Back to resultsA Study of Glucocorticoid Use to Evaluate Systematic Methylprednisolone Reduction in Patients With Rheumatoid Arthritis on Background RoActemra/Actemra (Tocilizumab) (ACT-ALONE)
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
methylprednisolone
tocilizumab [RoActemra/Actemra]
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
Non-interventional phase
- Adult patients, >/=18 years of age
- Moderate to severe active rheumatoid arthritis defined as Disease Activity Score using 28-joint count (DAS28) >/=5.1
- Patients with inadequate clinical response to a current treatment with 2 or more non-biologic disease-modifying anti-rheumatic drugs (DMARDs), one of them being methotrexate (MTX) optimally administered during a period of more than 3 months or inadequate response to a current anti-TNF therapy
- Current use of oral glucocorticoids started at least 4 weeks prior to enrolment Interventional phase
- Patients enrolled in the non-interventional phase
- Patients with low disease activity defined as DAS28 </=3.2 at Visit 2
- Use of oral glucocorticoids with methylprednisolone equivalent dose of >/=1mg and </=20mg/day at Visit 2
Exclusion Criteria:
Non-interventional & interventional phase
- Rheumatic autoimmune disease other than rheumatoid arthritis, or significant systemic involvement secondary to rheumatoid arthritis
- Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in rheumatoid arthritis
- Prior history or current inflammatory joint disease other than rheumatoid arthritis (e.g. gout)
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Outcomes
Primary Outcome Measures
Median GC Dose Taken During the Noninterventional Phase
During the noninterventional phase of the study participants received GC as prescribed by the physician. Doses of all GC administered are expressed as MP equivalents.
Number of Participants With GC Switches During the Noninterventional Phase
During the noninterventional phase of the study, once LDA was achieved, GC was switched to MP tablets.
Type of GC Taken at the End of the Noninterventional Phase
During the noninterventional phase of the study participants received GC as prescribed by the physician.
Percentage of Participants in the Interventional Phase Who Achieved LDA and Discontinued Oral GC Within 20 Weeks
The percentage of participants with rheumatoid arthritis (RA) with LDA was defined as DAS28 ≤3.2, able to discontinue oral GC within 20 weeks and at the latest at V8, confirmed at the Consolidation Visit without loss of clinical response defined as DAS28 (CRP) >3.2.
Secondary Outcome Measures
Percentage of Participants Able to Acheive LDA Assessed Using DAS28 While Receiving Oral GC on Background Tocilizumab Treatment During the Noninterventional Phase
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the CRP and Patient's Global Assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 and oral GC intake with MP equivalent dose of ≥1 mg and ≤20 mg/day= LDA.
Percentage of Participants Acheiving Remission Assessed Using DAS28 While Receiving Oral GC on Background TocilizumabTreatment During the Noninterventional Phase
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the CRP and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <2.6 = remission.
Percentage of Participants With Erosions During the NonInterventional Phase
In RA, the presence, number and size of bone erosions and the number of joints with erosions on conventional radiographs (CRs) are hallmarks for diagnosis, staging and prediction of damage progression and are used for treatment monitoring in randomized controlled studies.
Number of Erosions During the NonInterventional Phase
In RA, the presence, number, and size of bone erosions and the number of joints with erosions on CRs are hallmarks for diagnosis, staging and prediction of damage progression and are used for treatment monitoring in randomized controlled studies.
Percentage of Participants Positive for Rheumatoid Factor (RF) During the Noninterventional Phase
RF is the auto antibody directed against immunoglobulin G (IgG) and its concentration is observed in human serum or plasma. RF value higher than 20 units per milliliter (U/mL) is considered positive.
Percentage of Participants Positive for Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibody During the Noninterventional Phase
Anti-CCP antibodies are important markers of bone erosion in RA. Anti-CCP antibodies were classified as positive if >7 U/mL.
Health Assessment Questionnaire Disability Index (HAQ-DI) During the Noninterventional Phase
HAQ-DI is a self-reported, valid assessment of functional disability in RA. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ-DI score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. Timepoint was V2, or before V2 for participants withdrawn before V2.
