Study to Compare the Efficacy of Tocilizumab With or With... | NCT02573012

ID	Type	Description	Link
2014-004673-16	EudraCT Number

Label	Type	Description	Intervention Names
Tocilizumab+prednisone (constant dose)	Experimental	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.	Drug: Placebo matched to prednisone Drug: Prednisone Biological: Tocilizumab
Tocilizumab+prednisone (tapering dose)	Experimental	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Drug: Placebo matched to prednisone Drug: Prednisone Biological: Tocilizumab

Name	Type	Description	Arm Group Labels	Other Names
Placebo matched to prednisone	Drug	Participants will receive placebo matched to prednisone orally for 24 weeks.	Tocilizumab+prednisone (constant dose) Tocilizumab+prednisone (tapering dose)

Measure	Description	Time Frame
Change From Baseline in Disease Activity Score in 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24 Post-randomization	The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint count, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100-millimeter (mm) visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.	Baseline to Week 24

Measure	Description	Time Frame
Treatment Success	Treatment success was defined as the percentage of participants with stable low disease activity (LDA) (DAS28-ESR score ≤ 3.2) at Week 24 post-randomization, who did not suffer a flare due to RA and who showed no confirmed adrenal insufficiency that required replacement therapy. DAS28 has the following standardized cut-offs for disease activity and remission: DAS28 > 5.1 = high disease activity; DAS28 between 3.2 and 5.1 = moderate disease activity; DAS28 ≤ 3.2 = low disease activity; DAS28 ≤ 2.6 = remission.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Tocilizumab-experienced participants:

Comply with the requirements of the study protocol (including treatment on an outpatient basis)
Rheumatoid arthritis (RA) of greater than or equal to (>=) 6 months duration diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria or 2010 ACR / European League Against Rheumatism (EULAR) criteria
Have received tocilizumab either subcutaneous (162 milligram [mg] once in a week) or intravenously (8 milligram per kilogram [mg/kg] once every 4 weeks) for the treatment of RA for at least 24 weeks prior to randomization
Have received 5 - 15 milligrams per day [mg/day] of glucocorticoids (prednisone or equivalent) for the treatment of RA for at least 20 weeks prior to screening
Currently receiving 5 mg/day of prednisone
Have attained and maintained LDA (DAS28 ESR score <=3.2) or remission (DAS28 ESR score less than [<] 2.6) for at least 4 weeks prior to randomization

Tocilizumab-naïve participants:

Comply with the requirements of the study protocol (including treatment on an outpatient basis)
RA of >=6 months duration diagnosed according to the revised 1987 ACR criteria or 2010 ACR / EULAR criteria
Have active RA (defined as DAS28 ESR score greater than [>] 3.2)
Are considered by the investigator as inadequate responders to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or biologic disease-modifying anti-rheumatic drugs (bDMARDs)
Are receiving 5 - 15 mg/day prednisone (or equivalent) for the treatment of RA

Exclusion Criteria:

General

Major surgery (including joint surgery) within 8 weeks prior to screening, or planned major surgery during the study and up to 6 months after randomization
Pregnant women or nursing (breastfeeding) mothers
In females of childbearing potential, a positive serum pregnancy test at screening
Females of childbearing potential unwilling or unable to use a reliable means of contraception (for example, physical barrier [participant or partner], contraceptive pill or patch, spermicide and barrier, or intrauterine device) during study treatment and for a minimum of 3 months after the last dose of tocilizumab
Body weight of >=150 kilogram (kg)
Lack of peripheral venous access

Disease-related

RA of functional Class 4, as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to RA (for example, vasculitis, pulmonary fibrosis, or Felty syndrome). Secondary Sjögren syndrome with RA may be allowed per the discretion of the investigator
Diagnosed with juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16 years
Prior or current inflammatory joint disease other than RA (for example, gout, Lyme disease, sero-negative spondyloarthropathy, including reactive arthritis, psoriatic arthritis, arthropathy of inflammatory bowel disease), or prior or current joint infections
Previous history of primary or secondary adrenal insufficiency

