Rheumatoid Arthritis
Conditions
Brief summary
This single arm, open-label study will assess the safety and efficacy with regar d to reduction of signs and symptoms of treatment with tocilizumab in combinatio n with methotrexate, in patients with moderate to severe active rheumatoid arthr itis. Patients will receive tocilizumab 8mg/kg iv, every 4 weeks and methotrexat e 10-25mg weekly. The anticipated time on study treatment is 3-12 months, and th e target sample size is \<500 individuals.
Interventions
DRUGtocilizumab [RoActemra/Actemra]
8mg/kg iv, every 4 weeks
DRUGmethotrexate
10-25mg oral or parenteral weekly.
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
* patients \>=18 years with moderate to severe active RA for at least 6 months; * swollen joint count \>=6 (66 joint count) and tender joint count \>=8 (68 joint count) at screening; * inadequate response to stable dose of MTX; * patients of reproductive potential must be using a reliable means of contraception.
Exclusion criteria
* rheumatic autoimmune disease other than RA; * patients with functional class IV RA; * diagnosis of juvenile idiopathic or rheumatoid arthritis before age 16 or a history of current inflammatory joint disease other than RA; * prior treatment failure with anti-tumor necrosis factor agent; * pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24 | Week 24 | ACR50 is defined as 50 percent (%) improvement in: a) Swollen Joints Count (SJC) and Tender Joints Count (TJC) and b) Three of the following 5 assessments: 1. Participant's global assessment of pain by Visual Analog Scale (VAS) 2. Participant's global assessment of disease activity (VAS) 3. Investigator/Physician's global assessment of disease activity (VAS) 4. Participant's assessment of disability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) 5. Acute phase reactant levels - Erythrocyte Sedimentation Rate or C-Reactive Protein (ESR or CRP) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ACR20 and ACR70 Response at Week 24 | Week 24 | ACR20 and ACR70 are defined as 20 and 70 percent improvement respectively in: a) SJC and TJC and b) Three of the following 5 assessments: 1. Participant's global assessment of pain by VAS 2. Participant's global assessment of disease activity (VAS) 3. Investigator/Physician's global assessment of disease activity (VAS) 4. Participant's assessment of disability measured by HAQ-DI 5. Acute phase reactant (ESR or CRP) |
| Time to Onset of ACR20, ACR50, and ACR70 | Baseline and Week 24 | ACR20, ACR50 and ACR70 are defined as 20, 50 and 70 percent improvement respectively in: a) SJC and TJC and b) Three of the following 5 assessments: 1. Participant's global assessment of pain by VAS 2. Participant's global assessment of disease activity (VAS) 3. Investigator/Physician's global assessment of disease activity (VAS) 4. Participant's assessment of disability measured by HAQ-DI 5. Acute phase reactant (ESR or CRP) |
| Change From Baseline in Hemoglobin at Week 24 | Baseline and Week 24 | — |
| SJC and TJC at Baseline and Week 24 | Baseline and Week 24 | The number of swollen joints (66 joint count) were scored as swollen=1 and not swollen=0, and the number of tender joints (68 joint count ) were scored as tender=1 and not tender=0, and counted. Scores ranged from 0 to 66 for swollen joint counts and from 0 to 68 for tender joint counts. A positive change from baseline represents an improvement (a reduction in the number of swollen or tender joints). |
| Percent Change From Baseline in SJC and TJC at Week 24 | Baseline and Week 24 | The number of swollen joints (66 joint count) were scored as swollen=1 and not swollen=0, and the number of tender joints (68 joint count ) were scored as tender=1 and not tender=0, and counted. Scores ranged from 0 to 66 for swollen joint counts and from 0 to 68 for tender joint counts. A positive change from baseline represents an improvement (a reduction in the number of swollen or tender joints). |
| Pain as Assessed by the Participant at Baseline and Week 24 | Baseline and Week 24 | The participants assessed their pain using a 0 to 100 millimeter (mm) VAS. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm as unbearable pain. The participants marked the line corresponding to the level of their pain and the distance from the left edge was measured. A positive change from baseline represents an improvement. |
| Percent Change From Baseline in Pain as Assessed by the Participant at Week 24 | Baseline and Week 24 | The participants assessed their pain using a 0 to 100 millimeter (mm) VAS. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm as unbearable pain. The participants marked the line corresponding to the level of their pain and the distance from the left edge was measured. A positive change from baseline represents an improvement. |
