Rheumatoid Arthritis
Conditions
Brief summary
This non-interventional study will evaluate the use and efficacy of RoActemra/Actemra (tocilizumab) in patients with moderate to severe rheumatoid arthritis. Eligible patients initiated on RoActemra/Actemra treatment according to the local label will be followed for 12 months.
Interventions
None listed
Sponsors
Hoffmann-La Roche
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/= 18 years of age * Moderate to severe rheumatoid arthritis according to the revised (1987) ACR criteria * Patients in whom the treating physician has made the decision to commence RoActemra/Actemra treatment (in accordance with the local label); this can include patients who have received RoActemra/Actemra treatment within 8 week prior to the enrolment visit
Exclusion criteria
* Patients who have received RoActemra/Actemra more than 8 weeks prior to the enrolment visit * Patients who have previously received RoActemra/Actemra in a clinical trial or for compassionate use * Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational agent, whichever is longer) before starting treatment with RoActemra/Actemra * History of autoimmune disease or any joint inflammatory disease other than rheumatoid arthritis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Tocilizumab Treatment at 6 Months After Treatment Initiation | 6 Months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Tocilizumab Dose Modification, Interruption, and Irregularity | Up to Month 12 | Dose modification was defined as an increase or decrease in the dose of study drug compared to the previous dose received. Interruption was defined as temporary or permanent discontinuation of study drug due to any reason, for example adverse event. Irregularity was defined as a time interval of greater than and equal to (\>=) 75 days between two consecutive doses of study drug. |
| Number of Participants With Comorbidities at Baseline | Baseline | Participants were assessed for any comorbidity at study entry including anemia, fatigue, conventional risk factors for cardiovascular disease, C-reactive protein (CRP) level above upper limit of normal, rheumatoid nodules, rheumatoid vasculitis, interstitial lung disease, and so on. Number of participants with each comorbidity was reported. One participant could have presented with more than 1 comorbidity. |
| Number of Participants With Prior Exposure to Disease Modifying Anti-rheumatic Drugs (DMARDs) | Baseline | — |
| Number of Participants With Prior Exposure of Biologics | Baseline | — |
| Disease Activity Score Based on 28-joints Count (DAS28) | Baseline, Month 3, 6, and 12 | DAS28 calculated from the number of swollen joints (SJC) and tender joints (TJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hr\]) and patient's global assessment (PtGA) of disease activity. DAS28 total score range = 0 to 10, where higher scores indicates higher disease activity. DAS28 less than and equal to (\<=) 2.6 meant clinical remission; DAS28 \<=3.2 meant low disease activity; DAS28 greater than (\>) 3.2 to 5.1 implied moderate disease activity; and DAS28 \>5.1 implied high disease activity. |
| Number of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Month 3, 6, and 12 | The 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. Description of DAS28 calculation is provided in Outcome Measure 7. Good responders: decrease from baseline \>1.2 with DAS28 \<= 3.2; moderate responders: decrease from baseline \>1.2 with DAS28 \>3.2 or decrease from baseline \>0.6 to \<=1.2 with DAS28 \<=5.1; non-responders: decrease from baseline \<= 0.6 or decrease from baseline \>0.6 and \<=1.2 with DAS28 \>5.1. |
| Physician Global Assessment (PGA) of Disease Activity | Baseline, Month 6, and 12 | PGA of disease activity was measured on a 0 to 100 millimeter (mm) visual analog scale (VAS), with 0 mm = no disease activity and 100 mm = highest possible disease activity. |
| Patient Global Assessment (PtGA) of Disease Activity Score | Baseline, Month 6, and 12 | PtGA of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm = highest possible disease activity. |
| Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Baseline, Month 6, and 12 | HAQ-DI: participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item was scored on a 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores divided by the number of domains answered. Total possible score range was 0-3 where 0 = least difficulty and 3 = extreme difficulty. |
| Visual Analog Scale (VAS)-Pain | Baseline, Month 6, and 12 | Intensity of pain was measured on a 100 mm line VAS marked by participant. It ranged (over the past week): 0 = no pain to 100 = worst possible pain. |
| Visual Analog Fatigue Scale (VAFS) | Baseline, Month 6, and 12 | Participants assessed their fatigue using a 0 - 100 mm VAS, where 0 mm = no fatigue and 100 mm = worst possible fatigue. |
| Visual Analog Scale-Morning Stiffness (VAS-MS) | Baseline, Month 6, and 12 | Participants assessed their morning stiffness using a 0 - 100 mm VAS, where 0 mm = no stiffness and 100 mm = worst possible stiffness. |
| Percentage of Participants With Tocilizumab Treatment at 12 Months After Treatment Initiation | Month 12 | — |
| C-Reactive Protein (CRP) | Baseline, Month 6, and 12 | The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range is up to 10 milligram per liter (mg/L). A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. |
| Number of Swollen and Tender Joints Based on 66 and 68 Joints | Baseline, Month 6, and 12 | Number of swollen joints was determined by examination of 66 joints (SJC66) and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, 0 = no swelling, 1 = swelling. Number of tender joints was determined by examining 68 joints (TJC68) and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, 0 = no tenderness, 1 = tenderness. |
| Number of Swollen and Tender Joints Based on 28 Joints | Baseline, Month 6, and 12 | Number of swollen joints was determined by examination of 28 (SJC28) joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, 0 = no swelling, 1 = swelling. Number of tender joints was determined by examining 28 joints (TJC28) and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, 0 = no tenderness, 1 = tenderness. |
| Simplified Disease Activity Index (SDAI) Score | Baseline, Month 6, and 12 | The SDAI is the numerical sum of five outcome parameters: TJC28, SJC28, PtGA, PGA, and CRP. Description of these outcome parameters is given in outcome measure 9, 10, 16, and 18. SDAI total score = 0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity. |
| Clinical Disease Activity Index (CDAI) Score | Baseline, Month 6, and 12 | The CDAI is the numerical sum of 4 outcome parameters: TJC28, SJC28, PtGA, and PGA. Description of these outcome parameters is given come measure 9, 10, and 18. CDAI total score = 0-76. CDAI \<= 2.8 indicates disease remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high disease activity. |
| Number of Participants Who Received Tocilizumab as Monotherapy | Baseline, Study end (at Month 12 or at time of study discontinuation) | — |
| Number of Participants Who Received Tocilizumab in Combination With Disease Modifying Anti-rheumatic Drugs (DMARDs) | Baseline, Study end (at Month 12 or at time of study discontinuation) | — |
| Number of Participants Receiving Oral Corticosteroids | Baseline, Month 3, 6, and 12 | — |
| Number of Participants With Disease Activity Status Based on DAS28 Score | Baseline, Month 3, 6, and 12 | Participants were assigned the disease activity status on the basis of DAS28 score. Description of DAS28 calculation is provided in Outcome Measure 7. Remission: DAS28 score \<= 2.6; low disease activity: DAS28 \<=3.2; moderate disease activity: DAS28 \<=5.1; and high disease activity: DAS28 \>5.1. |
| Number of Participants With Disease Activity Status Based on SDAI Score | Baseline, Month 3, 6, and 12 | Participants were assigned the disease activity status on the basis of SDAI score. Description of SDAI score calculation is provided in Outcome Measure 19. Remission: SDAI score \<= 3.3; low disease activity: SDAI \<=11.0; moderate disease activity: SDAI \<=26.0; and high disease activity: SDAI \>26.0. |
| Number of Participants With Disease Activity Status Based on CDAI Score | Baseline, Month 3, 6, and 12 | Participants were assigned the disease activity status on the basis of CDAI score. Description of CDAI score calculation is provided in Outcome Measure 20. Remission: CDAI score \<= 2.8; low disease activity: CDAI \<=10.0; moderate disease activity: CDAI \<=22.0; and high disease activity: CDAI \>22.0. |
| Erythrocyte Sedimentation Rate (ESR) | Baseline, Month 6, and 12 | ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hr. A higher rate is consistent with inflammation. |
Countries
Estonia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Participants with moderate to severe rheumatoid arthritis, in whom treating physician had made a decision to commence tocilizumab treatment according to local labeling (including participants who had started tocilizumab treatment within 8 weeks before enrollment) were observed prospectively for 12 months. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Consent Withdrawal by Subject | 1 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Switched to Subcutaneous Tocilizumab | 2 |
Baseline characteristics
| Characteristic | Tocilizumab |
|---|---|
| Age, Continuous | 52.4 years STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 23 |
| other Total, other adverse events | 10 / 23 |
| serious Total, serious adverse events | 4 / 23 |
Outcome results
Primary
Percentage of Participants With Tocilizumab Treatment at 6 Months After Treatment Initiation
Time frame: 6 Months
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants With Tocilizumab Treatment at 6 Months After Treatment Initiation | 73.9 percentage of participants |
Secondary
Clinical Disease Activity Index (CDAI) Score
The CDAI is the numerical sum of 4 outcome parameters: TJC28, SJC28, PtGA, and PGA. Description of these outcome parameters is given come measure 9, 10, and 18. CDAI total score = 0-76. CDAI \<= 2.8 indicates disease remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high disease activity.
Time frame: Baseline, Month 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Clinical Disease Activity Index (CDAI) Score | Baseline (n=20) | 28.68 units on a scale | Standard Deviation 10.21 |
| Tocilizumab | Clinical Disease Activity Index (CDAI) Score | Month 6 (n=15) | 13.12 units on a scale | Standard Deviation 11.55 |
| Tocilizumab | Clinical Disease Activity Index (CDAI) Score | Month 12 (n=10) | 6.77 units on a scale | Standard Deviation 5.33 |
Comparison: Change from Baseline at Month 6p-value: <0.01Wilcoxon's signed-rank test
Comparison: Change from Baseline at Month 12p-value: <0.001Wilcoxon's signed-rank test
Secondary
C-Reactive Protein (CRP)
The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range is up to 10 milligram per liter (mg/L). A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
Time frame: Baseline, Month 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | C-Reactive Protein (CRP) | Baseline (n=23) | 30.16 mg/L | Standard Deviation 41.14 |
| Tocilizumab | C-Reactive Protein (CRP) | Month 6 (n=18) | 8.54 mg/L | Standard Deviation 17.54 |
| Tocilizumab | C-Reactive Protein (CRP) | Month 12 (n=14) | 4.07 mg/L | Standard Deviation 7.7 |
Comparison: Change from Baseline at Month 6p-value: <0.05Wilcoxon's signed-rank test
Comparison: Change from Baseline at Month 12p-value: <0.01Wilcoxon's signed-rank test
Secondary
Disease Activity Score Based on 28-joints Count (DAS28)
DAS28 calculated from the number of swollen joints (SJC) and tender joints (TJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hr\]) and patient's global assessment (PtGA) of disease activity. DAS28 total score range = 0 to 10, where higher scores indicates higher disease activity. DAS28 less than and equal to (\<=) 2.6 meant clinical remission; DAS28 \<=3.2 meant low disease activity; DAS28 greater than (\>) 3.2 to 5.1 implied moderate disease activity; and DAS28 \>5.1 implied high disease activity.
Time frame: Baseline, Month 3, 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Disease Activity Score Based on 28-joints Count (DAS28) | Baseline (n=22) | 5.35 units on a scale | Standard Deviation 1.21 |
| Tocilizumab | Disease Activity Score Based on 28-joints Count (DAS28) | Month 3 (n=19) | 3.54 units on a scale | Standard Deviation 1.2 |
| Tocilizumab | Disease Activity Score Based on 28-joints Count (DAS28) | Month 6 (n=17) | 2.91 units on a scale | Standard Deviation 1.59 |
| Tocilizumab | Disease Activity Score Based on 28-joints Count (DAS28) | Month 12 (n=11) | 2.29 units on a scale | Standard Deviation 1.11 |
Comparison: Change from Baseline at Month 3p-value: <0.01Wilcoxon's signed-rank test
Comparison: Change from Baseline at Month 6p-value: <0.01Wilcoxon's signed-rank test
Comparison: Change from Baseline at Month 12p-value: <0.01Wilcoxon's signed-rank test
Secondary
Erythrocyte Sedimentation Rate (ESR)
ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hr. A higher rate is consistent with inflammation.
Time frame: Baseline, Month 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Erythrocyte Sedimentation Rate (ESR) | Baseline (n=23) | 36.83 mm/hr | Standard Deviation 27.53 |
| Tocilizumab | Erythrocyte Sedimentation Rate (ESR) | Month 6 (n=16) | 9.81 mm/hr | Standard Deviation 14.11 |
| Tocilizumab | Erythrocyte Sedimentation Rate (ESR) | Month 12 (n=13) | 6.54 mm/hr | Standard Deviation 6.77 |
Comparison: Change from Baseline at Month 6p-value: <0.001Wilcoxon's signed-rank test
Comparison: Change from Baseline at Month 12p-value: <0.01Wilcoxon's signed-rank test
Secondary
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
HAQ-DI: participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item was scored on a 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores divided by the number of domains answered. Total possible score range was 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time frame: Baseline, Month 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Baseline (n=20) | 1.22 units on a scale | Standard Deviation 0.8 |
| Tocilizumab | Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Month 6 (n=10) | 0.98 units on a scale | Standard Deviation 0.81 |
| Tocilizumab | Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Month 12 (n=6) | 0.65 units on a scale | Standard Deviation 0.52 |
Secondary
Number of Participants Receiving Oral Corticosteroids
Time frame: Baseline, Month 3, 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tocilizumab | Number of Participants Receiving Oral Corticosteroids | Baseline (n=23) | 18 Participants |
| Tocilizumab | Number of Participants Receiving Oral Corticosteroids | Month 3 (n=21) | 14 Participants |
| Tocilizumab | Number of Participants Receiving Oral Corticosteroids | Month 6 (n=19) | 12 Participants |
| Tocilizumab | Number of Participants Receiving Oral Corticosteroids | Month 12 (n=15) | 9 Participants |
Secondary
Number of Participants Who Received Tocilizumab as Monotherapy
Time frame: Baseline, Study end (at Month 12 or at time of study discontinuation)
Population: FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants Who Received Tocilizumab as Monotherapy | Baseline | 2 participants |
| Tocilizumab | Number of Participants Who Received Tocilizumab as Monotherapy | Study end | 9 participants |
Secondary
Number of Participants Who Received Tocilizumab in Combination With Disease Modifying Anti-rheumatic Drugs (DMARDs)
Time frame: Baseline, Study end (at Month 12 or at time of study discontinuation)
Population: FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants Who Received Tocilizumab in Combination With Disease Modifying Anti-rheumatic Drugs (DMARDs) | Baseline | 21 participants |
| Tocilizumab | Number of Participants Who Received Tocilizumab in Combination With Disease Modifying Anti-rheumatic Drugs (DMARDs) | Study end | 14 participants |
Secondary
Number of Participants With Comorbidities at Baseline
Participants were assessed for any comorbidity at study entry including anemia, fatigue, conventional risk factors for cardiovascular disease, C-reactive protein (CRP) level above upper limit of normal, rheumatoid nodules, rheumatoid vasculitis, interstitial lung disease, and so on. Number of participants with each comorbidity was reported. One participant could have presented with more than 1 comorbidity.
Time frame: Baseline
Population: FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Anemia | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Iron deficiency anemia | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Atrial fibrillation | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Hypothyroidism | 3 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Chronic gastritis | 2 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Duodenitis | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Duodenal ulcer perforation | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Dyspepsia | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Gastric disorder | 2 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Inguinal hernia | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Large intestine polyp | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Cholelithiasis | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Hepatic steatosis | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Latent tuberculosis | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Pulmonary tuberculosis | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Hyperlipidaemia | 2 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Spinal osteoarthritis | 2 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Osteoarthritis | 5 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Osteopenia | 2 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Osteoporosis | 2 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Rotator cuff syndrome | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Scoliosis | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Spondyloarthropathy | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Spondylolisthesis | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Spinal column stenosis | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Haemangioma of liver | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Ovarian cancer | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Radiculopathy | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Cervical radiculopathy | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Gynaecomastia | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Chronic obstructive pulmonary disease | 1 participants |
| Tocilizumab | Number of Participants With Comorbidities at Baseline | Hypertension | 9 participants |
Secondary
Number of Participants With Disease Activity Status Based on CDAI Score
Participants were assigned the disease activity status on the basis of CDAI score. Description of CDAI score calculation is provided in Outcome Measure 20. Remission: CDAI score \<= 2.8; low disease activity: CDAI \<=10.0; moderate disease activity: CDAI \<=22.0; and high disease activity: CDAI \>22.0.
Time frame: Baseline, Month 3, 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Disease Activity Status Based on CDAI Score | Month 12: moderate disease activity (n=10) | 2 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on CDAI Score | Baseline: moderate disease activity (n=20) | 5 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on CDAI Score | Baseline: high disease activity (n=20) | 15 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on CDAI Score | Month 3: low disease activity (n=17) | 4 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on CDAI Score | Month 3: moderate disease activity (n=17) | 9 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on CDAI Score | Month 3: high disease activity (n=17) | 4 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on CDAI Score | Month 6: Remission (n=15) | 3 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on CDAI Score | Month 6: low disease activity (n=15) | 4 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on CDAI Score | Month 6: moderate disease activity (n=15) | 5 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on CDAI Score | Month 6: high disease activity (n=15) | 3 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on CDAI Score | Month 12: Remission (n=10) | 2 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on CDAI Score | Month 12: low disease activity (n=10) | 6 participants |
Secondary
Number of Participants With Disease Activity Status Based on DAS28 Score
Participants were assigned the disease activity status on the basis of DAS28 score. Description of DAS28 calculation is provided in Outcome Measure 7. Remission: DAS28 score \<= 2.6; low disease activity: DAS28 \<=3.2; moderate disease activity: DAS28 \<=5.1; and high disease activity: DAS28 \>5.1.
Time frame: Baseline, Month 3, 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Baseline: Remission (n=22) | 1 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Baseline: low disease activity (n=22) | 1 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Baseline: moderate disease activity (n=22) | 4 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Baseline: high disease activity (n=22) | 16 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Month 3: Remission (n=19) | 5 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Month 3: low disease activity (n=19) | 3 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Month 3: moderate disease activity (n=19) | 8 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Month 3: high disease activity (n=19) | 3 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Month 6: Remission (n=17) | 8 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Month 6: low disease activity (n=17) | 3 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Month 6: moderate disease activity (n=17) | 4 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Month 6: high disease activity (n=17) | 2 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Month 12: Remission (n=11) | 9 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on DAS28 Score | Month 12: moderate disease activity (n=11) | 2 participants |
Secondary
Number of Participants With Disease Activity Status Based on SDAI Score
Participants were assigned the disease activity status on the basis of SDAI score. Description of SDAI score calculation is provided in Outcome Measure 19. Remission: SDAI score \<= 3.3; low disease activity: SDAI \<=11.0; moderate disease activity: SDAI \<=26.0; and high disease activity: SDAI \>26.0.
Time frame: Baseline, Month 3, 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Disease Activity Status Based on SDAI Score | Baseline: moderate disease activity (n=20) | 5 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on SDAI Score | Baseline: high disease activity (n=20) | 15 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on SDAI Score | Month 3: low disease activity (n=16) | 5 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on SDAI Score | Month 3: moderate disease activity (n=16) | 8 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on SDAI Score | Month 3: high disease activity (n=16) | 3 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on SDAI Score | Month 6: Remission (n=15) | 3 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on SDAI Score | Month 6: low disease activity (n=15) | 4 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on SDAI Score | Month 6: moderate disease activity (n=15) | 7 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on SDAI Score | Month 6: high disease activity (n=15) | 1 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on SDAI Score | Month 12: Remission (n=10) | 2 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on SDAI Score | Month 12: low disease activity (n=10) | 6 participants |
| Tocilizumab | Number of Participants With Disease Activity Status Based on SDAI Score | Month 12: moderate disease activity (n=10) | 2 participants |
Secondary
Number of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
The 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. Description of DAS28 calculation is provided in Outcome Measure 7. Good responders: decrease from baseline \>1.2 with DAS28 \<= 3.2; moderate responders: decrease from baseline \>1.2 with DAS28 \>3.2 or decrease from baseline \>0.6 to \<=1.2 with DAS28 \<=5.1; non-responders: decrease from baseline \<= 0.6 or decrease from baseline \>0.6 and \<=1.2 with DAS28 \>5.1.
Time frame: Month 3, 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Month 3: Good responders (n=18) | 6 participants |
| Tocilizumab | Number of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Month 3: Moderate responders (n=18) | 8 participants |
| Tocilizumab | Number of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Month 3: Non-responders (n=18) | 4 participants |
| Tocilizumab | Number of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Month 6: Good responders (n=16) | 11 participants |
| Tocilizumab | Number of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Month 6: Moderate responders (n = 16) | 2 participants |
| Tocilizumab | Number of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Month 6: Non-responders (n=16) | 3 participants |
| Tocilizumab | Number of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Month 12: Good responders (n=11) | 8 participants |
| Tocilizumab | Number of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Month 12: Moderate responders (n=11) | 2 participants |
| Tocilizumab | Number of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Month 12: Non-responders (n=11) | 1 participants |
Secondary
Number of Participants With Prior Exposure of Biologics
Time frame: Baseline
Population: FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Prior Exposure of Biologics | No Prior Biologics | 12 participants |
| Tocilizumab | Number of Participants With Prior Exposure of Biologics | 1 Prior Biologic | 8 participants |
| Tocilizumab | Number of Participants With Prior Exposure of Biologics | 2 Prior Biologics | 3 participants |
Secondary
Number of Participants With Prior Exposure to Disease Modifying Anti-rheumatic Drugs (DMARDs)
Time frame: Baseline
Population: FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Prior Exposure to Disease Modifying Anti-rheumatic Drugs (DMARDs) | 3 Prior DMARDs | 7 participants |
| Tocilizumab | Number of Participants With Prior Exposure to Disease Modifying Anti-rheumatic Drugs (DMARDs) | No Prior DMARDs | 1 participants |
| Tocilizumab | Number of Participants With Prior Exposure to Disease Modifying Anti-rheumatic Drugs (DMARDs) | 1 Prior DMARD | 1 participants |
| Tocilizumab | Number of Participants With Prior Exposure to Disease Modifying Anti-rheumatic Drugs (DMARDs) | 2 Prior DMARDs | 5 participants |
| Tocilizumab | Number of Participants With Prior Exposure to Disease Modifying Anti-rheumatic Drugs (DMARDs) | 4 Prior DMARDs | 5 participants |
| Tocilizumab | Number of Participants With Prior Exposure to Disease Modifying Anti-rheumatic Drugs (DMARDs) | 5 Prior DMARDs | 4 participants |
Secondary
Number of Swollen and Tender Joints Based on 28 Joints
Number of swollen joints was determined by examination of 28 (SJC28) joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, 0 = no swelling, 1 = swelling. Number of tender joints was determined by examining 28 joints (TJC28) and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, 0 = no tenderness, 1 = tenderness.
Time frame: Baseline, Month 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Number of Swollen and Tender Joints Based on 28 Joints | SJC28: Baseline (n=23) | 6.78 joints count | Standard Deviation 4.06 |
| Tocilizumab | Number of Swollen and Tender Joints Based on 28 Joints | TJC28: Baseline (n=23) | 9.13 joints count | Standard Deviation 7.23 |
| Tocilizumab | Number of Swollen and Tender Joints Based on 28 Joints | SJC28: Month 6 (n=18) | 2.56 joints count | Standard Deviation 2.79 |
| Tocilizumab | Number of Swollen and Tender Joints Based on 28 Joints | TJC28: Month 6 (n=18) | 4.11 joints count | Standard Deviation 6.03 |
| Tocilizumab | Number of Swollen and Tender Joints Based on 28 Joints | SJC28: Month 12 (n=13) | 1.54 joints count | Standard Deviation 2.4 |
| Tocilizumab | Number of Swollen and Tender Joints Based on 28 Joints | TJC28: Month 12 (n=13) | 1.92 joints count | Standard Deviation 1.85 |
Comparison: SJC28: Change from Baseline at Month 6p-value: <0.01Wilcoxon's signed-rank test
Comparison: TJC28: Change from Baseline at Month 6p-value: <0.01Wilcoxon's signed-rank test
Comparison: SJC28: Change from Baseline at Month 12p-value: <0.001Wilcoxon's signed-rank test
Comparison: TJC28: Change from Baseline at Month 12p-value: <0.01Wilcoxon's signed-rank test
Secondary
Number of Swollen and Tender Joints Based on 66 and 68 Joints
Number of swollen joints was determined by examination of 66 joints (SJC66) and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, 0 = no swelling, 1 = swelling. Number of tender joints was determined by examining 68 joints (TJC68) and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, 0 = no tenderness, 1 = tenderness.
Time frame: Baseline, Month 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Number of Swollen and Tender Joints Based on 66 and 68 Joints | SJC66: Baseline (n=7) | 4.29 joints count | Standard Deviation 2.21 |
| Tocilizumab | Number of Swollen and Tender Joints Based on 66 and 68 Joints | TJC68: Baseline (n=7) | 6.86 joints count | Standard Deviation 7.99 |
| Tocilizumab | Number of Swollen and Tender Joints Based on 66 and 68 Joints | SJC66: Month 6 (n=1) | 0 joints count | — |
| Tocilizumab | Number of Swollen and Tender Joints Based on 66 and 68 Joints | TJC68: Month 6 (n=1) | 0 joints count | — |
| Tocilizumab | Number of Swollen and Tender Joints Based on 66 and 68 Joints | SJC66: Month 12 (n=1) | 1.00 joints count | — |
| Tocilizumab | Number of Swollen and Tender Joints Based on 66 and 68 Joints | TJC68: Month 12 (n=1) | 2.00 joints count | — |
Secondary
Patient Global Assessment (PtGA) of Disease Activity Score
PtGA of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm = highest possible disease activity.
Time frame: Baseline, Month 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Patient Global Assessment (PtGA) of Disease Activity Score | Month 6 (n=17) | 36.85 mm | Standard Deviation 24.22 |
| Tocilizumab | Patient Global Assessment (PtGA) of Disease Activity Score | Baseline (n=22) | 62.68 mm | Standard Deviation 17.67 |
| Tocilizumab | Patient Global Assessment (PtGA) of Disease Activity Score | Month 12 (n=11) | 22.27 mm | Standard Deviation 21 |
Comparison: Change from Baseline at Month 6p-value: <0.05Wilcoxon's signed-rank test
Comparison: Change from Baseline at Month 12p-value: <0.0001Wilcoxon's signed-rank test
Secondary
Percentage of Participants With Tocilizumab Dose Modification, Interruption, and Irregularity
Dose modification was defined as an increase or decrease in the dose of study drug compared to the previous dose received. Interruption was defined as temporary or permanent discontinuation of study drug due to any reason, for example adverse event. Irregularity was defined as a time interval of greater than and equal to (\>=) 75 days between two consecutive doses of study drug.
Time frame: Up to Month 12
Population: FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Tocilizumab Dose Modification, Interruption, and Irregularity | Dose Modification | 26.1 percentage of participants |
| Tocilizumab | Percentage of Participants With Tocilizumab Dose Modification, Interruption, and Irregularity | Dose Modification + Interruption | 39.1 percentage of participants |
| Tocilizumab | Percentage of Participants With Tocilizumab Dose Modification, Interruption, and Irregularity | Dose Modification + Interruption + Irregularity | 39.1 percentage of participants |
Secondary
Percentage of Participants With Tocilizumab Treatment at 12 Months After Treatment Initiation
Time frame: Month 12
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants With Tocilizumab Treatment at 12 Months After Treatment Initiation | 69.6 percentage of participants |
Secondary
Physician Global Assessment (PGA) of Disease Activity
PGA of disease activity was measured on a 0 to 100 millimeter (mm) visual analog scale (VAS), with 0 mm = no disease activity and 100 mm = highest possible disease activity.
