Rheumatoid Arthritis
Conditions
Brief summary
This extension study of WA19926 will assess the long-term safety and the efficacy of RoActemra/Actemra (tocilizumab) treatment in participants with rheumatoid arthritis. Participants who have completed the core study WA19926 are eligible to participate. Participants will receive RoActemra/Actemra 8 mg/kg intravenously every 4 weeks. The anticipated time on study drug is 104 weeks.
Interventions
DRUGtocilizumab [RoActemra/Actemra]
8 mg/kg intravenously every 4 weeks for 104 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult participants, \>/=18 years of age who have completed the core study WA19926 and according to the investigator may benefit from RoActemra/Actemra treatment * No current or recent adverse event or laboratory finding preventing the use of the study drug dose at baseline * Receiving treatment on an outpatient basis
Exclusion criteria
* Females who are pregnant * Participants who have prematurely withdrawn from the core study WA19926 for any reason * Treatment with any investigational drug since the last administration of the study drug in the core study WA19926 * Treatment with an anti-tumor necrosis (TNF), anti-interleukin 1 agent or T-cell costimulation modulator since the last administration of the study drug in the core study WA19926 * Immunization with live/attenuated vaccine since the last administration of the study drug in the core study WA19926 * Diagnosis since the last WA19926 visit of rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis * Abnormal laboratory values
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs) | End of Study (Week 104 or early withdrawal) | 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. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. Adverse Events of Special Interest for this study were: Serious and/or medically significant infections; myocardial infarction/Acute coronary syndrome; Gastrointestinal perforation; Malignancies; Anaphylaxis/hypersensitivity reactions; Demyelinating disorders; Stroke and Serious and/or medically significant bleeding and hepatic events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) | Screening and End of Study (Week 104 or early withdrawal) | The SDAI was defined as the numerical sum of 5 outcome parameters: tender and swollen joint count (based on a 28-joint assessment), participant and physician global assessment of disease activity on a 100 millimeter (mm) Visual analogue scale (VAS) (VAS; 0 = no disease activity and 100 = worst disease activity) and level of C-reactive protein (CRP) (milligram per deciliter \[mg/dl\], normal \< 1 mg/dl). SDAI total score = 0-86 where a higher score reflects worsening disease. SDAI \<=3.3 indicates clinical remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity. |
| Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) | Week 12 and Week 104 | Tender joint count was performed by a skilled assessor, evaluating 68 joints for tenderness. |
| Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) | Week 12 and Week 104 | Swollen joint count was performed by a skilled assessor, evaluating 66 joints for swelling. |
| Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) | Screening and End of Study (Week 104 or early withdrawal) | The DAS28 (ESR) score is a measure of the participant's disease activity. It is calculated using the tender joint count (28 joints), swollen joint count (28 joints), erythrocyte sedimentation rate (ESR) and general health status. The DAS28-ESR scale ranges from 0 to 10, where higher scores represent higher disease activity. DAS28 \<=3.2 implied low disease activity, DAS \>3.2 to 5.1 implied moderate disease activity, DAS \>5.1 implied high disease activity, and DAS28 \<2.6 = clinical remission. |
| Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity | Week 12 and Week 104 | The participant global assessment of disease activity was measured using a 100 mm VAS ranging from 0=very good to 100=very bad. |
| Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain | Week 12 and Week 104 | A participant's overall assessment of pain on a VAS was assessed with a question concerning the amount of pain due to arthritis. Pain was assessed on a 100 mm VAS scale with a left-hand marker no pain (0 mm) or right-hand marker extreme pain (100 mm). |
| Health Assessment Questionnaire Disability Index (HAQ-DI) | End of Study (Week 104 or early withdrawal) | The Health Assessment Questionnaire Disability Index (HAQ-DI) is a participant-completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each item was scored on 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 scores range from 0 to 3, where 0=least difficulty, and 3=extreme difficulty. |
| Time to Rheumatoid Arthritis (RA) Flare | End of Study (Week 104 or early withdrawal) | RA flare was defined as any worsening of the participant's disease activity that in the opinion of the Investigator required treatment intensification beyond supportive therapy which included restarting of the study drug treatment. Time to RA flare was defined as the period of drug-free remission until documentation of RA flare. Drug-free remission was defined as clinical remission (based on DAS28-ESR \< 2.6 and /or SDAI ≤ 3.3) for two consecutive assessment visits, followed by discontinuation of tocilizumab, at the Investigator's discretion, at the second assessment visit. |
Countries
Hungary
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Tocilizumab (RoActemra/Actemra) 8 mg/kg intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative/Other | 8 |
Baseline characteristics
| Characteristic | Tocilizumab |
|---|---|
| Age, Continuous | 51.25 years STANDARD_DEVIATION 8.67 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and 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. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. Adverse Events of Special Interest for this study were: Serious and/or medically significant infections; myocardial infarction/Acute coronary syndrome; Gastrointestinal perforation; Malignancies; Anaphylaxis/hypersensitivity reactions; Demyelinating disorders; Stroke and Serious and/or medically significant bleeding and hepatic events.
Time frame: End of Study (Week 104 or early withdrawal)
Population: Analysis population included all the enrolled participants in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs) | AEs | 75 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs) | SAEs | 0 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs) | AESI | 0 percentage of participants |
Secondary
Health Assessment Questionnaire Disability Index (HAQ-DI)
The Health Assessment Questionnaire Disability Index (HAQ-DI) is a participant-completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each item was scored on 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 scores range from 0 to 3, where 0=least difficulty, and 3=extreme difficulty.
