A Study of Subcutaneous Tocilizumab as Monotherapy and/or... | NCT01941095

NCT01941095

ID	Type	Description	Link
2013-000359-42	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Tocilizumab	Experimental	Participants will receive tocilizumab 162 milligrams (mg) SC injection once a week (QW) either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment is according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant may either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52. After Week 52, participants who remain in study will enter a 8 week wash-out period and then (from Week 60) will proceed to the extension phase until tocilizumab is commercially available in Greece. Permitted DMARDs include methotrexate, azathioprine, chloroquine, hydroxychloroquine, leflunomide, and sulfasalazine.	Drug: Azathioprine Drug: Chloroquine Drug: Hydroxychloroquine Drug: Leflunomide Drug: Methotrexate Drug: Sulfasalazine Drug: Tocilizumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Azathioprine	Drug	Participants may receive azathioprine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Achieved Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) Remission at Week 24	DAS28-ESR score is a measure of participant's disease activity calculated using tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), patient global assessment of disease activity (PGA) (general health [GH]) using visual analog scale (VAS): 0 millimeter (mm)=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in millimeters per hour [mm/hr]). The score is calculated using the following formula: DAS28-ESR = [0.56 multiplied by () square root (√) of TJC28] plus (+) [0.28√SJC28]+[0.70the natural logarithm (ln) ESR]+[0.014GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score of less than (<) 2.6 represents DAS28-ESR remission.	Week 24

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24	DAS28-ESR score is a measure of participant's disease activity calculated using TJC28, SJC28, PGA using VAS 0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in mm/hr) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28-ESR = [0.56 * √TJC28 + [0.28√SJC28]+[0.70ln ESR]+[0.014*GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score <2.6 represents DAS28-ESR remission. The percentage reported for Week 24 is based on confirmation on switching to SC tocilizumab monotherapy.](streamdown:incomplete-link)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosis of active rheumatoid arthritis according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria
Oral corticosteroids (less than or equal to [</=] 10 milligrams per day [mg/day] prednisolone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if on a stable dose regimen for greater than or equal to [>/=] 4 weeks prior to baseline
Permitted non biologic DMARDs are allowed if a 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 a reliable means of contraception during the study; females of childbearing potential must use a reliable means of contraception for at least 3 month 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 rheumatoid arthritis; secondary Sjögren's syndrome with rheumatoid arthritis is permitted
Functional Class 4 as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
Diagnosis of juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis before the age of 16
Prior history of or current inflammatory joint disease other than rheumatoid arthritis
Participants with lack of peripheral venous access
Exposure to tocilizumab (either intravenous [IV] 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-depending therapies
Treatment with IV gamma globulin, plasmapheresis within 6 months of baseline
Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
Immunization with a live/attenuated vaccine within 4 weeks prior to baseline
Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation
History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal disease
Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections
Any major episode of infection requiring hospitalization of 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 surface antigen or hepatitis C antibody
Primary or secondary immunodeficiency (history of or currently active)
Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (except for basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years
Pregnant or breast feeding women
History of alcohol, drug or chemical abuse within 1 year prior to screening
Neuropathies or other conditions that interfere with pain evaluation

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
District Gen. Hosp. of Athens Laiko; A Propedeutic Internal Medicine Clinic & Research Center		Athens		115 27	Greece

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
30649524	Derived	Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Devenport J, Petho-Schramm A. Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis. Rheumatology (Oxford). 2019 Jun 1;58(6):1056-1064. doi: 10.1093/rheumatology/key393.
29244149	Derived

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Tocilizumab	Participants received tocilizumab 162 milligrams (mg) subcutaneous (SC) injection once a week (QW) either as monotherapy or in combination with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Full analysis set included all recruited participants who received at least one dose of SC tocilizumab.

Arm/Group Information

ID	Title	Description
BG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00040

Secondary

Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24

DAS28-ESR score is a measure of participant's disease activity calculated using TJC28, SJC28, PGA using VAS 0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in mm/hr) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28-ESR = [0.56 * √TJC28 + [0.28*√SJC28]+[0.70*ln ESR]+[0.014*GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score <2.6 represents DAS28-ESR remission. The percentage reported for Week 24 is based on confirmation on switching to SC tocilizumab monotherapy.](streamdown:incomplete-link)

Per protocol analysis. Overall number of participants analyzed = participants evaluable for this outcome measure. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.

Posted

Number

percentage of participants

Weeks 24, 28, 32, 36, 40, 44, 48, 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Secondary

Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24

DAS28-ESR score is a measure of participant's disease activity calculated using TJC28, SJC28, PGA using VAS 0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in mm/hr) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28-ESR = [0.56 * √TJC28 + [0.28*√SJC28]+[0.70*ln ESR]+[0.014*GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score <2.6 represents DAS28-ESR remission. DAS28-ESR score greater than or equal to (>/=) 2.6 and <3.2 represents LDA.](streamdown:incomplete-link)

Full analysis set. Overall number of participants analyzed = participants evaluable for this outcome measure. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.

