A Study on Safety and Efficacy of Tocilizumab (RoActemra/Actemra) Alone or in Combination With Non-Biologic Antirheumatics in Participants With Rheumatoid Arthritis

Multi-Center, Open Label, Single Arm Phase IIIB Study on Safety and Efficacy of Subcutaneous Tocilizumab in Monotherapy or in Combination With Methotrexate or Other Non-Biologic Disease Modifying Antirheumatic Drugs in Rheumatoid Arthritis Patients With an Inadequate Response to Non-Biologic DMARDs - OSCAR

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01987479

Acronym

OSCAR

Enrollment

150

Registered

2013-11-19

Start date

2014-01-30

Completion date

2016-05-26

Last updated

2017-06-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Brief summary

This multi-center, open-label single arm Phase IIIb study will evaluate the safety and efficacy of subcutaneous (SC) tocilizumab administered as monotherapy and/or in combination with methotrexate or other non-biologic disease modifying antirheumatic drugs (DMARDs) in participants with rheumatoid arthritis (RA) with an inadequate response to non-biologic DMARDs.

Interventions

DRUGNon-Biologic DMARDs

Treatment with non-biologic DMARDs, at a stable dose that was initiated at least 4 weeks prior to baseline, is permitted during the study and is at the investigator's discretion.

DRUGTocilizumab

Tocilizumab 162 mg will be administered once a week by SC injection and as a single fixed dose, irrespective of body weight, for the treatment duration of 24 weeks.

DRUGMethotrexate

Methotrexate will be administered per investigator's discretion.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Participants with a diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria. * Oral corticosteroids (≤10 mg/day prednisone or equivalent), nonsteroidal anti-inflammatory drugs (NSAIDs) and non-biologic DMARDs are permitted if on a stable dose regimen for greater than or equal to (≥\]) 4 weeks prior to Baseline. * Use of effective contraception throughout the study as defined by protocol; female participants of childbearing potential cannot be pregnant.

Exclusion criteria

* Presence of clinically significant medical conditions. * History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal disease that might predispose to perforation. * Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections. * Any infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening. * Clinically significant findings on laboratory tests. * Positive hepatitis B surface antigen or hepatitis C antibody. * Active tuberculosis requiring treatment within the previous 3 years. * Evidence of active malignant disease, malignancies diagnosed within the previous 10 years, or breast cancer diagnosed within the previous 20 years. * History of alcohol, drug, or chemical abuse within 1 year prior to Screening. * Neuropathies or other conditions that might interfere with pain evaluation. * Major surgery (including joint surgery) within 8 weeks prior to Screening or planned major surgery within 6 months following Baseline. * Rheumatic autoimmune disease other than RA, including systemic lupus erythematosis, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Secondary Sjögren's syndrome with RA is permitted. * Functional Class IV as defined by the ACR Classification of Functional Status in RA. * Diagnosis of juvenile idiopathic arthritis or juvenile RA, and/or RA before the age of 16 years. * Prior history of or current inflammatory joint disease other than RA. * Exposure to tocilizumab (either intravenous or SC) at any time prior to Baseline. * Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening. * Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, with alkylating agents such as chlorambucil, or with total lymphoid irradiation. * Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline. * Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Adverse Events	Baseline up to Week 32	An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Adverse events included serious as well as non-serious adverse events.

