Trial Outcomes & Findings for A Prospective Observational Study of Tocilizumab (RoActemra/Actemra) in Participants With Rheumatoid Arthritis (NCT NCT01462162)

NCT ID: NCT01462162

Last Updated: 2016-10-31

Results Overview

Regression analysis between change in FACIT-F scale and change in following variable were assessed: DAS28-ESR (total score range: 0-9.4, higher score=more disease activity), Epworth sleepiness scale (total score range: 0-24, higher score=higher degree of sleepiness), back depression inventory (total score range: 0-63, score higher than 18 indicates moderate to severe symptoms of depression). The total score of the FACIT-F questionnaire ranges from 0=worse score to 52=better score. Regression coefficient (R) and coefficient of determination (R\^2) were calculated. Difference (1-R\^2)=the variation in the changes in fatigue not explained by independent variables, that is, independent contribution of these changes in fatigue to the assessment of RA. Only variables with available data were reported.

• Recruitment status: COMPLETED
• Target enrollment: 122 participants
• Primary outcome timeframe: Week 12
• Results posted on: 2016-10-31

Participant Flow

Total of 122 participants were recruited, 2 participants were excluded from analysis, one due to non-compliance with the inclusion criteria and other due to compliance with the exclusion criteria.

Participant milestones

Measure	Rheumatoid Arthritis Participants Participants with moderate to severe rheumatoid arthritis (RA) who had been considered and proposed by rheumatologist to start treatment with tocilizumab (RoActemra) according to the indications of the summary of product characteristics and the standard clinical practice of each participating center were followed-up for 6 months.
Overall Study STARTED	120
Overall Study COMPLETED	108
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Measure	Rheumatoid Arthritis Participants Participants with moderate to severe rheumatoid arthritis (RA) who had been considered and proposed by rheumatologist to start treatment with tocilizumab (RoActemra) according to the indications of the summary of product characteristics and the standard clinical practice of each participating center were followed-up for 6 months.
Overall Study Adverse Event	5
Overall Study Lack of Efficacy	4
Overall Study Abnormal laboratory parameters	1
Overall Study Other	2

Baseline Characteristics

A Prospective Observational Study of Tocilizumab (RoActemra/Actemra) in Participants With Rheumatoid Arthritis

Baseline characteristics by cohort

Measure	Rheumatoid Arthritis Participants n=120 Participants Participants with moderate to severe rheumatoid arthritis (RA) who had been considered and proposed by rheumatologist to start treatment with tocilizumab (RoActemra) according to the indications of the summary of product characteristics and the standard clinical practice of each participating center were followed-up for 6 months.
Age, Continuous	52.2 years STANDARD_DEVIATION 12.6 • n=5 Participants
Sex: Female, Male Female	104 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 12

Population: Effectiveness analysis population included all participants who had all measurements of effectiveness and had complete information of the FACIT questionnaire throughout the study. Here, Number of participants analyzed (N) = number of participants evaluable for this measure.

Regression analysis between change in FACIT-F scale and change in following variable were assessed: DAS28-ESR (total score range: 0-9.4, higher score=more disease activity), Epworth sleepiness scale (total score range: 0-24, higher score=higher degree of sleepiness), back depression inventory (total score range: 0-63, score higher than 18 indicates moderate to severe symptoms of depression). The total score of the FACIT-F questionnaire ranges from 0=worse score to 52=better score. Regression coefficient (R) and coefficient of determination (R^2) were calculated. Difference (1-R^2)=the variation in the changes in fatigue not explained by independent variables, that is, independent contribution of these changes in fatigue to the assessment of RA. Only variables with available data were reported.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=65 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Regression Coefficient Between Change in Fatigue Score as Measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) at Week 12 and Change in Main Variables at Week 12 DAS-28	-2.200 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) at Week 12 and Change in Main Variables at Week 12 Sleepiness	-0.944 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) at Week 12 and Change in Main Variables at Week 12 Depression	-0.707 unstandardized regression coefficient

PRIMARY outcome

Timeframe: Week 24

Population: Effectiveness analysis population. Here, N=number of participants evaluable for this measure.

