A Study of RoActemra/Actemra (Tocilizumab) in Combination... | NCT01661140

ID	Type	Description	Link
2011-005260-20	EudraCT Number

Label	Type	Description	Intervention Names
Methotrexate (MTX) Tapering Dosage	Experimental	At Week 0 participants will start open-label tocilizumab and open-label MTX for 24 weeks. At Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response will be randomized to the MTX Tapering group or MTX Maintenance group. In this arm participants will receive a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. Participants will also continue to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants will receive tocilizumab monotherapy.	Drug: Tocilizumab Drug: Methotrexate (tapering dose)
Methotrexate (MTX) Maintenance Dosage	Active Comparator	At Week 0 participants will start open-label tocilizumab and open-label MTX for 24 weeks. At Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response will be randomized to the MTX Tapering group or MTX Maintenance group. In this arm participants will continue to be administered a stable dose of MTX in a double-blind fashion between Week 24 and Week 56. Participants will also continue to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants will receive tocilizumab monotherapy.	Drug: Methotrexate (stable dose) Drug: Tocilizumab

Name	Type	Description	Arm Group Labels	Other Names
Methotrexate (stable dose)	Drug	Methotrexate (MTX) was administered weekly according to the subject's pre-study MTX dose	Methotrexate (MTX) Maintenance Dosage

Measure	Description	Time Frame
Percentage of Participants Maintaining Previous Disease Activity (European League Against Rheumatism [EULAR] Response) From Week 24 (Time of Randomization) to Week 60	Response was determined using EULAR criteria based upon (Disease Activity Score In 28 Joints) DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference 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 <=1.2 points, or any score with reduction <=0.6 points, were assessed as non-responders with response recorded as 'none.'	From randomization to Week 60

Measure	Description	Time Frame
Change From Baseline in Disease Activity Score In 28 Joints (DAS28) Score at Week 60	The DAS28 defined as a combined index for measuring disease activity in rheumatoid arthritis (RA). The index included swollen (range 0-28) and tender joint counts (TJC) (range 0-28), acute phase response Erythrocyte Sedimentation Rate (ESR), and general health status (range 1-100). The index was calculated using the following formula: The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x patient global assessment of disease activity]. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

ID	Title	Description
FG000	Initial Phase	At Week 0 participants started open-label tocilizumab and open-label methotrexate (MTX) for 24 weeks, which was the initial phase of the study.
FG001	Methotrexate (MTX) Tapering Group

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

Percentage of Participants Maintaining Previous Disease Activity (European League Against Rheumatism [EULAR] Response) From Week 24 (Time of Randomization) to Week 60

Response was determined using EULAR criteria based upon (Disease Activity Score In 28 Joints) DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference 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 <=1.2 points, or any score with reduction <=0.6 points, were assessed as non-responders with response recorded as 'none.'

Intention to treat (ITT) population included all randomized participants.

Posted

Number

percentage of participants

From randomization to Week 60

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.

Units	Counts
Participants	OG000136 OG001136

Title

Denominators

Categories

Title	Measurements
	OG00076.5 OG00165.4

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	Comparison was Tapering MTX : MTX maintenance. Last post-baseline EULAR response recorded used for participants with a missing result at Week 60.	Analysis by logistic regression		0.036		Odds Ratio (OR)	1.803			2-Sided	95	1.037	3.133				Yes	Non-Inferiority or Equivalence	Non-inferiority if the difference between treatments is statistically significant and the lower limit of the 95% confidence interval (CI) is greater than 0.9.

Secondary

Change From Baseline in Disease Activity Score In 28 Joints (DAS28) Score at Week 60

The DAS28 defined as a combined index for measuring disease activity in rheumatoid arthritis (RA). The index included swollen (range 0-28) and tender joint counts (TJC) (range 0-28), acute phase response Erythrocyte Sedimentation Rate (ESR), and general health status (range 1-100). The index was calculated using the following formula: The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x patient global assessment of disease activity]. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.

ITT population included all randomized participants. Here, number of participants analyzed signifies those participants who were evaluable for this end point.

Posted

Mean

Standard Deviation

units on a scale

Randomization (Week 24), Week 60

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001

Secondary

Change From Baseline in Disease Activity Score In 28 Joints (DAS28) Score at Week 72

ITT population included all randomized participants. Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

units on a scale

Randomization (Week 24), Week 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001

Secondary

Percentage of Participants Who Achieve Score of <=1 in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 60 and 72

Percentage of participants who achieve score of =1 in TJC and SJC at week 60 and 72 were reported. 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. 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.

ITT population included all randomized participants.

Posted

Number

percentage of participants

Week 60, 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy..

Secondary

Percentage of Participants Who Achieve a Disease Activity Score In 28 Joints (DAS28) <= 3.2

The DAS28 index was calculated using the following formula: The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x patient global assessment of disease activity]. Participants who achieve score <=3.2 at weeks 60 and 72 were reported.

ITT population included all randomized participants.

