A Study of Tocilizumab (RoActemra/Actemra) in Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Participants With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-TNF Biologic Agent

Rheumatoid Arthritis Clinical Trial

— ACT-MOVE  

Official title:

Open-Label, Phase IIIb Study to Evaluate the Efficacy and Safety of Subcutaneous (SC) Tocilizumab Monotherapy or Combination Therapy With Methotrexate (MTX) or Other Non-Biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) in Patients With Active Rheumatoid Arthritis (RA) Who Have an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-Tumour Necrosis Factor (Anti-TNF) Biologic Agent

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02046603
• Other study ID #: ML28641
• Secondary ID: 2013-000054-22
• Status: Completed
• Phase: Phase 3
• Start date: March 4, 2014
• Est. completion date: August 4, 2016

Study information

• Verified date: May 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This open-label study will evaluate the efficacy and safety of tocilizumab as monotherapy or in combination with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) in participants with active rheumatoid arthritis (RA) and an inadequate response to current non-biologic DMARD therapy or the first anti-tumour necrosis factor (anti-TNF) agent. Participants will receive tocilizumab 162 milligrams (mg) subcutaneously once a week for 52 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: August 4, 2016
• Est. primary completion date: August 4, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria

• Participants who have an inadequate response to current non-biologic DMARD therapy or the first anti-TNF agent (in monotherapy or in combination with MTX or other non-biologic DMARDs). Inadequate response to anti-TNF treatment is defined as DAS28 score improvement of less than 1.2 or participants achieving a DAS28 score improvement of 1.2 but not achieving low disease activity (current DAS28-ESR above 3.2) according to a treat-to-target strategy and have not been previously exposed to treatment with tocilizumab. Inadequate response to non-biologic DMARD therapy will be assessed according to local guidelines and the participants will need to be eligible for biologic therapy according to local guidelines

• Oral corticosteroids (=10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to recommended dose) are permitted if on stable dose regimen for greater than or equal to [=] 4 weeks prior to baseline

• Permitted non-biologic DMARDs are allowed if on stable dose for at least 4 weeks prior to baseline

• Receiving treatment on an outpatient basis, not including tocilizumab

• Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception as defined by protocol during the study and for at least 3 months following the last dose of tocilizumab

Exclusion Criteria:

• 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

• Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis

• Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16

• 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 5 half-lives of the investigational drug, whichever is longer) of screening

• Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline

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

• Known active current or history of recurrent infections

• Major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening

• Active tuberculosis (TB) requiring treatment within the previous 3 years

• Positive for hepatitis B or hepatitis C virus infection

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

• Pregnant or lactating women

• Inadequate hematologic, renal or liver function

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Tocilizumab
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 52 weeks.
• 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. The study protocol does not specify any particular therapy.
• Oral Corticosteroids
Stable oral corticosteroids doses (=10 mg/day prednisone or equivalent) are allowed. The study protocol does not specify any additional detail on types of oral corticosteroids.
• Methotrexate
Methotrexate per investigator's discretion.

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Christchurch Hospital; Rheumatology	Bournemouth
United Kingdom	Royal Sussex County Hospital; Clinical Investigation Research Unit	Brighton
United Kingdom	Queens Hospital	Burton on Trent
United Kingdom	West Suffolk Hospital	Bury Saint Edmonds
United Kingdom	Addenbrooke'S Hospital; Rheumatology Research Unit	Cambridge
United Kingdom	Cannock Chase Hospital; Rheumatology	Cannock
United Kingdom	University Hospital of Wales; Dept of Rhematology	Cardiff
United Kingdom	Broomfield Hospital	Chelmsford
United Kingdom	Countess of Chester Hospital; Dept of Rheumatology	Chester
United Kingdom	Dewsbury & District Hospital; Dept of Rheumatology	Dewsbury
United Kingdom	Russells Hall Hospital; Rheumatology Department	Dudley
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Eastbourne District General Hospital; Dept of Rheumatology	Eastbourne
United Kingdom	Western General Hospital; Pharmacy Department	Edinburgh
United Kingdom	Gartnavel General Hospital; Rheumatology	Glasgow
United Kingdom	Diana Princess of Wales Hosp.	Grimsby
United Kingdom	Princess Alexandra Hospital	Harlow
United Kingdom	Northwick Park Hospital	Harrow
United Kingdom	Hemel Hempstead General Hospital; Rheumatology Dept	Hemel Hempstead
United Kingdom	Hull Royal Infirmary; Rheumatology Department	Hull
United Kingdom	Llandudno General Hospital	Llandudno
United Kingdom	Royal Free Hospital; Department of Rheumatology	London
United Kingdom	Whipps Cross Hospital; Rheumatology Dept	London
United Kingdom	Maidstone Hospital; Dept of Rheumatology	Maidstone
United Kingdom	Wythenshawe Hospital	Manchester
United Kingdom	Freeman Hospital; Dept of Rheumatology	Newcastle Upon Tyne
United Kingdom	North Tyneside General Hospital	North Shields
United Kingdom	Norfolk & Norwich Hospital; Rheumatology	Norwich
United Kingdom	Integrated Care Centre	Oldham
United Kingdom	Solihull Hospital	Solihull
United Kingdom	Haywood Hospital; Staffordshire Rheumatology Centre	Stoke-on-trent
United Kingdom	Great Western Hospital; Dept of Rheumatology	Swindon
United Kingdom	Torbay Hospital; Dept of Rhematology	Torquay
United Kingdom	Royal Cornwall Hospital; Rhuematololgy Dept	Truro
United Kingdom	Warrington Hospital	Warrington
United Kingdom	Wrightington Hospital; Rheumatology	Wigan
United Kingdom	Wishaw General Hospital	Wishaw

