Rheumatoid Arthritis
Conditions
Brief summary
This open-label, single arm, multicenter long-term extension study of WA19926 evaluated the safety and efficacy of tocilizumab (RoActemra/Actemra) in participants with moderate to severe rheumatoid arthritis who completed the 104-week WA19926 core study. Eligible patients received tocilizumab 8 mg/kg intravenously every 4 weeks for up to 104 weeks.
Interventions
DRUGTocilizumab
8 mg/kg administered intravenously (IV) every 4 weeks for 104 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult participants, \>/= 18 years of age * Participants who complete their last WA19926 core study visit (Week 104) and who may benefit from study drug treatment according to the Investigator's assessment * No current or recent adverse event or laboratory finding preventing the use of the study drug dose of RoActemra/Actemra 8 mg/kg at baseline visit * Women of childbearing potential must agree to use adequate contraception as defined by protocol during the treatment period
Exclusion criteria
* Pregnant females * Participants who have withdrawn prematurely from the WA19926 core study for any reason * Treatment with any investigational agent or cell-depleting therapies since the last administration of study drug in WA19926 * Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL) 1 agent, or a T-cell costimulation modulator since the last administration of study drug in WA19926 * Immunization with a live/attenuated vaccine since the last administration of study drug in WA19926 * Diagnosis since last WA19926 visit (Week 104) of rheumatic autoimmune disease other than rheumatoid arthritis * Diagnosis since last WA19926 visit (Week 104) of inflammatory joint disease other than rheumatoid arthritis * History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, including tocilizumab and its excipients * Evidence of severe uncontrolled concomitant disease or disorder * Known active or history of recurrent infections * Active tuberculosis requiring treatment in the previous 3 years * History of alcohol, drug or chemical abuse since inclusion in the WA19926 study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESIs) | Up to 112 weeks | An AE is any untoward medical occurrence in a study participant given administered a pharmaceutical product, regardless of the cause of the AE. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. AESIs included serious infections (including opportunistic infections) and abnormal liver function tests. |
| Percentage of Adverse Events (AEs) Leading to Dose Modification and AEs Leading to Study Withdrawal | Up to 112 weeks | An AE is any untoward medical occurrence in a study participant given administered a pharmaceutical product, regardless of the cause of the AE. |
| Percentage of Adverse Events With Severity as Mild, Moderate, and Severe | Up to 112 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Swollen Joint Count 66 (SJC 66) Over Time | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 | Number of swollen joints was determined by examination of 66 joints, as assessed through pressure and passive joint motion during physical examination. |
| Percentage of Participants With Treatment-Free Remission According to DAS28-ESR/SDAI Remission Criteria | Up to 104 weeks | Treatment-free remission is remission at two consecutive assessment visits (every 12 weeks) after discontinuing study drug on the second assessment visit. Clinical remission is DAS28-ESR score \<2.6 and/or SDAI score ≤3.3. The DAS28-ESR scale is a measure of a participant's disease activity based on tender joint count (28 joints), swollen joint count (28 joints), a participant's assessment of disease activity, and ESR. DAS28-ESR scored on a scale with a minimum score of 0 (low disease activity) to a maximum score of 10 (high disease activity). The SDAI is sum of TJC and SJC, based on a 28-joint assessment, patient and physician global assessment assessed on 0-10 centimeter visual analogue scale (VAS), where 0 = no disease activity and 10 = worst disease activity, and level of C-reactive protein (CRP, mg/dL). SDAI total score = 0-86. SDAI \<=3.3 indicates clinical remission, \>3.4 to 11=low disease activity, \>11 to 26=moderate disease activity, and \>26=high (or severe) disease activity. |
| Time to Rheumatoid Arthritis Recurrence in Participants Who Achieved Treatment-Free Remission | Up to 104 weeks | Time to rheumatoid arthritis (RA) recurrence = period from treatment-free remission to RA recurrence. RA recurrence was worsening of disease activity with treatment beyond supportive therapy. |
| Percent Change From Baseline in the Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Over Time | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 | The DAS28-ESR Scale is a measure of a participant's disease activity. It is based on tender joint count (28 joints), swollen joint count (28 joints), a participant's assessment of disease activity, and erythrocyte sedimentation rate. DAS28-ESR is expressed as a score on a scale with a minimum score of 0 (low disease activity ) to a maximum score of 10 (high disease activity). A negative mean percent change from baseline indicates a decrease in disease activity, and a positive mean percent change from baseline indicates an increase in disease activity. |