| Participant's Global Assessment of Disease Activity at Baseline and Week 24 | Baseline and Week 24 | The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity). A positive change from baseline represents an improvement (reduced level of disease activity). |
| Percent Change From Baseline in Participant's Global Assessment of Disease Activity at Week 24 | Baseline and Week 24 | The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity). A positive change from baseline represents an improvement (reduced level of disease activity). |
| Physician's Global Assessment of Disease Activity at Baseline and Week 24 | Baseline and Week 24 | The physician's global assessment of disease activity is assessed on a 0 to 100 mm VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity). The physicians marked the line corresponding to their assessment and the distance from the left edge was measured. A positive change from baseline represents an improvement (reduced level of disease activity). |
| Percent Change From Baseline in Physician's Global Assessment of Disease Activity at Week 24 | Baseline and Week 24 | The physician's global assessment of disease activity is assessed on a 0 to 100 mm VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity). The physicians marked the line corresponding to their assessment and the distance from the left edge was measured. A positive change from baseline represents an improvement (reduced level of disease activity). |
| HAQ-DI at Baseline and Week 24 | Baseline and Week 24 | HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 =without difficulties; 1= with some difficulties; 2=with great difficulties; and 3= unable to perform these actions at all. Minimum score was 0, maximum score was 3. A positive change from baseline represents an improvement (reduced level of impairment). |
| Percent Change From Baseline in HAQ-DI at Week 24 | Baseline and Week 24 | HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. A positive change from baseline represents an improvement (reduced level of impairment). |
| Area Under The Curve (AUC) of the ACR(n) | Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 | ACR-n was defined as the lowest of 3 values (the percent change in the swollen joint count, the percent change in the tender joint count, and the median of the other 5 measures in the ACR core data set which included Participant's global assessment of pain (VAS), Participant's global assessment of disease activity (VAS), Investigator/Physician's global assessment of disease activity (VAS), Participant's assessment of disability measured by the HAQ-DI Acute phase reactant levels - ESR or CRP). Therefore, a percentage value was assigned to each participant at each timepoint. AUC was calculated for each participant from baseline to Week 112. Mean and standard deviation values are are provided in percent\*years. |
| Percentage of Participants Achieving ACR20 Response | Week 2 | ACR20 is defined as 20% improvement in: a) SJC and TJC and b) Three of the following 5 assessments: 1. Participant's global assessment of pain (VAS) 2. Participant's global assessment of disease activity (VAS) 3. Investigator/Physician's global assessment of disease activity (VAS) 4. Participant's assessment of disability measured by the HAQ-DI 5. Acute phase reactant levels - ESR or CRP |
| Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Weeks 2, 4, 8, 12, 16, 20, 24 | The probability of ACR positive response was determined using the GEE. |
| Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) at Week 24 | Baseline and Week 24 | DAS28 calculated from the number of SJC and TJC using the 28 joints count, the ESR (mm/hour) and participant's global assessment 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 (less than or equal to ) ≤3.2 = low disease activity, DAS28 (greater than) \>3.2 to 5.1 = moderate to high disease activity. |
| Percentage of Participants With a Response by Categorical DAS28 Responses According to The European League Against Rheumatism (EULAR Response) at Week 24 | Week 24 | DAS28- based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline \>1.2 with DAS28 \< 3.2; moderate response: change from baseline \>1.2 with DAS28 \>3.2 to \<5.1 or change from baseline \>0.6 to \<1.2 with DAS28 \<5.1; No response: change from baseline \< 0.6 or change from baseline \>0.6 and \<1.2 with DAS28 \>5.1. |
| AUC of DAS28 | Weeks 2, 4, 8, 12, 16, 20 and 24 | The AUC was computed using the trapezoidal rule, considering baseline value as 0, through NCSS software. For each participant, AUC for DAS28 units was calculated. Each individual AUC DAS28 value was divided by 52 to have the conversion of AUC DAS28 in unit weeks to AUC DAS28 in unit years, as 1 week is approximately 1/52 years. The set of individual AUC DAS28 was computed as summary statistics. |
| Fatigue as Assessed Using the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue) Score at Week 24 | Week 24 | FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the participant's health status. |
| Percentage of Participants Achieving Remission (DAS28 Less Than [<] 2.6) at Week 24 | Week 24 | DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and participant's global assessment 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 (less than or equal to ) ≤3.2 = low disease activity, DAS28 (greater than) \>3.2 to 5.1 = moderate to high disease activity and DAS28\<2.6 = remission |
| Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24 | Week 24 | 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, and mental health. Total of 3 variables were analyzed (2 composite subscales and vitality score). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). |
| Mean Change in Rheumatoid Factor (RF) at Week 24 in Participants With Positive RF | Baseline and Week 24 | — |
Countries
Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Mexico, Peru, Uruguay, Venezuela
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study. | 418 |
| Total | 418 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative Reason | 3 |
| Overall Study | Adverse Event | 19 |
| Overall Study | Death | 1 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 39 |
| Overall Study | Protocol Violation | 3 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Tocilizumab |
|---|---|
| Age, Continuous | 48.69 years STANDARD_DEVIATION 12.36 |
| Sex: Female, Male Female | 371 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 324 / 418 |
| serious Total, serious adverse events | 30 / 418 |
Outcome results
Primary
Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24
ACR50 is defined as 50 percent (%) improvement in: a) Swollen Joints Count (SJC) and Tender Joints Count (TJC) and b) Three of the following 5 assessments: 1. Participant's global assessment of pain by Visual Analog Scale (VAS) 2. Participant's global assessment of disease activity (VAS) 3. Investigator/Physician's global assessment of disease activity (VAS) 4. Participant's assessment of disability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) 5. Acute phase reactant levels - Erythrocyte Sedimentation Rate or C-Reactive Protein (ESR or CRP)
Time frame: Week 24
Population: ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24 | 73.23 percentage of participants |
Secondary
Area Under The Curve (AUC) of the ACR(n)
ACR-n was defined as the lowest of 3 values (the percent change in the swollen joint count, the percent change in the tender joint count, and the median of the other 5 measures in the ACR core data set which included Participant's global assessment of pain (VAS), Participant's global assessment of disease activity (VAS), Investigator/Physician's global assessment of disease activity (VAS), Participant's assessment of disability measured by the HAQ-DI Acute phase reactant levels - ESR or CRP). Therefore, a percentage value was assigned to each participant at each timepoint. AUC was calculated for each participant from baseline to Week 112. Mean and standard deviation values are are provided in percent\*years.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24
Population: ITT Population; All participants with endpoint values collected were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Area Under The Curve (AUC) of the ACR(n) | 20.8 percent*years | Standard Deviation 9.4 |
Secondary
AUC of DAS28
The AUC was computed using the trapezoidal rule, considering baseline value as 0, through NCSS software. For each participant, AUC for DAS28 units was calculated. Each individual AUC DAS28 value was divided by 52 to have the conversion of AUC DAS28 in unit weeks to AUC DAS28 in unit years, as 1 week is approximately 1/52 years. The set of individual AUC DAS28 was computed as summary statistics.
Time frame: Weeks 2, 4, 8, 12, 16, 20 and 24
Population: ITT Population; All participants with endpoint values collected were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | AUC of DAS28 | 11.8 scores on a scale * years | Standard Deviation 4.2 |
Secondary
Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) at Week 24
DAS28 calculated from the number of SJC and TJC using the 28 joints count, the ESR (mm/hour) and participant's global assessment 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 (less than or equal to ) ≤3.2 = low disease activity, DAS28 (greater than) \>3.2 to 5.1 = moderate to high disease activity.
Time frame: Baseline and Week 24
Population: ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) at Week 24 | 4.4 score on a scale | Standard Deviation 1.6 |
Secondary
Change From Baseline in Hemoglobin at Week 24
Time frame: Baseline and Week 24
Population: Data were not analyzed because of inconsistencies in the pooled data between countries.
Secondary
Fatigue as Assessed Using the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue) Score at Week 24
FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the participant's health status.
Time frame: Week 24
Population: ITT Population. All participants with endpoint values collected at Week 24 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Fatigue as Assessed Using the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue) Score at Week 24 | 39.9 score on a scale | Standard Deviation 9.4 |
Secondary
HAQ-DI at Baseline and Week 24
HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 =without difficulties; 1= with some difficulties; 2=with great difficulties; and 3= unable to perform these actions at all. Minimum score was 0, maximum score was 3. A positive change from baseline represents an improvement (reduced level of impairment).
Time frame: Baseline and Week 24
Population: ITT Population. All participants with endpoint values collected at the specified timepoints were included in the analysis. n=number of participants analyzed for the given parameter at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | HAQ-DI at Baseline and Week 24 | Week 24 (n=376) | 0.79 units on a scale | Standard Deviation 0.68 |
| Tocilizumab | HAQ-DI at Baseline and Week 24 | Baseline (n=384) | 1.70 units on a scale | Standard Deviation 0.63 |
Secondary
Mean Change in Rheumatoid Factor (RF) at Week 24 in Participants With Positive RF
Time frame: Baseline and Week 24
Population: Data were not analyzed because of inconsistencies in the pooled data between countries.
Secondary
Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
The probability of ACR positive response was determined using the GEE.
Time frame: Weeks 2, 4, 8, 12, 16, 20, 24
Population: ITT Population; All participants with endpoint values collected were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 2 Odds ACR50 | 0.10 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 4 Odds ACR50 | 0.33 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 8 Odds ACR50 | 0.87 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 12 Odds ACR50 | 1.39 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 16 Odds ACR50 | 1.55 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 20 Odds ACR50 | 1.86 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 24 Odds ACR50 | 2.39 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 2 Odds ACR20 | 0.63 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 4 Odds ACR20 | 1.50 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 8 Odds ACR20 | 4.80 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 12 Odds ACR20 | 4.80 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 16 Odds ACR20 | 4.65 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 20 Odds ACR20 | 6.46 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 24 Odds ACR20 | 6.88 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 4 Odds ACR70 | 0.08 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 8 Odds ACR70 | 0.27 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 12 Odds ACR70 | 0.41 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 16 Odds ACR70 | 0.53 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 20 Odds ACR70 | 0.75 odds |
| Tocilizumab | Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models | Week 24 Odds ACR70 | 0.92 odds |
Secondary
Pain as Assessed by the Participant at Baseline and Week 24
The participants assessed their pain using a 0 to 100 millimeter (mm) VAS. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm as unbearable pain. The participants marked the line corresponding to the level of their pain and the distance from the left edge was measured. A positive change from baseline represents an improvement.
Time frame: Baseline and Week 24
Population: ITT Population; All participants with endpoint values collected at the specified timepoints were included in the analysis. number (n) equals (=) number of participants analyzed for the given parameter at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Pain as Assessed by the Participant at Baseline and Week 24 | Baseline (n=384) | 68.01 mm | Standard Deviation 20.39 |
| Tocilizumab | Pain as Assessed by the Participant at Baseline and Week 24 | Week 24 (n=381) | 22.94 mm | Standard Deviation 22.53 |
Secondary
Participant's Global Assessment of Disease Activity at Baseline and Week 24
The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity). A positive change from baseline represents an improvement (reduced level of disease activity).
Time frame: Baseline and Week 24
Population: ITT Population. All participants with endpoint values collected at the specified timepoints were included in the analysis. n= number of participants analyzed for the given parameter at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Participant's Global Assessment of Disease Activity at Baseline and Week 24 | Baseline (n=384) | 69.46 mm | Standard Deviation 20.84 |
| Tocilizumab | Participant's Global Assessment of Disease Activity at Baseline and Week 24 | Week 24 (n=381) | 23.60 mm | Standard Deviation 22.68 |
Secondary
Percentage of Participants Achieving ACR20 Response
ACR20 is defined as 20% improvement in: a) SJC and TJC and b) Three of the following 5 assessments: 1. Participant's global assessment of pain (VAS) 2. Participant's global assessment of disease activity (VAS) 3. Investigator/Physician's global assessment of disease activity (VAS) 4. Participant's assessment of disability measured by the HAQ-DI 5. Acute phase reactant levels - ESR or CRP
Time frame: Week 2
Population: ITT Population; All participants with endpoint values collected at Week 2 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants Achieving ACR20 Response | 40.10 percentage of participants |
Secondary
Percentage of Participants Achieving Remission (DAS28 Less Than [<] 2.6) at Week 24
DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and participant's global assessment 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 (less than or equal to ) ≤3.2 = low disease activity, DAS28 (greater than) \>3.2 to 5.1 = moderate to high disease activity and DAS28\<2.6 = remission
Time frame: Week 24
Population: ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants Achieving Remission (DAS28 Less Than [<] 2.6) at Week 24 | 48.41 percentage of participants |
Secondary
Percentage of Participants With ACR20 and ACR70 Response at Week 24
ACR20 and ACR70 are defined as 20 and 70 percent improvement respectively in: a) SJC and TJC and b) Three of the following 5 assessments: 1. Participant's global assessment of pain by VAS 2. Participant's global assessment of disease activity (VAS) 3. Investigator/Physician's global assessment of disease activity (VAS) 4. Participant's assessment of disability measured by HAQ-DI 5. Acute phase reactant (ESR or CRP)
Time frame: Week 24
Population: ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With ACR20 and ACR70 Response at Week 24 | ACR 70 | 50.39 percentage of participants |
| Tocilizumab | Percentage of Participants With ACR20 and ACR70 Response at Week 24 | ACR 20 | 90.55 percentage of participants |
Secondary
Percentage of Participants With a Response by Categorical DAS28 Responses According to The European League Against Rheumatism (EULAR Response) at Week 24
DAS28- based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline \>1.2 with DAS28 \< 3.2; moderate response: change from baseline \>1.2 with DAS28 \>3.2 to \<5.1 or change from baseline \>0.6 to \<1.2 with DAS28 \<5.1; No response: change from baseline \< 0.6 or change from baseline \>0.6 and \<1.2 with DAS28 \>5.1.
Time frame: Week 24
Population: ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With a Response by Categorical DAS28 Responses According to The European League Against Rheumatism (EULAR Response) at Week 24 | Good Response | 68.17 Percentage of Participants |
| Tocilizumab | Percentage of Participants With a Response by Categorical DAS28 Responses According to The European League Against Rheumatism (EULAR Response) at Week 24 | Moderate Response | 29.57 Percentage of Participants |
| Tocilizumab | Percentage of Participants With a Response by Categorical DAS28 Responses According to The European League Against Rheumatism (EULAR Response) at Week 24 | No Response | 2.26 Percentage of Participants |
Secondary
Percent Change From Baseline in HAQ-DI at Week 24
HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. A positive change from baseline represents an improvement (reduced level of impairment).
Time frame: Baseline and Week 24
Population: ITT Population. All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Percent Change From Baseline in HAQ-DI at Week 24 | 52.0 percent change | Standard Deviation 49.3 |
Secondary
Percent Change From Baseline in Pain as Assessed by the Participant at Week 24
The participants assessed their pain using a 0 to 100 millimeter (mm) VAS. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm as unbearable pain. The participants marked the line corresponding to the level of their pain and the distance from the left edge was measured. A positive change from baseline represents an improvement.
Time frame: Baseline and Week 24
Population: ITT Population; All participants with endpoint values collected at Baseline and Week 24 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Percent Change From Baseline in Pain as Assessed by the Participant at Week 24 | 54.2 percent change | Standard Deviation 177 |
Secondary
Percent Change From Baseline in Participant's Global Assessment of Disease Activity at Week 24
The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity). A positive change from baseline represents an improvement (reduced level of disease activity).
Time frame: Baseline and Week 24
Population: ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Percent Change From Baseline in Participant's Global Assessment of Disease Activity at Week 24 | 61.7 percent change | Standard Deviation 43.1 |
Secondary
Percent Change From Baseline in Physician's Global Assessment of Disease Activity at Week 24
The physician's global assessment of disease activity is assessed on a 0 to 100 mm VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity). The physicians marked the line corresponding to their assessment and the distance from the left edge was measured. A positive change from baseline represents an improvement (reduced level of disease activity).
Time frame: Baseline and Week 24
Population: ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Percent Change From Baseline in Physician's Global Assessment of Disease Activity at Week 24 | 71.2 percent change | Standard Deviation 38.7 |
Secondary
Percent Change From Baseline in SJC and TJC at Week 24
The number of swollen joints (66 joint count) were scored as swollen=1 and not swollen=0, and the number of tender joints (68 joint count ) were scored as tender=1 and not tender=0, and counted. Scores ranged from 0 to 66 for swollen joint counts and from 0 to 68 for tender joint counts. A positive change from baseline represents an improvement (a reduction in the number of swollen or tender joints).
Time frame: Baseline and Week 24
Population: ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Percent Change From Baseline in SJC and TJC at Week 24 | SJC | 84.8 percent change | Standard Deviation 22.5 |
| Tocilizumab | Percent Change From Baseline in SJC and TJC at Week 24 | TJC | 81.2 percent change | Standard Deviation 28.1 |
Secondary
Physician's Global Assessment of Disease Activity at Baseline and Week 24
The physician's global assessment of disease activity is assessed on a 0 to 100 mm VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity). The physicians marked the line corresponding to their assessment and the distance from the left edge was measured. A positive change from baseline represents an improvement (reduced level of disease activity).
Time frame: Baseline and Week 24
Population: ITT Population. All participants with endpoint values collected at the specified timepoints were included in the analysis. n=number of participants analyzed for the given parameter at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Physician's Global Assessment of Disease Activity at Baseline and Week 24 | Week 24 (n=381) | 17.92 mm | Standard Deviation 18.16 |
| Tocilizumab | Physician's Global Assessment of Disease Activity at Baseline and Week 24 | Baseline (n=384) | 67.32 mm | Standard Deviation 16.64 |
Secondary
Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24
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, and mental health. Total of 3 variables were analyzed (2 composite subscales and vitality score). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Time frame: Week 24
Population: ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24 | Role limitations due to physical health | 64.0 score on a scale | Standard Deviation 23.9 |
| Tocilizumab | Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24 | General Health | 42.5 score on a scale | Standard Deviation 12.9 |
| Tocilizumab | Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24 | Physical functioning | 63.0 score on a scale | Standard Deviation 24.2 |
| Tocilizumab | Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24 | Role limitations due to emotional problems | 66.0 score on a scale | Standard Deviation 24.1 |
| Tocilizumab | Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24 | Energy/fatigue | 48.9 score on a scale | Standard Deviation 10.6 |
| Tocilizumab | Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24 | Emotional well-being | 54.5 score on a scale | Standard Deviation 10.3 |
| Tocilizumab | Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24 | Social functioning | 38.2 score on a scale | Standard Deviation 12.7 |
| Tocilizumab | Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24 | Pain | 63.6 score on a scale | Standard Deviation 24.8 |
Secondary
SJC and TJC at Baseline and Week 24
The number of swollen joints (66 joint count) were scored as swollen=1 and not swollen=0, and the number of tender joints (68 joint count ) were scored as tender=1 and not tender=0, and counted. Scores ranged from 0 to 66 for swollen joint counts and from 0 to 68 for tender joint counts. A positive change from baseline represents an improvement (a reduction in the number of swollen or tender joints).
Time frame: Baseline and Week 24
Population: ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | SJC and TJC at Baseline and Week 24 | TJC-Week 24 | 4.57 joints | Standard Deviation 7.57 |
| Tocilizumab | SJC and TJC at Baseline and Week 24 | TJC-Baseline | 25.06 joints | Standard Deviation 13.83 |
| Tocilizumab | SJC and TJC at Baseline and Week 24 | SJC-Baseline | 16.09 joints | Standard Deviation 8.69 |
| Tocilizumab | SJC and TJC at Baseline and Week 24 | SJC-Week 24 | 2.56 joints | Standard Deviation 4.26 |
Secondary
Time to Onset of ACR20, ACR50, and ACR70
ACR20, ACR50 and ACR70 are defined as 20, 50 and 70 percent improvement respectively in: a) SJC and TJC and b) Three of the following 5 assessments: 1. Participant's global assessment of pain by VAS 2. Participant's global assessment of disease activity (VAS) 3. Investigator/Physician's global assessment of disease activity (VAS) 4. Participant's assessment of disability measured by HAQ-DI 5. Acute phase reactant (ESR or CRP)
Time frame: Baseline and Week 24
Population: Data were not analyzed because of inconsistencies in the pooled data between countries.