Secondary

Measure	Time frame	Description
Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)	A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0 mm=no pain to 100 mm=unbearable pain\]; 4) 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 5) an acute-phase reactant (either C-reactive protein \[CRP\] or ESR).
Percentage of Participants Achieving an ACR50 Response	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)	A participant had an ACR50 response if there was at least a 50% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0 mm=no pain to 100 mm=unbearable pain\]; 4) 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 5) an acute-phase reactant (either CRP or ESR).
Percentage of Participants Achieving an ACR70 Response	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)	A participant had an ACR70 response if there was at least a 70% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0 mm=no pain to 100 mm=unbearable pain\]; 4) 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 5) an acute-phase reactant (either CRP or ESR).
Percentage of Participants Achieving an ACR90 Response	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)	A participant had an ACR90 response if there was at least a 90% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0 mm=no pain to 100 mm=unbearable pain\]; 4) 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 5) an acute-phase reactant (either CRP or ESR).
Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)	DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). DAS28-ESR scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. The DAS28-ESR based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline \>1.2 with a DAS28 score ≤3.2; moderate responders had a change from baseline \>1.2 with a DAS28 score \>3.2 or a change from baseline \>0.6 to ≤1.2 with a DAS28 score ≤5.1. Participants with change from baseline \>0.6 to ≤1.2 with a DAS28 score \>5.1, or any score with change from baseline ≤0.6, were assessed as non-responders.
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)	The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician global assessment of disease activity assessed on 0-10 centimeter (cm) VAS (0 cm= no disease activity and 10 cm= worst disease activity), and CRP in milligrams per liter (mg/L). SDAI total score = 0-86. SDAI \<=3.3 indicates clinical remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity .
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)	The CDAI is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician's global assessment of disease activity assessed on 0-10 cm VAS (0 cm= no disease activity and 10 cm= worst disease activity). CDAI total score = 0-76. CDAI \<= 2.8 indicates clinical remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high (or severe) disease activity.
Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)	Number of tender joints was determined by examining 28 joints for TJC28 and 68 joints for TJC68, and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28 for a TJC28 and 68 for a TJC68. A reduction in number of tender joints compared to baseline indicates improvement.
Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)	Number of swollen joints was determined by examination of 28 joints for SJC28 and 66 joints for SJC66 and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28 for a SJC28 and 66 for a SJC66. A reduction in number of swollen joints compared to baseline indicates improvement.
Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons	From Week 16 and before Week 20; From Week 20 and before Week 24	Results are reported for percentage of participants who had NSAIDs dose reductions or discontinuation by reasons for dose reductions or discontinuation (unknown reasons, safety reasons, other reasons, lack of efficacy, and discomfort).
Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)	DAS28 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, erythrocyte sedimentation rate (ESR; millimeters per hour \[mm/hour\]), and patient's global assessment of disease activity (measured on a 0 to 100 mm Visual Analog Scale \[VAS\] where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR less than or equal to (≤) 3.2 implied low disease activity and greater than (\>) 3.2 to 5.1 implied moderate to high disease activity, and DAS28-ESR less than (\<) 2.6 implied clinical remission.
Time to Discontinuation or First Dose Reduction of Corticosteroids or NSAIDs	Baseline up to Week 32	Time to discontinuation or first dose reduction of corticosteroids or NSAIDs (weeks) = (Date of the first dose reduction or end date of corticosteroids or NSAIDs treatment - date of first drug intake of this study) + 1. Time to discontinuation or first dose reduction was based on the first occurring event (corticosteroid discontinuation or corticosteroid first dose reduction or NSAIDs discontinuation or NSAIDs first dose reduction, whichever occurred first).
Percentage of Participants With Anti-Tocilizumab Antibodies	Baseline, Weeks 12 and 24, early withdrawal (up to Week 24), follow-up visit (8 weeks after last dose of tocilizumab, up to 32 weeks)	—
Serum Levels of Tocilizumab	Baseline, Weeks 12 and 24, Early Withdrawal (up to Week 24), Follow-up Visit (8 weeks after last dose of tocilizumab, up to 32 weeks)	—
Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)	Baseline, Weeks 12 and 24, Early Withdrawal (up to Week 24), Follow-up Visit (8 weeks after last dose of tocilizumab, up to 32 weeks)	—
Patient Global Assessment of Disease Activity VAS Scores	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and Early withdrawal (up to Week 24)	Patient global assessment of disease activity was measured on a 0 to 100 mm horizontal VAS where 0 mm=no disease activity and 100 mm=maximum disease activity.
Patient Pain VAS Scores	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and Early withdrawal (up to Week 24)	This assessment represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS where 0 mm= no pain to 100 mm= unbearable pain.
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and early withdrawal (up to Week 24)	The HAQ-DI questionnaire measures functional status (disability) and health-related quality of life. It measures the participant's ability to perform everyday tasks. The index consists of 20 questions regarding the function of the upper and lower extremities. These questions are summarized in 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common activities over past week. Each question is evaluated according to the degree of severity on a 4-point scale. Total score for HAQ-DI was the average of all questions and ranges from 0 = without any difficulty to 3 = unable to do.
Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records	Weeks 2, 4, 8, 12, 16, 20, 24, and early withdrawal (up to Week 24)	A diary card was provided to participants to record home injections. Participants were asked to return all empty drug supply boxes, unused pre-filled syringe, and diary cards to the clinic at each visit as a measure of drug accountability and participant compliance. A participant was considered compliant if the participant correctly administered all scheduled doses of SC tocilizumab during the assessment period.
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and early withdrawal (up to Week 24)	The FACIT-F score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participants 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 participant'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).
Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons	From Week 16 and before Week 20; From Week 20 and before Week 24	Results are reported for percentage of participants who had corticosteroid dose reductions or discontinuation by reasons for dose reductions or discontinuation (unknown reasons, safety reasons, other reasons, lack of efficacy, and discomfort).