Previous or Concomitant Prohibited Therapy

Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies (for example, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, anti-CD20)
Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of screening
Intraarticular (IA) or parenteral glucocorticoids for the treatment of RA within 4 weeks prior to screening
Previous treatment with glucocorticoids for conditions other than RA, at any dose and in any formulation used continuously for >1 week, during the last 1 year prior to screening. Topical glucocorticoid creams or ointments for the treatment of skin conditions (for example eczema) are allowed
Immunization with a live/attenuated vaccine within 30 days prior to screening. Participants must agree not to take live attenuated vaccines (including seasonal nasal flu vaccine, varicella vaccine for shingles or chickenpox, vaccines for measles, mumps or rubella without or with varicella [MMR or MMRV], oral polio vaccine and vaccines for yellow fever), within 30 days before the Screening Visit, throughout the duration of the trial and for 60 days following the last dose of study drug
Any previous treatment with alkylating agents such as chlorambucil or with total lymphoid irradiation

Laboratory Exclusion Criteria

Inadequate haematological, renal and liver function
Positive hepatitis B surface antigen or hepatitis C antibody Previous or Concomitant Conditions
History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
Evidence of current serious uncontrolled cardiovascular (including uncontrolled hyperlipidemia), nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or gastrointestinal (GI) disease
Current liver disease as determined by the investigator
History of diverticulitis, peptic ulcer disease, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower gastrointestinal conditions that might predispose to perforations
Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other opportunistic infections (including, but not limited to, tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, Epstein-Barr virus, cytomegalovirus and herpes zoster, but excluding fungal infections of nail beds)
Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation
Any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
Active TB requiring treatment within the previous 3 years (participants previously treated for TB with no recurrence within 3 years are permitted). All Track tocilizumab-naïve participants must be screened for latent TB and if positive, should be treated following local practice guidelines prior to initiating tocilizumab
History of or currently active, primary or secondary immunodeficiency
Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including haematological malignancies and solid tumours, except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that was excised and cured), or breast cancer diagnosed within the previous 20 years
History of alcohol, drug or chemical abuse within 1 year prior to screening
Pre-existing central nervous system (CNS) demyelination or seizure disorders
Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Hopital Pellegrin; Rhumatologie		Bordeaux		33076	France
Hopital de La Source

PubMed Identifier	Type	Citation	Retractions
32711802	Derived	Burmester GR, Buttgereit F, Bernasconi C, Alvaro-Gracia JM, Castro N, Dougados M, Gabay C, van Laar JM, Nebesky JM, Pethoe-Schramm A, Salvarani C, Donath MY, John MR; SEMIRA collaborators. Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial. Lancet. 2020 Jul 25;396(10246):267-276. doi: 10.1016/S0140-6736(20)30636-X.

ID	Title	Description
FG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 22, 2016

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Disease Activity Score in 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24 Post-randomization

The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint count, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100-millimeter (mm) visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.

Posted

Least Squares Mean

95% Confidence Interval

Score on a scale

Baseline to Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants	OG000131 OG001128

Title

Denominators

Categories

Title	Measurements
	OG0000.538(0.346 to 0.729) OG001-0.075(-0.271 to 0.121)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.001		Least Square Means	0.613			2-Sided	95	0.346	0.879					Superiority

Secondary

Treatment Success

Treatment success was defined as the percentage of participants with stable low disease activity (LDA) (DAS28-ESR score ≤ 3.2) at Week 24 post-randomization, who did not suffer a flare due to RA and who showed no confirmed adrenal insufficiency that required replacement therapy. DAS28 has the following standardized cut-offs for disease activity and remission: DAS28 > 5.1 = high disease activity; DAS28 between 3.2 and 5.1 = moderate disease activity; DAS28 ≤ 3.2 = low disease activity; DAS28 ≤ 2.6 = remission.

Posted

Number

95% Confidence Interval

Percentage of Participants

Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts

Secondary

Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24

Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index is calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter (cm) visual analog scale (VAS) + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 100 mm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores range from 0 to 76, with higher scores indicating increased disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.

