Rheumatoid Arthritis
Conditions
Brief summary
This single arm study will evaluate the efficacy and safety of MabThera in patients with active rheumatoid arthritis whose current treatment with one or more TNF blocker had produced an inadequate response. Patients will receive MabThera (1g infusion) on day 1 and day 15, and will continue on their basic methotrexate therapy (10-25mg/week). The anticipated time on study treatment is 3-12 months, and the target sample size is \<100 individuals.
Interventions
DRUGrituximab [MabThera/Rituxan]
1g iv on days 1 and 15
DRUGMethotrexate
10-25mg po/week
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 patients, \>=18 years of age; * diagnosed RA for \>=3 months prior to first administration of study medication; * inadequate response or intolerance to \>=1 anti-TNF therapies, alone or in combination with methotrexate; * if using NSAIDS, analgesics or oral corticosteroids, must be on a stable dose for \>=2 weeks prior to start of study.
Exclusion criteria
* other chronic inflammatory diseases; * use of parental corticosteroids within 4 weeks prior to screening; * severe heart failure, or severe, uncontrolled cardiac disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Activity Score Based on 28-Joint Count (DAS28) | Day 0 and Week 24 | DAS28 consists of swollen joint count (SJC) and tender joint count (TJC) measurements, erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hr\]), and Patient Global Assessment of Disease Activity (participant-rated assessment of arthritis) with transformed scores ranging from 0 to 10. Higher scores indicated greater affectation due to disease activity. DAS28 equal to or less than (≤)3.2 equals (=) low disease activity, greater than (\>)3.2 to 5.1 = moderate to high disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| C-Reactive Protein (CRP) | Day 0 and Week 24 | CRP was measured in milligrams per liter (mg/L). |
| Health Assessment Questionnaire - Disability Index (HAQ-DI) Scores | Day 0 and Week 24 | The HAQ-DI score consists of questions referring to 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. For each of the categories, participants reported the amount of difficulty they had in performing 2 or 3 specific subcategory items. The standard disability score was calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered, yielding a score from 0 (without any difficulty) to 3 (unable to do). |
| Anti-cyclic Citrullinated Peptide (Anti-CCP) | Day 0 and Week 24 | Anti-CCP measured as absorbance units per milliliter (AU/mL). |
| Vascular Endothelial Growth Factor (VEGF) | Day 0 and Week 24 | VEGF was measured as picograms per milliliter (pg/mL). |
| Erythrocyte Sedimentation Rate (ESR) | Day 0 and Week 24 | ESR was measured in mm/hr. |
Countries
Hungary
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab 1000 mg Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 0 and 14. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Rituximab 1000 mg |
|---|---|
| Age, Continuous | 48.70 years STANDARD_DEVIATION 12.88 |
| Sex: Female, Male Female | 16 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 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Disease Activity Score Based on 28-Joint Count (DAS28)
DAS28 consists of swollen joint count (SJC) and tender joint count (TJC) measurements, erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hr\]), and Patient Global Assessment of Disease Activity (participant-rated assessment of arthritis) with transformed scores ranging from 0 to 10. Higher scores indicated greater affectation due to disease activity. DAS28 equal to or less than (≤)3.2 equals (=) low disease activity, greater than (\>)3.2 to 5.1 = moderate to high disease activity.
Time frame: Day 0 and Week 24
Population: All enrolled participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab 1000 mg | Disease Activity Score Based on 28-Joint Count (DAS28) | Day 0 | 6.03 units on a scale | Standard Deviation 0.96 |
| Rituximab 1000 mg | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 24 | 4.01 units on a scale | Standard Deviation 1.49 |
Comparison: Change from Baseline to Week 24p-value: <0.000195% CI: [1.39, 2.64]t-test, 2 sided
Secondary
Anti-cyclic Citrullinated Peptide (Anti-CCP)
Anti-CCP measured as absorbance units per milliliter (AU/mL).
Time frame: Day 0 and Week 24
Population: All participants who received at least 1 dose of study drug; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab 1000 mg | Anti-cyclic Citrullinated Peptide (Anti-CCP) | Day 0 (n=20) | 731.07 AU/mL | Standard Deviation 569.83 |
| Rituximab 1000 mg | Anti-cyclic Citrullinated Peptide (Anti-CCP) | Week 24 (n=19) | 846.41 AU/mL | Standard Deviation 988.18 |
Secondary
C-Reactive Protein (CRP)
CRP was measured in milligrams per liter (mg/L).
Time frame: Day 0 and Week 24
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab 1000 mg | C-Reactive Protein (CRP) | Day 0 | 6.13 mg/L | Standard Deviation 9.77 |
| Rituximab 1000 mg | C-Reactive Protein (CRP) | Week 24 | 4.32 mg/L | Standard Deviation 6.51 |
Comparison: Change from baseline to Week 24p-value: 0.33795% CI: [-2.03, 5.65]t-test, 2 sided
Secondary
Erythrocyte Sedimentation Rate (ESR)
ESR was measured in mm/hr.
Time frame: Day 0 and Week 24
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab 1000 mg | Erythrocyte Sedimentation Rate (ESR) | Day 0 | 45.25 mm/hr | Standard Deviation 22.4 |
| Rituximab 1000 mg | Erythrocyte Sedimentation Rate (ESR) | Week 24 | 30.85 mm/hr | Standard Deviation 4.58 |
Comparison: Change from baseline to Week 24p-value: 0.01295% CI: [3.52, 25.28]t-test, 2 sided
Secondary
Health Assessment Questionnaire - Disability Index (HAQ-DI) Scores
The HAQ-DI score consists of questions referring to 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. For each of the categories, participants reported the amount of difficulty they had in performing 2 or 3 specific subcategory items. The standard disability score was calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered, yielding a score from 0 (without any difficulty) to 3 (unable to do).
Time frame: Day 0 and Week 24
Population: All enrolled participants. n (number) = number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab 1000 mg | Health Assessment Questionnaire - Disability Index (HAQ-DI) Scores | Day 0 (n=20) | 1.14 units on a scale | Standard Deviation 0.31 |
| Rituximab 1000 mg | Health Assessment Questionnaire - Disability Index (HAQ-DI) Scores | Week 24 (n=19) | 0.87 units on a scale | Standard Deviation 0.36 |
Comparison: Change from baseline to Week 24p-value: <0.000195% CI: [0.151, 0.401]t-test, 2 sided
Secondary
Vascular Endothelial Growth Factor (VEGF)
VEGF was measured as picograms per milliliter (pg/mL).
Time frame: Day 0 and Week 24
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab 1000 mg | Vascular Endothelial Growth Factor (VEGF) | Day 0 | 516.68 pg/mL | Standard Deviation 523.89 |
| Rituximab 1000 mg | Vascular Endothelial Growth Factor (VEGF) | Week 24 | 520.15 pg/mL | Standard Deviation 451.1 |