Assessment of Pain [Over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain] converted to a score of 0-10 and the Patient'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] converted to a score of 0-10. The 3 individual scales are summed for a raw score of 0-30 which is divided by 3 to achieve a total possible adjusted score of 0-10. A negative change from Baseline indicates improvement.

18. Change From Baseline in Hemoglobin at Week 24 [Baseline, Week 24]

    Blood was collected at Baseline and Week 24. The samples were sent to a central laboratory for Hemoglobin analysis reported in gram/deciliter (g/dL). A positive number change from Baseline (a higher hemoglobin level compared to Baseline) indicated improvement

19. Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Discontinuation Due to AEs and Deaths [32 weeks]

    An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Adult patients, >/= 18 years of age

• Rheumatoid arthritis of >/= 6 months duration (according to American College of Rheumatology (ACR) criteria)(according to ACR criteria)

• Inadequate response due to inefficacy of treatment (for at least 3 months) with only one approved Tumor Necrosis Factor (TNF)-agent other than adalimumab Depending on the TNF-inhibitor, last dose of TNF-inhibitor should have been 1 to 8 weeks before randomization to the study

• On methotrexate treatment for >/=12 weeks immediately prior to baseline, with stable dose (10-25 mg/week) for the last 8 weeks

• Disease Activity Score (DAS28) >3.2 at baseline

• Oral corticosteroids (</=10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs) are permitted if the dose has been stable for >/=6 weeks prior to baseline.

Exclusion Criteria:

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 6 months following randomization

• Rheumatic autoimmune disease other than rheumatoid arthritis

• Prior history of or current inflammatory joint disease other than rheumatoid arthritis

• Functional class IV (ACR criteria)

• History of severe allergic reaction to human, humanized or murine monoclonal antibodies

• Known active current or history of recurrent infection (including tuberculosis)

• Primary or secondary immunodeficiency (history of or currently active)

• Body weight >150 kg

• Previous treatment with any cell-depleting therapies

• Previous treatment with tocilizumab

• Intra-articular or parenteral corticosteroids within 6 weeks prior to baseline.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Huntsville	Alabama	United States	35801
2		Phoenix	Arizona	United States	85027
3		Tucson	Arizona	United States	85712
4		Covina	California	United States	91723
5		Escondido	California	United States	92025
6		Huntington Beach	California	United States	92646
7		La Mesa	California	United States	91942
8		Lakewood	California	United States	90712
9		Long Beach	California	United States	90806
10		Los Angeles	California	United States	90048
11		Sacramento	California	United States	95816-5119
12		San Diego	California	United States	92108
13		Westlake Village	California	United States	91361
14		Whittier	California	United States	90603
15		Whittier	California	United States	90606
16		Bridgeport	Connecticut	United States	06606
17		Hamden	Connecticut	United States	06518
18		Norwich	Connecticut	United States	06360
19		Newark	Delaware	United States	19713
20		Aventura	Florida	United States	33180
21		Fort Lauderdale	Florida	United States	33334
22		Jupiter	Florida	United States	33458
23		Melbourne	Florida	United States	32901
24		Naples	Florida	United States	34102
25		Ocala	Florida	United States	34474
26		Orlando	Florida	United States	32806
27		Ormond Beach	Florida	United States	32174
28		Palm Habor	Florida	United States	34684
29		Palm Harbor	Florida	United States	34684
30		Sarasota	Florida	United States	34239
31		Tamarac	Florida	United States	33321
32		Tampa	Florida	United States	33609
33		Atlanta	Georgia	United States	30342
34		Valdosta	Georgia	United States	31602
35		Idaho Falls	Idaho	United States	83404
36		Chicago	Illinois	United States	60611
37		Maywood	Illinois	United States	60153
38		Moline	Illinois	United States	61265
39		Springfield	Illinois	United States	62704
40		Fort Wayne	Indiana	United States	46804
41		South Bend	Indiana	United States	46601
42		Lexington	Kentucky	United States	40515
43		Baton Rouge	Louisiana	United States	70808
44		Monroe	Louisiana	United States	71203
45		Annapolis	Maryland	United States	21401
46		Cumberland	Maryland	United States	21502
47		Frederick	Maryland	United States	21702
48		Hagerstown	Maryland	United States	21740
49		Fall River	Massachusetts	United States	02720
50		Worcester	Massachusetts	United States	01610
51		Battle Creek	Michigan	United States	49015
52		Lansing	Michigan	United States	48910
53		Petoskey	Michigan	United States	49770
54		St. Claire Shores	Michigan	United States	48081
55		Biloxi	Mississippi	United States	39531
56		Flowood	Mississippi	United States	39232
57		Tupelo	Mississippi	United States	38802
58		Saint Louis	Missouri	United States	63117
59		Springfield	Missouri	United States	65807
60		Reno	Nevada	United States	89502
61		Clifton	New Jersey	United States	07012
62		Manalapan	New Jersey	United States	07726
63		New Brunswick	New Jersey	United States	08903
64		Brooklyn	New York	United States	11201
65		New York	New York	United States	10016
66		New York	New York	United States	10029-6574
67		Syracuse	New York	United States	13210
68		Charlotte	North Carolina	United States	28204
69		Charlotte	North Carolina	United States	28210
70		Greensboro	North Carolina	United States	27408
71		Greenville	North Carolina	United States	27834
72		Raleigh	North Carolina	United States	27617
73		Washington	North Carolina	United States	27889
74		Cleveland	Ohio	United States	44195
75		Middleburg Heights	Ohio	United States	44130
76		Toledo	Ohio	United States	43606
77		Oklahoma City	Oklahoma	United States	73109
78		Lake Oswego	Oregon	United States	97035
79		Duncansville	Pennsylvania	United States	16635
80		Philadelphia	Pennsylvania	United States	19152
81		Pittsburgh	Pennsylvania	United States	15237
82		Pittsburgh	Pennsylvania	United States	15261
83		Willow Grove	Pennsylvania	United States	19090
84		Wynnewood	Pennsylvania	United States	19096
85		Wyomissing	Pennsylvania	United States	19610
86		Charleston	South Carolina	United States	29406
87		Myrtle Beach	South Carolina	United States	29572
88		Jackson	Tennessee	United States	38305
89		Memphis	Tennessee	United States	38104
90		Memphis	Tennessee	United States	38119
91		Austin	Texas	United States	78731
92		Carrollton	Texas	United States	75007
93		Corpus Christi	Texas	United States	78404
94		Houston	Texas	United States	77004
95		Houston	Texas	United States	77034
96		Houston	Texas	United States	77070
97		Houston	Texas	United States	77074
98		Mesquite	Texas	United States	75150
99		San Antonio	Texas	United States	78217
100		San Antonio	Texas	United States	78258
101		Sugar Land	Texas	United States	77479
102		Arlington	Virginia	United States	22205
103		Kennewick	Washington	United States	99336
104		Spokane	Washington	United States	99204
105		Tacoma	Washington	United States	98405
106		Clarksburg	West Virginia	United States	26301
107		Franklin	Wisconsin	United States	53132
108		Alborg		Denmark	9000
109		Helsingør		Denmark	3000
110		Silkeborg		Denmark	8600
111		Helsinki		Finland	00290
112		Hyvinkää		Finland	05800
113		Jyvaeskylae		Finland	40100
114		Grenoble		France	38042
115		Lille		France	59037
116		Limoges		France	87042
117		Metz		France	57077
118		Montpellier		France	34295
119		Mulhouse		France	68070
120		Nantes		France	44035
121		Orleans		France	45000
122		Paris		France	75651
123		Toulouse		France	31059
124		Berlin		Germany	14059
125		Düsseldorf		Germany	40217
126		Erfurt		Germany	99096
127		Erlangen		Germany	91056
128		Frankfurt Am Main		Germany	60590
129		Gommern		Germany	39245
130		Hamburg		Germany	22081
131		Hannover		Germany	30625
132		Heidelberg		Germany	69120
133		Herne		Germany	44652
134		Hildesheim		Germany	31134
135		München		Germany	81541
136		Osnabrück		Germany	49074
137		Regensburg		Germany	93053
138		Rostock		Germany	18059
139		Tübingen		Germany	72076
140		Athens		Greece	11527
141		Herakleion		Greece	71110
142		Thessaloniki		Greece	546 42
143		Thessaloniki		Greece	54642
144		Firenze		Italy	50139
145		Milano		Italy	20162
146		Pavia		Italy	27100
147		Pisa		Italy	56100
148		Roma		Italy	00161
149		Nijmegen		Netherlands	6522 JV
150		Caguas		Puerto Rico	00725
151		Kemerovo		Russian Federation	650099
152		Moscow		Russian Federation	115522
153		Moscow		Russian Federation	119049
154		UFA		Russian Federation	450005
155		Ulyanovsk		Russian Federation	432063
156		Oviedo	Asturias	Spain	33006
157		Sabadell	Barcelona	Spain	08208
158		La Coruna	La Coruña	Spain	15006
159		Santiago de Compostela	La Coruña	Spain	15706
160		Valenica	Valencia	Spain	46009
161		Barakaldo	Vizcaya	Spain	48903
162		Madrid		Spain	28007
163		Madrid		Spain	28046
164		Malaga		Spain	29010
165		Goteborg		Sweden	413 45
166		Huddinge		Sweden	SE-141 86
167		Lund		Sweden	221 85
168		Malmo		Sweden	205 02
169		Umea		Sweden	90185
170		Västerås		Sweden	72189

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: NCT01283971
• Other Study ID Numbers: MA25522; 2010-023587-40
• First Posted: Jan 26, 2011
• Last Update Posted: Feb 10, 2014
• Last Verified: Jan 1, 2014

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

Study Results

Participant Flow

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Period Title: Overall Study
STARTED	48	48
Intent to Treat Population	46	48
COMPLETED	33	36
NOT COMPLETED	15	12

Baseline Characteristics

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate	Total
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Total of all reporting groups
Overall Participants	48	48	96
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.3 (11.89)	51.3 (12.51)	52.8 (12.2)
Age, Customized (Number) [Number]
<50 years	16 33.3%	20 41.7%	36 37.5%
50 to 64 years	22 45.8%	18 37.5%	40 41.7%
≥65 to 75 years	9 18.8%	10 20.8%	19 19.8%
>75 years	1 2.1%	0 0%	1 1%
Sex: Female, Male (Count of Participants)
Female	40 83.3%	38 79.2%	78 81.3%
Male	8 16.7%	10 20.8%	18 18.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Disease Activity Score 28 Joints (DAS28) Remission at Week 24
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 2 to 10. DAS28 Remission is defined as a DAS28 score <2.6.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24. Last observation carried forward was used to impute missing tender and swollen joint counts. All other ACR components were used as observed.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	33	36
Number [Percentage of participants]	30.3 63.1%	36.1 75.2%

2. Secondary Outcome

Title	Percentage of Participants With American College of Rheumatology (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 additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) 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, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with ACR score data available. Last observation carried forward was used to impute missing tender and swollen joint counts. All other ACR components were used as observed.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	33	35
Number [Percentage of participants]	66.7 139%	62.9 131%

3. Secondary Outcome

Title	Percentage of Participants With 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 additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) 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, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with ACR score data available. Last observation carried forward was used to impute missing tender and swollen joint counts. All other ACR components were used as observed.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	33	35
Number [Percentage of participants]	24.2 50.4%	42.9 89.4%

4. Secondary Outcome

Title	Percentage of Participants With 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 additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) 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, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with ACR score data available. Last observation carried forward was used to impute missing tender and swollen joint counts. All other ACR components were used as observed.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	33	35
Number [Percentage of participants]	18.2 37.9%	22.9 47.7%

5. Secondary Outcome

Title	Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) DAS28 Responses at Week 24
Description	The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28 total score ranges from 0 (best) to 10 (worst). A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 or a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Week 24. Last observation carried forward was used to impute missing tender and swollen joint counts. All other EULAR components were used as observed.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	33	36
Moderate Response	39.4 82.1%	27.8 57.9%
Good Response	30.3 63.1%	58.3 121.5%

