Rheumatoid Arthritis
Conditions
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
Interventions
DRUGmethylprednisolone
starting dose \>/= 1 mg and \</= 20 mg orally daily, according to dose-reduction schedule
DRUGtocilizumab [RoActemra/Actemra]
background therapy: 8 mg/kg iv every 4 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median GC Dose Taken During the Noninterventional Phase | V1 and V2 (up to 6 months after V1) | 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 | V1 and V2 (up to 6 months after V1) | 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 | V1 and V2 (up to 6 months after V1) | 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 | Visits 3 (7 months), 4 (8 months), 5 (9 months), 6 (10 months), 7 (11 months), and 8 (12 months) | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Positive for Rheumatoid Factor (RF) During the Noninterventional Phase | V1 and V2 (up to 6 months after V1) | 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 | V1 and V2 (up to 6 months after V1) | 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 | V1 and V2 (up to 6 months after V1) | 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 | V1 and V2 (up to 6 months after V1) | 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. |
| Percentage of Participants Able to Reduce Oral GCs by ≥50 Percent (%) During the Interventional Phase by V9 | V9 (24 weeks after V3) | — |
| Percentage of Participants Able to Discontinue GCs During the Interventional Phase by V9 | V9 (24 weeks after V3) | — |
| DAS28-ESR During the Noninterventional Phase | V1 and V2 (up to 6 months after V1) | 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 | V1 and V2 (up to 6 months after V1) | 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 | V1 and V2 (up to 6 months after V1) | 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 | V1 and V2 (up to 6 months after V1) | — |
| Number of Participants With Changes in Tocilizumab Dose During the Noninterventional Phase | V1 and V2 (up to 6 months after V1) | 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 | V1 and V2 (up to 6 months after V1) | — |
| Percentage of Participants Able to Acheive LDA Assessed Using DAS28 While Receiving Oral GC on Background Tocilizumab Treatment During the Noninterventional Phase | V1 and V2 (up to 6 months after V1) | 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-Averaged GC Dose Changes During the Interventional Phase | V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) | 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 | V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) | 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 | Visit 3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) | 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 | V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) | 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 | V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) | 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 | V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) | 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 | V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) | 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 | V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) | 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 | V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) | 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 | V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) | 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 | 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) | 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 | 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) | 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. |
| Percentage of Participants Able to Start the GC Reduction Phase at V3 | V3 (7 months) | 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 Acheiving Remission Assessed Using DAS28 While Receiving Oral GC on Background TocilizumabTreatment During the Noninterventional Phase | V1 and V2 (up to 6 months after V1) | 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 | V1 and V2 (up to 6 months after V1) | 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 | V1 and V2 (up to 6 months after V1) | 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. |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment. | 68 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | GC free | 1 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | No LDA maintained | 7 |
| Overall Study | No LDA reached | 5 |
| Overall Study | Protocol Violation | 8 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Tocilizumab |
|---|---|
| Age, Continuous | 58.0 years STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 68 | 26 / 43 |
| serious Total, serious adverse events | 4 / 68 | 1 / 43 |
Outcome results
Primary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety obs population; n (number) equals (=) number of participants analyzed for a given parameter at a specified timepoint
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tocilizumab | Median GC Dose Taken During the Noninterventional Phase | Start dose V1 (n=68) | 6 mg |
| Tocilizumab | Median GC Dose Taken During the Noninterventional Phase | Stop dose (V2; n=50) | 4 mg |
| Tocilizumab | Median GC Dose Taken During the Noninterventional Phase | Change from start to stop (n=50) | 0 mg |
| Tocilizumab | Median GC Dose Taken During the Noninterventional Phase | Cumulative dose from V1 to V2 (n=45) | 320 mg |
| Tocilizumab | Median GC Dose Taken During the Noninterventional Phase | Start dose (V1) for Interventional phase (n=50) | 6 mg |
Primary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety obs population; n=number of participants analyzed for a given parameter at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Number of Participants With GC Switches During the Noninterventional Phase | 0 participants |
Primary
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.
Time frame: Visits 3 (7 months), 4 (8 months), 5 (9 months), 6 (10 months), 7 (11 months), and 8 (12 months)
Population: Intent-to-Treat (ITT) population: all participants included in the interventional GC reduction phase of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants in the Interventional Phase Who Achieved LDA and Discontinued Oral GC Within 20 Weeks | 58.1 percentage of participants |
Primary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety obs population; n=number of participants analyzed for a given parameter at a specified timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Type of GC Taken at the End of the Noninterventional Phase | Prednisolone | 28.0 percentage of participants |
| Tocilizumab | Type of GC Taken at the End of the Noninterventional Phase | Prednisone | 2.0 percentage of participants |
| Tocilizumab | Type of GC Taken at the End of the Noninterventional Phase | MP | 70.0 percentage of participants |
Secondary
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.