Regression analysis between change in FACIT-F scale and change in following variable were assessed: DAS28-ESR (total score range: 0-9.4, higher score=more disease activity), Epworth sleepiness scale (total score range: 0-24, higher score=higher degree of sleepiness), back depression inventory (total score range: 0-63, score higher than 18 indicates moderate to severe symptoms of depression). The total score of the FACIT-F questionnaire ranges from 0=worse score to 52=better score. Regression coefficient (R) and coefficient of determination (R^2) were calculated. Difference (1-R^2)=the variation in the changes in fatigue not explained by independent variables, that is, independent contribution of these changes in fatigue to the assessment of RA. Only variables with available data were reported.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=71 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 24 and Change in Main Variables at Week 24 DAS-28	-1.743 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 24 and Change in Main Variables at Week 24 Sleepiness	-0.990 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 24 and Change in Main Variables at Week 24 Depression	-0.658 unstandardized regression coefficient

SECONDARY outcome

Timeframe: Baseline, Week 12, Week 24

Population: Effectiveness analysis population.

FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).

Outcome measures

Measure	Rheumatoid Arthritis Participants n=85 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline to Week 12 and 24 in Fatigue Score as Assessed by FACIT-F Baseline	26.8 units on a scale Standard Deviation 12.4
Change From Baseline to Week 12 and 24 in Fatigue Score as Assessed by FACIT-F Change at Week 12	4.6 units on a scale Standard Deviation 10.4
Change From Baseline to Week 12 and 24 in Fatigue Score as Assessed by FACIT-F Change at Week 24	5.4 units on a scale Standard Deviation 11.2

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Population: Effectiveness analysis population. N=participants who were evaluable for this outcome measure. n=number of evaluable participants for each category.

The hemoglobin level was measured in grams per liter (g/L). Baseline data is reported separately for Weeks 12 and 24 to include only those participants who had available data at Weeks 12 and 24, respectively.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=73 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline to Week 12 and 24 in Serum Hemoglobin Baseline for Week 12 (n=70)	12.3 g/L Standard Deviation 1.4
Change From Baseline to Week 12 and 24 in Serum Hemoglobin Change at Week 12 (n=70)	0.7 g/L Standard Deviation 1.2
Change From Baseline to Week 12 and 24 in Serum Hemoglobin Baseline for Week 24 (n=73)	12.4 g/L Standard Deviation 1.5
Change From Baseline to Week 12 and 24 in Serum Hemoglobin Change at Week 24 (n=73)	0.56 g/L Standard Deviation 1.1

SECONDARY outcome

Timeframe: Week 12, 24

Population: Effectiveness analysis population. Here, N=number of participants analyzed for this measure.

Regression analysis between change in FACIT-F scale and change in following variable were assessed: DAS28-ESR (total score range: 0-9.4, higher score=more disease activity), Epworth sleepiness scale (total score range: 0-24, higher score=higher degree of sleepiness), back depression inventory (total score range: 0-63, score higher than 18 indicates moderate to severe symptoms of depression), serum hemoglobin, swollen joint count, morning stiffness (time taken to achieve maximum improvement), degree of pain (assessed on horizontal visual scale, 0=no pain; 10=maximum pain). The total score of the FACIT-F questionnaire ranges from 0=worse score to 52=better score. Regression coefficient (R) and coefficient of determination (R^2) were calculated. Difference (1-R^2)=the variation in the changes in fatigue not explained by independent variables, that is, independent contribution of these changes in fatigue to the assessment of RA. Only variables with available data were reported.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=84 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 DAS-28 (Week 12)	-3.241 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 DAS-28 (Week 24)	-2.596 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 Serum hemoglobin (Week 12)	0.335 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 Serum hemoglobin (Week 24)	-0.242 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 Swollen joint count (Week 12)	-0.333 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 Swollen joint count (Week 24)	-0.600 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 Morning stiffness (Week 12)	-0.559 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 Morning stiffness (Week 24)	-0.718 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 Degree of pain (Week 12)	-0.947 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 Degree of pain (Week 24)	-0.839 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 Sleepiness (Week 12)	-0.742 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 Sleepiness (Week 24)	1.193 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 Depression (Week 12)	-0.714 unstandardized regression coefficient
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 Depression (Week 24)	-0.777 unstandardized regression coefficient

SECONDARY outcome

Timeframe: Week 12, 24

Population: Effectiveness analysis population. N=number of participants analyzed for this measure.