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 2	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 greater than or equal to (=) 2.6 to less than or equal to (=) 3.2 implied low disease activity, greater than (>) 3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and less than (<) 2.6 implied clinical remission.	Baseline, Week 2
Primary	Change From Baseline in DAS28-ESR at Week 4	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, Week 4
Primary	Change From Baseline in DAS28-ESR at Week 8	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, Week 8
Primary	Change From Baseline in DAS28-ESR at Week 12	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, Week 12
Primary	Change From Baseline in DAS28-ESR at Week 16	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, Week 16
Primary	Change From Baseline in DAS28-ESR at Week 20	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, Week 20
Primary	Change From Baseline in DAS28-ESR at Week 24	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, Week 24
Primary	Change From Baseline in DAS28-ESR at Week 28	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, Week 28
Primary	Change From Baseline in DAS28-ESR at Week 32	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, Week 32
Primary	Change From Baseline in DAS28-ESR at Week 36	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, Week 36
Primary	Change From Baseline in DAS28-ESR at Week 40	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, Week 40
Primary	Change From Baseline in DAS28-ESR at Week 44	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, Week 44
Primary	Change From Baseline in DAS28-ESR at Week 48	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, Week 48
Primary	Change From Baseline in DAS28-ESR at Week 52	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, Week 52
Primary	Change From Baseline in DAS28-ESR at Early Withdrawal	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity, >3.2 to =5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.	Baseline, early withdrawal (up to Week 52)
Secondary	Number 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 (68 joints) and SJC (66 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, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either C-reactive protein [CRP] or ESR).	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
Secondary	Number 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 (68 joints) and SJC (66 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, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
Secondary	Number 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 (68 joints) and SJC (66 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, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
Secondary	Number 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.	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
Secondary	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at 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, >3.3 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity.	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
Secondary	Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at 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.	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
Secondary	Percent Change From Baseline in Total TJC on 68 Joints at Week 52	Number of tender joints was determined by examining 68 joints 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 68. A reduction in number of tender joints compared to baseline indicates improvement. The outcome is reported as the percent change from baseline to end of treatment (52 weeks).	Baseline, Week 52
Secondary	Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal	Number of tender joints was determined by examining 28 joints 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. A reduction in number of tender joints compared to baseline indicates improvement.	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
Secondary	Percent Change From Baseline in Total SJC on 66 Joints at Week 52	Number of swollen joints was determined by examination of 66 joints 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 66. A reduction in number of swollen joints compared to baseline indicates improvement. The outcome is reported as the percent change from baseline to end of treatment (52 weeks).	Baseline, Week 52
Secondary	Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal	Number of swollen joints was determined by examination of 28 joints 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. A reduction in number of swollen joints compared to baseline indicates improvement.	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
Secondary	Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR =3.2	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 =2.6 to =3.2 implied low disease activity.	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
Secondary	Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm 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 <2.6 implied clinical remission.	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
Secondary	Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation	Results are reported for number of participants who had non-biologic DMARD/corticosteroid dose reductions and/or discontinuation by reasons for dose reductions or discontinuation (safety reasons, discomfort, lack of efficacy, other reasons, and unknown reasons). Participants may be included under more than one reason.	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, at early withdrawal (up to Week 52), follow-up Week 4 (up to Week 56), and follow-up Week 8 (up to Week 60)
Secondary	Percentage of Methotrexate Adherence as Assessed by Methotrexate Adherence Questionnaire	Methotrexate adherence was determined from responses to the question 'Over the last 3 months you were prescribed 12 doses of methotrexate, how many (approximately) have you taken?' Adherence (%) was calculated as: (Approximate number of doses taken/12)*100.	Baseline, Weeks 12, 24, 36, 52, and at early withdrawal (up to Week 52)
Secondary	Patient Global Assessment of Disease Activity VAS Score	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.	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
Secondary	Patient Pain VAS Score	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.	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
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.	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
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 participant'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 participant's response). The sum of all responses resulted in the FACIT-F score for a total possible score of 0 (worse score) to 52 (better score).	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
Secondary	Number 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.	Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
Secondary	Number of Participants With Anti-Tocilizumab Antibodies		Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)
Secondary	Serum Levels of Tocilizumab		Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)
Secondary	Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)		Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)