DAS28-CRP During the Noninterventional Phase
DAS28-CRP was calculated from the swollen joint count (SJC) and tender joint count (TJC) using the 28-joint count and CRP (mg/L). Total score range: 0 to 10, higher score indicated more disease activity. DAS28-CRP ≤3.2=LDA and >3.2 to 5.1=moderate to high disease activity, and DAS28-CRP <2.6=remission. Timepoint was V2, or before V2 for participants withdrawn before V2; DAS28-CRP values indicated in the Case Report Form (CRF) were recalculated by the data manager. The recalculated values were used in the statistical analyses.
DAS28-ESR During the Noninterventional Phase
DAS28-ESR was calculated from the SJC and TJC using the 28 joints count and ESR (millimeters per hour [mm/hr]). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-ESR ≤3.2=LDA and >3.2 to 5.1=moderate to high disease activity, and DAS28-ESR <2.6=remission. Timepoint was V2, or before V2 for participants withdrawn before V2; DAS28-ESR values indicated in the CRF were recalculated by the data manager. The recalculated values were used in the statistical analyses.
Clinical Disease Activity Index (CDAI) During the Noninterventional Phase
The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and Physician Global Assessment (PGA) of disease assessed on 0-100 mm Visual analog scale (VAS); higher scores=greater affection due to disease activity. CDAI total score=0-76. CDAI ≤2.8=disease remission, >2.8 to 10=LDA, >10 to 22=moderate disease activity, and >22=high disease activity.
Median Time Interval Between V1 and V2
The noninterventional phase was planned to last for a maximum of 6 months per participant. The time between V1 and V2 was measured in months.
Median Dose of Tocilizumab During the Noninterventional Phase
Number of Participants With Changes in Tocilizumab Dose During the Noninterventional Phase
The dose of tocilizumab could have been reduced from the recommended 8 mg/kg to 4 mg/kg in participants in the case of adverse events.
Percentage of Participants With Changes in RA Treatment During the Noninterventional Phase
Percentage of Participants Able to Start the GC Reduction Phase at V3
All participants who maintained LDA (defined as DAS28-CRP ≤3.2) from V2 to V3 were included in the interventional phase for reduction of GC.
Percentage of Participants Able to Reduce Oral GCs by ≥50 Percent (%) During the Interventional Phase by V9
Percentage of Participants Able to Discontinue GCs During the Interventional Phase by V9
Time-Averaged GC Dose Changes During the Interventional Phase
Area Under the Curve (AUC) of GC dose during the interventional phase was determined using the trapezoidal method and was calculated as:
AUC = sigma(Ti+1 - Ti) x [(Di+1+Di)/2]
With Di=dosage at time Ti
It corresponds to the total GC dose received between Baseline (visit 3) and visit 9 and has been calculated only for the 30 patients achieving visit 9.
DAS28-CRP During the Interventional Phase
DAS28-CRP was calculated from the SJC and TJC using the 28-joint count and CRP (mg/L). Total score range: 0 to 10, higher score indicated more disease activity. DAS28-CRP) ≤3.2=LDA and >3.2 to 5.1=moderate to high disease activity, and DAS28-CRP <2.6=remission. DAS28-CRP values indicated in the CRF were recalculated by the data manager. The cumulative DAS28 (CRP) value (AUC method) was performed using the calculated DAS28. The recalculated values were used in the statistical analyses.
HAQ-DI During the Interventional Phase
HAQ-DI is a self-reported, valid assessment of functional disability in RA. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ-DI score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. V3, CV, and the change from V3 to CV was determined.
VAS-Physician's Global Assessment of Disease Activity (GDA) During the Interventional Phase
Physician's were asked to determine the overall GDA for each participant using a 100-mm VAS, where 0=no disease activity and 100=maximum disease activity. The physician marked the line corresponding to their assessment and the distance from the left edge was measured. V3, CV, and the change from V3 to CV was determined.
VAS for Pain (VAS-Pain) During the Interventional Phase
Participants were asked to mark the line corresponding to the intensity of their pain on a 100-mm VAS, where 0=no pain and 100=worst possible pain. The distance from the left edge was measured. Change = V3 mean minus CV mean.
