Optimization of Infliximab Withdrawal Strategy for Rheumatoid Arthritis

Study Overview
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Brief Summary
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This multicenter prospective clinical trial investigates the accuracy of ultrasound to predict relapse after discontinuation of infliximab and the efficacy/safety of readministration of infliximab in patients with rheumatoid arthritis in a low disease activity state.

Detailed Description
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The objective of this multicenter prospective clinical trial is to determine whether ultrasound predicts relapse after discontinuation of infliximab more accurately than does clinical index and to investigate the efficacy and safety of restarting infliximab after relapse in patients with rheumatoid arthritis in remission or low disease activity on infliximab treatment. Infliximab is discontinued in all enrolled patients. Patients are followed up for 48 weeks for monitoring relapse. If relapse occurs, patients receive readministration of infliximab and are further followed up for 24 weeks to determine the efficacy and safety of infliximab readministration. Primary endpoint is the difference in area under curve (AUC) of receiver operator characteristics (ROC) analysis between total power Doppler score and Disease Activity Score (DAS) 28 at baseline to predict relapse within 48 weeks after discontinuation of infliximab.

Official Title
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Multicenter Prospective Trial to Investigate Accuracy of Ultrasound to Predict Relapse After Discontinuation of Infliximab and Efficacy/Safety of Readministration of Infliximab in Patients With Rheumatoid Arthritis in Low Disease Activity

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: Infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older RA patients who fulfill 2010 ACR/EULAR Classification Criteria Patients who have been treated with infliximab (Remicade) for 26 weeks or longer DAS28 (CRP) < 3.2 at screening Patients who give written informed consent after receiving sufficient information - Exclusion Criteria: Receiving prednisolone > 10 mg/day Receiving biological or molecular-target anti-rheumatic drug Alteration of the dose of corticosteroid or anti-rheumatic drug within 8 weeks prior to screening visit Alteration of the dose of non-steroid anti-inflammatory drug within 4 weeks prior to screening visit History of infusion reaction to infliximab Current infection which requires treatment Current or previous demyelinating disorder Current congestive heart failure which requires treatment Breast-feeding or pregnant/possibly pregnant woman, or woman who does not agree to prevent conception during and 6 months after study period Patients whom investigator or co-investigator consider inappropriate for other reasons -

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All patients<br>Discontinue infliximab; Receive infliximab when relapse | Drug: Infliximab<br>* Discontinue infliximab; receive Infliximab when relapse<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the Receiver Operator Characteristic (ROC) curve for total power Doppler score to predict relapse | Area under the ROC curve for total power Doppler score at baseline to predict relapse within 48 weeks after discontinuation of infliximab | 48 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the ROC curve for total gray-scale score to predict relapse | Area under the ROC curve for total gray-scale score at baseline to predict relapse within 48 weeks after discontinuation of infliximab | 48 week | 
| Change in van der Heijde modified Sharp score | Change in van der Heijde modified Sharp score at 48 week | 48 week | 
| Change in Health Assessment Questionnaire-Disability Index | Change in Health Assessment Questionnaire-Disability Index at 48 week | 48 week | 
| Change in EuroQoL 5 dimensions-5L | Change in EuroQoL 5 dimensions-5L at 48 week | 48 week | 
| EULAR response criteria based on DAS28 after readministration of infliximab | EULAR response criteria based on DAS28 at 12 week after relapse and readministration of infliximab | 12 week after relapse | 
| Number of adverse events as assessed by CTCAE v4.0 | Number of adverse events as assessed by CTCAE v4.0 through study completion, an average of 60 weeks | Through study completion, an average of 60 weeks |