Optimization of Infliximab Withdrawal Strategy for Rheumatoid Arthritis (OPTIWIT)

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

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.

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Drug: Infliximab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 years or older
2. RA patients who fulfill 2010 ACR/EULAR Classification Criteria
3. Patients who have been treated with infliximab (Remicade) for 26 weeks or longer
4. DAS28 (CRP) < 3.2 at screening
5. Patients who give written informed consent after receiving sufficient information -

Exclusion Criteria:

1. Receiving prednisolone > 10 mg/day
2. Receiving biological or molecular-target anti-rheumatic drug
3. Alteration of the dose of corticosteroid or anti-rheumatic drug within 8 weeks prior to screening visit
4. Alteration of the dose of non-steroid anti-inflammatory drug within 4 weeks prior to screening visit
5. History of infusion reaction to infliximab
6. Current infection which requires treatment
7. Current or previous demyelinating disorder
8. Current congestive heart failure which requires treatment
9. Breast-feeding or pregnant/possibly pregnant woman, or woman who does not agree to prevent conception during and 6 months after study period
10. Patients whom investigator or co-investigator consider inappropriate for other reasons -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All patients; Discontinue infliximab; Receive infliximab when relapse	Drug: Infliximab; Discontinue infliximab; receive Infliximab when relapse

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chiba University

Publications and helpful links

General Publications

• Iwamoto T, Ikeda K, Hosokawa J, Yamagata M, Tanaka S, Norimoto A, Sanayama Y, Nakagomi D, Takahashi K, Hirose K, Sugiyama T, Sueishi M, Nakajima H. Prediction of relapse after discontinuation of biologic agents by ultrasonographic assessment in patients with rheumatoid arthritis in clinical remission: high predictive values of total gray-scale and power Doppler scores that represent residual synovial inflammation before discontinuation. Arthritis Care Res (Hoboken). 2014 Oct;66(10):1576-81. doi: 10.1002/acr.22303.
• Tanaka Y, Takeuchi T, Mimori T, Saito K, Nawata M, Kameda H, Nojima T, Miyasaka N, Koike T; RRR study investigators. Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study. Ann Rheum Dis. 2010 Jul;69(7):1286-91. doi: 10.1136/ard.2009.121491. Epub 2010 Apr 1.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): August 14, 2020
• Study Completion (Actual): August 14, 2020

Study Registration Dates

• First Submitted: May 11, 2016
• First Submitted That Met QC Criteria: May 11, 2016
• First Posted (Estimate): May 12, 2016

Study Record Updates

• Last Update Posted (Actual): January 20, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: 137

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO