Non-inferiority of Reduced-dose Rituximab in Rheumatoid Arthritis in Low Disease Activity and Remission

Study Overview
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Brief Summary
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To investigate whether a reduced-dose dosing regimen (1x500mg semiannually) of rituximab (RTX) (Mabthera®) is non-inferior in patients with rheumatoid arthritis (RA) whose disease is in persistent low disease activity (LDA) or clinical remission (REM) (pLDA/pREM) as compared to the standard dosing regimen of 1x1000mg semi-annual infusions.

Detailed Description
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Randomized, controlled, single-centre study with 1x500mg or 1x1000 semi-annual infusions of RTX (Mabthera) as intervention and a follow-up period of 2 years. Patients as well as assessors will be blinded to the type of treatment. Patients in the 1x500mg group who experience a flare as defined by the disease activity score 28-ESR (DAS28) will receive 1x1000mg RTX (Mabthera) at their upcoming scheduled infusion appointment. Patients in the 1x1000mg group whose disease activity reaches DAS28 >3.2 during the duration of the study will be re-evaluated for a change in biological therapy and will discontinue the study.

Official Title
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Randomized, Prospective, Active-comparator Controlled, Patient-blinded Study to Demonstrate Non-inferiority of Reduced-dose Rituximab in Rheumatoid Arthritis Patients in Low Disease Activity and Remission - the REDOREM Study

Conditions
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Rheumatoid Arthritis, Remission

Intervention / Treatment
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* Drug: 500mg RTX Group
* Drug: 1000mg RTX Group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of RA according to the 2010 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) classification criteria Current treatment with RTX (at time of inclusion have already received at least 2 cycles of 1000mg RTX) at the Day-Clinic of the Division of Rheumatology of the Medical University of Vienna Persistent low disease activity or clinical remission as defined below Persistent clinical remission (pREM) will be defined as a simplified disease activity index (CDAI) (12) ≤2.8 measured at two time-points 6 months apart. The CDAI is calculated as follows: tender joint count (TJC) + swollen joint count (SJC) + patient's assessment of general health on a 100 mm visual analogue scale (GH) + evaluator's assessment of general health on a 100 mm visual analogue scale (EGH) Persistent low disease activity (pLDA) will be defined as a CDAI ≤10 measured at two timepoints 6 months apart Patients who achieve REM at only either one of the two successive time-points will be considered as having pLDA with regard to the current trial Exclusion Criteria: Patients ≤ 18 yrs Patients receiving RTX for a disease other than RA Patients who fail to meet criteria for REM or LDA at either one of the two successive timepoints (i.e. having a disease activity >10 as measured by the clinical disease activity index, (CDAI))

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 500mg RTX Group<br>Patients in this group will receive 1x500mg (500mg RTX group) RTX (Mabthera) at baseline (time-point of their upcoming semi-annual infusion) and at months 6, 12, 18 and 24 | Drug: 500mg RTX Group<br>* Patients will receive 1x500mg RTX (Mabthera) at baseline (time-point of their upcoming semi-annual infusion) and at months 6, 12, 18 and 24<br>* Other names: Mabthera 500mg;|
| Active Comparator: 1000mg RTX group<br>Patients in this group will receive 1x1000mg RTX (Mabthera) at baseline (time-point of their upcoming semi-annual infusion) and at months 6, 12, 18 and 24 | Drug: 1000mg RTX Group<br>* Patients will receive 1x1000mg RTX (Mabthera) at baseline (time-point of their upcoming semi-annual infusion) and at months 6, 12, 18 and 24<br>* Other names: Mabthera 1000mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of flare | Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse) | month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic progression | Sharp modified van der Heijde (SvdH) score, Scale 0 (best) - 488 (worse) | month 12 | 
| Radiographic progression | Sharp modified van der Heijde (SvdH) score, Scale 0 (best) - 488 (worse) | month 24 | 
| Physical function | Health assessment questionnaire disability index (HAQ-DI), Scale 0 (best) - 3.0 worse | months 12 | 
| Physical function | Health assessment questionnaire disability index (HAQ-DI), Scale 0 (best) - 3.0 worse | months 24 | 
| Proportion of flare | Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse) | month 21 | 
| Proportion of flare | Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse) | month 18 | 
| Proportion of flare | Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse) | month 15 | 
| Proportion of flare | Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse) | month 12 | 
| Proportion of flare | Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse) | month 9 | 
| Proportion of flare | Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse) | month 6 | 
| Proportion of flare | Disease activity score 28-Erythrocyte sedimentation sate (DAS28-ESR), Scale 0 (best) - 10 (worse) | month 3 |