Posted

Number

percentage of participants

Week 60, 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.

Secondary

Percentage of Participants Who Achieve DAS28 Remission (DAS28 < 2.6)

ITT population included all randomized participants.

Posted

Number

percentage of participants

Week 60, 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.

Secondary

Percentage of Participants Who Achieve Change in Disease Activity Score (cDAS) >=1.2

ITT population included all randomized participants.

Posted

Number

percentage of participants

Week 60, 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.

Secondary

Percentage of Participants Who Achieve Clinical Disease Activity Index (CDAI) Remission (CDAI < 2.8) at Week 60 and 72

Clinical Disease Activity Index (CDAI) was an index for measuring disease activity in RA. The index was calculated using the following formula: CDAI: SJC28 + TJC28 + patient global assessment of disease (PGA) 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity.

ITT population included all randomized participants.

Posted

Number

percentage of participants

Randomization (Week 24), Week 60, 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.

Secondary

Percentage of Participants Who Achieve Simplified Disease Activity Index (SDAI) Remission (SDAI < 3.3) at Week 60 and 72

Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA. The index was calculated using the following formula: CDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity.

ITT population included all randomized participants.

Posted

Number

percentage of participants

Randomization (Week 24), Week 60, 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.

Secondary

Percentage of Participants With Improvement in Physical Function Using Health Assessment Questionnaire [HAQ] at Week 60 and 72

The HAQ-disability index (DI) evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores and 20 questions. Each category contains multiple questions, which were answered using a 4-point scale from 0 to 3. The overall index score was an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. Improvement was defined as a decrease from Week 24 to Week 60 and 72. Reported is the percentage of participants with an improvement in HAQ-DI score.

ITT population included all randomized participants.

Posted

Number

percentage of participants

Randomization (Week 24), Week 60, 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group

Secondary

Percentage of Participants With Improvement in Physical Function Using Functional Assessment of Chronic Illness Therapy - Fatigue [FACIT-F] at Week 60 and 72

The FACIT-fatigue assessment was a 13-item questionnaire with participants scoring each item on a 5-point scale (not at all; a little bit; somewhat; quite a bit and very much). The total score ranges from 0 to 65 and higher scores indicate more fatigue. Improvement was defined as a decrease from Week 24 to Week 60 and 72. Reported is the percentage of subjects with an improvement in total FACIT score.

ITT population included all randomized participants.

Posted

Number

percentage of participants

Randomization (Week 24), Week 60, 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.

Secondary

Percentage of Participants With Improvement in Physical Function Using 12-item Short Form Health Survey [SF-12]) at Week 60 and 72

Quality of life questionnaire (SF-12) scores were computed using the scores of 12 questions and ranged from 0 to 100, where a 0 score indicated the lowest level of health measured by the scales and 100 indicated the highest level of health. Improvement was defined as a decrease from Week 24 to Week 60 and 72. Reported is the percentage of subjects with an improvement in SF-12 score.

ITT population included all randomized participants.

Posted

Number

percentage of participants

Randomization (Week 24), Week 60, 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.

Secondary

Percentage of Participants With Anemia

Safety population included all the randomized participants.

Posted

Number

percentage of participants

Week 0 up to Week 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.

Secondary

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was any adverse event that can be fatal, life threatening, requires long or prolong hospitalization, results in persistent or significant disability/incapacity, congenital anomaly or significant medical event in the investigator's judgment.

Safety population included all the randomized participants.

Posted

Number

participants

Week 0 up to Week 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.

Secondary

Percentage of Participants Able to Discontinue Methotrexate

Data were not collected for this outcome measure.

Posted

Week 0 up to Week 60

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.

Secondary

Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP)

ITT population included all randomized participants.

Posted

Number

participants

Randomization (Week 24), Week 60, 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.

Secondary

Hours Actually Worked and Work Hours Missed Assessed Using the WPAI-SHP

The WPAI-SHP questionnaire assesses work productivity and activity impairment. It is a patient-reported assessment regarding hours missed and hours worked at employment and degree to which a specified health problem affected work productivity and regular activities. It consists of 6 questions to assess the impact of a specific health problem on work productivity and on regular daily activities. Reported here are hours actually worked, work hours missed due to rheumatoid arthritis (RA), work hours missed due to other reasons and the change from Week 24 for each of these parameters reported at Week 60 and Week 72.

Participants in the ITT population with available data were analyzed.

Posted

Median

Full Range

hours

Randomization (Week 24), Week 60, Week 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group

Secondary

Change in Productivity and Regular Daily Activities Affected by Rheumatoid Arthritis Assessed Using the WPAI-SHP

The WPAI-SHP questionnaire assesses work productivity and activity impairment. It is a patient-reported assessment regarding hours missed and hours worked at employment and degree to which a specified health problem affected work productivity and regular activities. It consists of 6 questions to assess the impact of a specific health problem on work productivity and on regular daily activities. Assessments were made using a visual analogue scale ranging from 0 to 10 where 0 = minimum impact and 10 = maximum impact.