Regression analysis between change in hemoglobin level and change in following variable were assessed: Epworth sleepiness scale (total score range: 0-24, higher score=higher degree of sleepiness), back depression inventory (total score range: 0-63, score higher than 18 indicates moderate to severe symptoms of depression), swollen joint count, morning stiffness (time taken to achieve maximum improvement), degree of pain (assessed on horizontal visual scale, 0=no pain; 10=maximum pain). Hemoglobin level was measure in g/L. The regression coefficient (R) and coefficient of determination (R^2) were calculated. Difference (1-R^2) indicates the variation in the changes in hemoglobin not explained by the independent variables, that is, independent contribution of these changes in hemoglobin to the assessment of RA. Only variables with available data were reported.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=73 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 Swollen joint count (Week 12)	-0.011 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 Swollen joint count (Week 24)	0.028 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 Morning stiffness (Week 12)	0.017 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 Morning stiffness (Week 24)	-0.055 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 Degree of pain (Week 12)	0.021 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 Degree of pain (Week 24)	0.013 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 Sleepiness (Week 12)	0.004 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 Sleepiness (Week 24)	0.062 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 Depression (Week 12)	-0.016 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 Depression (Week 24)	-0.007 unstandardized regression coefficient

SECONDARY outcome

Timeframe: Week 12, 24

Population: Safety analysis population. Here, N=number of participants analyzed for this measure.

Regression analysis between change in hemoglobin level and change in following variable were assessed: Epworth sleepiness scale (total score range: 0-24, higher score=higher degree of sleepiness), back depression inventory (total score range: 0-63, score higher than 18 indicates moderate to severe symptoms of depression), swollen joint count, morning stiffness (time taken to achieve maximum improvement), degree of pain (assessed on horizontal visual scale, 0=no pain; 10=maximum pain). Hemoglobin level was measure in g/L. The regression coefficient (R) and coefficient of determination (R^2) were calculated. Difference (1-R^2) indicates the variation in the changes in hemoglobin not explained by the independent variables, that is, independent contribution of these changes in hemoglobin to the assessment of RA. Only variables with available data were reported.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=84 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 - Safety Population Degree of pain (Week 12)	0.022 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 - Safety Population Swollen joint count (Week 12)	0.025 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 - Safety Population Swollen joint count (Week 24)	0.018 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 - Safety Population Morning stiffness (Week 12)	0.019 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 - Safety Population Morning stiffness (Week 24)	-0.05 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 - Safety Population Degree of pain (Week 24)	0.012 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 - Safety Population Sleepiness (Week 12)	0.002 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 - Safety Population Sleepiness (Week 24)	0.059 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 - Safety Population Depression (Week 12)	-0.02 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 - Safety Population Depression (Week 24)	-0.016 unstandardized regression coefficient

SECONDARY outcome

Timeframe: Week 12, 24

Population: Safety analysis population. N=participants who were evaluable for this outcome measure. n=number of participants evaluable in each category.

Regression analysis between the change in hemoglobin level and number of swollen joints was evaluated. Hemoglobin level was measure in g/L. The regression coefficient (R) and coefficient of determination (R^2) were calculated. Difference (1-R^2) indicates the variation in the changes in hemoglobin not explained by the independent variables, that is, independent contribution of these changes in hemoglobin to the assessment of RA. Only variables with available data were reported.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=98 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in the Number of Swollen Joints (SJC 28) at Week 12 and 24 - Safety Population Week 12 (n=91)	0.186 unstandardized regression coefficient
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in the Number of Swollen Joints (SJC 28) at Week 12 and 24 - Safety Population Week 24 (n=98)	0.005 unstandardized regression coefficient

SECONDARY outcome

Timeframe: Baseline, Week 12, Week 24

Population: Effectiveness analysis population. N=participants who were evaluable for this outcome measure.

Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. Baseline data is reported separately for Weeks 12 and 24 to include only those participants who had available data at Weeks 12 and 24, respectively.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=83 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline in Number of Swollen Joint Count (SJC) at Week 12, 24 Baseline for Week 12	5.9 swollen joints Standard Deviation 4.6
Change From Baseline in Number of Swollen Joint Count (SJC) at Week 12, 24 Change at Week 12	1.9 swollen joints Standard Deviation 3.5
Change From Baseline in Number of Swollen Joint Count (SJC) at Week 12, 24 Baseline for Week 24	6.0 swollen joints Standard Deviation 4.6
Change From Baseline in Number of Swollen Joint Count (SJC) at Week 12, 24 Change at Week 24	1.8 swollen joints Standard Deviation 3.5

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Population: Safety population. N=participants who were evaluable for this outcome measure. n=number of participants evaluable in each category.

Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. Baseline data is reported separately for Weeks 12 and 24 to include only those participants who had available data at Weeks 12 and 24, respectively.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=113 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline in Number of Swollen Joint Count (SJC) at Week 12, 24 - Safety Population Baseline for Week 12 (n=109)	5.7 swollen joints Standard Deviation 4.2
Change From Baseline in Number of Swollen Joint Count (SJC) at Week 12, 24 - Safety Population Change at Week 12 (n=109)	2.1 swollen joints Standard Deviation 4.1
Change From Baseline in Number of Swollen Joint Count (SJC) at Week 12, 24 - Safety Population Baseline for Week 24 (n=113)	5.9 swollen joints Standard Deviation 4.3
Change From Baseline in Number of Swollen Joint Count (SJC) at Week 12, 24 - Safety Population Change at Week 24 (n=113)	1.8 swollen joints Standard Deviation 3.4

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Population: Effectiveness analysis population. N=participants who were evaluable for this outcome measure.

Duration of morning stiffness assessed as time taken to achieve maximum improvement from time participant rises. Baseline data is reported separately for Weeks 12 and 24 to include only those participants who had available data at Weeks 12 and 24, respectively.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=83 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline in Duration of Morning Stiffness at Week 12, 24 Baseline for Week 12	1.4 hours Standard Deviation 2.7
Change From Baseline in Duration of Morning Stiffness at Week 12, 24 Change at Week 12	0.5 hours Standard Deviation 0.9
Change From Baseline in Duration of Morning Stiffness at Week 12, 24 Baseline for Week 24	1.4 hours Standard Deviation 2.8
Change From Baseline in Duration of Morning Stiffness at Week 12, 24 Change at Week 24	0.4 hours Standard Deviation 0.9

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Population: Safety population. N=participants who were evaluable for this outcome measure. n=number of participants evaluable in each category.

Duration of morning stiffness assessed as time taken to achieve maximum improvement from time participant rises. Baseline data is reported separately for Weeks 12 and 24 to include only those participants who had available data at Weeks 12 and 24, respectively.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=112 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline in Duration of Morning Stiffness at Week 12, 24 - Safety Population Change at Week 24 (n=112)	0.4 hours Standard Deviation 0.8
Change From Baseline in Duration of Morning Stiffness at Week 12, 24 - Safety Population Baseline for Week 12 (n=109)	1.4 hours Standard Deviation 2.5
Change From Baseline in Duration of Morning Stiffness at Week 12, 24 - Safety Population Change at Week 12 (n=109)	0.5 hours Standard Deviation 0.8
Change From Baseline in Duration of Morning Stiffness at Week 12, 24 - Safety Population Baseline for Week 24 (n=112)	1.4 hours Standard Deviation 2.5

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Population: Effectiveness analysis population. N=participants who were evaluable for this outcome measure.

Change from Baseline in 10 centimeter (cm) VAS pain score; 10-point pain intensity ordinal rating system: 0 = no pain, 1-3 = mild pain, 4-6 = moderate pain, 7-9 = severe pain, 10 = worst possible pain. Change = scores at observation minus score at Baseline. Baseline data is reported separately for Weeks 12 and 24 to include only those participants who had available data at Weeks 12 and 24, respectively.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=83 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline in Pain Scores as Assessed by Visual Analogue Scale (VAS) at Week 12, 24 Baseline for Week 12	6.8 centimeter Standard Deviation 2.1
Change From Baseline in Pain Scores as Assessed by Visual Analogue Scale (VAS) at Week 12, 24 Change at Week 12	2.57 centimeter Standard Deviation 2.52
Change From Baseline in Pain Scores as Assessed by Visual Analogue Scale (VAS) at Week 12, 24 Baseline for Week 24	6.8 centimeter Standard Deviation 2.1
Change From Baseline in Pain Scores as Assessed by Visual Analogue Scale (VAS) at Week 12, 24 Change at Week 24	2.57 centimeter Standard Deviation 2.95

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Population: Safety population. N=participants who were evaluable for this outcome measure. n=number of participants evaluable in each category.