Countries

Netherlands

Participant flow

Pre-assignment details

A total of 174 participants were screened, out of which 150 participants met eligibility criteria and were enrolled into the study.

Participants by arm

Arm	Count
Tocilizumab Alone or in Combination With Methotrexate or DMARD Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or other non-biologic DMARDs for 24 weeks.	150
Total	150

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	7
Overall Study	Lost to Follow-up	1
Overall Study	Other	5
Overall Study	Participant/legal guardian decision	1
Overall Study	Physician Decision	2
Overall Study	Protocol Violation	1

Baseline characteristics

Characteristic	Tocilizumab Alone or in Combination With Methotrexate or DMARD
Age, Continuous	55.85 years STANDARD_DEVIATION 11.2
Sex: Female, Male Female	110 Participants
Sex: Female, Male Male	40 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	77 / 150
serious Total, serious adverse events	14 / 150

Outcome results

Primary

Percentage of Participants With Adverse Events

An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Adverse events included serious as well as non-serious adverse events.

Time frame: Baseline up to Week 32

Population: FAS population

Arm	Measure	Value (NUMBER)
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Adverse Events	91.3 percentage of participants

Secondary

Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal

The CDAI is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician's global assessment of disease activity assessed on 0-10 cm VAS (0 cm= no disease activity and 10 cm= worst disease activity). CDAI total score = 0-76. CDAI \<= 2.8 indicates clinical remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high (or severe) disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

Population: FAS population. Here, n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal	Baseline (n=150)	24.32 units on a scale	Standard Deviation 11.84
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal	Change at Week 2 (n=148)	-4.7 units on a scale	Standard Deviation 7.3
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal	Change at Week 4 (n=144)	-9.4 units on a scale	Standard Deviation 7.2
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal	Change at Week 8 (n=135)	-13.4 units on a scale	Standard Deviation 8.7
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal	Change at Week 12 (n=132)	-15.4 units on a scale	Standard Deviation 9.2
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal	Change at Week 16 (n=129)	-16.7 units on a scale	Standard Deviation 10.1
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal	Change at Week 20 (n=122)	-17.8 units on a scale	Standard Deviation 10.2
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal	Change at Week 24 (n=121)	-18.3 units on a scale	Standard Deviation 11.1
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal	Change at early withdrawal visit (n=27)	-6.4 units on a scale	Standard Deviation 10.3

Secondary

Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal

DAS28 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, erythrocyte sedimentation rate (ESR; millimeters per hour \[mm/hour\]), and patient's global assessment of disease activity (measured on a 0 to 100 mm Visual Analog Scale \[VAS\] where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR less than or equal to (≤) 3.2 implied low disease activity and greater than (\>) 3.2 to 5.1 implied moderate to high disease activity, and DAS28-ESR less than (\<) 2.6 implied clinical remission.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

Population: FAS population. Here, n = participants who were evaluable at the specified timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Baseline (n=150)	4.8 units on a scale	Standard Deviation 1.3
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 2 (n=148)	1.337 units on a scale	Standard Deviation 0.989
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 4 (n=144)	2.037 units on a scale	Standard Deviation 0.991
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 8 (n=136)	2.635 units on a scale	Standard Deviation 1.098
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 12 (n=133)	2.908 units on a scale	Standard Deviation 1.135
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 16 (n=128)	3.014 units on a scale	Standard Deviation 1.24
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 20 (n=122)	3.169 units on a scale	Standard Deviation 1.17
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 24 (n=121)	3.232 units on a scale	Standard Deviation 1.247
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at early withdrawal visit (n=27)	1.653 units on a scale	Standard Deviation 1.562

Secondary

Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal

The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician global assessment of disease activity assessed on 0-10 centimeter (cm) VAS (0 cm= no disease activity and 10 cm= worst disease activity), and CRP in milligrams per liter (mg/L). SDAI total score = 0-86. SDAI \<=3.3 indicates clinical remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity .

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

Population: FAS population. Here, Overall Number of Participants Analyzed = participants who were evaluable for this outcome. n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Baseline (n=145)	26.03 units on a scale	Standard Deviation 12.55
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 2 (n=97)	-6.2 units on a scale	Standard Deviation 7.4
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 4 (n=78)	-11.3 units on a scale	Standard Deviation 8
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 8 (n=64)	-14.4 units on a scale	Standard Deviation 9.2
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 12 (n=63)	-17.2 units on a scale	Standard Deviation 10.8
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 16 (n=67)	-18.5 units on a scale	Standard Deviation 11.1
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 20 (n=57)	-19.7 units on a scale	Standard Deviation 11.2
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at Week 24 (n=56)	-19.9 units on a scale	Standard Deviation 11.8
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	Change at early withdrawal visit (n=18)	-8.0 units on a scale	Standard Deviation 10.7

Secondary

Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal

Number of swollen joints was determined by examination of 28 joints for SJC28 and 66 joints for SJC66 and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28 for a SJC28 and 66 for a SJC66. A reduction in number of swollen joints compared to baseline indicates improvement.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

Population: FAS population. Here, n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC28: Baseline (n=150)	6.2 swollen joints	Standard Deviation 5.4
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC28: Change at Week 2 (n=148)	-1.18 swollen joints	Standard Deviation 3.04
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC28: Change at Week 4 (n=144)	-2.44 swollen joints	Standard Deviation 3.33
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC28: Change at Week 8 (n=136)	-3.62 swollen joints	Standard Deviation 3.86
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC28: Change at Week 12 (n=133)	-4.24 swollen joints	Standard Deviation 4.17
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC28: Change at Week 16 (n=130)	-4.61 swollen joints	Standard Deviation 4.14
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC28: Change at Week 20 (n=123)	-4.92 swollen joints	Standard Deviation 4.24
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC28: Change at Week 24 (n=121)	-5.23 swollen joints	Standard Deviation 4.63
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC28: Change at early withdrawal visit (n=27)	-1.33 swollen joints	Standard Deviation 4.18
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC66: Baseline (n=150)	9.1 swollen joints	Standard Deviation 7.3
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC66: Change at Week 2 (n=148)	-1.84 swollen joints	Standard Deviation 4.16
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC66: Change at Week 4 (n=144)	-3.94 swollen joints	Standard Deviation 4.35
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC66: Change at Week 8 (n=136)	-5.61 swollen joints	Standard Deviation 4.74
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC66: Change at Week 12 (n=133)	-6.50 swollen joints	Standard Deviation 5.79
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC66: Change at Week 16 (n=130)	-6.78 swollen joints	Standard Deviation 5.95
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC66: Change at Week 20 (n=123)	-7.52 swollen joints	Standard Deviation 6.44
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC66: Change at Week 24 (n=121)	-7.80 swollen joints	Standard Deviation 6.86
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	SJC66: Change at early withdrawal visit (n=27)	-2.33 swollen joints	Standard Deviation 4.89

Secondary

Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal

Number of tender joints was determined by examining 28 joints for TJC28 and 68 joints for TJC68, and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28 for a TJC28 and 68 for a TJC68. A reduction in number of tender joints compared to baseline indicates improvement.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

Population: FAS population. Here, n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC28: Baseline (n=150)	7.7 tender joints	Standard Deviation 6.5
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC28: Change at Week 2 (n=148)	-1.38 tender joints	Standard Deviation 3.71
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC28: Change at Week 4 (n=144)	-2.94 tender joints	Standard Deviation 3.89
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC28: Change at Week 8 (n=136)	-4.33 tender joints	Standard Deviation 4.82
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC28: Change at Week 12 (n=133)	-4.68 tender joints	Standard Deviation 5.05
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC28: Change at Week 16 (n=130)	-5.36 tender joints	Standard Deviation 5.55
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC28: Change at Week 20 (n=123)	-5.79 tender joints	Standard Deviation 5.24
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC28: Change at Week 24 (n=121)	-5.96 tender joints	Standard Deviation 5.67
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC28: Change at early withdrawal visit (n=27)	-1.07 tender joints	Standard Deviation 4.59
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC68: Baseline (n=150)	13.2 tender joints	Standard Deviation 10
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC68: Change at Week 2 (n=148)	-2.40 tender joints	Standard Deviation 5.84
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC68: Change at Week 4 (n=144)	-5.15 tender joints	Standard Deviation 6.25
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC68: Change at Week 8 (n=136)	-7.19 tender joints	Standard Deviation 7.57
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC68: Change at Week 12 (n=133)	-7.98 tender joints	Standard Deviation 8.46
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC68: Change at Week 16 (n=130)	-9.45 tender joints	Standard Deviation 9.07
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC68: Change at Week 20 (n=123)	-9.86 tender joints	Standard Deviation 9.04
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC68: Change at Week 24 (n=121)	-10.02 tender joints	Standard Deviation 8.94
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal	TJC68: Change at early withdrawal visit (n=27)	-1.93 tender joints	Standard Deviation 8.53

Secondary

Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score

The FACIT-F score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participants 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 participant'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).