Time frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | CDAI Score During the Interventional Phase | Change from V3 to CV (n=25) | 1.4 units on a scale | Standard Deviation 5.2 |
| Tocilizumab | CDAI Score During the Interventional Phase | V3 (n=40) | 5.6 units on a scale | Standard Deviation 3.8 |
| Tocilizumab | CDAI Score During the Interventional Phase | CV (n=27) | 6.5 units on a scale | Standard Deviation 5.4 |
Secondary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Clinical Disease Activity Index (CDAI) During the Noninterventional Phase | V1 (n=62) | 33.8 units on a scale | Standard Deviation 12.2 |
| Tocilizumab | Clinical Disease Activity Index (CDAI) During the Noninterventional Phase | V2 (n=52) | 14.6 units on a scale | Standard Deviation 10.3 |
| Tocilizumab | Clinical Disease Activity Index (CDAI) During the Noninterventional Phase | Change from V1 to V2 (n=50) | -20.4 units on a scale | Standard Deviation 13.7 |
Secondary
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.
Time frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | DAS28-CRP During the Interventional Phase | V3 (n=42) | 2.2 units on a scale | Standard Deviation 0.7 |
| Tocilizumab | DAS28-CRP During the Interventional Phase | CV (n=27) | 2.3 units on a scale | Standard Deviation 0.8 |
| Tocilizumab | DAS28-CRP During the Interventional Phase | Change from V3 to CV (n=27) | 0.2 units on a scale | Standard Deviation 0.8 |
Secondary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | DAS28-CRP During the Noninterventional Phase | V1 (n=67) | 5.4 units on a scale | Standard Deviation 1 |
| Tocilizumab | DAS28-CRP During the Noninterventional Phase | V2 (n=66) | 2.9 units on a scale | Standard Deviation 1.1 |
| Tocilizumab | DAS28-CRP During the Noninterventional Phase | Change from V1 to V2 (n=65) | -2.5 units on a scale | Standard Deviation 1.3 |
Secondary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | DAS28-ESR During the Noninterventional Phase | V1 (n=62) | 5.8 units on a scale | Standard Deviation 1 |
| Tocilizumab | DAS28-ESR During the Noninterventional Phase | V2 (n=52) | 3.3 units on a scale | Standard Deviation 1.4 |
| Tocilizumab | DAS28-ESR During the Noninterventional Phase | Change from V1 to V2 (n=50) | -2.7 units on a scale | Standard Deviation 1.3 |
Secondary
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.
Time frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score During the Interventional Phase | V3 (n=37) | 37.5 units on a scale | Standard Deviation 9.9 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score During the Interventional Phase | CV (n=26) | 35.6 units on a scale | Standard Deviation 10.8 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score During the Interventional Phase | Change from V3 to CV (n=22) | 8.8 units on a scale | Standard Deviation 19 |
Secondary
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.
Time frame: Visit 3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | HAQ-DI During the Interventional Phase | V3 (n=41) | 1.0 units on a scale | Standard Deviation 0.7 |
| Tocilizumab | HAQ-DI During the Interventional Phase | CV (n=28) | 0.8 units on a scale | Standard Deviation 0.7 |
| Tocilizumab | HAQ-DI During the Interventional Phase | Change from V3 to CV (n=26) | 0.0 units on a scale | Standard Deviation 0.4 |
Secondary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Health Assessment Questionnaire Disability Index (HAQ-DI) During the Noninterventional Phase | V1 (n=66) | 1.7 units on a scale | Standard Deviation 0.6 |
| Tocilizumab | Health Assessment Questionnaire Disability Index (HAQ-DI) During the Noninterventional Phase | V2 (n=61) | 1.2 units on a scale | Standard Deviation 0.7 |
| Tocilizumab | Health Assessment Questionnaire Disability Index (HAQ-DI) During the Noninterventional Phase | Change from V1 to V2 (n=60) | -0.5 units on a scale | Standard Deviation 0.6 |
Secondary
Median Dose of Tocilizumab During the Noninterventional Phase
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | Median Dose of Tocilizumab During the Noninterventional Phase | 8.0 mg/kg |
Secondary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | Median Time Interval Between V1 and V2 | 2.3 months |
Secondary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Number of Erosions During the NonInterventional Phase | V1 (n=11) | 5.1 erosions | Standard Deviation 6 |
| Tocilizumab | Number of Erosions During the NonInterventional Phase | Between V1 and V2 (n=6) | 3.2 erosions | Standard Deviation 2.3 |
Secondary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Number of Participants With Changes in Tocilizumab Dose During the Noninterventional Phase | 1 participants |
Secondary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants Able to Acheive LDA Assessed Using DAS28 While Receiving Oral GC on Background Tocilizumab Treatment During the Noninterventional Phase | 72.1 percentage of participants |
Secondary
Percentage of Participants Able to Discontinue GCs During the Interventional Phase by V9
Time frame: V9 (24 weeks after V3)
Population: Safety Int run-in; pnly those participants who completed the study at V9 were included in analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants Able to Discontinue GCs During the Interventional Phase by V9 | 3.3 percentage of participants |
Secondary
Percentage of Participants Able to Reduce Oral GCs by ≥50 Percent (%) During the Interventional Phase by V9
Time frame: V9 (24 weeks after V3)
Population: Safety Int run-in; only those participants who completed the study at V9 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants Able to Reduce Oral GCs by ≥50 Percent (%) During the Interventional Phase by V9 | 93.3 percentage of participants |
Secondary
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.
