Success of Tocilizumab in RA Patients With Remission Induction and Sustained Efficacy After Discontinuation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Success of Tocilizumab in RA Patients With Remission Induction and Sustained Efficacy After Discontinuation

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Tocilizumab plus methotrexate
* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SWITCH<br>Tocilizumab monotherapy | Drug: Tocilizumab<br>* tocilizumab 8mg/kg/4weeks (i.v.) up to 52weeks.<br>* Other names: Actemra;|
| Active Comparator: ADD-ON<br>Tocilizumab plus methotrexate combination | Drug: Tocilizumab plus methotrexate<br>* 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.<br>* Other names: Methotrexate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DAS28-ESR remission at 24 weeks | Step 1: Investigation of the efficacy and safety of TCZ in combination therapy with MTX | at 24 week | 
| Changes over time in the number of patients maintaining discontinuation (maintenance rate) | Step 2: Investigation of discontinuation | Week 52 to Week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in TSS score | Step 1 | at 52 weeks (after treatment initiation) | 
| Change of DAS28-ESR remission rate | Step 1 | Week 0 to Week 52 | 
| Change of ACR response rate | Step 1 | Week 0 to Week 52 | 
| EQ5D scores over time | Step 1 | Week 0 to Week 52 | 
| J-HAQ/HAQ scores over time | Step 1 | Week 0 to Week 52 | 
| SDAI, CDAI, and Boolean remission rates | Step 1 | Week 0 to Week 52 | 
| TNF-α over time | Step 1 | Week 0 to Week 52 | 
| Between-group comparison of the discontinuation rate after an achievement of remission | Step 2 | Week 0 to Week 104 | 
| Factor analysis of patients maintaining discontinuation | Step 2 | Week 0 to Week 104 | 
| Time course of DAS28 after restarting TCZ (between-group comparison) | Step 2 | Week 52 to Week 104 | 
| Change in TSS score | Step 2 | Week 52 to Week 104 | 
| Time course of DAS28 after restarting MTX following suspension of discontinuation in the TCZ monotherapy group in Step 1 | Step 2 | Week 52 to Week 104 | 
| SDAI, CDAI, and Boolean remission rates |  | Week 52 to Week 104 |