Change from Baseline in 10 cm VAS pain score; 10-point pain intensity ordinal rating system: 0 = no pain, 1-3 = mild pain, 4-6 = moderate pain, 7-9 = severe pain, 10 = worst possible pain. Change = scores at observation minus score at Baseline. Baseline data is reported separately for Weeks 12 and 24 to include only those participants who had available data at Weeks 12 and 24, respectively.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=112 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline in Pain Scores as Assessed by Visual Analogue Scale (VAS) at Week 12, 24 - Safety Population Baseline for Week 12 (n=107)	6.9 centimeter Standard Deviation 2.0
Change From Baseline in Pain Scores as Assessed by Visual Analogue Scale (VAS) at Week 12, 24 - Safety Population Change at Week 12 (n=107)	2.59 centimeter Standard Deviation 2.5
Change From Baseline in Pain Scores as Assessed by Visual Analogue Scale (VAS) at Week 12, 24 - Safety Population Baseline for Week 24 (n=112)	6.9 centimeter Standard Deviation 2.1
Change From Baseline in Pain Scores as Assessed by Visual Analogue Scale (VAS) at Week 12, 24 - Safety Population Change at Week 24 (n=112)	2.69 centimeter Standard Deviation 2.97

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Population: Effectiveness analysis population. N=participants who were evaluable for this outcome measure. n=number of evaluable participants in each category.

Degree of sleepiness was assessed by Epworth Sleepiness Scale. The Epworth Sleepiness Scale evaluates how likely a person is to doze off or fall asleep in 8 different sedentary situations, using for each item possible scores of 0 to 3 (0=never, 1=mild, 2=moderate and 3=severe). A final score is obtained between 0-24, where a higher score indicates a higher degree of sleepiness. Baseline data is reported separately for Weeks 12 and 24 to include only those participants who had available data at Weeks 12 and 24, respectively.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=83 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline in Sleepiness Score as Assessed on Epworth Sleepiness Scale at Week 12, 24 Baseline for Week 12 (n=82)	6.0 score on a scale Standard Deviation 4.6
Change From Baseline in Sleepiness Score as Assessed on Epworth Sleepiness Scale at Week 12, 24 Change at Week 12 (n=82)	5.4 score on a scale Standard Deviation 5.0
Change From Baseline in Sleepiness Score as Assessed on Epworth Sleepiness Scale at Week 12, 24 Baseline for Week 24 (n=83)	6.1 score on a scale Standard Deviation 4.6
Change From Baseline in Sleepiness Score as Assessed on Epworth Sleepiness Scale at Week 12, 24 Change at Week 24 (n=83)	5.3 score on a scale Standard Deviation 4.4

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Population: Safety population. N=participants who were evaluable for this outcome measure. n=number of participants evaluable in each category.

Degree of sleepiness was assessed by Epworth Sleepiness Scale. The Epworth Sleepiness Scale evaluates how likely a person is to doze off or fall asleep in 8 different sedentary situations, using for each item possible scores of 0 to 3 (0=never, 1=mild, 2=moderate and 3=severe). A final score is obtained between 0-24, where a higher score indicates a higher degree of sleepiness. Baseline data is reported separately for Weeks 12 and 24 to include only those participants who had available data at Weeks 12 and 24, respectively.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=113 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline in Sleepiness Score as Assessed on Epworth Sleepiness Scale at Week 12, 24 - Safety Population Baseline for Week 12 (n=109)	6.4 score on a scale Standard Deviation 5.0
Change From Baseline in Sleepiness Score as Assessed on Epworth Sleepiness Scale at Week 12, 24 - Safety Population Change at Week 12 (n=109)	6.0 score on a scale Standard Deviation 4.4
Change From Baseline in Sleepiness Score as Assessed on Epworth Sleepiness Scale at Week 12, 24 - Safety Population Baseline for Week 24 (n=113)	6.4 score on a scale Standard Deviation 4.5
Change From Baseline in Sleepiness Score as Assessed on Epworth Sleepiness Scale at Week 12, 24 - Safety Population Change at Week 24 (n=113)	5.4 score on a scale Standard Deviation 4.5

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Population: Effectiveness analysis population. N=participants who were evaluable for this outcome measure.

Mood assessed by the Beck Depression Inventory. The Beck Depression Inventory is a 21-item self-administered scale that evaluates severity of depression and is validated in Spanish on a 3 point scale (0=none to 3=severe). It measures the characteristic attitudes and symptoms of depression such as mood, pessimism, sense of failure, self-dissatisfaction, guilt, punishment, self-dislike, self-accusation, etc. The total score ranges from 0 to 63. A score higher than 18 indicates moderate to severe symptoms of depression. Analysis include only those participants who had available data at Weeks 12 and 24, respectively.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=84 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline in Depression Score as Assessed by the Beck Depression Inventory at Week 12, 24 Baseline for Week 12	17.4 score on a scale Standard Deviation 11.7
Change From Baseline in Depression Score as Assessed by the Beck Depression Inventory at Week 12, 24 Change at Week 12	3.07 score on a scale Standard Deviation 9.09
Change From Baseline in Depression Score as Assessed by the Beck Depression Inventory at Week 12, 24 Change at Week 24	3.5 score on a scale Standard Deviation 8.99

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Population: Safety population. N=participants who were evaluable for this outcome measure. n=number of participants evaluable in each category.