6. Secondary Outcome

Title	Percentage of Participants With DAS28 Low Disease Activity (LDAS) at Week 24
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 2 to 10. LDAS is defined as DAS28 ≤3.2.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24. Last observation carried forward was used to impute missing tender and swollen joint counts. All other DAS28 components were used as observed.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	33	36
Number [Percentage of participants]	30.3 63.1%	58.3 121.5%

7. Secondary Outcome

Title	Change From Baseline in DAS28 Score at Week 24
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 2 to 10. A higher value indicated higher disease activity. A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24. Last observation carried forward was used to impute missing tender and swollen joint counts. All other DAS28 components were used as observed.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	33	36
Mean (Standard Deviation) [Score on a scale]	-1.65 (1.541)	-2.80 (1.553)

8. Secondary Outcome

Title	Change From Baseline in Swollen Joint Count (SJC) at Week 24
Description	66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment. Last observation was used to impute missing swollen joint counts.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	46	48
Mean (Standard Deviation) [Joint count]	-5.7 (7.56)	-11.3 (15.84)

9. Secondary Outcome

Title	Change From Baseline in Tender Joint Count (TJC) at Week 24
Description	68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment. Last observation carried forward was used to impute missing tender joint counts.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	46	48
Mean (Standard Deviation) [Joint count]	-8.0 (14.62)	-13.9 (16.50)

10. Secondary Outcome

Title	Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS) at Week 24
Description	The patient assessed their pain using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	33	36
Mean (Standard Deviation) [Score on a scale]	-30.1 (20.57)	-23.8 (29.28)

11. Secondary Outcome

Title	Change From Baseline in the Patient Global Assessment of Disease Activity VAS at Week 24
Description	The patient's global assessment of disease activity is assessed on a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	33	36
Mean (Standard Deviation) [Score on a scale]	-30.2 (22.17)	-21.5 (28.89)

12. Secondary Outcome

Title	Change From Baseline in the Physician Global Assessment of Disease Activity VAS at Week 24
Description	The physician global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	33	36
Mean (Standard Deviation) [Score on a scale]	-37.0 (23.20)	-36.8 (32.34)

13. Secondary Outcome

Title	Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) at Week 24
Description	Blood was collected for C-Reactive Protein (CRP) (a test for analysis of inflammatory and infectious disorders) and was analyzed at a central laboratory. The concentration of CRP was measured in milligram/liter (mg/L). A reduction in the level is considered an improvement
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24 for this outcome measure.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	33	35
Mean (Standard Deviation) [mg/L]	-1.127 (11.1261)	-7.474 (10.8446)

14. Secondary Outcome

Title	Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24
Description	Blood was collected for Erythrocyte Sedimentation Rate (ESR) (a test that assesses tissue inflammation) and was analyzed at a local laboratory. ESR was measured in millimeter/hour (mm/hr). A reduction in the level is considered an improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24 for this outcome measure.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	33	36
Mean (Standard Deviation) [mm/hr]	-1.2 (16.78)	-25.7 (25.52)

15. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24
Description	The Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis, consisting of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. There are 4 possible responses for each question: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. The score for each of the domains is the highest (worst) score in each domain. A patient must have a domain score for at least 6 of 8 domains to calculate a valid HAQ-DI score which is the sum of domain scores, divided by the number of domains that have a score for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	30	35
Mean (Standard Deviation) [Score on a scale]	-0.19 (0.437)	-0.36 (0.543)

16. Secondary Outcome

Title	Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue) Score at Week 24
Description	FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status. A positive change from Baseline indicates improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	32	34
Mean (Standard Deviation) [Score on a scale]	5.6 (9.60)	8.0 (9.33)

17. Secondary Outcome

Title	Change From Baseline in Quality of Life Short Form (SF-36) Score at Week 24
Description	The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24 for this outcome measure.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	29	33
Physical Component Summary Score	4.39 (6.110)	5.84 (7.980)
Mental Component Summary Score	6.07 (12.171)	6.84 (11.907)