Time frame: End of Study (Week 104 or early withdrawal)
Population: Analysis population included all the enrolled participants in the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Health Assessment Questionnaire Disability Index (HAQ-DI) | 1.18 units on a scale | Standard Deviation 0.953 |
Secondary
Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain
A participant's overall assessment of pain on a VAS was assessed with a question concerning the amount of pain due to arthritis. Pain was assessed on a 100 mm VAS scale with a left-hand marker no pain (0 mm) or right-hand marker extreme pain (100 mm).
Time frame: Week 12 and Week 104
Population: Analysis population included all the evaluable participants for this outcome measure. n included all the participants analyzed on that particular time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain | Unchanged (Week 12; n=11) | 4 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain | Increased (Week 12;n=11) | 0 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain | Decreased (Week 104;n=4) | 2 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain | Unchanged (Week 104;n=4) | 0 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain | Increased (Week 104;n=4) | 2 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain | Decreased (Week 12; n=11) | 7 participants |
Secondary
Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity
The participant global assessment of disease activity was measured using a 100 mm VAS ranging from 0=very good to 100=very bad.
Time frame: Week 12 and Week 104
Population: Analysis population included all the evaluable participants for this outcome measure. n included all the participants analyzed on that particular time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity | Decreased (Week 12; n=11) | 6 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity | Unchanged (Week 12; n=11) | 0 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity | Increased (Week 12;n=11) | 5 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity | Decreased (Week 104;n=4) | 2 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity | Unchanged (Week 104;n=4) | 0 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity | Increased (Week 104;n=4) | 2 participants |
Secondary
Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC)
Swollen joint count was performed by a skilled assessor, evaluating 66 joints for swelling.
Time frame: Week 12 and Week 104
Population: Analysis population included all the evaluable participants for this outcome measure. n included all the participants analyzed on that particular time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) | Decreased (Week 12; n=11) | 3 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) | Unchanged (Week 12; n=11) | 7 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) | Increased (Week 12;n=11) | 1 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) | Decreased (Week 104;n=4) | 2 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) | Unchanged (Week 104;n=4) | 2 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) | Increased (Week 104;n=4) | 0 participants |
Secondary
Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC)
Tender joint count was performed by a skilled assessor, evaluating 68 joints for tenderness.
Time frame: Week 12 and Week 104
Population: Analysis population included all the evaluable participants for this outcome measure. n included all the participants analyzed on that particular time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) | Decreased (Week 12; n=11) | 5 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) | Unchanged (Week 12; n=11) | 4 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) | Increased (Week 12;n=11) | 2 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) | Decreased (Week 104;n=4) | 2 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) | Unchanged (Week 104;n=4) | 2 participants |
| Tocilizumab | Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) | Increased (Week 104;n=4) | 0 participants |
Secondary
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR)
The DAS28 (ESR) score is a measure of the participant's disease activity. It is calculated using the tender joint count (28 joints), swollen joint count (28 joints), erythrocyte sedimentation rate (ESR) and general health status. The DAS28-ESR scale ranges from 0 to 10, where higher scores represent higher disease activity. DAS28 \<=3.2 implied low disease activity, DAS \>3.2 to 5.1 implied moderate disease activity, DAS \>5.1 implied high disease activity, and DAS28 \<2.6 = clinical remission.
Time frame: Screening and End of Study (Week 104 or early withdrawal)
Population: Analysis population included all the enrolled participants in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) | Remission (Baseline) | 5 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) | Low Disease Activity (Baseline) | 1 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) | Moderate Disease Activity (Baseline) | 4 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) | High Disease Activity (Baseline) | 2 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) | Remission (End of Study) | 10 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) | Low Disease Activity (End of Study) | 1 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) | Moderate Disease Activity (End of Study) | 0 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) | High Disease Activity (End of Study) | 1 participants |
Secondary
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI)
The SDAI was defined as the numerical sum of 5 outcome parameters: tender and swollen joint count (based on a 28-joint assessment), participant and physician global assessment of disease activity on a 100 millimeter (mm) Visual analogue scale (VAS) (VAS; 0 = no disease activity and 100 = worst disease activity) and level of C-reactive protein (CRP) (milligram per deciliter \[mg/dl\], normal \< 1 mg/dl). SDAI total score = 0-86 where a higher score reflects worsening disease. SDAI \<=3.3 indicates clinical remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity.
Time frame: Screening and End of Study (Week 104 or early withdrawal)
Population: Analysis population included all the enrolled participants in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) | Moderate Disease Activity (End of Study) | 1 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) | Remission (Baseline) | 0 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) | Low Disease Activity (Baseline) | 6 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) | Moderate Disease Activity (Baseline) | 3 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) | High Disease Activity (Baseline) | 3 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) | Remission (End of Study) | 3 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) | High Disease Activity (End of Study) | 1 participants |
| Tocilizumab | Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) | Low Disease Activity (End of Study) | 7 participants |
Secondary
Time to Rheumatoid Arthritis (RA) Flare
RA flare was defined as any worsening of the participant's disease activity that in the opinion of the Investigator required treatment intensification beyond supportive therapy which included restarting of the study drug treatment. Time to RA flare was defined as the period of drug-free remission until documentation of RA flare. Drug-free remission was defined as clinical remission (based on DAS28-ESR \< 2.6 and /or SDAI ≤ 3.3) for two consecutive assessment visits, followed by discontinuation of tocilizumab, at the Investigator's discretion, at the second assessment visit.
Time frame: End of Study (Week 104 or early withdrawal)
Population: This outcome could not be evaluated as there were no participants who had achieved drug-free remission, per protocol definition.