Screening for Flare After b/tsDMARD Discontinuation in Rheumatoid Arthritis

Not Applicable

Not yet recruiting

• Conditions: Rheumatoid Arthritis
• Interventions: Other: Discontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD)

• Registration Number: NCT05119452
• Lead Sponsor: Medical University of Vienna

Brief Summary

To evaluate whether stringent follow-up consisting of combined laboratory and ultrasound surveillance is superior to clinical monitoring alone to maintain clinical remission in rheumatoid arthritis.

Detailed Description

Randomized, controlled, parallel-group, multi-centre study in which patients with rheumatoid arthritis treated with biological/targeted synthetic disease modifying antirheumatic drug (b/tsDMARD) in mono- or combination therapy with conventional synthetic disease modifying antirheumatic drug (csDMARD) in a stable dosage and interval for ≥6 months with low disease activity or remission will receive an power Doppler musculoskeletal ultrasound examination (PDUS) and monitoring of C-reactive protein (CRP) levels at baseline and several timepoints within a 24 month study period (primary endpoint) and within a 48 month long-term extension. At baseline, b/tsDMARD medication will be withdrawn in all patients, who will be randomized in a 1:1 ratio in an "Assisted monitoring" (arm A) or a "Clinical monitoring" (arm B) arm respectively. Further stratification for remission vs. low disease activity and mono- vs combination therapy will be implemented in the randomisation process. In arm A, CRP and PDUS information will be made available to the clinical assessors who, at each time-point will use this information along with that from clinical examination, to identify patients experiencing recurrence of inflammation which will then be counted as subclinical flare according to predefined criteria. In arm B the results of CRP and PDUS will be recorded but will not be made available to the clinical assessor who will have to identify clinical flares according to predefined criteria based on information from the clinical examination only.

Study Timeline

• Status Verified: 2021-11
• Study First Submitted: 2021-11-02
• Study First Submitted QC: 2021-11-12
• Last Update Submitted: 2021-11-12
• Study First Posted: 2021-11-15
• Last Update Posted: 2021-11-15
• Study Start: 2022-03
• Primary Completion: 2024-09
• Study Completion: 2024-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 85

Inclusion Criteria

Patients with rheumatoid arthritis classified by the American College of Rheumatology/European League Against Rheumatism classification criteria

• biological disease-modifying anti-rheumatic drug (bDMARD) or targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD) treatment in monotherapy or in combination therapy with conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) in a stable dosage and interval for ≥6 months. Previous extension of bDMARD or tsDMARD interval will also be accepted. bDMARDs and tsDMARDs will include all currently available originator and biosimilar compounds, with the exception of rituximab and its biosimilar compounds
• No swollen joint by 28-joint count at baseline, and screening
• C-reactive protein of ≤0.5mg/dL at baseline AND history of C-reactive protein >0,5mg/dl related to rheumatoid arthritis activity
• Clinical disease activity index ≤10
• Shared decision between patient and physician to attempt b/tsDMARD withdrawal
• Willing and able to understand and follow the study procedures
• Written informed consent
• Female and male subjects aged ≥ 18 years

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Exclusion Criteria

• History of or current extra-articular manifestation of rheumatoid arthritis, with exception of rheumatoid nodules
• Systemic glucocorticoid treatment in the past 3 months
• Intraarticular injection with glucocorticoids in the past 1 month
• Joint replacement surgery other than total knee or hip arthroplasty or complete joint destruction
• Power Doppler signal ≥2 in any assessed joint and/or tendon at screening or baseline

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Assisted monitoring	Discontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD)	In the Assisted monitoring arm, C-reactive protein and musculoskeletal ultrasound information will be made available to the clinical assessors who, at each time-point will use this information, along with information from the clinical examination, to identify patients experiencing recurrence of inflammation which will then be counted as subclinical flare according to predefined criteria.
Clinical monitoring	Discontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD)	In the Clinical monitoring arm, the results of C-reactive protein and musculoskeletal ultrasound information will be recorded but will not be made available to the clinical assessor who at each time-point will make the decision on whether the patient is experiencing or has experienced a clinical flare according to predefined criteria based on information from the clinical examination.

Primary Outcome Measures

Name	Time	Method
Proportion of subjects without a clinical flare until week 24	week 24	Proportion of subjects without a clinical flare

Secondary Outcome Measures

Name	Time	Method
Time to clinical flare (days)	study period	Time to clinical flare (days)
World Health Organization Quality of Life Questionnaire	week 24	World Health Organization Quality of Life Questionnaire, scale 0 (worse) - 100 (best)
Evaluator's global assessment	week 24	Evaluator's global assessment, scale 0 (best) - 100 (worst)
Proportion of patients in low disease activity or remission based on simplified disease activity index	week 48	Proportion of patients in low disease activity or remission based on simplified disease activity index
28 swollen joint count	week 24	28 swollen joint count, scale 0 (best) - 28 (worse)
Proportion of subjects with a clinical flare in the assisted monitoring arm vs. clinical monitoring arm, the latter stratified according to b/tsDMARD reinitiation	week 24	Proportion of subjects with a clinical flare in the assisted monitoring arm vs. clinical monitoring arm, the latter stratified according to b/tsDMARD reinitiation
Radiographic progression	at week 48 weeks from baseline	change in Sharp Van der Heijde score, scale 0 (best) - 488 (worse)
Health Assessment Questionnaire Disability Index	week 24	Health Assessment Questionnaire Disability Index, scale 0 (best) - 3.0 (worse)
Fatigue	week 24	Fatigue, visual analogue scale, scale 0 (worse) - 100 (best)
Proportion of subjects without a clinical flare	week 48	Proportion of subjects without a clinical flare
28 tender joint count	week 24	28 tender joint count, scale 0 (best) - 28 (worse)
Patient's global assessment	week 24	Patient's global assessment, scale 0 (best) - 100 (worst)
C-reactive protein	week 24	C-reactive protein, scale 0 (best) - infinite (worst)
Morning stiffness	week 24	Morning joint stiffness, (minutes), scale 0 (best) - infinite (worst)