Rheumatoid Arthritis
Conditions
Brief summary
The objective of this study is to investigate the efficacy and safety of the humanized anti-human IL-6 receptor monoclonal antibody tocilizumab (TCZ) either in monotherapy or in combination therapy with methotrexate (MTX) in patients with an inadequate response to treatment with MTX. Furthermore, in patients who have been able to achieve control of disease activity via the above therapy, we investigate the possibility of stopping TCZ and verify safety when TCZ is restarted after disease recurrence.
Detailed description
In this study, we aim to prospectively and randomly evaluate efficacy for changes in clinical remission and joint destruction in RA patients in treatment with TCZ monotherapy(SWITCH) and in combination therapy with MTX(ADD-ON), and also to investigate the best therapeutic approach to achieve discontinuation.
Interventions
DRUGTocilizumab plus methotrexate
Tocilizumab 8mg/kg 4weeks (i.v.) plus methotrexate up to 52weeks.The dosage of MTX will be fixed at least 24 weeks from the start of the study.
DRUGTocilizumab
tocilizumab 8mg/kg/4weeks (i.v.) up to 52weeks.
Sponsors
SURPRISE Study Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with RA in accordance with the 1987 classification criteria of ACR * Aged 20 to 75 years inclusive at enrolment (within 2 weeks before starting treatment with the investigational drug) * Treated with MTX at ≥6 mg/week for at least 8 weeks immediately before enrolment * Rheumatoid arthritis of duration ≤10 years * DAS28-ESR ≥3.2 (within 2 weeks before starting treatment with the investigational drug) * Having received and thoroughly understood an adequate explanation about participation in the study, patients who have personally and voluntarily provided written informed consent Major
Exclusion criteria
* Patients who were Steinbrocker Class IV. * Patients who received leflunomide within 12 weeks, DMARDs other than MTX within 8 weeks , or tacrolimus within 4 weeks before the 1st TCZ infusion. * Patients who previously received biologic DMARDs including TCZ.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes over time in the number of patients maintaining discontinuation (maintenance rate) | Week 52 to Week 104 | Step 2: Investigation of discontinuation |
| DAS28-ESR remission at 24 weeks | at 24 week | Step 1: Investigation of the efficacy and safety of TCZ in combination therapy with MTX |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of DAS28-ESR remission rate | Week 0 to Week 52 | Step 1 |
| Change of ACR response rate | Week 0 to Week 52 | Step 1 |
| EQ5D scores over time | Week 0 to Week 52 | Step 1 |
| J-HAQ/HAQ scores over time | Week 0 to Week 52 | Step 1 |
| SDAI, CDAI, and Boolean remission rates | Week 0 to Week 52 | Step 1 |
| TNF-α over time | Week 0 to Week 52 | Step 1 |
| Between-group comparison of the discontinuation rate after an achievement of remission | Week 0 to Week 104 | Step 2 |
| Factor analysis of patients maintaining discontinuation | Week 0 to Week 104 | Step 2 |
| Time course of DAS28 after restarting TCZ (between-group comparison) | Week 52 to Week 104 | Step 2 |
| Time course of DAS28 after restarting MTX following suspension of discontinuation in the TCZ monotherapy group in Step 1 | Week 52 to Week 104 | Step 2 |
| Change in TSS score | at 52 weeks (after treatment initiation) | Step 1 |
Other
| Measure | Time frame |
|---|---|
| Adverse events | During the study period |
Countries
Japan
Outcome results
None listed