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and early withdrawal (up to Week 24)

Population: FAS population. Here, n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score	Baseline (n=133)	29.84 units on a scale	Standard Deviation 9.43
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score	Week 2 (n=134)	33.07 units on a scale	Standard Deviation 9.34
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score	Week 4 (n=133)	35.10 units on a scale	Standard Deviation 10.37
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score	Week 8 (n=126)	37.34 units on a scale	Standard Deviation 9.25
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score	Week 12 (n=126)	37.89 units on a scale	Standard Deviation 8.52
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score	Week 16 (n=122)	37.93 units on a scale	Standard Deviation 9.11
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score	Week 20 (n=118)	39.65 units on a scale	Standard Deviation 8.87
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score	Week 24 (n=114)	39.93 units on a scale	Standard Deviation 8.65
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score	Early withdrawal (n=27)	33.48 units on a scale	Standard Deviation 12.06

Secondary

Health Assessment Questionnaire-Disability Index (HAQ-DI) Score

The HAQ-DI questionnaire measures functional status (disability) and health-related quality of life. It measures the participant's ability to perform everyday tasks. The index consists of 20 questions regarding the function of the upper and lower extremities. These questions are summarized in 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common activities over past week. Each question is evaluated according to the degree of severity on a 4-point scale. Total score for HAQ-DI was the average of all questions and ranges from 0 = without any difficulty to 3 = unable to do.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and early withdrawal (up to Week 24)

Population: FAS population. Here, n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	Baseline (n=147)	1.2329 units on a scale	Standard Deviation 0.5708
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	Week 2 (n=147)	1.0978 units on a scale	Standard Deviation 0.5906
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	Week 4 (n=143)	0.9673 units on a scale	Standard Deviation 0.5734
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	Week 8 (n=134)	0.8249 units on a scale	Standard Deviation 0.5587
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	Week 12 (n=131)	0.7460 units on a scale	Standard Deviation 0.533
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	Week 16 (n=129)	0.6996 units on a scale	Standard Deviation 0.5682
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	Week 20 (n=122)	0.6620 units on a scale	Standard Deviation 0.5333
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	Week 24 (n=119)	0.6681 units on a scale	Standard Deviation 0.5745
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	Early withdrawal (n=27)	1.2315 units on a scale	Standard Deviation 0.6853

Secondary

Patient Global Assessment of Disease Activity VAS Scores

Patient global assessment of disease activity was measured on a 0 to 100 mm horizontal VAS where 0 mm=no disease activity and 100 mm=maximum disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and Early withdrawal (up to Week 24)

Population: FAS population. Here, n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Global Assessment of Disease Activity VAS Scores	Baseline (n=150)	54.8 mm	Standard Deviation 22.3
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Global Assessment of Disease Activity VAS Scores	Week 2 (n=148)	43.6 mm	Standard Deviation 23
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Global Assessment of Disease Activity VAS Scores	Week 4 (n=144)	35.5 mm	Standard Deviation 23
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Global Assessment of Disease Activity VAS Scores	Week 8 (n=136)	27.2 mm	Standard Deviation 21.8
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Global Assessment of Disease Activity VAS Scores	Week 12 (n=133)	22.2 mm	Standard Deviation 20.3
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Global Assessment of Disease Activity VAS Scores	Week 16 (n=129)	21.3 mm	Standard Deviation 21
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Global Assessment of Disease Activity VAS Scores	Week 20 (n=123)	19.2 mm	Standard Deviation 18.6
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Global Assessment of Disease Activity VAS Scores	Week 24 (n=121)	18.8 mm	Standard Deviation 19.5
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Global Assessment of Disease Activity VAS Scores	Early withdrawal (n=27)	40.4 mm	Standard Deviation 30.9

Secondary

Patient Pain VAS Scores

This assessment represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS where 0 mm= no pain to 100 mm= unbearable pain.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and Early withdrawal (up to Week 24)

Population: FAS population. Here, n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Pain VAS Scores	Week 2 (n=148)	44.4 mm	Standard Deviation 21.9
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Pain VAS Scores	Baseline (n=150)	52.5 mm	Standard Deviation 22.1
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Pain VAS Scores	Week 4 (n=144)	35.8 mm	Standard Deviation 22.3
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Pain VAS Scores	Week 8 (n=136)	27.6 mm	Standard Deviation 21.3
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Pain VAS Scores	Week 12 (n=133)	21.7 mm	Standard Deviation 19
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Pain VAS Scores	Week 16 (n=129)	20.9 mm	Standard Deviation 20.2
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Pain VAS Scores	Week 20 (n=123)	19.5 mm	Standard Deviation 18
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Pain VAS Scores	Week 24 (n=121)	19.6 mm	Standard Deviation 18.8
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Patient Pain VAS Scores	Early withdrawal (n=27)	42.8 mm	Standard Deviation 30.4

Secondary

Percentage of Participants Achieving an ACR50 Response

A participant had an ACR50 response if there was at least a 50% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0 mm=no pain to 100 mm=unbearable pain\]; 4) 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 5) an acute-phase reactant (either CRP or ESR).