Time frame: Baseline, Month 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Physician Global Assessment (PGA) of Disease Activity | Baseline (n=20) | 58.40 mm | Standard Deviation 10.08 |
| Tocilizumab | Physician Global Assessment (PGA) of Disease Activity | Month 6 (n=15) | 27.00 mm | Standard Deviation 18.34 |
| Tocilizumab | Physician Global Assessment (PGA) of Disease Activity | Month 12 (n=10) | 13.80 mm | Standard Deviation 13.83 |
Comparison: Change from Baseline at Month 6p-value: <0.001Wilcoxon's signed-rank test
Comparison: Change from Baseline at Month 12p-value: <0.0001Wilcoxon's signed-rank test
Secondary
Simplified Disease Activity Index (SDAI) Score
The SDAI is the numerical sum of five outcome parameters: TJC28, SJC28, PtGA, PGA, and CRP. Description of these outcome parameters is given in outcome measure 9, 10, 16, and 18. SDAI total score = 0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity.
Time frame: Baseline, Month 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Simplified Disease Activity Index (SDAI) Score | Baseline (n=20) | 31.99 units on a scale | Standard Deviation 10.77 |
| Tocilizumab | Simplified Disease Activity Index (SDAI) Score | Month 6 (n=15) | 13.69 units on a scale | Standard Deviation 11.6 |
| Tocilizumab | Simplified Disease Activity Index (SDAI) Score | Month 12 (n=10) | 7.17 units on a scale | Standard Deviation 6.12 |
Comparison: Change from Baseline at Month 6p-value: <0.01Wilcoxon's signed-rank test
Comparison: Change from Baseline at Month 12p-value: <0.001Wilcoxon's signed-rank test
Secondary
Visual Analog Fatigue Scale (VAFS)
Participants assessed their fatigue using a 0 - 100 mm VAS, where 0 mm = no fatigue and 100 mm = worst possible fatigue.
Time frame: Baseline, Month 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Visual Analog Fatigue Scale (VAFS) | Baseline (n=6) | 67.00 mm | Standard Deviation 30.66 |
| Tocilizumab | Visual Analog Fatigue Scale (VAFS) | Month 6 (n=5) | 39.80 mm | Standard Deviation 30.38 |
| Tocilizumab | Visual Analog Fatigue Scale (VAFS) | Month 12 (n=3) | 5.67 mm | Standard Deviation 6.66 |
Comparison: Change from Baseline at Month 12p-value: <0.01Wilcoxon's signed-rank test
Secondary
Visual Analog Scale-Morning Stiffness (VAS-MS)
Participants assessed their morning stiffness using a 0 - 100 mm VAS, where 0 mm = no stiffness and 100 mm = worst possible stiffness.
Time frame: Baseline, Month 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Visual Analog Scale-Morning Stiffness (VAS-MS) | Baseline (n=6) | 67.00 mm | Standard Deviation 12.54 |
| Tocilizumab | Visual Analog Scale-Morning Stiffness (VAS-MS) | Month 6 (n=5) | 23.60 mm | Standard Deviation 33.22 |
| Tocilizumab | Visual Analog Scale-Morning Stiffness (VAS-MS) | Month 12 (n=2) | 16.00 mm | Standard Deviation 19.8 |
Secondary
Visual Analog Scale (VAS)-Pain
Intensity of pain was measured on a 100 mm line VAS marked by participant. It ranged (over the past week): 0 = no pain to 100 = worst possible pain.
Time frame: Baseline, Month 6, and 12
Population: FAS. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Visual Analog Scale (VAS)-Pain | Baseline (n=22) | 56.18 mm | Standard Deviation 21.64 |
| Tocilizumab | Visual Analog Scale (VAS)-Pain | Month 6 (n=17) | 35.00 mm | Standard Deviation 23.25 |
| Tocilizumab | Visual Analog Scale (VAS)-Pain | Month 12 (n=11) | 22.91 mm | Standard Deviation 22.87 |
Comparison: Change from Baseline at Month 6p-value: <0.05Wilcoxon's signed-rank test
Comparison: Change from Baseline at Month 12p-value: <0.01Wilcoxon's signed-rank test