Rheumatoid Arthritis
Conditions
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 At baseline, b/tsDMARD medication will be withdrawn in all patients, who will be randomized in a 1:1 ratio in an Assisted monitoring (arm A) or a Clinical monitoring (arm B) arm respectively.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.
Interventions
OTHERDiscontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD)
The biological/targeted synthetic disease modifying anti-rheumatic drug will be discontinued in both arms at baseline
Sponsors
Medical University of Graz
Medical University Innsbruck
Hospital Hietzing
Krankenhaus Bruneck
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Masking description
After checking the inclusion- and exclusion criteria and after the patients´ consent the study investigator contacts the administrative office of the coordinating center. The online computerised randomisation algorithm Randomizer for Clinical Trials by the Medical University of Vienna (MUW) will be used for randomisation for all centres.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects without a clinical flare until week 24 | week 24 | Proportion of subjects without a clinical flare |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to clinical flare (days) | study period | Time to clinical flare (days) |
| 28 swollen joint count | week 24 | 28 swollen joint count, scale 0 (best) - 28 (worse) |
| 28 tender joint count | week 24 | 28 tender 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 |
| Proportion of patients in low disease activity or remission based on simplified disease activity index | week 24 | Proportion of patients in low disease activity or remission based on simplified disease activity index |
| Patient's global assessment | week 24 | Patient's global assessment, scale 0 (best) - 100 (worst) |
| Proportion of subjects without a clinical flare | week 48 | Proportion of subjects without a clinical flare |
| C-reactive protein | week 24 | C-reactive protein, scale 0 (best) - infinite (worst) |
| 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) |
| World Health Organization Quality of Life Questionnaire | week 24 | World Health Organization Quality of Life Questionnaire, scale 0 (worse) - 100 (best) |
| Morning stiffness | week 24 | Morning joint stiffness, (minutes), scale 0 (best) - infinite (worst) |
| Fatigue | week 24 | Fatigue, visual analogue scale, scale 0 (worse) - 100 (best) |
| Evaluator's global assessment | week 24 | Evaluator's global assessment, scale 0 (best) - 100 (worst) |
Outcome results
None listed