Participants in the ITT population with available data at the respective time points were analyzed.

Posted

Median

Full Range

units on a scale

Randomization (Week 24), Week 60, 72

ID	Title	Description
OG000	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.
OG001	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diverticulitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected427 at risk EG0012 affected136 at risk EG0020 affected136 at risk
Pneumonia	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0002 affected427 at risk EG0012 affected136 at risk EG0020 affected136 at risk
Abdominal Sepsis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected427 at risk EG0011 affected136 at risk EG0020 affected136 at risk
Bursitis Infective	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected427 at risk EG0010 affected136 at risk EG0021 affected136 at risk
Lymph Node Tuberculosis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected427 at risk EG0010 affected136 at risk EG0021 affected136 at risk
Necrotising Fasciitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected427 at risk EG0011 affected136 at risk EG0020 affected136 at risk
Device Dislocation	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected427 at risk EG0011 affected136 at risk EG0020 affected136 at risk
Ankle Fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected427 at risk EG0011 affected136 at risk EG0020 affected136 at risk
Joint Dislocation	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected427 at risk EG0011 affected136 at risk EG0020 affected136 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected427 at risk EG0011 affected136 at risk EG0020 affected136 at risk
Colon Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 affected427 at risk EG0011 affected136 at risk EG0020 affected136 at risk
Telangiectasia	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected427 at risk EG0010 affected136 at risk EG0021 affected136 at risk
Arthritis Infective	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Bronchitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Cellulitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0002 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Clostridium Difficile Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Lower Respiratory Tract Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Pneumocystis Jirovecii Pneumonia	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Pyelonephritis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Tooth Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Urinary Tract Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Viral Labyrinthitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Chest Pain	General disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Multiple Fractures	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Costochondritis	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Pain In Extremity	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Carcinoid Tumour Of The Gastrointestinal Tract	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Enterovesical Fistula	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Rectal Haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Hypersensitivity	Immune system disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Blood Bilirubin Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0002 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Carotid Artery Dissection	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Migraine	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Interstitial Lung Disease	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Pulmonary Fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected427 at risk EG0010 affected136 at risk EG0020 affected136 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Aberdeen		AB25 2ZN	United Kingdom

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
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D004358	Drug Therapy
D013812	Therapeutics

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Initial Phase	At Week 0 participants will start open-label tocilizumab and open-label MTX for 24 weeks, which is the initial phase of the study. Adverse events in this reporting group are those occurring in the open-label phase only.	21	427	263	427
EG001	Methotrexate (MTX) Tapering Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Tapering Group participants received a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. In addition, participants continued to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy. Adverse events in this reporting group are those occurring in the double-blind phase only.	9	136	62	136
EG002	Methotrexate (MTX) Maintenance Group	After the open-label period ended at Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response were randomized to the MTX Tapering Group or MTX Maintenance Group. In the MTX Maintenance Group participants continued to be administered the same dose of MTX in a double-blind fashion from Week 25 to Week 56. In addition, participants continued to receive open-label tocilizumab from Week 25 to Week 56. From Week 56 to Week 72 participants received tocilizumab monotherapy. Adverse events in this reporting group are those occurring in the double-blind phase only.	3	136	70	136

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00061 affected427 at risk EG00116 affected136 at risk EG00217 affected136 at risk
Lower Respiratory Tract Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00041 affected427 at risk EG00111 affected136 at risk EG00212 affected136 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00023 affected427 at risk EG00112 affected136 at risk EG0027 affected136 at risk
Urinary Tract Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00019 affected427 at risk EG0019 affected136 at risk EG0026 affected136 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00054 affected427 at risk EG0017 affected136 at risk EG00211 affected136 at risk
Mouth Ulceration	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00048 affected427 at risk EG0015 affected136 at risk EG0029 affected136 at risk
Nausea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00028 affected427 at risk EG0015 affected136 at risk EG0028 affected136 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00016 affected427 at risk EG0018 affected136 at risk EG0029 affected136 at risk
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00013 affected427 at risk EG0017 affected136 at risk EG0026 affected136 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00016 affected427 at risk EG0012 affected136 at risk EG0027 affected136 at risk
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG00023 affected427 at risk EG0019 affected136 at risk EG0028 affected136 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG00029 affected427 at risk EG0018 affected136 at risk EG0026 affected136 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG00016 affected427 at risk EG0017 affected136 at risk EG0026 affected136 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG00015 affected427 at risk EG0018 affected136 at risk EG0024 affected136 at risk
Headache	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG00038 affected427 at risk EG0018 affected136 at risk EG0026 affected136 at risk
Alanine Aminotransferase Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG00051 affected427 at risk EG0016 affected136 at risk EG0027 affected136 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00032 affected427 at risk EG0013 affected136 at risk EG0027 affected136 at risk

ID	Term
D008727	Methotrexate
C502936	tocilizumab
D000084862	Drug Tapering