Posted

Number

percentage of participants

Weeks 28, 32, 36, 40, 44, 48, 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Secondary

Change From Baseline in DAS28-ESR up to Week 52

DAS28-ESR score is a measure of participant's disease activity calculated using TJC28, SJC28, PGA using VAS 0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in mm/hr) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28-ESR = [0.56 * √TJC28 + [0.28*√SJC28]+[0.70*ln ESR]+[0.014*GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. A negative change from baseline indicates an improvement.](streamdown:incomplete-link)

Posted

Mean

95% Confidence Interval

units on a scale

Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Secondary

Number of Participants With American College of Rheumatology 20 (ACR20) Response

ACR20 response was defined as >/=20% improvement from baseline in both TJC28 and SJC28 as well as in 3 out of 5 additional parameters: Separate patient and physician's global assessment of disease activity on VAS (0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS), patient's assessment of pain on VAS (0 mm=no pain to 100 mm=unbearable pain, displayed on the 100 mm horizontal VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI) (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without any difficulty to 3=unable to do), and acute phase response (ESR in mm/hr, for a total possible score of 0 to 10).

Posted

Number

participants

Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Secondary

Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria

Response to treatment was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the baseline visit. Participants with a score lesser than or equal to (</=) 3.2 and reduction of greater than (>) 1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score </=5.1 with reduction of >0.6 to </=1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to \

Posted

Number

percentage of participants

Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Secondary

Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52

SDAI is an index for measuring disease activity. SDAI is the numerical sum of five outcome parameters: TJC28 and SJC28, PGA and physician global assessment of disease activity assessed on VAS (0 centimeter [cm]-10 cm); 0 cm= no disease activity and 10 cm= worst disease activity, and CRP (in milligrams per deciliter [mg/dL]). SDAI total score ranges from 0 to 86, with higher scores indicating increased (or severe) disease activity. SDAI score </=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.

Posted

Mean

95% Confidence Interval

units on a scale

Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Secondary

Change From Baseline in TJC28 up to Week 52

28 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 28. A negative change from baseline indicated improvement.

Posted

Mean

95% Confidence Interval

tender joints

Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Units	Counts
Participants

Secondary

Change From Baseline in SJC28 up to Week 52

28 joints were assessed for swelling and joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 28. A negative change from baseline indicated improvement.

Posted

Mean

95% Confidence Interval

swollen joints

Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Units	Counts
Participants

Secondary

Percentage of Participants With Corticosteroid Dose Reduction or Discontinuation

Full analysis set. Overall number of participants analyzed = participants who used corticosteroids during the study.

Posted

Number

percentage of participants

From Baseline up to Week 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Units	Counts
Participants	OG000

Secondary

Number of Participants by Reasons (Categories) for Corticosteroid Dose Reduction or Discontinuation

Reasons for corticosteroid dose reduction included: Safety Reasons (including elevated liver function test results, respiratory infections, infections and infestations, gastrointestinal disorders etc.); Other Reasons (disease remission, improvement etc.); and Unknown Reasons (including no reason). Number of participants by reasons (Safety, Other, Unknown) for corticosteroid dose reduction or discontinuation were reported.

Full analysis set. Overall number of participants analyzed = participants with corticosteroid dose reduction/discontinuation.

Posted

Number

participants

From Baseline up to Week 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Units	Counts
Participants

Secondary

Number of Participants With Anti-Tocilizumab Antibodies (ATA)

All samples were tested using a screening assay and, if positive, by a confirmation assay to determine specificity and a neutralizing assay to test for the ability to inhibit the activity of tocilizumab. Number of participants with a positive assay result for screening assay (ATA - Screen), confirmatory assay (ATA - Confirmatory), and neutralizing assay (ATA - Neutralizing) was reported separately.

Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.

Posted

Number

participants

Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Units	Counts
Participants

Secondary

Soluble Interleukin-6 Receptor (sIL-6R) Levels

Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.

Posted

Mean

Standard Deviation

nanograms per milliliter (ng/mL)

Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Units	Counts
Participants	OG000

Secondary

Tocilizumab Serum Levels

Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.

Posted

Mean

Standard Deviation

microgrms per milliliter (mcg/mL)

Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Units	Counts
Participants	OG000

Secondary

PGA, Using VAS Score

PGA was assessed on a 0 to 100 mm horizontal VAS. The extreme left end of the line = 0 mm, and was described as "no disease activity" (symptom-free and no arthritis symptoms) and the extreme right end = 100 mm, and was described as "maximum disease activity" (maximum arthritis disease activity). Higher values correspond to worst state of participant (high disease activity).

Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.

Posted

Mean

Standard Deviation

Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Units	Counts
Participants

Secondary

Patient Assessment of Pain, Using VAS Score

The participant's level of pain was assessed on a 0 to 100 mm horizontal VAS. The extreme left end of the line = 0 mm, and was described as "no pain" and the extreme right end = 100 mm, and was described as "unbearable pain". Higher values correspond to worst state of participant (higher level of pain).

Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.

Posted

Mean

Standard Deviation

Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Units	Counts
Participants

Secondary

HAQ-DI Score

The Stanford HAQ-DI is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Responses in each component set were scored from 0 (without any difficulty) to 3 (unable to do). The highest score recorded for any question in a category determines the score for the category, unless aids, devices, or help from another person was required. The HAQ-DI score was calculated as the sum of the category scores divided by the number of categories scored, giving a possible range of scores from 0 to 3. Scores of 0 to 1 are generally considered to represent "mild to moderate difficulty", 1 to 2 as "moderate to severe disability", and 2 to 3 as "severe to very severe disability".

Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.

Posted

Mean

Standard Deviation

units on a scale

Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Secondary

Percentage of Participants Who Received All Planned Study Medication (Compliance)

Compliance (in terms of percentage of participants who received all planned study medication) was assessed on the basis of participant diary cards and return records.

Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.

Posted

Number

percentage of participants

Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Units	Counts
Participants	OG000

Secondary

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

FACIT-Fatigue total score is sum of FACIT-General subscale score and FACIT-Fatigue (additional concerns) subscale score. FACT-General consists of 27 questions grouped in 4 domains of general health-related quality of life: physical well-being, social/family well-being, emotional well-being, and functional well-being; each item ranges from 0 (not at all) to 4 (very much). FACT-General score ranges between 0-108. FACIT-Fatigue subscale is a 13-item questionnaire that evaluates self-reported fatigue and its impact upon daily activities. Each item ranges from 0 (Not at all) to 4 (Very much). For all items, 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 subscale score for a total possible score of 0 (worse score) to 52 (better score). FACIT-Fatigue total score (FACT-G plus FACT-F subscale scores) ranges from 0 (better score) to 160 (worse score).

Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.

Posted

Mean

Standard Deviation

units on a scale

Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

ID	Title	Description
OG000	Tocilizumab	Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52.

Arm/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 Monotherapy	Participants received tocilizumab 162 mg SC injection QW as monotherapy during the treatment period of 52 weeks.			2	31	19	31
EG001	Tocilizumab + Methotrexate or Other Non-Biologic DMARDs	Participants received tocilizumab 162 mg SC injection QW in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks.			5	66	38	66

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected31 at risk EG0011 affected66 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected31 at risk EG0011 affected66 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected31 at risk EG0011 affected66 at risk
Bronchitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 affected31 at risk EG0011 affected66 at risk
Respiratory tract infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0001 affected31 at risk EG0010 affected66 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected31 at risk EG0010 affected66 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected31 at risk EG0012 affected66 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Leukopenia	Blood and lymphatic system disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected31 at risk EG0018 affected66 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected31 at risk EG0014 affected66 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 19.1	Non-systematic Assessment	EG0006 affected31 at risk EG0015 affected66 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected31 at risk EG0014 affected66 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected31 at risk EG0012 affected66 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected31 at risk EG0010 affected66 at risk
Injection site erythema	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected31 at risk EG0015 affected66 at risk
Oedema peripheral	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected31 at risk EG0012 affected66 at risk
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected31 at risk EG0016 affected66 at risk
Bronchitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0003 affected31 at risk EG0015 affected66 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0002 affected31 at risk EG0014 affected66 at risk
Nasopharyngitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0004 affected31 at risk EG0018 affected66 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 affected31 at risk EG0014 affected66 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0002 affected31 at risk EG0015 affected66 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 19.1	Non-systematic Assessment	EG0003 affected31 at risk EG0012 affected66 at risk
Alanine aminotransferase increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0009 affected31 at risk EG00113 affected66 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0008 affected31 at risk EG0019 affected66 at risk
Blood glucose increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0002 affected31 at risk EG0013 affected66 at risk
Blood triglycerides increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0003 affected31 at risk EG0013 affected66 at risk
Blood urea increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0001 affected31 at risk EG0013 affected66 at risk
Blood uric acid increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0003 affected31 at risk EG0011 affected66 at risk
Hepatic enzyme increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0001 affected31 at risk EG0015 affected66 at risk
White blood cell count decreased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0003 affected31 at risk EG0011 affected66 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected31 at risk EG0014 affected66 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0003 affected31 at risk EG0011 affected66 at risk
Dizziness	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected31 at risk EG0010 affected66 at risk
Headache	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected31 at risk EG0012 affected66 at risk
Sciatica	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected31 at risk EG0011 affected66 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0005 affected31 at risk EG0014 affected66 at risk
Hypertension	Vascular disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected31 at risk EG0012 affected66 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected31 at risk EG0011 affected66 at risk
Injection site pruritus	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected31 at risk EG0011 affected66 at risk
Neutrophil count decreased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0003 affected31 at risk EG0012 affected66 at risk

ID	Term
D001172	Arthritis, Rheumatoid

Ancestor Terms

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
D001379	Azathioprine
D002738	Chloroquine
D006886	Hydroxychloroquine
D000077339	Leflunomide
D008727	Methotrexate
D012460	Sulfasalazine
C502936	tocilizumab

Ancestor Terms

ID	Term
D013872	Thionucleosides
D013457	Sulfur Compounds
D009930	Organic Chemicals
D015122	Mercaptopurine
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D000634	Aminoquinolines
D011804	Quinolines
D007555	Isoxazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D013449	Sulfonamides
D000577	Amides
D013450	Sulfones

Units	Counts
Participants	OG00096