Rheumatoid Arthritis
Conditions
Brief summary
In this open-label single arm study the safety and efficacy of Mabthera will be evaluated in patients with active rheumatoid arthritis who have had an inadequate response to methotrexate. Patients will receive MabThera (1000mg iv infusion) on days 1 and 15, and background methotrexate (10-25mg po or sc weekly). After the initial study period of 24 weeks, eligible patients may receive up to 3 re-treatments with MabThera. The anticipated time on study treatment is 1-2 years and target sample size is \<50
Interventions
DRUGrituximab [MabThera/Rituxan]
1000 mg iv infusion on days 1 and 15
DRUGmethotrexate
10-25 mg weekly (oral or parenteral)
DRUGmethylprednisolone
100 mg iv prior to each rituximab infusion
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 * rheumatoid arthritis DAS28 \>/= 3.2 * receiving treatment on an outpatient basis * experienced an inadequate response to previous or current treatment with methotrexate
Exclusion criteria
* rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA * history of or current inflammatory joint disease other than RA * previous treatment with any cell-depleting therapies
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Reporting Adverse Events (AEs) | Days 1 and 15, every 8 weeks up to Week 24 and and then every 3 months up to 18 months for a total of 104 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Disease Activity Score 28 (DAS28) From Baseline to Week 24 | Baseline and Week 24 | The DAS28 score is a measure of the participant's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], participant's global assessment of disease activity \[visual analog scale: \[VAS\] 0 equals (=) no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to 10. Scores less than (\<) 2.6 indicate best disease control and scores greater than or equal to (≥) 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6. The average improvement at each visit to the group score is equal to the formula (Previous DAS28 minus \[-\] current DAS 28)/ Previous DAS 28 x 100. Negative percentages indicate that the participant has worsened in comparison to last evaluation, and positive percentages indicate improvement of its DAS28 score and correlated with a bettering of clinical situation. |
| Percentage of Participants Whose DAS28 Improved by >1.2 at Week 24 | Baseline and Week 24 | The DAS28 score is a measure of the participant's disease activity calculated using the TJC \[28 joints\], SJC \[28 joints\], participant's global assessment of disease activity \[VAS: 0 = no disease activity to 100 = maximum disease activity\] and the ESR for a total possible score of 0 to 10. Scores \< 2.6 indicate best disease control and scores ≥ 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6. An improvement of \>1.2 was considered to be clinically significant improvement. |
| Change in Bone Density (in Participants Untreated With Bisphosphonates) | Screening and Week 84 | Bone mineral density test was performed using x-ray radiation and the values of bone density were provided directly by the apparatus as grams per square centimeter (g/cm\^2) . T-score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as the participant. A T-score with above -1 is normal bone density level. A T-score between -1 and -2.5 means that the bone density is below normal and it might be a sign of an osteopenia and may also lead into osteoporosis. A T-score below -2.5 indicates osteoporosis. |
Countries
Tunisia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Participants received rituximab 1000 mg iv infusion on Days 1 and 15 along with methotrexate 10-25 mg weekly, orally or parenterally. Participants could receive concomitant treatment with corticosteroids (≤ 10 mg/day prednisone or equivalent) or intra-articular corticosteroids, NSAIDs and analgesics throughout the study period at the discretion of the investigator. All participants received methylprednisolone 100 mg iv prior to each rituximab infusion. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Treatment failure | 1 |
Baseline characteristics
| Characteristic | Rituximab |
|---|---|
| Age, Continuous | 53.4 years STANDARD_DEVIATION 7.91 |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 18 |
| serious Total, serious adverse events | 6 / 18 |
Outcome results
Primary
Number of Participants Reporting Adverse Events (AEs)
Time frame: Days 1 and 15, every 8 weeks up to Week 24 and and then every 3 months up to 18 months for a total of 104 weeks
Population: Safety Population: Included all participants who have received any part of an infusion of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants Reporting Adverse Events (AEs) | Participants who experienced an AE | 11 number of participants |
| Rituximab | Number of Participants Reporting Adverse Events (AEs) | Participants who experienced more than 1 AE | 7 number of participants |
Secondary
Change in Bone Density (in Participants Untreated With Bisphosphonates)
Bone mineral density test was performed using x-ray radiation and the values of bone density were provided directly by the apparatus as grams per square centimeter (g/cm\^2) . T-score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as the participant. A T-score with above -1 is normal bone density level. A T-score between -1 and -2.5 means that the bone density is below normal and it might be a sign of an osteopenia and may also lead into osteoporosis. A T-score below -2.5 indicates osteoporosis.
Time frame: Screening and Week 84
Population: ITT population; only participants with an assessment at both screening and Week 84 were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Change in Bone Density (in Participants Untreated With Bisphosphonates) | Screening | -1.82 t-score |
| Rituximab | Change in Bone Density (in Participants Untreated With Bisphosphonates) | Week 84 | -1.6 t-score |
Secondary
Percentage Change in Disease Activity Score 28 (DAS28) From Baseline to Week 24
The DAS28 score is a measure of the participant's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], participant's global assessment of disease activity \[visual analog scale: \[VAS\] 0 equals (=) no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to 10. Scores less than (\<) 2.6 indicate best disease control and scores greater than or equal to (≥) 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6. The average improvement at each visit to the group score is equal to the formula (Previous DAS28 minus \[-\] current DAS 28)/ Previous DAS 28 x 100. Negative percentages indicate that the participant has worsened in comparison to last evaluation, and positive percentages indicate improvement of its DAS28 score and correlated with a bettering of clinical situation.
Time frame: Baseline and Week 24
Population: ITT population; Only participants with DAS28 values at both Baseline and Week 24 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Percentage Change in Disease Activity Score 28 (DAS28) From Baseline to Week 24 | -1.7 percentage change from baseline | Standard Deviation 49.4 |
Secondary
Percentage of Participants Whose DAS28 Improved by >1.2 at Week 24
The DAS28 score is a measure of the participant's disease activity calculated using the TJC \[28 joints\], SJC \[28 joints\], participant's global assessment of disease activity \[VAS: 0 = no disease activity to 100 = maximum disease activity\] and the ESR for a total possible score of 0 to 10. Scores \< 2.6 indicate best disease control and scores ≥ 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6. An improvement of \>1.2 was considered to be clinically significant improvement.
Time frame: Baseline and Week 24
Population: ITT population; Only participants with DAS28 values at both Baseline and Week 24 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Percentage of Participants Whose DAS28 Improved by >1.2 at Week 24 | 75.0 percentage of participants |