Time frame: V3 (7 months)
Population: Safety Int (intervention) run-in: all participants eligible to enter the interventional phase at V2 and who had taken at least 1 dose of MP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants Able to Start the GC Reduction Phase at V3 | 87.8 percentage of participants |
Secondary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants Acheiving Remission Assessed Using DAS28 While Receiving Oral GC on Background TocilizumabTreatment During the Noninterventional Phase | 41.2 percentage of participants |
Secondary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Positive for Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibody During the Noninterventional Phase | Between V1 and V2 (n=6) | 83.3 percentage of participants |
| Tocilizumab | Percentage of Participants Positive for Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibody During the Noninterventional Phase | V1 (n=20) | 75.0 percentage of participants |
Secondary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Positive for Rheumatoid Factor (RF) During the Noninterventional Phase | V1 (n=39) | 56.4 percentage of participants |
| Tocilizumab | Percentage of Participants Positive for Rheumatoid Factor (RF) During the Noninterventional Phase | Between V1 and V2 (n=21) | 52.4 percentage of participants |
Secondary
Percentage of Participants With Changes in RA Treatment During the Noninterventional Phase
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants With Changes in RA Treatment During the Noninterventional Phase | 15.2 percentage of participants |
Secondary
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.
Time frame: V1 and V2 (up to 6 months after V1)
Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Erosions During the NonInterventional Phase | V1 (n=57) | 47.4 percentage of participants |
| Tocilizumab | Percentage of Participants With Erosions During the NonInterventional Phase | Between V1 and V2 (n=36) | 41.7 percentage of participants |
Secondary
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.
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)
Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V4 LDA (n=41) | 82.9 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V4 Remission (n=41) | 39.0 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V5 LDA (n=38) | 81.6 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V5 Remission (n=38) | 47.4 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V6 LDA (n=35) | 71.4 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V7 LDA (n=33) | 75.8 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V7 Remission (n=33) | 33.3 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V8 LDA (n=31) | 80.6 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V8 Remission (n=31) | 38.7 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V9 LDA (n=29) | 69.0 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | CV LDA (n=27) | 77.8 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | CV Remission (n=27) | 33.3 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V3 LDA (n=40) | 85.0 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V3 Remission (n=40) | 27.5 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V6 Remission (n=35) | 37.1 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI | V9 Remission (n=29) | 31.0 percentage of participants |
Secondary
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.
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)
Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V3 LDA (n=42) | 90.5 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V3 Remission (n=42) | 73.8 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V4 LDA (n=41) | 85.4 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V4 Remission (n=41) | 73.2 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V5 LDA (n=35) | 88.6 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V5 Remission (n=35) | 71.4 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V6 LDA (n=35) | 82.9 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V7 Remission (n=33) | 57.6 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V8 LDA (n=32) | 87.5 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V8 Remission (n=32) | 62.5 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V9 LDA (n=30) | 73.3 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V9 Remission (n=30) | 56.7 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V6 Remission (n=35) | 62.9 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | V7 LDA (n=33) | 90.9 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | CV LDA (n=27) | 88.9 percentage of participants |
| Tocilizumab | Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP | CV Remission (n=27) | 59.3 percentage of participants |
Secondary
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.
Time frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Population: ITT Population; n=number of participants analyzed for the given parameter at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Physical functioning V3 (n=36) | 41.52 units on a scale | Standard Deviation 10.37 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Physical functioning CV (n=26) | 41.92 units on a scale | Standard Deviation 10.44 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | General health V3 (n=37) | 43.11 units on a scale | Standard Deviation 9.42 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | General health CV (n=26) | 40.82 units on a scale | Standard Deviation 8.77 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Change in general health V3 to CV (n=22) | -3.78 units on a scale | Standard Deviation 7.35 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Vitality V3 (n=37) | 50.51 units on a scale | Standard Deviation 8.74 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Change in physical functioning V3 to CV (n=22) | -1.80 units on a scale | Standard Deviation 6.77 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Physical sub-score V3 (n=37) | 40.61 units on a scale | Standard Deviation 7.53 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Physical sub-score CV (n=26) | 39.85 units on a scale | Standard Deviation 8.23 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Change in physical sub-score V3 to CV (n=22) | -2.79 units on a scale | Standard Deviation 7.68 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Bodily pain V3 (n=37) | 45.88 units on a scale | Standard Deviation 8.35 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Bodily pain CV (n=26) | 44.65 units on a scale | Standard Deviation 9.7 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Change in bodily pain V3 to CV (n=22) | -3.21 units on a scale | Standard Deviation 8.67 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Vitality CV (n=26) | 48.91 units on a scale | Standard Deviation 9.13 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Change in vitality V3 to CV (n=22) | -4.37 units on a scale | Standard Deviation 9.98 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Social functioning V3 (n=37) | 45.42 units on a scale | Standard Deviation 9.63 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Social functioning CV (n=26) | 45.58 units on a scale | Standard Deviation 9.29 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Change in social functioning V3 to CV (n=22) | -2.73 units on a scale | Standard Deviation 9.63 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Emotional sub-score V3 (n=37) | 40.59 units on a scale | Standard Deviation 9.98 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Emotional sub-score CV (n=26) | 40.37 units on a scale | Standard Deviation 10.53 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Change in emotional sub-score V3 to CV (n=22) | -2.45 units on a scale | Standard Deviation 10.29 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Mental health V3 (n=37) | 47.14 units on a scale | Standard Deviation 10 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Mental health CV (n=26) | 45.94 units on a scale | Standard Deviation 10.37 |
| Tocilizumab | SF-36 Subscale Scores During the Interventional Phase | Change in Mental health V3 to CV (n=22) | -5.47 units on a scale | Standard Deviation 10.98 |
Secondary
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.
Time frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase | PCS V3 (n=36) | 42.5 units on a scale | Standard Deviation 7.6 |
| Tocilizumab | Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase | PCS CV (n=26) | 41.8 units on a scale | Standard Deviation 8.8 |
| Tocilizumab | Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase | PCS: Change from V3 to CV (n=22) | -2.1 units on a scale | Standard Deviation 6.4 |
| Tocilizumab | Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase | MCS V3 (n=37) | 47.0 units on a scale | Standard Deviation 9.9 |
| Tocilizumab | Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase | MCS CV (n=26) | 46.2 units on a scale | Standard Deviation 9 |
| Tocilizumab | Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase | MCS: Change from V3 to CV (n=22) | -4.4 units on a scale | Standard Deviation 10.6 |
Secondary
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.
Time frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | SJC and TJC During the Interventional Phase | SJC V3 (n=43) | 0.9 joints | Standard Deviation 1.3 |
| Tocilizumab | SJC and TJC During the Interventional Phase | TJC Change from V3 to CV (n=29) | 1.0 joints | Standard Deviation 2.6 |
| Tocilizumab | SJC and TJC During the Interventional Phase | SJC CV (n=29) | 0.4 joints | Standard Deviation 0.9 |
| Tocilizumab | SJC and TJC During the Interventional Phase | SJC Change from V3 to CV (n=29) | -0.3 joints | Standard Deviation 0.8 |
| Tocilizumab | SJC and TJC During the Interventional Phase | TJC V3 (n=43) | 0.9 joints | Standard Deviation 1.2 |
| Tocilizumab | SJC and TJC During the Interventional Phase | TJC CV (n=29) | 1.8 joints | Standard Deviation 2.7 |
Secondary
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.
Time frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Population: Safety Int run-in; only participants who completed the study were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Time-Averaged GC Dose Changes During the Interventional Phase | 341.8 mg | Standard Deviation 364.2 |
Secondary
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.
Time frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint. Only participants with values at both visits were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | VAS for Pain (VAS-Pain) During the Interventional Phase | V3 (n=43) | 19.9 mm | Standard Deviation 16.5 |
| Tocilizumab | VAS for Pain (VAS-Pain) During the Interventional Phase | CV (n=28) | 24.9 mm | Standard Deviation 19 |
| Tocilizumab | VAS for Pain (VAS-Pain) During the Interventional Phase | Change from V3 to CV (n=28) | 6.9 mm | Standard Deviation 22.4 |
Secondary
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.
Time frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint. Only participants with values at both visits were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | VAS-Physician's Global Assessment of Disease Activity (GDA) During the Interventional Phase | CV (n=28) | 16.7 mm | Standard Deviation 15.9 |
| Tocilizumab | VAS-Physician's Global Assessment of Disease Activity (GDA) During the Interventional Phase | Change from V3 to CV (n=26) | 3.1 mm | Standard Deviation 15.4 |
| Tocilizumab | VAS-Physician's Global Assessment of Disease Activity (GDA) During the Interventional Phase | V3 (n=40) | 16.6 mm | Standard Deviation 12.5 |