| Percent Change in Participant's Assessment of Pain (VAS) Over Time | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 | Participants' pain was assessed using a 10-mm horizontal VAS (0 to 10 mm) where 0=pain absent and 10=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain; the distance from the left edge to the mark was recorded. |
| Change From Baseline in Health Assessment Questionnaire (HAQ-DI) Score Over Time | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 | The HAQ-DI was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from 4 response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability. |
| Percent Change in Participant's General Assessment of Disease Activity (Severity of Disease) VAS Over Time | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 | The participant's overall assessment of their current disease activity was displayed on a 100-millimeter (mm) horizontal VAS. The left-hand extreme (0 mm) of the line was described as no disease activity (symptom free and no arthritis symptoms) and the right-hand extreme (100 mm) was described as maximum disease activity (maximum arthritis disease activity). The change in Patient Global Assessment of Disease Activity was determined as the difference in values from baseline at each visit. |
| Percent Change From Baseline in the Simplified Disease Activity Index (SDAI) Over Time | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 | The Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: tender joint count (TJC) and swollen joint count (SJC), based on a 28-joint assessment, patient and physician global assessment assessed on 0-10 centimeter (cm) visual analogue scale (VAS), where 0 = no disease activity and 10 = worst disease activity, and level of C-reactive protein (CRP, mg/dL). SDAI total score = 0-86. SDAI \<=3.3 indicates clinical remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity. A negative mean percent change from baseline indicates a decrease in disease activity, and a positive mean percent change from baseline indicates an increase in disease activity. |
| Change From Baseline in Tender Joint Count 66 (TJC 66) Over Time | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104 | Number of tender joints was determined by examination of 66 joints, as assessed through pressure and passive joint motion during physical examination. |
Countries
Russia
Participant flow
Pre-assignment details
Participants who completed the 104-week core study WA19926 and could benefit from tocilizumab treatment based on the Investigator's judgment were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Tocilizumab: 8 mg/kg administered intravenously (IV) every 4 weeks for 104 weeks | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Sponsor Decision | 1 |
| Overall Study | Withdrawal of Informed Consent | 4 |
Baseline characteristics
| Characteristic | Tocilizumab |
|---|---|
| Age, Continuous | 53.3 years STANDARD_DEVIATION 10.8 |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 49 |
| other Total, other adverse events | 22 / 49 |
| serious Total, serious adverse events | 5 / 49 |
Outcome results
Primary
Percentage of Adverse Events (AEs) Leading to Dose Modification and AEs Leading to Study Withdrawal
An AE is any untoward medical occurrence in a study participant given administered a pharmaceutical product, regardless of the cause of the AE.
Time frame: Up to 112 weeks
Population: FAS included all randomized participants enrolled in the study who received at least one dose of tocilizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Adverse Events (AEs) Leading to Dose Modification and AEs Leading to Study Withdrawal | AEs Leading to Dose Modification | 34.5 percentage of adverse events |
| Tocilizumab | Percentage of Adverse Events (AEs) Leading to Dose Modification and AEs Leading to Study Withdrawal | AEs Leading to Study Withdrawal | 1.1 percentage of adverse events |
Primary
Percentage of Adverse Events With Severity as Mild, Moderate, and Severe
Time frame: Up to 112 weeks
Population: FAS included all randomized participants enrolled in the study who received at least one dose of tocilizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Adverse Events With Severity as Mild, Moderate, and Severe | Mild | 62.1 percentage of adverse events |
| Tocilizumab | Percentage of Adverse Events With Severity as Mild, Moderate, and Severe | Moderate | 36.8 percentage of adverse events |
| Tocilizumab | Percentage of Adverse Events With Severity as Mild, Moderate, and Severe | Severe | 1.1 percentage of adverse events |
Primary
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESIs)
An AE is any untoward medical occurrence in a study participant given administered a pharmaceutical product, regardless of the cause of the AE. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. AESIs included serious infections (including opportunistic infections) and abnormal liver function tests.