Mood assessed by the Beck Depression Inventory. The Beck Depression Inventory is a 21-item self-administered scale that evaluates severity of depression and is validated in Spanish on a 3 point scale (0=none to 3=severe). It measures the characteristic attitudes and symptoms of depression such as mood, pessimism, sense of failure, self-dissatisfaction, guilt, punishment, self-dislike, self-accusation, etc. The total score ranges from 0 to 63. A score higher than 18 indicates moderate to severe symptoms of depression. Baseline data is reported separately for Weeks 12 and 24 to include only those participants who had available data at Weeks 12 and 24, respectively.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=113 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline in Depression Score as Assessed by the Beck Depression Inventory at Week 12, 24 - Safety Population Baseline for Week 12 (n=111)	18.3 score on a scale Standard Deviation 12.6
Change From Baseline in Depression Score as Assessed by the Beck Depression Inventory at Week 12, 24 - Safety Population Change at Week 12 (n=111)	3.5 score on a scale Standard Deviation 9.4
Change From Baseline in Depression Score as Assessed by the Beck Depression Inventory at Week 12, 24 - Safety Population Baseline for Week 24 (n=113)	18.5 score on a scale Standard Deviation 12.7
Change From Baseline in Depression Score as Assessed by the Beck Depression Inventory at Week 12, 24 - Safety Population Change at Week 24 (n=113)	3.89 score on a scale Standard Deviation 11.7

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Population: Effectiveness analysis: All participants who had at least one measurement of effectiveness subsequent to the start of tocilizumab (RoActemra) treatment were included. N=participants who were evaluable for this outcome measure. n=number of evaluable participants in each category.

DAS28-4 erythrocyte sedimentation rate (ESR) was calculated from SJC and tender joint count (TJC) using 28 joints count, ESR millimeter per hour (mm/hr) and patient global assessment (PtGA) of disease activity (participant rated arthritis activity assessment). The DAS28-ESR score (14) was calculated using the following formula: DAS28 = 0.56 x (square root TJC) + 0.28 x (square root SJC) + 0.70 x [Ln(ESR)] + 0.014 x (PtGA).Total score range: 0-9.4, higher score=more disease activity. DAS28-4 (ESR) less than or equal to (<=) 3.2 implied low disease activity and greater than (>)3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) less than (<)2.6 = remission. PtGA measured using a 100 mm VAS ranging from 0 = very good to 100 = very bad. Baseline data is reported separately for Weeks 12 and 24 to include only those participants who had available data at Weeks 12 and 24, respectively.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=71 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline in Disease Activity Scale (DAS28) Score at Week 12, 24 Baseline for Week 12 (n=66)	3.0 score on a scale Standard Deviation 1.2
Change From Baseline in Disease Activity Scale (DAS28) Score at Week 12, 24 Change at Week 12 (n=66)	2.53 score on a scale Standard Deviation 1.2
Change From Baseline in Disease Activity Scale (DAS28) Score at Week 12, 24 Baseline for Week 24 (n=71)	2.7 score on a scale Standard Deviation 1.3
Change From Baseline in Disease Activity Scale (DAS28) Score at Week 12, 24 Change at Week 24 (n=71)	2.73 score on a scale Standard Deviation 1.44

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Population: Safety population. N=participants who were evaluable for this outcome measure.