18. Secondary Outcome

Title	Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Score at Week 24
Description	RAPID3 is a patient self reported assessment that combines the HAQ-DI [20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions answered on a 4-point scale where 0=without any difficulty to 3=unable to do} converted to a score of 0-10, the Patients Assessment of Pain [Over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain] converted to a score of 0-10 and the Patient'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] converted to a score of 0-10. The 3 individual scales are summed for a raw score of 0-30 which is divided by 3 to achieve a total possible adjusted score of 0-10. A negative change from Baseline indicates improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24 for this outcome measure.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	30	35
Mean (Standard Deviation) [Score on a scale]	-2.17 (1.611)	-1.83 (2.257)

19. Secondary Outcome

Title	Change From Baseline in Hemoglobin at Week 24
Description	Blood was collected at Baseline and Week 24. The samples were sent to a central laboratory for Hemoglobin analysis reported in gram/deciliter (g/dL). A positive number change from Baseline (a higher hemoglobin level compared to Baseline) indicated improvement
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with hemoglobin data available at Baseline and Week 24.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	32	35
Mean (Standard Deviation) [g/dL]	1.2 (8.70)	6.5 (12.01)

20. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Discontinuation Due to AEs and Deaths
Description	An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Time Frame	32 weeks

Outcome Measure Data

Analysis Population Description

Safety Population included all participants who received study drug and who had at least 1 post-dose safety assessment.

Arm/Group Title	Adalimumab + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Measure Participants	48	48
Any Adverse Event (AE)	35 72.9%	33 68.8%
Any Serious Adverse Event	2 4.2%	8 16.7%
AE leading to withdrawal	3 6.3%	5 10.4%
Death	0 0%	0 0%

Adverse Events

Arm/Group Title	Adalimumab + Methotrexate		Tocilizumab + Methotrexate
Arm/Group Description	Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.		Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
All Cause Mortality
	Adalimumab + Methotrexate		Tocilizumab + Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Adalimumab + Methotrexate		Tocilizumab + Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/48 (4.2%)		8/48 (16.7%)
Cardiac disorders
Ventricular tachycardia	0/48 (0%)		1/48 (2.1%)
Infections and infestations
Pneumonia	1/48 (2.1%)		1/48 (2.1%)
Appendicitis	0/48 (0%)		1/48 (2.1%)
Bursitis infective	0/48 (0%)		1/48 (2.1%)
Urinary tract infection	0/48 (0%)		1/48 (2.1%)
Injury, poisoning and procedural complications
Hip fracture	0/48 (0%)		1/48 (2.1%)
Tibia fracture	0/48 (0%)		1/48 (2.1%)
Investigations
Alanine aminotransferase increased	1/48 (2.1%)		0/48 (0%)
Transaminases increased	0/48 (0%)		1/48 (2.1%)
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	0/48 (0%)		1/48 (2.1%)
Psychiatric disorders
Depression	0/48 (0%)		1/48 (2.1%)
Skin and subcutaneous tissue disorders
Rash	0/48 (0%)		1/48 (2.1%)
Other (Not Including Serious) Adverse Events
	Adalimumab + Methotrexate		Tocilizumab + Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/48 (43.8%)		11/48 (22.9%)
Infections and infestations
Upper respiratory tract infection	6/48 (12.5%)		3/48 (6.3%)
Nasopharyngitis	6/48 (12.5%)		1/48 (2.1%)
Bronchitis	3/48 (6.3%)		2/48 (4.2%)
Gastroenteritis	1/48 (2.1%)		3/48 (6.3%)
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	2/48 (4.2%)		3/48 (6.3%)
Nervous system disorders
Headache	1/48 (2.1%)		3/48 (6.3%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	4/48 (8.3%)		0/48 (0%)
Cough	3/48 (6.3%)		0/48 (0%)

Limitations/Caveats

Data interpretation was limited by the very small sample size (enrollment 1/7 of planned sample size; not powered for formal statistical analysis) and the open-label observation (study un-blinded following protocol amendment to terminate enrollment).

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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.