Time frame: Up to 112 weeks
Population: Full Analysis Set (FAS) included all randomized participants enrolled in the study who received at least one dose of tocilizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESIs) | Adverse Events | 69.4 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESIs) | SAEs | 10.2 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESIs) | AESIs | 17.2 percentage of participants |
Secondary
Change From Baseline in Health Assessment Questionnaire (HAQ-DI) Score Over Time
The HAQ-DI was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from 4 response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104
Population: FAS included all randomized participants enrolled in the study who received at least one dose of tocilizumab. Here, number of participants analyzed is the total participants who were evaluable for this outcome measure and 'n' is the total number of participants who were evaluated at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire (HAQ-DI) Score Over Time | Change at Week 12 (n=49) | -0.2 score on a scale | Standard Deviation 0.4 |
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire (HAQ-DI) Score Over Time | Change at Week 24 (n=46) | -0.2 score on a scale | Standard Deviation 0.4 |
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire (HAQ-DI) Score Over Time | Change at Week 36 (n=46) | -0.1 score on a scale | Standard Deviation 0.4 |
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire (HAQ-DI) Score Over Time | Change at Week 48 (n=45) | 0.0 score on a scale | Standard Deviation 0.5 |
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire (HAQ-DI) Score Over Time | Change at Week 56 (n=44) | -0.1 score on a scale | Standard Deviation 0.6 |
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire (HAQ-DI) Score Over Time | Change at Week 68 (n=45) | -0.2 score on a scale | Standard Deviation 0.5 |
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire (HAQ-DI) Score Over Time | Change at Week 80 (n=45) | -0.2 score on a scale | Standard Deviation 0.5 |
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire (HAQ-DI) Score Over Time | Change at Week 92 (n=43) | 0.0 score on a scale | Standard Deviation 0.6 |
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire (HAQ-DI) Score Over Time | Change at Week 104 (n=43) | -0.1 score on a scale | Standard Deviation 0.5 |
Secondary
Change From Baseline in Swollen Joint Count 66 (SJC 66) Over Time
Number of swollen joints was determined by examination of 66 joints, as assessed through pressure and passive joint motion during physical examination.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104
Population: FAS included all randomized participants enrolled in the study who received at least one dose of tocilizumab. Here, 'n' is the total number of participants who were evaluated at a specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in Swollen Joint Count 66 (SJC 66) Over Time | Change at Week 104 (n=43) | -5.0 swollen joints | Standard Deviation 10 |
| Tocilizumab | Change From Baseline in Swollen Joint Count 66 (SJC 66) Over Time | Change at Week 12 (n=49) | -3.5 swollen joints | Standard Deviation 7.9 |
| Tocilizumab | Change From Baseline in Swollen Joint Count 66 (SJC 66) Over Time | Change at Week 24 (n=47) | -3.7 swollen joints | Standard Deviation 8.2 |
| Tocilizumab | Change From Baseline in Swollen Joint Count 66 (SJC 66) Over Time | Change at Week 36 (n=47) | -4.5 swollen joints | Standard Deviation 9.9 |
| Tocilizumab | Change From Baseline in Swollen Joint Count 66 (SJC 66) Over Time | Change at Week 48 (n=46) | -4.6 swollen joints | Standard Deviation 9.9 |
| Tocilizumab | Change From Baseline in Swollen Joint Count 66 (SJC 66) Over Time | Change at Week 56 (n=44) | -4.7 swollen joints | Standard Deviation 9.7 |
| Tocilizumab | Change From Baseline in Swollen Joint Count 66 (SJC 66) Over Time | Change at Week 68 (n=45) | -4.9 swollen joints | Standard Deviation 9.7 |
| Tocilizumab | Change From Baseline in Swollen Joint Count 66 (SJC 66) Over Time | Change at Week 80 (n=45) | -4.6 swollen joints | Standard Deviation 9.7 |
| Tocilizumab | Change From Baseline in Swollen Joint Count 66 (SJC 66) Over Time | Change at Week 92 (n=43) | -4.3 swollen joints | Standard Deviation 10.2 |
Secondary
Change From Baseline in Tender Joint Count 66 (TJC 66) Over Time
Number of tender joints was determined by examination of 66 joints, as assessed through pressure and passive joint motion during physical examination.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104
Population: FAS included all randomized participants enrolled in the study who received at least one dose of tocilizumab. Here, 'n' is the total number of participants who were evaluated at a specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in Tender Joint Count 66 (TJC 66) Over Time | Change at Week 12 (n=49) | -5.0 tender joints | Standard Deviation 6.7 |
| Tocilizumab | Change From Baseline in Tender Joint Count 66 (TJC 66) Over Time | Change at Week 24 (n=47) | -5.7 tender joints | Standard Deviation 9.5 |
| Tocilizumab | Change From Baseline in Tender Joint Count 66 (TJC 66) Over Time | Change at Week 36 (n=47) | -6.6 tender joints | Standard Deviation 10.4 |
| Tocilizumab | Change From Baseline in Tender Joint Count 66 (TJC 66) Over Time | Change at Week 48 (n=46) | -6.2 tender joints | Standard Deviation 11.8 |
| Tocilizumab | Change From Baseline in Tender Joint Count 66 (TJC 66) Over Time | Change at Week 56 (n=44) | -6.7 tender joints | Standard Deviation 10.6 |
| Tocilizumab | Change From Baseline in Tender Joint Count 66 (TJC 66) Over Time | Change at Week 68 (n=45) | -6.6 tender joints | Standard Deviation 10.6 |
| Tocilizumab | Change From Baseline in Tender Joint Count 66 (TJC 66) Over Time | Change at Week 80 (n=45) | -6.2 tender joints | Standard Deviation 10.8 |
| Tocilizumab | Change From Baseline in Tender Joint Count 66 (TJC 66) Over Time | Change at Week 92 (n=43) | -6.3 tender joints | Standard Deviation 11.9 |
| Tocilizumab | Change From Baseline in Tender Joint Count 66 (TJC 66) Over Time | Change at Week 104 (n=43) | -7.4 tender joints | Standard Deviation 10.9 |
Secondary
Percentage of Participants With Treatment-Free Remission According to DAS28-ESR/SDAI Remission Criteria
Treatment-free remission is remission at two consecutive assessment visits (every 12 weeks) after discontinuing study drug on the second assessment visit. Clinical remission is DAS28-ESR score \<2.6 and/or SDAI score ≤3.3. The DAS28-ESR scale is a measure of a participant's disease activity based on tender joint count (28 joints), swollen joint count (28 joints), a participant's assessment of disease activity, and ESR. DAS28-ESR scored on a scale with a minimum score of 0 (low disease activity) to a maximum score of 10 (high disease activity). The SDAI is sum of TJC and SJC, based on a 28-joint assessment, patient and physician global assessment assessed on 0-10 centimeter visual analogue scale (VAS), where 0 = no disease activity and 10 = worst disease activity, and level of C-reactive protein (CRP, mg/dL). SDAI total score = 0-86. SDAI \<=3.3 indicates clinical remission, \>3.4 to 11=low disease activity, \>11 to 26=moderate disease activity, and \>26=high (or severe) disease activity.
Time frame: Up to 104 weeks
Population: FAS included all randomized participants enrolled in the study who received at least one dose of tocilizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants With Treatment-Free Remission According to DAS28-ESR/SDAI Remission Criteria | 71.4 percentage of participants |
Secondary
Percent Change From Baseline in the Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Over Time
The DAS28-ESR Scale is a measure of a participant's disease activity. It is based on tender joint count (28 joints), swollen joint count (28 joints), a participant's assessment of disease activity, and erythrocyte sedimentation rate. DAS28-ESR is expressed as a score on a scale with a minimum score of 0 (low disease activity ) to a maximum score of 10 (high disease activity). A negative mean percent change from baseline indicates a decrease in disease activity, and a positive mean percent change from baseline indicates an increase in disease activity.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104
Population: FAS included all randomized participants enrolled in the study who received at least one dose of tocilizumab. Here, number of participants analyzed is the total participants who were evaluable for this outcome measure, and 'n' is the total number of participants who were evaluated at a specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Percent Change From Baseline in the Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Over Time | Change at Week 12 (n=42) | -35.4 percent change | Standard Deviation 30.4 |
| Tocilizumab | Percent Change From Baseline in the Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Over Time | Change at Week 24 (n=40) | -27.2 percent change | Standard Deviation 35.4 |
| Tocilizumab | Percent Change From Baseline in the Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Over Time | Change at Week 36 (n=39) | -29.3 percent change | Standard Deviation 48.4 |
| Tocilizumab | Percent Change From Baseline in the Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Over Time | Change at Week 48 (n=33) | -24.6 percent change | Standard Deviation 41 |
| Tocilizumab | Percent Change From Baseline in the Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Over Time | Change at Week 56 (n=34) | -32.5 percent change | Standard Deviation 31.9 |
| Tocilizumab | Percent Change From Baseline in the Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Over Time | Change at Week 68 (n=32) | -38.3 percent change | Standard Deviation 25.6 |
| Tocilizumab | Percent Change From Baseline in the Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Over Time | Change at Week 80 (n=28) | -29.4 percent change | Standard Deviation 33.5 |
| Tocilizumab | Percent Change From Baseline in the Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Over Time | Change at Week 92 (n=22) | -26.9 percent change | Standard Deviation 30.9 |
| Tocilizumab | Percent Change From Baseline in the Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Over Time | Change at Week 104 (n=26) | -38.1 percent change | Standard Deviation 25.9 |
Secondary
Percent Change From Baseline in the Simplified Disease Activity Index (SDAI) Over Time
The Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: tender joint count (TJC) and swollen joint count (SJC), based on a 28-joint assessment, patient and physician global assessment assessed on 0-10 centimeter (cm) visual analogue scale (VAS), where 0 = no disease activity and 10 = worst disease activity, and level of C-reactive protein (CRP, mg/dL). SDAI total score = 0-86. SDAI \<=3.3 indicates clinical remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity. A negative mean percent change from baseline indicates a decrease in disease activity, and a positive mean percent change from baseline indicates an increase in disease activity.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104
Population: FAS included all randomized participants enrolled in the study who received at least one dose of tocilizumab. Here, number of participants analyzed is the total participants who were evaluable for this outcome measure, and 'n' is the total number of participants who were evaluated at a specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Percent Change From Baseline in the Simplified Disease Activity Index (SDAI) Over Time | Change at Week 12 (n=37) | -45.5 percent change | Standard Deviation 33.9 |
| Tocilizumab | Percent Change From Baseline in the Simplified Disease Activity Index (SDAI) Over Time | Change at Week 24 (n=36) | -34.7 percent change | Standard Deviation 45.6 |
| Tocilizumab | Percent Change From Baseline in the Simplified Disease Activity Index (SDAI) Over Time | Change at Week 36 (n=38) | -6.3 percent change | Standard Deviation 221.1 |
| Tocilizumab | Percent Change From Baseline in the Simplified Disease Activity Index (SDAI) Over Time | Change at Week 48 (n=36) | -12.4 percent change | Standard Deviation 84.3 |
| Tocilizumab | Percent Change From Baseline in the Simplified Disease Activity Index (SDAI) Over Time | Change at Week 56 (n=34) | -39.3 percent change | Standard Deviation 66.4 |
| Tocilizumab | Percent Change From Baseline in the Simplified Disease Activity Index (SDAI) Over Time | Change at Week 68 (n=35) | -47.3 percent change | Standard Deviation 39.6 |
| Tocilizumab | Percent Change From Baseline in the Simplified Disease Activity Index (SDAI) Over Time | Change at Week 80 (n=36) | -30.3 percent change | Standard Deviation 66.9 |
| Tocilizumab | Percent Change From Baseline in the Simplified Disease Activity Index (SDAI) Over Time | Change at Week 92 (n=36) | -12.5 percent change | Standard Deviation 140.1 |
| Tocilizumab | Percent Change From Baseline in the Simplified Disease Activity Index (SDAI) Over Time | Change at Week 104 (n=35) | -28.8 percent change | Standard Deviation 115.7 |
Secondary
Percent Change in Participant's Assessment of Pain (VAS) Over Time
Participants' pain was assessed using a 10-mm horizontal VAS (0 to 10 mm) where 0=pain absent and 10=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain; the distance from the left edge to the mark was recorded.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104
Population: FAS included all randomized participants enrolled in the study who received at least one dose of tocilizumab. Here, number of participants analyzed is the total participants who were evaluable for this outcome measure and 'n' is the total number of participants who were evaluated at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Percent Change in Participant's Assessment of Pain (VAS) Over Time | Change at Week 12 (n=48) | -21.8 percent change | Standard Deviation 43.2 |