SJC and TJC During the Interventional Phase
TJC and SJC were assessed for 28 joints. An assessment of 28 joints for swelling and tenderness was made. Joints were assessed and classified as swollen (1)/not swollen (0) and tender (1)/not tender (0) by pressure and joint manipulation on physical examination for a total score range of 0-28. Higher scores indicated greater disease activity (tenderness/swelling). V3, CV, and the change from V3 to CV was determined.
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score During the Interventional Phase
FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater 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-F score for a total possible score of 0 (worse score) to 52 (better score). V3, CV, and the change from V3 to CV was determined.
Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase
36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component scores (PCS and MCS). Total of 11 variables were analyzed (8 subscales, 2 composite subscales and Question 2 "how would you rate your health in general now?" (range 1= better, 5= worst). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Higher scores reflect higher quality of life. V3, CV, and the change from V3 to CV was determined.
SF-36 Subscale Scores During the Interventional Phase
SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component scores (PCS and MCS). Total of 11 variables were analyzed (8 subscales, 2 composite subscales and Question 2 "how would you rate your health in general now?" (range 1= better, 5= worst). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Higher scores reflect higher quality of life. V3, CV, and the change from V3 to CV was determined.
CDAI Score During the Interventional Phase
The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on 0-100 mm VAS; higher scores=greater affection due to disease activity. CDAI total score=0-76. CDAI ≤2.8=disease remission, >2.8 to 10=LDA, >10 to 22=moderate disease activity, and >22=high disease activity. V3, CV, and the change from V3 to CV was determined.
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI
The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on 0-100 mm VAS; higher scores=greater affection due to disease activity. CDAI total score=0-76. CDAI ≤2.8=disease remission and >2.8 to 10=LDA.
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP
DAS28 calculated from the number of swollen joints (SJC) and tender joints (TJC) using the 28 joint count, the CRP and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28-CRP ≤3.2 and oral GC intake with MP equivalent dose of ≥1 mg and ≤20 mg/day=LDA; DAS28 <2.6 = remission.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01219933
Brief Title
A Study of Glucocorticoid Use to Evaluate Systematic Methylprednisolone Reduction in Patients With Rheumatoid Arthritis on Background RoActemra/Actemra (Tocilizumab) (ACT-ALONE)
Official Title
An Open-label, Single-arm Study to Describe Glucocorticoid Use in Rheumatoid Arthritis Patients Treated With Tocilizumab in Daily Clinical Practice and to Evaluate Systematic Glucocorticoid Dose Reduction Once Low Disease Activity is Reached (ACT-ALONE)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
This open-label, single-arm study will assess the use of glucocorticoids (GC) in daily clinical practice and will evaluate the dose reduction of glucocorticoids once low disease activity is achieved in patients with rheumatoid arthritis tre ated with GC and background RoActemra/Actemra (tocilizumab) 8mg/kg intravenously every 4 weeks. In the non-interventional phase, the use of GC in daily clinical Belgian practice will be evaluated and described. This period of maximum 6 mont hs will allow those patients to obtain the inclusion criteria for the secondary interventional phase. In the interventional phase, a systematic GC dose reductio n schedule will be evaluated in patients having achieved low disease activity wh ile receiving the same background therapy with RoActemra/Actemra 8 mg/kg. Methyl prednisolone will be given from a starting dose of >/= 1 mg to </=20 mg orally d aily and will be tapered down. The anticipated study duration is up to 13 months
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
68 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Intervention Description
starting dose >/= 1 mg and </= 20 mg orally daily, according to dose-reduction schedule
Intervention Type
Drug
Intervention Name(s)
tocilizumab [RoActemra/Actemra]
Intervention Description
background therapy: 8 mg/kg iv every 4 weeks
Primary Outcome Measure Information:
Title
Median GC Dose Taken During the Noninterventional Phase
Description
During the noninterventional phase of the study participants received GC as prescribed by the physician. Doses of all GC administered are expressed as MP equivalents.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Number of Participants With GC Switches During the Noninterventional Phase
Description
During the noninterventional phase of the study, once LDA was achieved, GC was switched to MP tablets.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Type of GC Taken at the End of the Noninterventional Phase
Description
During the noninterventional phase of the study participants received GC as prescribed by the physician.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Percentage of Participants in the Interventional Phase Who Achieved LDA and Discontinued Oral GC Within 20 Weeks
Description
The percentage of participants with rheumatoid arthritis (RA) with LDA was defined as DAS28 ≤3.2, able to discontinue oral GC within 20 weeks and at the latest at V8, confirmed at the Consolidation Visit without loss of clinical response defined as DAS28 (CRP) >3.2.