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

Population: FAS population. n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (NUMBER)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR50 Response	Week 2 (n=148)	6.1 percentage of participants	0.989
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR50 Response	Week 4 (n=144)	18.1 percentage of participants	0.991
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR50 Response	Week 8 (n=136)	33.1 percentage of participants	1.098
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR50 Response	Week 12 (n=133)	43.6 percentage of participants	1.135
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR50 Response	Week 16 (n=130)	52.3 percentage of participants	1.24
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR50 Response	Week 20 (n=123)	54.5 percentage of participants	1.17
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR50 Response	Week 24 (n=121)	62.0 percentage of participants	1.247
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR50 Response	Early withdrawal visit (n=27)	18.5 percentage of participants	1.562

Secondary

Percentage of Participants Achieving an ACR70 Response

A participant had an ACR70 response if there was at least a 70% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0 mm=no pain to 100 mm=unbearable pain\]; 4) 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 5) an acute-phase reactant (either CRP or ESR).

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

Population: FAS population. n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (NUMBER)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR70 Response	Week 2 (n=148)	1.4 percentage of participants	0.989
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR70 Response	Week 4 (n=144)	6.9 percentage of participants	0.991
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR70 Response	Week 8 (n=136)	14.0 percentage of participants	1.098
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR70 Response	Week 12 (n=133)	21.1 percentage of participants	1.135
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR70 Response	Week 16 (n=130)	29.2 percentage of participants	1.24
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR70 Response	Week 20 (n=123)	38.2 percentage of participants	1.17
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR70 Response	Week 24 (n=121)	35.5 percentage of participants	1.247
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR70 Response	Early withdrawal visit (n=27)	14.8 percentage of participants	1.562

Secondary

Percentage of Participants Achieving an ACR90 Response

A participant had an ACR90 response if there was at least a 90% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0 mm=no pain to 100 mm=unbearable pain\]; 4) 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 5) an acute-phase reactant (either CRP or ESR).

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

Population: FAS population. n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (NUMBER)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR90 Response	Week 8 (n=136)	2.9 percentage of participants	1.098
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR90 Response	Week 2 (n=148)	0.0 percentage of participants	0.989
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR90 Response	Week 4 (n=144)	1.4 percentage of participants	0.991
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR90 Response	Week 12 (n=133)	6.8 percentage of participants	1.135
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR90 Response	Week 16 (n=130)	9.2 percentage of participants	1.24
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR90 Response	Week 20 (n=123)	11.4 percentage of participants	1.17
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR90 Response	Week 24 (n=121)	15.7 percentage of participants	1.247
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an ACR90 Response	Early withdrawal visit (n=27)	3.7 percentage of participants	1.562

Secondary

Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response

A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0 mm=no pain to 100 mm=unbearable pain\]; 4) 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 5) an acute-phase reactant (either C-reactive protein \[CRP\] or ESR).

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

Population: FAS population. n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (NUMBER)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response	Week 2 (n=148)	20.3 percentage of participants	0.989
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response	Week 4 (n=144)	40.3 percentage of participants	0.991
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response	Week 8 (n=136)	58.1 percentage of participants	1.098
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response	Week 12 (n=133)	69.9 percentage of participants	1.135
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response	Week 16 (n=130)	71.5 percentage of participants	1.24
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response	Week 20 (n=123)	78.9 percentage of participants	1.17
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response	Week 24 (n=121)	82.6 percentage of participants	1.247
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response	Early withdrawal visit (n=27)	37.0 percentage of participants	1.562

Secondary

Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records

A diary card was provided to participants to record home injections. Participants were asked to return all empty drug supply boxes, unused pre-filled syringe, and diary cards to the clinic at each visit as a measure of drug accountability and participant compliance. A participant was considered compliant if the participant correctly administered all scheduled doses of SC tocilizumab during the assessment period.