Posted

Least Squares Mean

95% Confidence Interval

Score on a scale

Baseline and Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Secondary

Percentage of Participants With >=1 Flare

Percentage of participants with >=1 flare

Posted

Number

Percentage of Participants

24 weeks

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Time to First RA Flare

The mean time of onset for the first RA flare since randomization.

Posted

Mean

Standard Deviation

Weeks

Randomization to 24 weeks

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percentage of Visits With RA Flares

Posted

Number

Percentage of visits with flares

Randomization to 24 weeks

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With >=1 Administration of Flare Rescue Medication

The proportion of participants with at least one administration of RA flare rescue medication.

Posted

Number

Percentage of Participants

Randomization to 24 weeks

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Time to First Administration of Flare Rescue Medication

Time of onset of first administration of RA flare rescue medication since randomization date

Posted

Mean

Standard Deviation

Weeks

Randomization to 24 weeks

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Number of Administrations of Flare Rescue Medication

Proportion of participants who received courses of RA flare rescue medication by number of courses received.

Posted

Number

Percentage of Participants

Randomization to 24 weeks

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Cumulative Prednisone Exposure (Dose)

In Post-randomization prednisone arm, Cumulative dose = (number of capsules taken during week 1 to 4 * 1 mg) + (3/4 * number of capsules taken during week 5 to 8 * 1 mg) + (1/2 * number of capsules taken during week 9 to 12 * 1 mg) + (1/4 * number of capsules taken during week 13 to 16 * 1 mg). In continued arm, cumulative dose = (1/4 * number of capsule taken * 5 mg).

Cumulative prednisone dose is defined as cumulative blinded prednisone + cumulative flare rescue prednisone.

Safety Population. The cumulative flare rescue prednisone dose population is based upon the number of participants who required rescue treatment.

Posted

Mean

Standard Deviation

Randomization to 24 weeks

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Secondary

Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level

The proportion of participants who maintained LDA and the proportion of participants who maintained the baseline disease activity level at Week 24.

LDA was defined as DAS28 ESR score <= 3.2. Remission was defined as DAS28 ESR score <= 2.6. Participants who maintained the baseline activity was defined as DAS28-ESR at Week 24 <= DAS28-ESR at baseline.

Intent to Treat population. The number of participants for LDA at Week 24 and Remission at Week 24 are based upon the number with LDA at baseline and DAS28-ESR ≤ 2.6 at baseline respectively.

Posted

Number

Percentage of Participants

Randomization to Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Secondary

Percentage of Participants Who Permanently Discontinue Study Treatment Due to Insufficient Flare Control

Percentage of participants who permanently discontinue study treatment due to insufficient flare control

Posted

Number

Percentage of Participants

24 weeks

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Swollen 66 Joint Counts

Count of swollen joints based upon 66 assessed joints.

Posted

Mean

Standard Deviation

Swollen joints

Baseline to Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Tender 68 Joint Counts

Count of tender joints based on 68 assessed joints.

Posted

Mean

Standard Deviation

Tender joints

Baseline to Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Assessment of Pain

The ACR patient's assessment of pain is scored on a visual analog scale (VAS) from 0 (no pain) to 100 mm (unbearable pain). A positive change in score indicates worsening, and a negative change indicates improvement.

Posted

Mean

Standard Deviation

Baseline to Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants

Secondary

Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Global Assessment of Disease Activity

The ACR patient's global assessment of disease activity is scored on a visual analog scale (VAS) from 0 (symptom-free and no arthritis symptoms) to 100 mm (maximum arthritis disease activity). A positive change in score indicates worsening, and a negative change indicates improvement.

Posted

Mean

Standard Deviation

Baseline to Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants

Secondary

Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Physician's Global Assessment of Disease Activity

The ACR physician's global assessment of disease activity is scored on a visual analog scale (VAS) from 0 (symptom-free and no arthritis symptoms) to 100 mm (maximum arthritis disease activity). A positive change in score indicates worsening, and a negative change indicates improvement.

Posted

Mean

Standard Deviation

Baseline to Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants

Secondary

Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Health Assessment Questionnaire-Disability Index (HAQ-DI)

A measure of self-perceived disability containing 20 questions in eight categories and including additional section about aid from other people and devices needed to correct the disabilities. Scores range from 0 to 3, with higher scores indicating worse disability.

Posted

Mean

Standard Deviation

Score on a scale

Baseline to Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants

Secondary

Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: High Sensitivity C-Reactive Protein (hsCRP)

Change from baseline in the acute phase reactant hsCRP

Posted

Mean

Standard Deviation

mg/dL

Baseline to Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Erythrocyte Sedimentation Rate (ESR)

Change from baseline in the acute phase reactant ESR

Posted

Mean

Standard Deviation

mm/hr

Baseline to Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Changes From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Final Score

The RAID is a participant-completed questionnaire specific for RA consisting of a 0-10 rating for pain, functional disability, fatigue, sleep, physical well-being, emotional well-being and coping. Scores are weighted to produce a final numerical result. A positive change in score indicates worsening, and a negative change indicates improvement.

Posted

Mean

Standard Deviation

Score on a scale

Baseline and Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Units	Counts
Participants

Secondary

Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score

The WPAI:SHP is a 6-item questionnaire to measure performance impairment of work and regular daily activity and yields 4 types of scores: work time missed (absenteeism), impairment while working (presenteeism or reduced on-the-job effectiveness), overall work impairment (WI) (work productivity loss or absenteeism plus presenteeism) and activity impairment (daily activity impairment). Total score and each score range from 0 (not affected/no impairment) to 100 (completely affected/impaired). Higher scores indicate greater impairment and less productivity. A positive change in score indicates impairment, and a negative change indicates improvement.

Intent to Treat population.

Posted

Mean

Standard Deviation

Score on a scale

Baseline and Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Secondary

Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 24

The SDAI is the numerical sum of 5 outcome parameters: tender and swollen joint count based on a 28-joint assessment, patient and physician global assessment of disease activity according to 100-mm visual analog scale (VAS) and level of C-reactive protein in milligrams per deciliter (mg/dL, normal <1 mg/dl). The total SDAI score range is 0-86, where higher scores indicate increased disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.

Posted

Least Squares Mean

95% Confidence Interval

Score on a scale

Randomization to Week 24

ID	Title	Description
OG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
OG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
SPINAL COLUMN STENOSIS	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 affected131 at risk EG0010 affected128 at risk
OSTEOARTHRITIS	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 affected131 at risk EG0010 affected128 at risk
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 affected131 at risk EG0010 affected128 at risk
ATRIAL FIBRILLATION	Cardiac disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 affected131 at risk EG0010 affected128 at risk
PNEUMONIA	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0001 affected131 at risk EG0011 affected128 at risk
CELLULITIS GANGRENOUS	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 affected131 at risk EG0011 affected128 at risk
BLOOD GLUCOSE FLUCTUATION	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0001 affected131 at risk EG0010 affected128 at risk
CEREBROVASCULAR ACCIDENT	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 affected131 at risk EG0010 affected128 at risk
SCIATICA	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 affected131 at risk EG0011 affected128 at risk
DRUG HYPERSENSITIVITY	Immune system disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 affected131 at risk EG0011 affected128 at risk
PSYCHOTIC DISORDER	Psychiatric disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 affected131 at risk EG0011 affected128 at risk
ASTHMA	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 affected131 at risk EG0011 affected128 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
NASOPHARYNGITIS	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG00013 affected131 at risk EG0019 affected128 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0007 affected131 at risk EG0015 affected128 at risk
ALANINE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0009 affected131 at risk EG0013 affected128 at risk
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0009 affected131 at risk EG0012 affected128 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0008 affected131 at risk EG0012 affected128 at risk

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds

ID	Title	Description
BG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
BG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Tocilizumab+Prednisone (Tapering Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	0	131	7	131	46	131
EG001	Tocilizumab+Prednisone (Constant Dose)	Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.	0	128	4	128	21	128