An Observational Study of the Impact of RoActemra/Actemra on Fatigue in Patients With Rheumatoid Arthritis (PEPS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01185522
First received: August 18, 2010
Last updated: May 16, 2016
Last verified: May 2016
  Purpose
This prospective, observational study will assess the effect of RoActemra/Actemra (tocilizumab) on fatigue in patients with moderate to severe rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs (DMARDS) or anti tumor necrosis factor (anti-TNF) drugs. Eligible patients receiving RoActemra/Actemra according to the standard of care will be followed for 4 months.

Condition
Rheumatoid Arthritis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacoepidemiological Study of the Impact of Roactemra® Treatment on Fatigue in Rheumatoid Arthritis Patients in a Real Life Setting

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With a Clinically Significant Improvement in Fatigue After 4 Months of Tocilizumab Treatment [ Time Frame: At Month 4 ] [ Designated as safety issue: No ]

    Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score assesses self-reported fatigue and its impact upon daily activities and function. It is calculated with 13-item questionnaire on 5-point scale: 0 (not at all) to 4 (very much). The larger the participant's response to the questions (exception of 2 negatively stated), the greater the participants fatigue. For all questions (except for 2 negatively stated), the code is reversed and a new score is calculated as 4 minus the participant's response. The sum of all responses resulted a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the participant's health status. Clinically relevant improvement is defined as a >= 4-point change from Baseline.

    This was performed using the last observation carried forward (LOCF) method and for participants who completed a FACIT-Fatigue score at Month 4 (completers).


  • Number of Participants With Clinically Significant Improvement in Fatigue at Month 4 With Respect to Predictive Factors [ Time Frame: At Month 4 ] [ Designated as safety issue: No ]
    Predictive factors of fatigue were taken into account included gender, age, time since initial diagnosis, Erosive RA, disease activity score (DAS, ranging from 0 [no disease activity] to 10 [worsening in disease activity]), erythrocyte sedimentation rate (ESR), anemia, treatment with corticosteroids, doses of corticosteroids, health assessment questionnaire (HAQ, ranging from 0 [without any difficulty] to 60 [worsening or unable to do physical activities]), FACIT-Fatigue score (ranging from 0 [worse score] to 52 [better score]), visual analogue score (VAS) for fatigue, pain, quality of sleep, and global assessment (ranging from 0 [symptom-free and no arthritis symptoms] to 100 [worsening of symptoms and arthritis disease activity]), Short Form 36 (SF36) vitality score (ranging from 0 [worst] to 100 [best]), Hospital Anxiety and Depression Scale (HADS; represented as score </= 7 [no case], 7 to 10 [doubtful case], and > 10 [certain case of HAD]).

  • Median Clinically Significant Improvement in C-Reactive Protein as a Predictive Factors After 4 Months of Tocilizumab Treatment [ Time Frame: At Month 4 ] [ Designated as safety issue: No ]
    Predictive factors were characteristics of participants that indicated greater or lesser likelihood of responding to a specific treatment regimen. C-reactive protein (CRP) is one of the biomarkers for the diagnosis and assessment of disease activity in RA.

  • Mean Clinically Significant Improvement in Tender Joints and Swollen Joints as Predictive Factors After 4 Months of Tocilizumab Treatment [ Time Frame: At Month 4 ] [ Designated as safety issue: No ]

    Predictive factors were characteristics of participants that indicated greater or lesser likelihood of responding to a specific treatment regimen.

    For tender joint count (TJC), a total of 68 joints were assessed. The presence of a tender joint was scored as 1 and absence as 0. Total score is calculated by adding the scores, which is ranging from 0 (best possible score or no tender joint) to 68 (worse possible score or all tender joints). Lower scores indicate no tender joint and higher scores indicate worsening tender joints.

    For swollen joint count (SJC), a total of 66 joints were assessed. The presence of a tender joint was scored as 1 and absence as 0. Total score is calculated by adding the scores, which is ranging from 0 (best possible score or no swollen joint) to 66 (worse possible score or all swollen joints). Lower scores indicate no swollen joint and higher scores indicate worsening swollen joints.



Secondary Outcome Measures:
  • Baseline Disease Characteristics: Mean Disease Duration [ Time Frame: Baseline (Day [D] 0) ] [ Designated as safety issue: No ]
    Mean disease (rheumatoid arthritis) duration at inclusion was recorded for all participants as baseline disease characteristics.