Time frame: Weeks 2, 4, 8, 12, 16, 20, 24, and early withdrawal (up to Week 24)

Population: FAS population. n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (NUMBER)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records	Week 2 (n=148)	90.5 percentage of participants	0.5906
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records	Week 4 (n=144)	95.8 percentage of participants	0.5734
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records	Week 8 (n=136)	91.9 percentage of participants	0.5587
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records	Week 12 (n=133)	97.7 percentage of participants	0.533
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records	Week 16 (n=130)	93.8 percentage of participants	0.5682
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records	Week 20 (n=123)	95.1 percentage of participants	0.5333
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records	Week 24 (n=121)	92.6 percentage of participants	0.5745
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records	Early withdrawal (n=27)	88.9 percentage of participants	0.6853

Secondary

Percentage of Participants With Anti-Tocilizumab Antibodies

Time frame: Baseline, Weeks 12 and 24, early withdrawal (up to Week 24), follow-up visit (8 weeks after last dose of tocilizumab, up to 32 weeks)

Population: FAS population. Here, n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (NUMBER)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Anti-Tocilizumab Antibodies	Baseline (n=147)	6.1 percentage of participants	0.5906
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Anti-Tocilizumab Antibodies	Week 12 (n=5)	40.0 percentage of participants	0.5734
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Anti-Tocilizumab Antibodies	Week 24 (n=121)	7.4 percentage of participants	0.5587
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Anti-Tocilizumab Antibodies	Early withdrawal (n=22)	9.1 percentage of participants	0.533
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Anti-Tocilizumab Antibodies	Follow-up visit (n=26)	11.5 percentage of participants	0.5682

Secondary

Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons

Results are reported for percentage of participants who had corticosteroid dose reductions or discontinuation by reasons for dose reductions or discontinuation (unknown reasons, safety reasons, other reasons, lack of efficacy, and discomfort).

Time frame: From Week 16 and before Week 20; From Week 20 and before Week 24

Population: FAS population

Arm	Measure	Group	Value (NUMBER)
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons	Unknown reasons (Week 16 to Week 20)	0.0 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons	Safety reasons (Week 16 to Week 20)	1.3 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons	Other reasons (Week 16 to Week 20)	0.7 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons	Lack of efficacy (Week 16 to Week 20)	0.0 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons	Discomfort (Week 16 to Week 20)	0.0 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons	Unknown reasons (Week 20 to Week 24)	0.0 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons	Safety reasons (Week 20 to Week 24)	0.0 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons	Other reasons (Week 20 to Week 24)	1.3 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons	Lack of efficacy (Week 20 to Week 24)	0.7 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons	Discomfort (Week 20 to Week 24)	0.0 percentage of participants

Secondary

Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR

DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). DAS28-ESR scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. The DAS28-ESR based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline \>1.2 with a DAS28 score ≤3.2; moderate responders had a change from baseline \>1.2 with a DAS28 score \>3.2 or a change from baseline \>0.6 to ≤1.2 with a DAS28 score ≤5.1. Participants with change from baseline \>0.6 to ≤1.2 with a DAS28 score \>5.1, or any score with change from baseline ≤0.6, were assessed as non-responders.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

Population: FAS population. n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (NUMBER)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 2: Good response (n=148)	34.5 percentage of participants	0.989
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 2: Moderate response (n=148)	41.9 percentage of participants	0.991
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 2: No response (n=148)	23.6 percentage of participants	1.098
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 4: Good response (n=144)	59.7 percentage of participants	1.135
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 4: Moderate response (n=144)	34.0 percentage of participants	1.24
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 4: No response (n=144)	6.3 percentage of participants	1.17
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 8: Good response (n=136)	78.7 percentage of participants	1.247
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 8: Moderate response (n=136)	17.6 percentage of participants	1.562
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 8: No response (n=136)	3.7 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 12: Good response (n=133)	85.0 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 12: Moderate response (n=133)	12.0 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 12: No response (n=133)	3.0 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 16: Good response (n=128)	89.1 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 16: Moderate response (n=128)	7.0 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 16: No response (n=128)	3.9 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 20: Good response (n=122)	91.8 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 20: Moderate response (n=122)	5.7 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 20: No response (n=122)	2.5 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 24: Good response (n=121)	92.6 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 24: Moderate response (n=121)	5.0 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Week 24: No response (n=121)	2.5 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Early withdrawal visit: Good response (n=27)	44.4 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Early withdrawal visit: Moderate response (n=27)	29.6 percentage of participants	—
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR	Early withdrawal visit: No response (n=27)	25.9 percentage of participants	—

Secondary

Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons

Results are reported for percentage of participants who had NSAIDs dose reductions or discontinuation by reasons for dose reductions or discontinuation (unknown reasons, safety reasons, other reasons, lack of efficacy, and discomfort).