| Tocilizumab | Percent Change in Participant's Assessment of Pain (VAS) Over Time | Change at Week 24 (n=46) | -20.3 percent change | Standard Deviation 44.9 |
| Tocilizumab | Percent Change in Participant's Assessment of Pain (VAS) Over Time | Change at Week 36 (n=46) | -25.4 percent change | Standard Deviation 50 |
| Tocilizumab | Percent Change in Participant's Assessment of Pain (VAS) Over Time | Change at Week 48 (n=45) | 4 percent change | Standard Deviation 131.4 |
| Tocilizumab | Percent Change in Participant's Assessment of Pain (VAS) Over Time | Change at Week 56 (n=43) | -19.8 percent change | Standard Deviation 66.3 |
| Tocilizumab | Percent Change in Participant's Assessment of Pain (VAS) Over Time | Change at Week 68 (n=44) | -19.9 percent change | Standard Deviation 57.6 |
| Tocilizumab | Percent Change in Participant's Assessment of Pain (VAS) Over Time | Change at Week 80 (n=44) | -17.1 percent change | Standard Deviation 54.2 |
| Tocilizumab | Percent Change in Participant's Assessment of Pain (VAS) Over Time | Change at Week 92 (n=43) | -10.9 percent change | Standard Deviation 59.2 |
| Tocilizumab | Percent Change in Participant's Assessment of Pain (VAS) Over Time | Change at Week 104 (n=42) | -20.5 percent change | Standard Deviation 61.3 |
Secondary
Percent Change in Participant's General Assessment of Disease Activity (Severity of Disease) VAS Over Time
The participant's overall assessment of their current disease activity was displayed on a 100-millimeter (mm) horizontal VAS. The left-hand extreme (0 mm) of the line was described as no disease activity (symptom free and no arthritis symptoms) and the right-hand extreme (100 mm) was described as maximum disease activity (maximum arthritis disease activity). The change in Patient Global Assessment of Disease Activity was determined as the difference in values from baseline at each visit.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104
Population: FAS included all randomized participants enrolled in the study who received at least one dose of tocilizumab. Here, number of participants analyzed is the total participants who were evaluable for this outcome measure and 'n' is the total number of participants who were evaluated at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Percent Change in Participant's General Assessment of Disease Activity (Severity of Disease) VAS Over Time | Change at Week 12 (n=48) | -19.6 percent change | Standard Deviation 45.7 |
| Tocilizumab | Percent Change in Participant's General Assessment of Disease Activity (Severity of Disease) VAS Over Time | Change at Week 24 (n=46) | -20.3 percent change | Standard Deviation 49.8 |
| Tocilizumab | Percent Change in Participant's General Assessment of Disease Activity (Severity of Disease) VAS Over Time | Change at Week 36 (n=46) | -17.5 percent change | Standard Deviation 60.6 |
| Tocilizumab | Percent Change in Participant's General Assessment of Disease Activity (Severity of Disease) VAS Over Time | Change at Week 48 (n=45) | 6.1 percent change | Standard Deviation 92.8 |
| Tocilizumab | Percent Change in Participant's General Assessment of Disease Activity (Severity of Disease) VAS Over Time | Change at Week 56 (n=43) | -14.2 percent change | Standard Deviation 63.8 |
| Tocilizumab | Percent Change in Participant's General Assessment of Disease Activity (Severity of Disease) VAS Over Time | Change at Week 68 (n=44) | -19.3 percent change | Standard Deviation 48.6 |
| Tocilizumab | Percent Change in Participant's General Assessment of Disease Activity (Severity of Disease) VAS Over Time | Change at Week 80 (n=44) | -9.2 percent change | Standard Deviation 58.1 |
| Tocilizumab | Percent Change in Participant's General Assessment of Disease Activity (Severity of Disease) VAS Over Time | Change at Week 92 (n=43) | -4.7 percent change | Standard Deviation 67.2 |
| Tocilizumab | Percent Change in Participant's General Assessment of Disease Activity (Severity of Disease) VAS Over Time | Change at Week 104 (n=42) | -14.2 percent change | Standard Deviation 75.7 |
Secondary
Time to Rheumatoid Arthritis Recurrence in Participants Who Achieved Treatment-Free Remission
Time to rheumatoid arthritis (RA) recurrence = period from treatment-free remission to RA recurrence. RA recurrence was worsening of disease activity with treatment beyond supportive therapy.
Time frame: Up to 104 weeks
Population: FAS included all randomized participants enrolled in the study who received at least one dose of tocilizumab. Analysis was performed on those participants who achieved treatment-free remission.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | Time to Rheumatoid Arthritis Recurrence in Participants Who Achieved Treatment-Free Remission | 23 weeks |