Rheumatoid Arthritis
Conditions
Brief summary
This observational study will evaluate the use and efficacy of RoActemra/Actemra (tocilizumab) in monotherapy in routine clinical practice in participants with rheumatoid arthritis. Eligible participants initiated on RoActemra/Actemra treatment according to the licensed label will be followed for 6 months.
Interventions
DRUGtocilizumab
Participants received tocilizumab monotherapy according to individualized physician-prescribed regimens.
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 participants, \>/= 18 years of age * Moderate to severe rheumatoid arthritis according to the revised (1987) ACR criteria * Participants in whom the treating physician has made the decision to commence RoActemra/Actemra treatment in monotherapy in accordance with the local label and the reimbursement criteria indicating that RoActemra/Actemra can be given in monotherapy in case of methotrexate intolerance or where continued treatment with methotrexate is inappropriate; this can include participants who have received RoActemra/Actemra treatment within 8 weeks prior to the enrolment visit * Concomitant treatment with NSAIDs and/or corticosteroids is allowed
Exclusion criteria
* Participants who have received RoActemra/Actemra more than 8 weeks prior to the enrolment visit * Participants who have previously received RoActemra/Actemra in a clinical trial or for compassionate use * Participants receiving concomitant DMARD treatment for rheumatoid arthritis at baseline (e.g. hydroxychloroquine, sulfasalazine, methotrexate, leflunomide, gold compounds, cyclosporine) will be excluded from the study * Participants who have received treatment with an investigational agent within 4 weeks (or 5 half-lives of the investigational agent, whichever is longer) before starting treatment with RoActemra/Actemra * Participants with a history of autoimmune disease or any joint inflammatory disease other than rheumatoid arthritis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants on Tocilizumab Treatment at Month 6 After Treatment Initiation | Month 6 after treatment initiation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Disease-Modifying Antirheumatic Drugs (DMARDs) Intolerance and Inadequate Response | Baseline | — |
| Number of Participants With Inadequate Response to Other Biologics | Baseline | — |
| Time to Addition of Disease-Modifying Anti-rheumatic Drugs (DMARDs) | Month 6 | The time to DMARD addition equals to the time (days) between tocilizumab start and first start date of DMARDs. |
| Percentage of Participants Who Had DMARDs During Study | Month 6 | — |
| Number of Participants With Dose Reductions | 6 months | — |
| Number of Participants With Starting Tocilizumab After Failing DMARDs | Baseline | — |
| Number of Participants With Starting Tocilizumab After Stopping Other Biologic Agents | Baseline | — |
| Time to Reduction/Withdrawal of Corticosteroids | Month 6 | — |
| Number of Dose Modifications Per Participant at Month 6 | Month 6 | Number of dose modification per participant at Month 6 was reported. |
| Mean Dosing Interval Per Participant at Month 6 | Month 6 | — |
| Percentage of Participants Discontinued From Tocilizumab for Safety Versus Efficacy | Month 6 | — |
| Time for Restoration of Initial Dosing Regimen | Month 6 | — |
| Percentage of Participants Who Were Not Adhering to Recommended Dosing Regimen | Month 6 | — |
| Number of Participants Who Were Not Adhering to Recommended Management of AEs | Month 6 | — |
| Percentage of Participants Still on Tocilizumab Monotherapy at Month 6 | Month 6 | — |
| Percentage of Participants With Reason for Choice of Monotherapy at Baseline | Baseline | — |
| Percentage of Participants With Systemic Manifestations of RA at Baseline | Baseline | Systemic manifestations of RA included anemia, fatigue, conventional risk factors for cardiovascular disease, C-Reactive Protein (CRP) above upper limit of normal, rheumatoid nodules, rheumatoid vasculitis and interstitial lung disease. Participants were included if they experienced at least any one of the conditions. |
| Swollen Joint Count (SJC) | Baseline, Month 3, 6 | SJC was determined by examining 28 and 66 joints and identifying when swelling was present. Swelling was recorded on the joint assessment form at baseline, no swelling = 0, swelling =1. |
| Percentage of Participants With Disease Activity Score-28 (DAS28) | Baseline, Month 3, 6 | DAS28 was calculated from SJC and TJC using 28 joints count, erythrocyte sedimentation rate (ESR) (millimeter per hour \[mm/hr\]), and patient global assessment of disease activity (PGH) (measured on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0=no disease activity and 100=worst disease activity). DAS28 is a measurement of RA activity on a 0 to 10 scale: a score greater than (\>) 5.1 indicates high disease activity; a score between 3.2 and 5.1 indicates moderate disease activity; a score of less than 3.2 indicates low disease activity; a score of less than (\<) 2.6 is considered remission. |
