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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01462162
First received: October 27, 2011
Last updated: September 8, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention
Rheumatoid Arthritis
Drug: Tocilizumab

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Prospective Observational Study to Evaluate and Correlate the Impact of Treatment With Tocilizumab (RoActemra®) on Fatigue and Different Factors Influencing Fatigue in Participants With Rheumatoid Arthritis in Routine Clinical Practice

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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:
  • Change From Baseline to Week 12 and 24 in Fatigue Score as Assessed by FACIT-F [ Time Frame: Baseline, Week 12, Week 24 ] [ Designated as safety issue: No ]
    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 to Week 12 and 24 in Serum Hemoglobin [ Time Frame: Baseline, Week 12, 24 ] [ Designated as safety issue: No ]
    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 Fatigue Score as Measured by the FACIT-F at Week 12 and 24 With Change in Disease Activity Parameters at Week 12 and 24 [ Time Frame: Week 12, 24 ] [ Designated as safety issue: No ]
    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.

  • Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 [ Time Frame: Week 12, 24 ] [ Designated as safety issue: No ]
    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.

  • Regression Coefficient Between Change in Hemoglobin Level at Week 12, 24 and Change in Disease Activity at Week 12 and 24 - Safety Population [ Time Frame: Week 12, 24 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Week 12, 24 ] [ Designated as safety issue: No ]
    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 Number of Swollen Joint Count (SJC) at Week 12, 24 [ Time Frame: Baseline, Week 12, Week 24 ] [ Designated as safety issue: No ]
    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 Number of Swollen Joint Count (SJC) at Week 12, 24 - Safety Population [ Time Frame: Baseline, Week 12, 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12, 24 ] [ Designated as safety issue: No ]
    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 Duration of Morning Stiffness at Week 12, 24 - Safety Population [ Time Frame: Baseline, Week 12, 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12, 24 ] [ Designated as safety issue: No ]
    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 Pain Scores as Assessed by Visual Analogue Scale (VAS) at Week 12, 24 - Safety Population [ Time Frame: Baseline, Week 12, 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Sleepiness Score as Assessed on Epworth Sleepiness Scale at Week 12, 24 [ Time Frame: Baseline, Week 12, 24 ] [ Designated as safety issue: No ]
    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 in Sleepiness Score as Assessed on Epworth Sleepiness Scale at Week 12, 24 - Safety Population [ Time Frame: Baseline, Week 12, 24 ] [ Designated as safety issue: No ]
    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 in Depression Score as Assessed by the Beck Depression Inventory at Week 12, 24 [ Time Frame: Baseline, Week 12, 24 ] [ Designated as safety issue: No ]
    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 Depression Score as Assessed by the Beck Depression Inventory at Week 12, 24 - Safety Population [ Time Frame: Baseline, Week 12, 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Disease Activity Scale (DAS28) Score at Week 12, 24 [ Time Frame: Baseline, Week 12, 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12, 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Week 12 and 24 [ Time Frame: Week 12, 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Week 12 and 24 - Safety Population [ Time Frame: Week 12, 24 ] [ Designated as safety issue: No ]
    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.


Enrollment: 122
Study Start Date: September 2011
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Rheumatoid Arthritis 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 will be followed-up for 6 months.
Drug: Tocilizumab
Other Names:
  • RoActemra
  • Actemra

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with Rheumatoid Arthritis
Criteria

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • Participants previously or currently treated with RoActemra/Actemra in clinical trials
  • Absolute neutrophil count less than or equal to (</=) 2x10^9 per liter (/L)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01462162

Locations
Spain
Hospitalet de Llobregat, Barcelona, Spain, 08906
Mollet del Valles, Barcelona, Spain, 08100
Sabadell, Barcelona, Spain, 08208
Sant Joan Despi, Barcelona, Spain, 08970
A Coruña, La Coruña, Spain, 15405
Cartagena, Murcia, Spain, 30203
El Palmar, Murcia, Spain, 30120
Lorca, Murcia, Spain, 30800
Ourense, Orense, Spain, 32005
Vigo, Pontevedra, Spain, 36204
Barcelona, Spain, 08035
Barcelona, Spain, 08907
Girona, Spain, 17002
Lugo, Spain, 27880
Tarragona, Spain, 43003
Tarragona, Spain, 43204
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01462162     History of Changes
Other Study ID Numbers: ML27833 
Study First Received: October 27, 2011
Results First Received: December 1, 2015
Last Updated: September 8, 2016
Health Authority: Spain: Agencia Espanola de Medicamentos y Productos Sanitarios

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on December 05, 2016