Time Frame
Visits 3 (7 months), 4 (8 months), 5 (9 months), 6 (10 months), 7 (11 months), and 8 (12 months)
Secondary Outcome Measure Information:
Title
Percentage of Participants Able to Acheive LDA Assessed Using DAS28 While Receiving Oral GC on Background Tocilizumab Treatment During the Noninterventional Phase
Description
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the CRP and Patient's Global Assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 and oral GC intake with MP equivalent dose of ≥1 mg and ≤20 mg/day= LDA.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Percentage of Participants Acheiving Remission Assessed Using DAS28 While Receiving Oral GC on Background TocilizumabTreatment During the Noninterventional Phase
Description
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the CRP and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <2.6 = remission.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Percentage of Participants With Erosions During the NonInterventional Phase
Description
In RA, the presence, number and size of bone erosions and the number of joints with erosions on conventional radiographs (CRs) are hallmarks for diagnosis, staging and prediction of damage progression and are used for treatment monitoring in randomized controlled studies.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Number of Erosions During the NonInterventional Phase
Description
In RA, the presence, number, and size of bone erosions and the number of joints with erosions on CRs are hallmarks for diagnosis, staging and prediction of damage progression and are used for treatment monitoring in randomized controlled studies.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Percentage of Participants Positive for Rheumatoid Factor (RF) During the Noninterventional Phase
Description
RF is the auto antibody directed against immunoglobulin G (IgG) and its concentration is observed in human serum or plasma. RF value higher than 20 units per milliliter (U/mL) is considered positive.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Percentage of Participants Positive for Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibody During the Noninterventional Phase
Description
Anti-CCP antibodies are important markers of bone erosion in RA. Anti-CCP antibodies were classified as positive if >7 U/mL.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Health Assessment Questionnaire Disability Index (HAQ-DI) During the Noninterventional Phase
Description
HAQ-DI is a self-reported, valid assessment of functional disability in RA. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ-DI score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. Timepoint was V2, or before V2 for participants withdrawn before V2.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
DAS28-CRP During the Noninterventional Phase
Description
DAS28-CRP was calculated from the swollen joint count (SJC) and tender joint count (TJC) using the 28-joint count and CRP (mg/L). Total score range: 0 to 10, higher score indicated more disease activity. DAS28-CRP ≤3.2=LDA and >3.2 to 5.1=moderate to high disease activity, and DAS28-CRP <2.6=remission. Timepoint was V2, or before V2 for participants withdrawn before V2; DAS28-CRP values indicated in the Case Report Form (CRF) were recalculated by the data manager. The recalculated values were used in the statistical analyses.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
DAS28-ESR During the Noninterventional Phase
Description
DAS28-ESR was calculated from the SJC and TJC using the 28 joints count and ESR (millimeters per hour [mm/hr]). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-ESR ≤3.2=LDA and >3.2 to 5.1=moderate to high disease activity, and DAS28-ESR <2.6=remission. Timepoint was V2, or before V2 for participants withdrawn before V2; DAS28-ESR values indicated in the CRF were recalculated by the data manager. The recalculated values were used in the statistical analyses.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Clinical Disease Activity Index (CDAI) During the Noninterventional Phase
Description
The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and Physician Global Assessment (PGA) of disease assessed on 0-100 mm Visual analog scale (VAS); higher scores=greater affection due to disease activity. CDAI total score=0-76. CDAI ≤2.8=disease remission, >2.8 to 10=LDA, >10 to 22=moderate disease activity, and >22=high disease activity.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Median Time Interval Between V1 and V2
Description
The noninterventional phase was planned to last for a maximum of 6 months per participant. The time between V1 and V2 was measured in months.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Median Dose of Tocilizumab During the Noninterventional Phase
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Number of Participants With Changes in Tocilizumab Dose During the Noninterventional Phase
Description
The dose of tocilizumab could have been reduced from the recommended 8 mg/kg to 4 mg/kg in participants in the case of adverse events.