| Percentage of Participants With Good European League Against Rheumatism (EULAR) Response at Month 3 and Month 6 | Month 3, 6 | Clinical response assessed as per EULAR categorical DAS28 response criteria was defined as clinically meaningful improvement at a particular time point. EULAR response was based on change from baseline (CFB) in the DAS28 score and also on the actual DAS28 score at the time point so was more reflective of the current status of the participant. EULAR Good response: DAS28 \<=3.2 and a CFB \<-1.2. EULAR Moderate response: DAS28 \>3.2 to ≤ 5.1 or a CFB \< -0.6 to ≥ -1.2. EULAR No response: DAS28 ≤3.2 or CFB greater than or equal to (\>=) -0.6, DAS28 \>3.2 to \<=5.1 or CFB\>=-0.6 and DAS28 \>5.1 or CFB \>=-0.6. The DAS28 score was a measure of the participant's disease activity, based on the TJC (28 joints), SJC (28 joints), PGH, and ESR. DAS28 total scores ranged from 0 to approximately 10. Scores \<2.6 = best disease control and scores \>5.1 = worse disease control. A negative CFB indicated clinically meaningful improvement. |
| Percentage of Participants With American College of Rheumatology (ACR) Response at Month 3 and Month 6 | Month 3, 6 | ACR response was calculated based on total joint count evaluation (28 or 66/68 joint count) and other clinical and laboratory assessments. A positive ACR20 response required at least a 20% improvement (reduction) compared to baseline in swollen joint count (66 joints) and tender joint count (68 joints) and at least 3 of the following 5 assessments: patient's global assessment of pain, PGH, PhGH (all 3 assessed at 0 \[good\] to 100 mm \[worst\] VAS scale), participant assessment of disability measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessed on a 0 to 3 scale, where higher scores represented higher disease activity), Acute phase reactant (CRP or ESR). A reduction in the level of and acute phase reactants was considered an improvement. ACR50, ACR70, ACR90 require a 50%, 70%, 90% improvement from baseline respectively. |
| Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response | Baseline, Month 3, 6 | CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PGH and physician global assessment of disease activity (PhGH) assessed on 0-10 cm VAS; 0 = no disease activity and 10 = worst disease activity. CDAI total score = 0-76. CDAI \<= 2.8 indicates clinical remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high (or severe) disease activity. |
| Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response | Baseline, Month 3, 6 | The SDAI was a combined index for measuring disease activity in RA which reflected the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PGH and PhGH, assessed on 0-100 mm VAS where 0 = no disease activity and 100 = worst disease activity, and C-reactive protein (CRP). SDAI total score = 0-86. A SDAI score \</= 3.3 represented clinical remission, a score of between 3.4 and 11.0 represented low disease activity, a score between 11 and 26.0 represented moderate disease activity and a score \> 26.0 represented high (or severe) disease. |
| Change From Baseline in Patient's Global Assessment of Disease Activity at Month 3 and Month 6 | Baseline, Month 3, 6 | The Patient Global Assessment of disease activity provides an overall assessment of how RA affects the participant using a visual analogue score, where 0 indicates they are managing very well and 100 indicates they are managing very poorly. A decrease in the score indicates improvement. |
| Change From Baseline in Physician Global Assessment of Disease Activity at Month 3 and Month 6 | Baseline, Month 3, 6 | The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal 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). A negative change from Baseline indicated improvement. |
| Change From Baseline in Health Assessment Questionnaire (HAQ) at Month 3 and Month 6 | Baseline, Month 3, 6 | The HAQ was a participant self-reported questionnaire for assessing the extent of a participant's functional ability. It consisted of 20 questions in 8 categories (dressing and grooming, rising, eating, walking, reach, grip, hygiene, and carrying out daily activities). Each question had 4 response options, ranging from 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The HAQ scale was an average of all the scores and ranged from 0 to 3, where higher scores represented higher disease activity. |
| Change From Baseline in VAS-Fatigue at Month 3 and Month 6 | Baseline, Month 3, 6 | The VAS-fatigue provides an overall assessment of the level of fatigue that the participant is experiencing using a visual analogue score, where 0 indicates no fatigue and 100 indicates extreme fatigue. A decrease in the score indicates improvement. |
| Change From Baseline in Patient's Global Assessment of Pain at Month 3 and Month 6 | Baseline, Month 3, 6 | The Patient Global Assessment of pain provides an overall assessment of the severity of pain that the participant is experiencing using a visual analogue score, where 0 indicates no pain and 100 indicates unbearable pain. A decrease in the score indicates improvement. |
| Change From Baseline in VAS-Morning Stiffness at Month 3 and Month 6 | Baseline, Month 3, 6 | Morning stiffness was defined by the time elapsed between the time of usual awakening (even if not in the morning) and the time the participant was as limber as he/she would be during a day involving typical activities. Morning stiffness was assessed on a 100 mm VAS, where 0= none and 100= very severe. |
| Percentage of Participants With an Adverse Event (AEs), Serious Adverse Events (SAEs), AEs of Special Interest (AESIs) | Month 6 | An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. An Serious Adverse Events (SAEs) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. AESI included- serious/medically significant infections; myocardial Infarction/acute coronary syndrome; gastrointestinal perforations; malignancies; anaphylaxis/hypersensitivity reactions; demyelinating disorders; stroke; serious/medically significant bleeding events; serious/medically significant hepatic events. |
| Percentage of Participants With AEs Leading to Dose Modifications | Month 6 | — |
| C-reactive Protein (CRP]) Level | Baseline, Month 3, 6 | CRP is an acute phase reactant and is a measure of inflammation. |
| Erythrocyte Sedimentation Rate (ESR) Level | Baseline, Month 3, 6 | ESR is an acute phase reactant and is a measure of inflammation. |
| Tender Joint Count (TJC) | Baseline, Month 3, 6 | TJC was determined by examining 28 and 68 joints and identifying the joints that were painful under pressure or to passive motion. Tenderness was recorded on the joint assessment form at baseline, no tenderness = 0, tenderness = 1. |
Countries
Belgium
Participant flow
Pre-assignment details
A total of 71 participants were enrolled in the study. Out of 71 participants, 68 received at least one dose of tocilizumab during the study and were included in the full analysis set.
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Participants with RA received tocilizumab monotherapy according to individualized physician-prescribed regimens. | 68 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Reason not Specified | 4 |
Baseline characteristics
| Characteristic | Tocilizumab |
|---|---|
| Age, Continuous | 59.3 years STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 45 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 68 |
| serious Total, serious adverse events | 3 / 68 |
Outcome results
Primary
Percentage of Participants on Tocilizumab Treatment at Month 6 After Treatment Initiation
Time frame: Month 6 after treatment initiation
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants on Tocilizumab Treatment at Month 6 After Treatment Initiation | 79.4 percentage of participants |
Secondary
Change From Baseline in Health Assessment Questionnaire (HAQ) at Month 3 and Month 6
The HAQ was a participant self-reported questionnaire for assessing the extent of a participant's functional ability. It consisted of 20 questions in 8 categories (dressing and grooming, rising, eating, walking, reach, grip, hygiene, and carrying out daily activities). Each question had 4 response options, ranging from 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The HAQ scale was an average of all the scores and ranged from 0 to 3, where higher scores represented higher disease activity.
Time frame: Baseline, Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire (HAQ) at Month 3 and Month 6 | Baseline (n=42) | 41.11 units on a scale | Standard Deviation 19.4 |
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire (HAQ) at Month 3 and Month 6 | Change at Month 3 (n=13) | -23.59 units on a scale | Standard Deviation 29.09 |
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire (HAQ) at Month 3 and Month 6 | Change at Month 6 (n=6) | -11.94 units on a scale | Standard Deviation 19.87 |
Secondary
Change From Baseline in Patient's Global Assessment of Disease Activity at Month 3 and Month 6
The Patient Global Assessment of disease activity provides an overall assessment of how RA affects the participant using a visual analogue score, where 0 indicates they are managing very well and 100 indicates they are managing very poorly. A decrease in the score indicates improvement.
Time frame: Baseline, Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in Patient's Global Assessment of Disease Activity at Month 3 and Month 6 | Baseline (n=40) | 65.6 units on a scale | Standard Deviation 15.2 |
| Tocilizumab | Change From Baseline in Patient's Global Assessment of Disease Activity at Month 3 and Month 6 | Change at Month 3 (n=12) | -27.8 units on a scale | Standard Deviation 27.5 |
| Tocilizumab | Change From Baseline in Patient's Global Assessment of Disease Activity at Month 3 and Month 6 | Change at Month 6 (n=7) | -30.1 units on a scale | Standard Deviation 16.2 |
Secondary
Change From Baseline in Patient's Global Assessment of Pain at Month 3 and Month 6
The Patient Global Assessment of pain provides an overall assessment of the severity of pain that the participant is experiencing using a visual analogue score, where 0 indicates no pain and 100 indicates unbearable pain. A decrease in the score indicates improvement.
Time frame: Baseline, Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in Patient's Global Assessment of Pain at Month 3 and Month 6 | Baseline (n=34) | 60.6 units on a scale | Standard Deviation 22.9 |
| Tocilizumab | Change From Baseline in Patient's Global Assessment of Pain at Month 3 and Month 6 | Change at Month 3 (n=9) | -31.8 units on a scale | Standard Deviation 25.1 |
| Tocilizumab | Change From Baseline in Patient's Global Assessment of Pain at Month 3 and Month 6 | Change at Month 6 (n=4) | -33.0 units on a scale | Standard Deviation 18.2 |
Secondary
Change From Baseline in Physician Global Assessment of Disease Activity at Month 3 and Month 6
The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal 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). A negative change from Baseline indicated improvement.
Time frame: Baseline, Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in Physician Global Assessment of Disease Activity at Month 3 and Month 6 | Baseline (n=34) | 57.6 units on a scale | Standard Deviation 23.1 |
| Tocilizumab | Change From Baseline in Physician Global Assessment of Disease Activity at Month 3 and Month 6 | Change at Month (n=9) | -41.9 units on a scale | Standard Deviation 22.6 |
| Tocilizumab | Change From Baseline in Physician Global Assessment of Disease Activity at Month 3 and Month 6 | Change at Month (n=3) | -53.0 units on a scale | Standard Deviation 20.7 |
Secondary
Change From Baseline in VAS-Fatigue at Month 3 and Month 6
The VAS-fatigue provides an overall assessment of the level of fatigue that the participant is experiencing using a visual analogue score, where 0 indicates no fatigue and 100 indicates extreme fatigue. A decrease in the score indicates improvement.
Time frame: Baseline, Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in VAS-Fatigue at Month 3 and Month 6 | Baseline (n=31) | 64 units on a scale | Standard Deviation 16.5 |
| Tocilizumab | Change From Baseline in VAS-Fatigue at Month 3 and Month 6 | Change at Month 3 (n=9) | -19.3 units on a scale | Standard Deviation 18.4 |
| Tocilizumab | Change From Baseline in VAS-Fatigue at Month 3 and Month 6 | Change at Month 6 (n=5) | -38.4 units on a scale | Standard Deviation 21.4 |
Secondary
Change From Baseline in VAS-Morning Stiffness at Month 3 and Month 6
Morning stiffness was defined by the time elapsed between the time of usual awakening (even if not in the morning) and the time the participant was as limber as he/she would be during a day involving typical activities. Morning stiffness was assessed on a 100 mm VAS, where 0= none and 100= very severe.
Time frame: Baseline, Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change From Baseline in VAS-Morning Stiffness at Month 3 and Month 6 | Baseline (n=22) | 37.8 units on a scale | Standard Deviation 22.9 |
| Tocilizumab | Change From Baseline in VAS-Morning Stiffness at Month 3 and Month 6 | Change at Month 3 (n=5) | -7.6 units on a scale | Standard Deviation 26.3 |
| Tocilizumab | Change From Baseline in VAS-Morning Stiffness at Month 3 and Month 6 | Change at Month 6 (n=3) | -30.3 units on a scale | Standard Deviation 18.5 |
Secondary
C-reactive Protein (CRP]) Level
CRP is an acute phase reactant and is a measure of inflammation.
Time frame: Baseline, Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | C-reactive Protein (CRP]) Level | Baseline (n= 51) | 9.94 milligram per liter (mg/L) | Standard Deviation 20.71 |
| Tocilizumab | C-reactive Protein (CRP]) Level | Month 3 (n= 52) | 5.04 milligram per liter (mg/L) | Standard Deviation 18.95 |
| Tocilizumab | C-reactive Protein (CRP]) Level | Month 6 (n= 28) | 2.49 milligram per liter (mg/L) | Standard Deviation 3.16 |
Secondary
Erythrocyte Sedimentation Rate (ESR) Level
ESR is an acute phase reactant and is a measure of inflammation.
Time frame: Baseline, Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Erythrocyte Sedimentation Rate (ESR) Level | Baseline (n= 42) | 24.31 millimeter per hour (mm/hr) | Standard Deviation 24.68 |
| Tocilizumab | Erythrocyte Sedimentation Rate (ESR) Level | Month 3 (n= 38) | 12.71 millimeter per hour (mm/hr) | Standard Deviation 23.84 |
| Tocilizumab | Erythrocyte Sedimentation Rate (ESR) Level | Month 6 (n= 17) | 8.88 millimeter per hour (mm/hr) | Standard Deviation 15.07 |
Secondary
Mean Dosing Interval Per Participant at Month 6
Time frame: Month 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Analysis was performed only participants reaching 6 month visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Mean Dosing Interval Per Participant at Month 6 | 25.86 days | Standard Deviation 2.64 |
Secondary
Number of Dose Modifications Per Participant at Month 6
Number of dose modification per participant at Month 6 was reported.
Time frame: Month 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Number of Dose Modifications Per Participant at Month 6 | 0.1 number of dose modifications | Standard Deviation 0.2 |
Secondary
Number of Participants Who Were Not Adhering to Recommended Management of AEs
Time frame: Month 6
Population: Only participants experiencing 'adverse events and/or abnormal laboratory tests requiring modification of drug dosage' are taken into account for this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Number of Participants Who Were Not Adhering to Recommended Management of AEs | 0 participants |
Secondary
Number of Participants With Disease-Modifying Antirheumatic Drugs (DMARDs) Intolerance and Inadequate Response
Time frame: Baseline
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Disease-Modifying Antirheumatic Drugs (DMARDs) Intolerance and Inadequate Response | DMARD Intolerance | 1 participants |
| Tocilizumab | Number of Participants With Disease-Modifying Antirheumatic Drugs (DMARDs) Intolerance and Inadequate Response | Inadequate Response | 67 participants |
Secondary
Number of Participants With Dose Reductions
Time frame: 6 months
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Number of Participants With Dose Reductions | 4 participants |
Secondary
Number of Participants With Inadequate Response to Other Biologics
Time frame: Baseline
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Number of Participants With Inadequate Response to Other Biologics | 35 participants |
Secondary
Number of Participants With Starting Tocilizumab After Failing DMARDs
Time frame: Baseline
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Number of Participants With Starting Tocilizumab After Failing DMARDs | 33 participants |
Secondary
Number of Participants With Starting Tocilizumab After Stopping Other Biologic Agents
Time frame: Baseline
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Number of Participants With Starting Tocilizumab After Stopping Other Biologic Agents | 35 participants |
Secondary
Percentage of Participants Discontinued From Tocilizumab for Safety Versus Efficacy
Time frame: Month 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, number of participants analyzed signifies the participants who were evaluable for the outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Discontinued From Tocilizumab for Safety Versus Efficacy | Adverse Event | 61.5 percentage of participants |
| Tocilizumab | Percentage of Participants Discontinued From Tocilizumab for Safety Versus Efficacy | Lack of efficacy | 7.7 percentage of participants |
| Tocilizumab | Percentage of Participants Discontinued From Tocilizumab for Safety Versus Efficacy | Other | 30.8 percentage of participants |
Secondary
Percentage of Participants Still on Tocilizumab Monotherapy at Month 6
Time frame: Month 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants Still on Tocilizumab Monotherapy at Month 6 | 98.1 percentage of participants |
Secondary