  • Baseline Disease Characteristics: Number of Participants With Positive Rheumatoid Factor and/or Anti-cyclic Citrullinated Protein Antibodies [ Time Frame: Baseline (D0) ] [ Designated as safety issue: No ]
    Blood was collected for Rheumatoid Factor (RF) at Baseline and was analyzed. RF level was reported in international units/milliliter (IU/mL). All participants were assessed for anti-cyclic citrullinated protein (anti-CCP) antibodies at baseline. Number of participants with a positive RF and/or anti-CCP antibodies were reported as baseline disease characteristics.

  • Baseline Disease Characteristics: Tender Joint Count and Swollen Joint Count [ Time Frame: Baseline (D0) ] [ Designated as safety issue: No ]

    For tender joint count, a total of 68 joints were assessed. The presence of a tender joint was scored as 1 and absence as 0. Total score is calculated by adding the scores, which is ranging from 0 (best possible score or no tender joint) to 68 (worse possible score or all tender joints). Lower scores indicate no tender joint and higher scores indicate worsening tender joints.

    For swollen joint count, a total of 66 joints were assessed. The presence of a tender joint was scored as 1 and absence as 0. Total score is calculated by adding the scores, which is ranging from 0 (best possible score or no swollen joint) to 66 (worse possible score or all swollen joints). Lower scores indicate no swollen joint and higher scores indicate worsening swollen joints. Tender joint count and swollen joint count were assessed at baseline and were used as baseline disease characteristics for assessment of rheumatoid arthritis.


  • Baseline Disease Characteristic: DAS28, Patient's Global Assessment, VAS Pain and HAQ Score as Rheumatoid Arthritis Assessment Parameters [ Time Frame: Baseline (D0) ] [ Designated as safety issue: No ]
    DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/h), and patient's global assessment of disease activity (measured on a 100-mm visual analog scale, where 0 is no disease activity and 100 is maximum disease activity). The DAS28 scale ranges from 0 to 10, where higher scores indicate worsening disease activity. VAS pain score calculated as 0 to 10 cm; where 0 = no pain, and 10 = worst possible pain. HAQ indicates how the disease affected participant's activities of daily life. It consisted of 20 questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale, 0=without any difficulty to 3=unable to do. Sum of scores was divided by number of domains with a score for a total possible score of 0 (best/no difficulties to perform activities) to 3 (worst/ unable to perform activities at all).

  • Baseline Disease Characteristic: Number of Participants With High Erythrocyte Sedimentation Rate, CRP Level, Anemia, and Unacceptable Patient Acceptable Symptom State Fatigue [ Time Frame: Baseline (D0) ] [ Designated as safety issue: No ]
    High Erythrocyte Sedimentation Rate (ESR) was defined as (1) for participants aged up to 50 years: > 15 mm/h for men and > 20 mm/h for women, and (2) for participants aged over 50 years: > 20 mm/h for men and > 25 mm/h for women. Anemia was defined as plasma hemoglobin level <12 gram per deciliter (g/dL) for women and <13 g/dL for men. The CRP test is evaluated for an acute phase reactant of inflammation. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. Patient-Acceptable Symptom State (PASS) that is defined as the highest level of symptom beyond which participants consider themselves well. PASS is a 1-question assessment of how rheumatoid arthritis has affected participant in last 48 hours.

  • Baseline Disease Characteristic: Mean FACIT-Fatigue Score and VAS Fatigue Score [ Time Frame: Baseline (D0) ] [ Designated as safety issue: No ]
    FACIT-fatigue score and VAS fatigue score were fatigue assessment parameters. FACIT-Fatigue score assesses self-reported fatigue and its impact upon daily activities and function. It is calculated with 13-item questionnaire on 5-point scale, 0 (not at all) to 4 (very much). The larger the participant's response to the questions (exception of 2 negatively stated), the greater the participants fatigue. For all questions (except for 2 negatively stated), the code is reversed and a new score is calculated as 4 minus the participant's response. The sum of all responses results a total possible score of 0 (worse score) to 52 (better score). VAS fatigue score ranges from 0 (symptom-free and no arthritis symptoms) to 100 (worsening in symptoms and arthritis disease activity). Clinically relevant improvement is defined as >/= 4-point change from Baseline.