Time frame: From Week 16 and before Week 20; From Week 20 and before Week 24

Population: FAS population

Arm	Measure	Group	Value (NUMBER)
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons	Unknown reasons (Week 16 to Week 20)	0.0 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons	Safety reasons (Week 16 to Week 20)	0.7 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons	Other reasons (Week 16 to Week 20)	0.7 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons	Lack of efficacy (Week 16 to Week 20)	0.0 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons	Discomfort (Week 16 to Week 20)	0.0 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons	Unknown reasons (Week 20 to Week 24)	0.0 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons	Safety reasons (Week 20 to Week 24)	0.0 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons	Other reasons (Week 20 to Week 24)	0.0 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons	Lack of efficacy (Week 20 to Week 24)	0.0 percentage of participants
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons	Discomfort (Week 20 to Week 24)	0.0 percentage of participants

Secondary

Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)

Time frame: Baseline, Weeks 12 and 24, Early Withdrawal (up to Week 24), Follow-up Visit (8 weeks after last dose of tocilizumab, up to 32 weeks)

Population: FAS population. n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)	Baseline (n=139)	38.3 nanograms per milliliter (ng/mL)	Standard Deviation 10.4
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)	Week 12 (n=126)	516.6 nanograms per milliliter (ng/mL)	Standard Deviation 137.7
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)	Week 24 (n=115)	536.5 nanograms per milliliter (ng/mL)	Standard Deviation 161.6
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)	Early withdrawal (n=21)	380.4 nanograms per milliliter (ng/mL)	Standard Deviation 215.2
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)	Follow-up visit (n=26)	117.5 nanograms per milliliter (ng/mL)	Standard Deviation 194.3

Secondary

Serum Levels of Tocilizumab

Time frame: Baseline, Weeks 12 and 24, Early Withdrawal (up to Week 24), Follow-up Visit (8 weeks after last dose of tocilizumab, up to 32 weeks)

Population: FAS population. n = participants who were evaluable at specified timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Serum Levels of Tocilizumab	Baseline (n=4)	0.5 micrograms per milliliter (mcg/mL)	Standard Deviation 0.3
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Serum Levels of Tocilizumab	Week 12 (n=123)	42.3 micrograms per milliliter (mcg/mL)	Standard Deviation 25.2
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Serum Levels of Tocilizumab	Week 24 (n=112)	46.5 micrograms per milliliter (mcg/mL)	Standard Deviation 29.2
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Serum Levels of Tocilizumab	Early withdrawal (n=17)	16.8 micrograms per milliliter (mcg/mL)	Standard Deviation 19.3
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Serum Levels of Tocilizumab	Follow-up visit (n=3)	60.9 micrograms per milliliter (mcg/mL)	Standard Deviation 29.7

Secondary

Time to Discontinuation or First Dose Reduction of Corticosteroids or NSAIDs

Time to discontinuation or first dose reduction of corticosteroids or NSAIDs (weeks) = (Date of the first dose reduction or end date of corticosteroids or NSAIDs treatment - date of first drug intake of this study) + 1. Time to discontinuation or first dose reduction was based on the first occurring event (corticosteroid discontinuation or corticosteroid first dose reduction or NSAIDs discontinuation or NSAIDs first dose reduction, whichever occurred first).

Time frame: Baseline up to Week 32

Population: FAS population

Arm	Measure	Value (MEDIAN)
Tocilizumab Alone or in Combination With Methotrexate or DMARD	Time to Discontinuation or First Dose Reduction of Corticosteroids or NSAIDs	25.3 weeks

Source: ClinicalTrials.gov · Data processed: Feb 25, 2026

A Study on Safety and Efficacy of Tocilizumab (RoActemra/Actemra) Alone or in Combination With Non-Biologic Antirheumatics in Participants With Rheumatoid Arthritis

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Percentage of Participants With Adverse Events

Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal

Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal

Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal

Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal

Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal

Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score

Health Assessment Questionnaire-Disability Index (HAQ-DI) Score

Patient Global Assessment of Disease Activity VAS Scores

Patient Pain VAS Scores

Percentage of Participants Achieving an ACR50 Response

Percentage of Participants Achieving an ACR70 Response

Percentage of Participants Achieving an ACR90 Response

Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response

Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records

Percentage of Participants With Anti-Tocilizumab Antibodies

Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons

Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR

Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons

Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)

Serum Levels of Tocilizumab

Time to Discontinuation or First Dose Reduction of Corticosteroids or NSAIDs