DAS28-4 ESR was calculated from SJC and TJC using 28 joints count, ESR mm/hr and PtGA of disease activity (participant rated arthritis activity assessment). The DAS28-ESR score (14) was calculated using the following formula: DAS28 = 0.56 x (square root TJC) + 0.28 x (square root SJC) + 0.70 x [Ln(ESR)] + 0.014 x (PtGA).Total score range: 0-9.4, higher score=more disease activity. DAS28-4 (ESR) <=3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = remission. PtGA measured using a 100 mm VAS ranging from 0 = very good to 100 = very bad. Analysis include only those participants who had available data at Weeks 12 and 24, respectively.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=115 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Change From Baseline in Disease Activity Scale (DAS28) Score at Week 12, 24 - Safety Population Baseline for Week 12	5.6 score on a scale Standard Deviation 1.0
Change From Baseline in Disease Activity Scale (DAS28) Score at Week 12, 24 - Safety Population Change at Week 12	2.5 score on a scale Standard Deviation 1.1
Change From Baseline in Disease Activity Scale (DAS28) Score at Week 12, 24 - Safety Population Change at Week 24	2.7 score on a scale Standard Deviation 1.4

SECONDARY outcome

Timeframe: Week 12, 24

Population: Effectiveness analysis population. N=participants who were evaluable for this outcome measure. n=number of evaluable participants in each category.

Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from Baseline. Participants with a score <=3.2 and reduction of >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 nonresponders with response recorded as 'none.' Participants with response is reported. DAS28 is described in outcome measure 19.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=71 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Week 12 and 24 Good response at Week 12 (n=66)	56.1 percentage of participants
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Week 12 and 24 Good response at Week 24 (n=71)	62.0 percentage of participants
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Week 12 and 24 Moderate or good response at Week 12 (n=66)	95.5 percentage of participants
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Week 12 and 24 Moderate or good response at Week 24 (n=71)	93.0 percentage of participants

SECONDARY outcome

Timeframe: Week 12, 24

Population: Safety population. N=participants who were evaluable for this outcome measure. n=number of evaluable participants in each category.

Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from Baseline. Participants with a score <=3.2 and reduction of >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 nonresponders with response recorded as 'none.' Participants with response is reported. DAS28 is described in outcome measure 19.

Outcome measures

Measure	Rheumatoid Arthritis Participants n=115 Participants Participants with moderate to severe rheumatoid arthritis (RA) who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Week 12 and 24 - Safety Population Good response at Week 12 (n=85)	51 percentage of participants
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Week 12 and 24 - Safety Population Good response at Week 24 (n=92)	61 percentage of participants
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Week 12 and 24 - Safety Population Moderate or good response at Week 12 (n=85)	95.3 percentage of participants
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Week 12 and 24 - Safety Population Moderate or good response at Week 24 (n=92)	94.6 percentage of participants

Adverse Events

All Participants

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Measure	All Participants n=120 participants at risk Participants with moderate to severe RA who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Infections and infestations Arthritis infective	0.83% 1/120 • Up to 1.5 year Safety analysis population: All participants who received at least one dose of the tocilizumab.
Infections and infestations Pilonidal cyst	0.83% 1/120 • Up to 1.5 year Safety analysis population: All participants who received at least one dose of the tocilizumab.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.83% 1/120 • Up to 1.5 year Safety analysis population: All participants who received at least one dose of the tocilizumab.
Infections and infestations Acute endocarditis	0.83% 1/120 • Up to 1.5 year Safety analysis population: All participants who received at least one dose of the tocilizumab.
Renal and urinary disorders Pyelonephritis acute	0.83% 1/120 • Up to 1.5 year Safety analysis population: All participants who received at least one dose of the tocilizumab.
Infections and infestations Respiratory tract infection	0.83% 1/120 • Up to 1.5 year Safety analysis population: All participants who received at least one dose of the tocilizumab.
Respiratory, thoracic and mediastinal disorders Rheumatoid lungs	0.83% 1/120 • Up to 1.5 year Safety analysis population: All participants who received at least one dose of the tocilizumab.

Other adverse events

Measure	All Participants n=120 participants at risk Participants with moderate to severe RA who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab (RoActemra) according to the indications of the summary of product characteristics of the product and the standard clinical practice of each participating center were followed-up for 6 months.
Gastrointestinal disorders Aphthous stomatitis	5.8% 7/120 • Up to 1.5 year Safety analysis population: All participants who received at least one dose of the tocilizumab.
Infections and infestations Viral infection	5.0% 6/120 • Up to 1.5 year Safety analysis population: All participants who received at least one dose of the tocilizumab.
Metabolism and nutrition disorders Hypercholesterolemia	13.3% 16/120 • Up to 1.5 year Safety analysis population: All participants who received at least one dose of the tocilizumab.
Vascular disorders Hypertension	5.8% 7/120 • Up to 1.5 year Safety analysis population: All participants who received at least one dose of the tocilizumab.

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER