Clinical trial NCT05119452: Screening for Flare After b/tsDMARD Discontinuation in Rheumatoid Arthritis
Official title: Screening for Flare After Discontinuation of Biological/Targeted Synthetic Disease Modifying Anti-rheumatic Drug (b/tsDMARD) in Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Rheumatoid Arthritis
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: Medical University of Graz
name: Medical University Innsbruck
name: Hospital Hietzing
name: Krankenhaus Bruneck
First posted: 2021-11-15
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: At baseline, patients will be randomised in a 1:1 ratio in an "Assisted monitoring" (arm A) or a "Clinical monitoring" (arm B) arm respectively.
Primary purpose: OTHER

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 At baseline, b/tsDMARD medication will be withdrawn in all patients, who will be randomized in a 1:1 ratio in an "Assisted monitoring" (arm A) or a "Clinical monitoring" (arm B) arm respectively.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.

Eligibility criteria: 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

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

Primary outcomes:
measure: Proportion of subjects without a clinical flare until week 24
timeFrame: week 24
Secondary outcomes:
measure: Proportion of subjects without a clinical flare
timeFrame: week 48
measure: Time to clinical flare (days)
timeFrame: study period
measure: 28 swollen joint count
timeFrame: week 24
measure: 28 tender joint count
timeFrame: week 24
measure: Proportion of subjects with a clinical flare in the assisted monitoring arm vs. clinical monitoring arm, the latter stratified according to b/tsDMARD reinitiation
timeFrame: week 24
measure: Proportion of patients in low disease activity or remission based on simplified disease activity index
timeFrame: week 24
measure: Proportion of patients in low disease activity or remission based on simplified disease activity index
timeFrame: week 48
measure: Patient's global assessment
timeFrame: week 24
measure: Evaluator's global assessment
timeFrame: week 24
measure: C-reactive protein
timeFrame: week 24
measure: Radiographic progression
timeFrame: at week 48 weeks from baseline
measure: Health Assessment Questionnaire Disability Index
timeFrame: week 24
measure: World Health Organization Quality of Life Questionnaire
timeFrame: week 24
measure: Morning stiffness
timeFrame: week 24
measure: Fatigue
timeFrame: week 24
Other outcomes:
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