A Prospective Observational Study of Tocilizumab (RoActemra/Actemra) in Participants With Rheumatoid Arthritis
- Registration Number
- NCT01462162
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This prospective observational study will investigate the effect of tocilizumab on fatigue in participants with moderate to severe rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs or anti-tumour necrosis factor (anti-TNF) drugs. Data will be collected from participants for 6 months.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 122
- Participants with moderate to severe RA who have been considered and proposed by the rheumatologist to start treatment with Tocilizumab according to his/her clinical judgment and the conditions approved in the Summary of Product Characteristics (SPC).
- Participants previously or currently treated with RoActemra/Actemra in clinical trials
- Absolute neutrophil count less than or equal to (</=) 2x10^9 per liter (/L)
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Rheumatoid Arthritis Participants Tocilizumab 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 will be followed-up for 6 months.
- Primary Outcome Measures
Name Time Method 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 Week 12 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.
Regression Coefficient Between Change in Fatigue Score as Measured by the FACIT-F at Week 24 and Change in Main Variables at Week 24 Week 24 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.
- Secondary Outcome Measures
Name Time Method Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 Week 12, 24 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.
Change From Baseline in Pain Scores as Assessed by Visual Analogue Scale (VAS) at Week 12, 24 Baseline, Week 12, 24 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.
Change From Baseline in Sleepiness Score as Assessed on Epworth Sleepiness Scale at Week 12, 24 Baseline, Week 12, 24 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.
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Week 12 and 24 Week 12, 24 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.
Change From Baseline to Week 12 and 24 in Fatigue Score as Assessed by FACIT-F Baseline, Week 12, Week 24 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).
Change From Baseline in Sleepiness Score as Assessed on Epworth Sleepiness Scale at Week 12, 24 - Safety Population Baseline, Week 12, 24 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.
Change From Baseline to Week 12 and 24 in Serum Hemoglobin Baseline, Week 12, 24 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.
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, 24 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.
Change From Baseline in Duration of Morning Stiffness at Week 12, 24 Baseline, Week 12, 24 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.
Change From Baseline in Depression Score as Assessed by the Beck Depression Inventory at Week 12, 24 Baseline, Week 12, 24 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.
Change From Baseline in Disease Activity Scale (DAS28) Score at Week 12, 24 Baseline, Week 12, 24 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.
Change From Baseline in Disease Activity Scale (DAS28) Score at Week 12, 24 - Safety Population Baseline, Week 12, 24 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.
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 Week 12, 24 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.
Change From Baseline in Number of Swollen Joint Count (SJC) at Week 12, 24 - Safety Population Baseline, Week 12, 24 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.
Change From Baseline in Duration of Morning Stiffness at Week 12, 24 - Safety Population Baseline, Week 12, 24 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.
Change From Baseline in Pain Scores as Assessed by Visual Analogue Scale (VAS) at Week 12, 24 - Safety Population Baseline, Week 12, 24 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.
Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 - Safety Population Week 12, 24 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.
Change From Baseline in Number of Swollen Joint Count (SJC) at Week 12, 24 Baseline, Week 12, Week 24 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.
Change From Baseline in Depression Score as Assessed by the Beck Depression Inventory at Week 12, 24 - Safety Population Baseline, Week 12, 24 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.
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Week 12 and 24 - Safety Population Week 12, 24 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.