Percentage of Participants Who Had DMARDs During Study
Time frame: Month 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, number of participants analyzed signifies those participants who had addition of DMARDs during study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Who Had DMARDs During Study | Hydroxychoroquine | 0.0 percentage of participants |
| Tocilizumab | Percentage of Participants Who Had DMARDs During Study | Sulfasalazine | 0.0 percentage of participants |
| Tocilizumab | Percentage of Participants Who Had DMARDs During Study | Methotrexate | 100.0 percentage of participants |
| Tocilizumab | Percentage of Participants Who Had DMARDs During Study | Leflunomide | 0.0 percentage of participants |
| Tocilizumab | Percentage of Participants Who Had DMARDs During Study | Gold compunds | 0.0 percentage of participants |
| Tocilizumab | Percentage of Participants Who Had DMARDs During Study | Cyclosporine | 0.0 percentage of participants |
| Tocilizumab | Percentage of Participants Who Had DMARDs During Study | Azatioprine | 0.0 percentage of participants |
| Tocilizumab | Percentage of Participants Who Had DMARDs During Study | Other DMARD | 0.0 percentage of participants |
Secondary
Percentage of Participants Who Were Not Adhering to Recommended Dosing Regimen
Time frame: Month 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants Who Were Not Adhering to Recommended Dosing Regimen | 20.6 percentage of participants |
Secondary
Percentage of Participants With AEs Leading to Dose Modifications
Time frame: Month 6
Population: Safety population included all participants that received a dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants With AEs Leading to Dose Modifications | 7.4 percentage of participants |
Secondary
Percentage of Participants With American College of Rheumatology (ACR) Response at Month 3 and Month 6
ACR response was calculated based on total joint count evaluation (28 or 66/68 joint count) and other clinical and laboratory assessments. A positive ACR20 response required at least a 20% improvement (reduction) compared to baseline in swollen joint count (66 joints) and tender joint count (68 joints) and at least 3 of the following 5 assessments: patient's global assessment of pain, PGH, PhGH (all 3 assessed at 0 \[good\] to 100 mm \[worst\] VAS scale), participant assessment of disability measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessed on a 0 to 3 scale, where higher scores represented higher disease activity), Acute phase reactant (CRP or ESR). A reduction in the level of and acute phase reactants was considered an improvement. ACR50, ACR70, ACR90 require a 50%, 70%, 90% improvement from baseline respectively.
Time frame: Month 3, 6
Population: The ACR analysis was not performed because the Health Assessment Questionnaire (HAQ) disability index score is needed; only HAQ total score expressed in % was available.
Secondary
Percentage of Participants With an Adverse Event (AEs), Serious Adverse Events (SAEs), AEs of Special Interest (AESIs)
An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. An Serious Adverse Events (SAEs) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. AESI included- serious/medically significant infections; myocardial Infarction/acute coronary syndrome; gastrointestinal perforations; malignancies; anaphylaxis/hypersensitivity reactions; demyelinating disorders; stroke; serious/medically significant bleeding events; serious/medically significant hepatic events.
Time frame: Month 6
Population: Safety population included all participants that received a dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With an Adverse Event (AEs), Serious Adverse Events (SAEs), AEs of Special Interest (AESIs) | AE | 61.8 percentage of participants |
| Tocilizumab | Percentage of Participants With an Adverse Event (AEs), Serious Adverse Events (SAEs), AEs of Special Interest (AESIs) | SAE | 4.4 percentage of participants |
| Tocilizumab | Percentage of Participants With an Adverse Event (AEs), Serious Adverse Events (SAEs), AEs of Special Interest (AESIs) | AESI | 8.8 percentage of participants |
Secondary
Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response
CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PGH and physician global assessment of disease activity (PhGH) assessed on 0-10 cm VAS; 0 = no disease activity and 10 = worst disease activity. CDAI total score = 0-76. CDAI \<= 2.8 indicates clinical remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high (or severe) disease activity.
Time frame: Baseline, Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response | Baseline Remission (n=30) | 0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response | Remission at Month 3 (n=8) | 75.0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response | Baseline LDA (n=30) | 13.3 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response | LDA at Month 3 (n=8) | 25.0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response | High Disease Activity at Month 6 (n=4) | 0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response | Remission at Month 6 (n=4) | 75.0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response | LDA at Month 6 (n=4) | 25.0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response | Baseline Moderate Disease Activity (n=30) | 50.0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response | Moderate Disease Activity at Month 3 (n=8) | 0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response | Moderate Disease Activity at Month 6 (n=4) | 0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response | Baseline High Disease Activity (n=30) | 36.7 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Clinical Disease Activity Index (CDAI) Response | High Disease Activity at Month 3 (n=8) | 0 percentage of participants |
Secondary
Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response
The SDAI was a combined index for measuring disease activity in RA which reflected the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PGH and PhGH, assessed on 0-100 mm VAS where 0 = no disease activity and 100 = worst disease activity, and C-reactive protein (CRP). SDAI total score = 0-86. A SDAI score \</= 3.3 represented clinical remission, a score of between 3.4 and 11.0 represented low disease activity, a score between 11 and 26.0 represented moderate disease activity and a score \> 26.0 represented high (or severe) disease.
Time frame: Baseline, Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response | High Disease Activity at Month 6 (n=4) | 0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response | Baseline Remission (n=28) | 0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response | Remission at Month 3 (n=8) | 75.0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response | Remission at Month 6 (n=4) | 75.0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response | Baseline LDA (n=28) | 17.9 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response | LDA at Month 3 (n=8) | 25.0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response | LDA at Month 6 (n=4) | 25.0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response | Baseline Moderate Disease Activity (n=28) | 46.4 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response | Moderate Disease Activity at Month 3 (n=8) | 0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response | Moderate Disease Activity at Month 6 (n=4) | 0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response | Baseline High Disease Activity (n=28) | 35.7 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity According to Simplified Disease Activity Index (SDAI) Response | High Disease Activity at Month 3 (n=8) | 0 percentage of participants |
Secondary
Percentage of Participants With Disease Activity Score-28 (DAS28)
DAS28 was calculated from SJC and TJC using 28 joints count, erythrocyte sedimentation rate (ESR) (millimeter per hour \[mm/hr\]), and patient global assessment of disease activity (PGH) (measured on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0=no disease activity and 100=worst disease activity). DAS28 is a measurement of RA activity on a 0 to 10 scale: a score greater than (\>) 5.1 indicates high disease activity; a score between 3.2 and 5.1 indicates moderate disease activity; a score of less than 3.2 indicates low disease activity; a score of less than (\<) 2.6 is considered remission.
Time frame: Baseline, Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Disease Activity Score-28 (DAS28) | Remission at Baseline (n=38) | 0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity Score-28 (DAS28) | LDA at Baseline (n=38) | 0 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity Score-28 (DAS28) | LDA at Month 3 (n=19) | 73.7 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity Score-28 (DAS28) | LDA at Month 6 (n=11) | 81.8 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity Score-28 (DAS28) | Remission at Month 3 (n=19) | 68.4 percentage of participants |
| Tocilizumab | Percentage of Participants With Disease Activity Score-28 (DAS28) | Remission at Month 6 (n=11) | 81.8 percentage of participants |
Secondary
Percentage of Participants With Good European League Against Rheumatism (EULAR) Response at Month 3 and Month 6
Clinical response assessed as per EULAR categorical DAS28 response criteria was defined as clinically meaningful improvement at a particular time point. EULAR response was based on change from baseline (CFB) in the DAS28 score and also on the actual DAS28 score at the time point so was more reflective of the current status of the participant. EULAR Good response: DAS28 \<=3.2 and a CFB \<-1.2. EULAR Moderate response: DAS28 \>3.2 to ≤ 5.1 or a CFB \< -0.6 to ≥ -1.2. EULAR No response: DAS28 ≤3.2 or CFB greater than or equal to (\>=) -0.6, DAS28 \>3.2 to \<=5.1 or CFB\>=-0.6 and DAS28 \>5.1 or CFB \>=-0.6. The DAS28 score was a measure of the participant's disease activity, based on the TJC (28 joints), SJC (28 joints), PGH, and ESR. DAS28 total scores ranged from 0 to approximately 10. Scores \<2.6 = best disease control and scores \>5.1 = worse disease control. A negative CFB indicated clinically meaningful improvement.
Time frame: Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response at Month 3 and Month 6 | Month 3 (n=10) | 90 percentage of participants |
| Tocilizumab | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response at Month 3 and Month 6 | Month 6 (n=5) | 80 percentage of participants |
Secondary
Percentage of Participants With Reason for Choice of Monotherapy at Baseline
Time frame: Baseline
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Reason for Choice of Monotherapy at Baseline | MTX Intolerance | 61.8 percentage of participants |
| Tocilizumab | Percentage of Participants With Reason for Choice of Monotherapy at Baseline | Continued MTX not Appropriate | 38.2 percentage of participants |
Secondary
Percentage of Participants With Systemic Manifestations of RA at Baseline
Systemic manifestations of RA included anemia, fatigue, conventional risk factors for cardiovascular disease, C-Reactive Protein (CRP) above upper limit of normal, rheumatoid nodules, rheumatoid vasculitis and interstitial lung disease. Participants were included if they experienced at least any one of the conditions.
Time frame: Baseline
Population: Data for this outcome measure was not collected.
Secondary
Swollen Joint Count (SJC)
SJC was determined by examining 28 and 66 joints and identifying when swelling was present. Swelling was recorded on the joint assessment form at baseline, no swelling = 0, swelling =1.
Time frame: Baseline, Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Swollen Joint Count (SJC) | Baseline for SJC28 (n=47) | 7.9 swollen joints | Standard Deviation 5.6 |
| Tocilizumab | Swollen Joint Count (SJC) | Month 3 for SJC28 (n=29) | 1.5 swollen joints | Standard Deviation 3.5 |
| Tocilizumab | Swollen Joint Count (SJC) | Month 6 for SJC 28 (n=17) | 0.9 swollen joints | Standard Deviation 1.4 |
| Tocilizumab | Swollen Joint Count (SJC) | Baseline for SJC66 (n=7) | 8.9 swollen joints | Standard Deviation 4.5 |
| Tocilizumab | Swollen Joint Count (SJC) | Month 3 for SJC66 (n=10) | 0.6 swollen joints | Standard Deviation 1.3 |
| Tocilizumab | Swollen Joint Count (SJC) | Month 6 for SJC66 (n=1) | 0.0 swollen joints | — |
Secondary
Tender Joint Count (TJC)
TJC was determined by examining 28 and 68 joints and identifying the joints that were painful under pressure or to passive motion. Tenderness was recorded on the joint assessment form at baseline, no tenderness = 0, tenderness = 1.
Time frame: Baseline, Month 3, 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, n signifies the number of participants who were evaluated for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Tender Joint Count (TJC) | Month 6 for TJC68 (n=1) | 0.0 tender joints | — |
| Tocilizumab | Tender Joint Count (TJC) | Baseline for TJC28 (n=47) | 10.3 tender joints | Standard Deviation 6 |
| Tocilizumab | Tender Joint Count (TJC) | Month 3 for TJC28 (n=29) | 2.9 tender joints | Standard Deviation 5 |
| Tocilizumab | Tender Joint Count (TJC) | Month 6 for TJC 28 (n=17) | 2.2 tender joints | Standard Deviation 3.3 |
| Tocilizumab | Tender Joint Count (TJC) | Baseline for TJC68 (n=7) | 8.6 tender joints | Standard Deviation 3.2 |
| Tocilizumab | Tender Joint Count (TJC) | Month 3 for TJC68 (n=10) | 2.0 tender joints | Standard Deviation 2.7 |
Secondary
Time for Restoration of Initial Dosing Regimen
Time frame: Month 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, number of participants analyzed signifies number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | Time for Restoration of Initial Dosing Regimen | NA days |
Secondary
Time to Addition of Disease-Modifying Anti-rheumatic Drugs (DMARDs)
The time to DMARD addition equals to the time (days) between tocilizumab start and first start date of DMARDs.
Time frame: Month 6
Population: Full analysis set included all participants that received at least one dose of tocilizumab during the study. Here, number of participants analyzed are the participants who had addition of DMARDs during study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | Time to Addition of Disease-Modifying Anti-rheumatic Drugs (DMARDs) | 84 days |
Secondary
Time to Reduction/Withdrawal of Corticosteroids
Time frame: Month 6
Population: Data was not collected for this outcome measure.