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Percentage of Participants With Changes in RA Treatment During the Noninterventional Phase
Time Frame
V1 and V2 (up to 6 months after V1)
Title
Percentage of Participants Able to Start the GC Reduction Phase at V3
Description
All participants who maintained LDA (defined as DAS28-CRP ≤3.2) from V2 to V3 were included in the interventional phase for reduction of GC.
Time Frame
V3 (7 months)
Title
Percentage of Participants Able to Reduce Oral GCs by ≥50 Percent (%) During the Interventional Phase by V9
Time Frame
V9 (24 weeks after V3)
Title
Percentage of Participants Able to Discontinue GCs During the Interventional Phase by V9
Time Frame
V9 (24 weeks after V3)
Title
Time-Averaged GC Dose Changes During the Interventional Phase
Description
Area Under the Curve (AUC) of GC dose during the interventional phase was determined using the trapezoidal method and was calculated as:
AUC = sigma(Ti+1 - Ti) x [(Di+1+Di)/2]
With Di=dosage at time Ti
It corresponds to the total GC dose received between Baseline (visit 3) and visit 9 and has been calculated only for the 30 patients achieving visit 9.
Time Frame
V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Title
DAS28-CRP During the Interventional Phase
Description
DAS28-CRP was calculated from the SJC and TJC using the 28-joint count and CRP (mg/L). Total score range: 0 to 10, higher score indicated more disease activity. DAS28-CRP) ≤3.2=LDA and >3.2 to 5.1=moderate to high disease activity, and DAS28-CRP <2.6=remission. DAS28-CRP values indicated in the CRF were recalculated by the data manager. The cumulative DAS28 (CRP) value (AUC method) was performed using the calculated DAS28. The recalculated values were used in the statistical analyses.
Time Frame
V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Title
HAQ-DI During the Interventional Phase
Description
HAQ-DI is a self-reported, valid assessment of functional disability in RA. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ-DI score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. V3, CV, and the change from V3 to CV was determined.
Time Frame
Visit 3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Title
VAS-Physician's Global Assessment of Disease Activity (GDA) During the Interventional Phase
Description
Physician's were asked to determine the overall GDA for each participant using a 100-mm VAS, where 0=no disease activity and 100=maximum disease activity. The physician marked the line corresponding to their assessment and the distance from the left edge was measured. V3, CV, and the change from V3 to CV was determined.
Time Frame
V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Title
VAS for Pain (VAS-Pain) During the Interventional Phase
Description
Participants were asked to mark the line corresponding to the intensity of their pain on a 100-mm VAS, where 0=no pain and 100=worst possible pain. The distance from the left edge was measured. Change = V3 mean minus CV mean.
Time Frame
V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Title
SJC and TJC During the Interventional Phase
Description
TJC and SJC were assessed for 28 joints. An assessment of 28 joints for swelling and tenderness was made. Joints were assessed and classified as swollen (1)/not swollen (0) and tender (1)/not tender (0) by pressure and joint manipulation on physical examination for a total score range of 0-28. Higher scores indicated greater disease activity (tenderness/swelling). V3, CV, and the change from V3 to CV was determined.
Time Frame
V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Title
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score During the Interventional Phase
Description
FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater 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-F score for a total possible score of 0 (worse score) to 52 (better score). V3, CV, and the change from V3 to CV was determined.
Time Frame
V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Title
Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase
Description
36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component scores (PCS and MCS). Total of 11 variables were analyzed (8 subscales, 2 composite subscales and Question 2 "how would you rate your health in general now?" (range 1= better, 5= worst). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Higher scores reflect higher quality of life. V3, CV, and the change from V3 to CV was determined.
Time Frame
V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Title
SF-36 Subscale Scores During the Interventional Phase
Description
SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component scores (PCS and MCS). Total of 11 variables were analyzed (8 subscales, 2 composite subscales and Question 2 "how would you rate your health in general now?" (range 1= better, 5= worst). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Higher scores reflect higher quality of life. V3, CV, and the change from V3 to CV was determined.
Time Frame
V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Title
CDAI Score During the Interventional Phase
Description
The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on 0-100 mm VAS; higher scores=greater affection due to disease activity. CDAI total score=0-76. CDAI ≤2.8=disease remission, >2.8 to 10=LDA, >10 to 22=moderate disease activity, and >22=high disease activity. V3, CV, and the change from V3 to CV was determined.
Time Frame
V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Title
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI
Description
The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on 0-100 mm VAS; higher scores=greater affection due to disease activity. CDAI total score=0-76. CDAI ≤2.8=disease remission and >2.8 to 10=LDA.
Time Frame
Visits 3 (7 months), 4 (8 months), 5 (9 months), 6 (10 months), 7 (11 months), 8 (12 months), and 9 (24 weeks after V3) or CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Title
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP
Description
DAS28 calculated from the number of swollen joints (SJC) and tender joints (TJC) using the 28 joint count, the CRP and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28-CRP ≤3.2 and oral GC intake with MP equivalent dose of ≥1 mg and ≤20 mg/day=LDA; DAS28 <2.6 = remission.
Time Frame
Visits 3 (7 months), 4 (8 months), 5 (9 months), 6 (10 months), 7 (11 months), 8 (12 months), 9 (24 weeks after V3) or CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Non-interventional phase
Adult patients, >/=18 years of age
Moderate to severe active rheumatoid arthritis defined as Disease Activity Score using 28-joint count (DAS28) >/=5.1
Patients with inadequate clinical response to a current treatment with 2 or more non-biologic disease-modifying anti-rheumatic drugs (DMARDs), one of them being methotrexate (MTX) optimally administered during a period of more than 3 months or inadequate response to a current anti-TNF therapy
Current use of oral glucocorticoids started at least 4 weeks prior to enrolment Interventional phase
Patients enrolled in the non-interventional phase
Patients with low disease activity defined as DAS28 </=3.2 at Visit 2
Use of oral glucocorticoids with methylprednisolone equivalent dose of >/=1mg and </=20mg/day at Visit 2
Exclusion Criteria:
Non-interventional & interventional phase
Rheumatic autoimmune disease other than rheumatoid arthritis, or significant systemic involvement secondary to rheumatoid arthritis
Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in rheumatoid arthritis
Prior history or current inflammatory joint disease other than rheumatoid arthritis (e.g. gout)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Aalst
ZIP/Postal Code
9300
Country
Belgium
City
Brugge
ZIP/Postal Code
8000
Country
Belgium
City
Bruxelles
ZIP/Postal Code
1020
Country
Belgium
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
City
Genk
ZIP/Postal Code
3600
Country
Belgium
City
Gilly
ZIP/Postal Code
6060
Country
Belgium
City
Godinne
ZIP/Postal Code
5530
Country
Belgium
City
Haine-Saint-Paul
ZIP/Postal Code
7100
Country
Belgium
City
Heusy
ZIP/Postal Code
4802
Country
Belgium
City
Kortrijk
ZIP/Postal Code
8500
Country
Belgium
City
La Louviere
ZIP/Postal Code
7100
Country
Belgium
City
Liege
ZIP/Postal Code
4000
Country
Belgium
City
Oostende
ZIP/Postal Code
8400
Country
Belgium
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
12. IPD Sharing Statement
Learn more about this trial
A Study of Glucocorticoid Use to Evaluate Systematic Methylprednisolone Reduction in Patients With Rheumatoid Arthritis on Background RoActemra/Actemra (Tocilizumab) (ACT-ALONE)
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