  • Correlation Between Relative Changes From Baseline of FACIT-Fatigue Score and VAS Fatigue to 4 Months of Tocilizumab Treatment [ Time Frame: From Baseline (D0) to Month (M) 4 ] [ Designated as safety issue: No ]
    Correlation between FACIT-Fatigue score and VAS fatigue was evaluated for all participants at inclusion and after 4 months of tocilizumab treatment (relative change from baseline) using a linear regression. FACIT-Fatigue score assesses self-reported fatigue and its impact upon daily activities and function. It is calculated with 13-item questionnaire on 5-point scale, 0 (not at all) to 4 (very much). The larger the participant's response to the questions (exception of 2 negatively stated), the greater the participants fatigue. For all questions (except for 2 negatively stated), the code is reversed and a new score is calculated as 4 minus the participant's response. The sum of all responses results a total possible score of 0 (worse score) to 52 (better score). VAS fatigue score ranging from 0 (symptom-free and no arthritis symptoms) to 100 (worsening in symptoms and arthritis disease activity)

  • Median Time to Onset of an Improvement of the FACIT-Fatigue Score [ Time Frame: Up to Month 4 ] [ Designated as safety issue: No ]
    The time of onset of a clinically significant improvement of fatigue was defined as the time between the date of the first tocilizumab infusion and the date of the first increase of at least 4 points of the FACIT-Fatigue score (date of questionnaire completion) during 4 months of tocilizumab treatment. FACIT-Fatigue score assesses self-reported fatigue and its impact upon daily activities and function. It is calculated with 13-item questionnaire on 5-point scale, 0 (not at all) to 4 (very much). The larger the participant's response to the questions (exception of 2 negatively stated), the greater the participants fatigue. For all questions (except for 2 negatively stated), the code is reversed and a new score is calculated as 4 minus the participant's response. The sum of all responses results a total possible score of 0 (worse score) to 52 (better score).

  • Relative Median Change From Baseline in DAS 28 and VAS Patient's Global Assessment to Month 1, Month 2, Month 3, and Month 4 [ Time Frame: From Baseline (D0) to M 1, M 2, M 3, and M 4 ] [ Designated as safety issue: No ]
    Relative change from Baseline (BL) in DAS 28 was evaluated for all participants at each evaluation time (on raw data at inclusion; at Month 1, Month 2, Month 3, and Month 4 using a linear regression. DAS-28 and VAS patient's global assessment (PGA) were described as continuous variables for all participants at each evaluation time points (Baseline to M4). DAS 28 ranging from 0 (no disease activity) to 10 (worsening in disease activity) and VAS PGA ranging from 0 (symptom-free and no arthritis symptoms) to 100 (worsening of symptoms and arthritis disease activity),

  • Relative Median Change From Baseline in Disease Activity (Tender Joint Count and Swollen Joint Count) to Month 1, Month 2, Month 3, and Month 4 [ Time Frame: From Baseline (D0) to M 1, M 2, M 3, and M 4 ] [ Designated as safety issue: No ]

    Relative change (RC) from Baseline (BL) in disease activity included TJC and SJC was evaluated as continuous variables for all participants at each evaluation time points.

    For tender joint count, a total of 68 joints were assessed. The presence of a tender joint was scored as 1 and absence as 0. Total score is calculated by adding the scores, which is ranging from 0 (best possible score or no tender joint) to 68 (worse possible score or all tender joints). Lower scores indicate no tender joint and higher scores indicate worsening tender joints. For swollen joint count, a total of 66 joints were assessed. The presence of a tender joint was scored as 1 and absence as 0. Total score is calculated by adding the scores, which is ranging from 0 (best possible score or no swollen joint) to 66 (worse possible score or all swollen joints). Lower scores indicate no swollen joint and higher scores indicate worsening swollen joints.


  • Relative Median Change From Baseline in ESR to Month 1, Month 2, Month 3, and Month 4 [ Time Frame: From Baseline (D0) to M 1, M 2, M 3, and M 4 ] [ Designated as safety issue: No ]
    The correlation between fatigue and ESR value was evaluated for all participants at each evaluation time (on raw data at inclusion; on relative changes at M1 to M4) using a linear regression. ESR values were described as continuous variables for all participants at each evaluation time (Baseline to M4).

  • Relative Median Change From Baseline in C - Reacting Protein at Month 1, Month 2, Month 3, and Month 4 [ Time Frame: From Baseline (D0) to M 1, M 2, M 3, and M 4 ] [ Designated as safety issue: No ]
    The correlation between fatigue and CRP value was evaluated for all participants at each evaluation time (on raw data at inclusion; on relative changes at M1 to M4) using a linear regression. CRP values were described as continuous variables for all participants at each evaluation time (Baseline to M4).

  • Number of Participants Achieving PASS Score at Baseline (Day 0) and Month 4 [ Time Frame: Baseline (D0) and Month 4 ] [ Designated as safety issue: No ]
    A PASS score at Day 0 and Month 4 calculated on participants with acceptable symptom state. PASS is defined as the highest level of symptom beyond which participants consider themselves well. PASS is a 1-question assessment of how rheumatoid arthritis has affected participant in last 48 hours.

  • Percentage of Participants With FACIT-Fatigue Score, SF36 Vitality Score, and VAS Fatigue at Day 0 and Month 4 [ Time Frame: Baseline (D0) and Month 4 ] [ Designated as safety issue: No ]
    FACIT-Fatigue score (ranging from 0 [worse score] to 52 [better score]), VAS (ranging from 0 [symptom-free and no arthritis symptoms] to 100 [worsening in arthritis disease activity]) and SF36 vitality score (ranging from 0 [worst] to 100 [best]) were calculated at Baseline and Month 4.

  • Correlations Between Fatigue and Other Participant Reported Outcomes at Day 0 and Month 4 [ Time Frame: Day 0 and Month 4 ] [ Designated as safety issue: No ]
    Fatigue was assessed by FACIT-Fatigue scale (ranging from 0 [worse score] to 52 [better score]) and VAS fatigue (ranging from 0 [symptom-free and no arthritis symptoms] to 100 [worsening of symptoms and arthritis disease activity]). Other participant reported outcomes (PROs) were VAS for pain and quality of sleep (ranging from 0 [symptom-free and no arthritis symptoms] to 100 [worsening in arthritis disease activity]), SF36 vitality score (ranging from 0 [worst] to 100 [best]) and HAD score (calculated using the 14 items and each item was scored 0, 1, 2 or 3 where a score of 3 corresponds to the most anxious/depressed. 7-item depression and 7-item anxiety subscales were summed; each resulting in a total score of 0-21). Correlation between fatigue as assessed by FACIT-Fatigue score or VAS fatigue was evaluated for all participants using a linear regression and were reported for D0 and M4.

  • Number of Participants for Rheumatoid Arthritis Management With Tocilizumab Treatment up to Month 4 [ Time Frame: From Baseline (D0) to M 1, M 2, M 3, and M 4 ] [ Designated as safety issue: No ]
    Participants with tocilizumab treatment were managed according to number of tocilizumab treatment received according to Summary of Product Characteristics recommendations, as 8 mg/kg, dose duration of 1-hour, correct infusion progress; and received DMARD, methotrexate, and corticosteroids concomitantly with tocilizumab during Months 1 to 4.

  • Number of Participants With Any Adverse Events and Serious Adverse Events [ Time Frame: Up to 4 months ] [ Designated as safety issue: No ]
    An Any Adverse Events (AEs) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An Serious Adverse Events (SAEs) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.


Enrollment: 719
Study Start Date: January 2010
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
Tocilizumab
Eligible participants receiving tocilizumab according to summary of product characteristics in a real life setting will be observed for 4 months

  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 inadequate response to DMARDs or anti-TNF receiving RoActemra/Actemra according to standard of care
Criteria

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Moderate to severe rheumatoid arthritis
  • Inadequate response to disease-modifying antirheumatic drugs (DMARDS) or anti-TNF (tumor necrosis factor) drugs

Exclusion Criteria:

  • Hypersensitivity to RoActemra/Actemra or any component
  • Active infection
  • Participation in a clinical trial in rheumatoid arthritis
  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: NCT01185522

Locations
France
Neuilly-sur-seine, France, 92521
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01185522     History of Changes
Other Study ID Numbers: ML22457 
Study First Received: August 18, 2010
Results First Received: March 30, 2016
Last Updated: May 16, 2016
Health Authority: France: Commission Nationale de l'Informatique et des Libertés (CNIL)

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

ClinicalTrials.gov processed this record on July 21, 2016