Optimization of Infliximab Withdrawal Strategy for Rheumatoid Arthritis

Arthritis, Rheumatoid Clinical Trial

— OPTIWIT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02770794
• Other study ID #: 137
• Status: Completed
• Phase: Phase 4
• Start date: April 1, 2016
• Est. completion date: August 14, 2020

Study information

• Verified date: January 2021
• Source: Chiba University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 211
• Est. completion date: August 14, 2020
• Est. primary completion date: August 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 -

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Infliximab
Discontinue infliximab; receive Infliximab when relapse

Locations

Country	Name	City	State
Japan	Chiba University Hospital	Chiba

Sponsors (1)

Lead Sponsor	Collaborator
Chiba University

Country where clinical trial is conducted

Japan, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Change in van der Heijde modified Sharp score	Change in van der Heijde modified Sharp score at 48 week	48 week
Secondary	Change in Health Assessment Questionnaire-Disability Index	Change in Health Assessment Questionnaire-Disability Index at 48 week	48 week
Secondary	Change in EuroQoL 5 dimensions-5L	Change in EuroQoL 5 dimensions-5L at 48 week	48 week
Secondary	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
Secondary	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