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| Name | Class |
|---|---|
| King Christian X´Hospital for Rheumatic Diseases | OTHER |
| Slagelse Hospital | OTHER |
| Glostrup University Hospital, Copenhagen | OTHER |
| Abbott |
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The purpose of this study is to examine whether an magnetic resonance imaging (MRI) -guided treatment strategy based on a predefined treatment algorithm can prevent progression of erosive joint damage, increase remission rate and improve functional level in the short and long term in patients with rheumatoid arthritis (RA).
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease. Patients typically experience pain, functional impairment and reduced quality of life, and are at risk of developing progressive joint damage. The disease primarily affects the small joints of the hands and feet. The current treatment strategy involves early and intensive treatment with close clinical follow up, which attempts to control the disease and avoid inflammation and thereby prevent pain, improve functional level and avoid joint damage. It is therefore important for optimal treatment of RA patients that methods used for diagnosis, disease monitoring and prognostication are highly sensitive. Erosive joint damage occurs early in the disease. Joint deformity is irreversible and causes serious functional impairment. Early and intensive treatment with close monitoring of the inflammation can slow the destructive disease and prevent function loss. However, it has been demonstrated that patients who are shown by conventional clinical and biochemical examination to have low disease activity or to be in remission can still have progressive joint damage. This demonstrates that current clinical/biochemical methods used in daily clinical practice are not sufficiently sensitive and other methods are required for the monitoring of disease activity and prognostication.
The presence of erosions (shown by X-ray examination) as well as anti-cyclic citrullinated peptide (anti-CCP) antibodies and bone marrow oedema (osteitis) on magnetic resonance imaging (MRI), are all independent predictors of subsequent radiographic progression. Bone marrow oedema has been shown to be the strongest independent predictor in early RA and MRI therefore has significant prognostic value.
It is therefore possible that supplementing conventional clinical and biochemical examinations of RA patients with MRI, and intensifying treatment where bone marrow oedema is present, will help reduce disease activity, avoid progressive joint damage and prevent function loss.
The current study is therefore based on the following hypothesis:
By supplementing conventional clinical and biochemical examination of RA patients with low disease activity/in remission with MRI and intensifying treatment in the case of sub-clinical inflammation as measured by the presence of bone marrow oedema, it is possible to prevent radiographic erosive progression, improve functional level and enable more patients to achieve clinical remission.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Conventional biochemical and clinical examinations | Active Comparator | Biochemical and clinical examinations |
|
| Conventional biochemical and clinical examinations and MRI. | Experimental | Biochemical and clinical examinations and MRI. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Magnetic resonance imaging (MRI) | Procedure | Treatment algorithm based on conventional biochemical/clinical examinations AND MRI of unilateral 2nd to 5th MCP joints and wrist on dominant side. Assessed month 0, 4, 8, 12, 16, 20, 24 with treatment intensification after predefined treatment algorithm in the case of "unsatisfactory inflammatory activity", which is defined as the presence of at least one physically swollen joint and DAS28>3.2 AND/OR MRI-detected bone marrow oedema score > 0 (RAMRIS-score) |
| Measure | Description | Time Frame |
|---|---|---|
| DAS28 remission (<2.6) | 24 month | |
| No radiographic progression (assessed by the Sharp/vdHeijde method). | 24 month |
| Measure | Description | Time Frame |
|---|---|---|
| No radiographic progression (Sharp/vdHeijde score). | No radiographic progression (Sharp/vdHeijde score) from 0-12 and 12-24 months and change in Sharp/vdHeijde score from 0-12, 0-24 and 12-24 months. | 24 month |
| No MRI erosion (RAMRIS) score |
| Measure | Description | Time Frame |
|---|---|---|
| Dynamic MRI | Dynamic MRI variable (including initial rate of enhancement (IRE) and maximum enhancement (ME)). | 24 month |
Inclusion Criteria:
Age > 18 years
RA according to ACR (American College of Rheumatology)/EULAR (European League Against Rheumatism) 2010 criteria.
Anti-CCP positivity
Erosions on conventional X-ray of hands, wrists and/or feet
No clinically swollen joints
DAS28 (4 variable, CRP) < 3.2
DMARD monotherapy treatment OR combination treatment, in the form of 2- or 3-drug therapy. If the patient is undergoing 3-drug therapy, at least one of the preparations must be administered at less than the "maximum inclusion dose"*
Unchanged anti-rheumatic treatment in the previous 6 weeks or more
No previous treatment with biological medication
No contra-indications for TNF-alpha-inhibiting treatment
No contra-indications for MRI
s-creatinine within normal range
Ability and willingness to give written and oral informed consent and fulfil the requirements of the study programme with reference to the protocol
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kim Hørslev-Petersen, Professor | King Christian X´Hospital for Rheumatic Diseases | Principal Investigator |
| Signe Møller-Bisgaard, MD | Dep. of Rheumatology, Rigshospitalet, Glostrup | Study Director |
| Mikkel Østergaard, Professor | Dep. of Rheumatology, Rigshospitalet, Glostrup | Study Chair |
| Bo Ejbjerg, MD, PhD | Dep. of Rheumatology Slagelse Hospital | Study Chair |
| Merete Hetland, MD, PhD, DMSci | Dep. of Rheumatology, Rigshospitalet, Glostrup | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dep. of Rheumatology Aarhus Hospital | Aarhus | 8600 | Denmark | |||
| Dep. of Rheumatology Frederiksberg Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34474649 | Derived | Moller-Bisgaard S, Horslev-Petersen K, Ejbjerg B, Hetland ML, Christensen R, Ornbjerg LM, Glinatsi D, Moller JM, Boesen M, Stengaard-Pedersen K, Madsen OR, Jensen B, Villadsen JA, Hauge EM, Bennett P, Hendricks O, Asmussen K, Kowalski M, Lindegaard H, Bliddal H, Krogh NS, Ellingsen T, Nielsen AH, Larsen L, Jurik AG, Thomsen HS, Ostergaard M. Effect of initiating biologics compared to intensifying conventional DMARDs on clinical and MRI outcomes in established rheumatoid arthritis patients in clinical remission: Secondary analyses of the IMAGINE-RA trial. Scand J Rheumatol. 2022 Jul;51(4):268-278. doi: 10.1080/03009742.2021.1935312. Epub 2021 Sep 2. | |
| 32929463 |
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| INDUSTRY |
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|
| Conventional biochemical and clinical examinations | Other | Treatment algorithm based on conventional biochemical and clinical examinations. Assessed month 0, 4, 8, 12, 16, 20, 24 with treatment intensification after predefined treatment algorithm in the case of "unsatisfactory inflammatory activity", which is defined as the presence of at least one clinically swollen joint and DAS28>3.2 |
|
No progression in MRI erosion (RAMRIS) score from 0-12 and 12-24 months and change in MRI erosion (RAMRIS) score from 0-12, 0-24 and 12-24 months.
| 24 month |
| MRI synovitis (RAMRIS) score | MRI synovitis (RAMRIS) score at 12 and 24 months | 24 months |
| MRI bone marrow oedema (RAMRIS) score | MRI bone marrow oedema (RAMRIS) score at 12 and 24 months | 24 months |
| HAQ score | Changes in HAQ score from 0-12 and 0-24 months | 24 month |
| SF-36 score | Changes in SF-36 score from 0-12 and 0-24 months | 24 month |
| EQ-5D score | Changes in EQ-5D score from 0-12 and 0-24 months | 24 month |
| ACR/EULAR 2011 remission | ACR/EULAR 2011 remission at 12 and 24 months | 24 month |
| DAS28 | DAS28 at 12 and 24 month | 24 month |
| DAS28 remission (<2.6) at 12 months | 24 months |
| biomarker analyses | 24 month |
| Copenhagen |
| 2000 |
| Denmark |
| Dep. of Rheumatology Glostrup Hospital | Copenhagen | 2600 | Denmark |
| Dep. of Rheumatology Gentofte Hospital | Copenhagen | 2900 | Denmark |
| Dep. of Rheumatology King Christian X´Hospital for Rheumatic Diseases | Gråsten | 6300 | Denmark |
| Department of Rheumatology University Hospital Vendsyssel | Hjørring | DK-9800 | Denmark |
| Dep. of rheumatology Odense Hospital | Odense | 5000 | Denmark |
| Dep. of Rheumatology Silkeborg Hospital | Silkeborg | 8600 | Denmark |
| Dep. of Rheumatology Slagelse Hospital | Slagelse | 4200 | Denmark |
| Derived |
| Moller-Bisgaard S, Georgiadis S, Horslev-Petersen K, Ejbjerg B, Hetland ML, Ornbjerg LM, Glinatsi D, Moller J, Boesen M, Stengaard-Pedersen K, Madsen OR, Jensen B, Villadsen JA, Hauge EM, Bennett P, Hendricks O, Asmussen K, Kowalski M, Lindegaard H, Bliddal H, Krogh NS, Ellingsen T, Nielsen AH, Balding L, Jurik AG, Thomsen HS, Ostergaard M. Predictors of joint damage progression and stringent remission in patients with established rheumatoid arthritis in clinical remission. Rheumatology (Oxford). 2021 Jan 5;60(1):380-391. doi: 10.1093/rheumatology/keaa496. |
| 30721294 | Derived | Moller-Bisgaard S, Horslev-Petersen K, Ejbjerg B, Hetland ML, Ornbjerg LM, Glinatsi D, Moller J, Boesen M, Christensen R, Stengaard-Pedersen K, Madsen OR, Jensen B, Villadsen JA, Hauge EM, Bennett P, Hendricks O, Asmussen K, Kowalski M, Lindegaard H, Nielsen SM, Bliddal H, Krogh NS, Ellingsen T, Nielsen AH, Balding L, Jurik AG, Thomsen HS, Ostergaard M. Effect of Magnetic Resonance Imaging vs Conventional Treat-to-Target Strategies on Disease Activity Remission and Radiographic Progression in Rheumatoid Arthritis: The IMAGINE-RA Randomized Clinical Trial. JAMA. 2019 Feb 5;321(5):461-472. doi: 10.1001/jama.2018.21362. |
| 25896862 | Derived | Moller-Bisgaard S, Horslev-Petersen K, Ejbjerg BJ, Boesen M, Hetland ML, Christensen R, Moller J, Krogh NS, Stengaard-Pedersen K, Ostergaard M. Impact of a magnetic resonance imaging-guided treat-to-target strategy on disease activity and progression in patients with rheumatoid arthritis (the IMAGINE-RA trial): study protocol for a randomized controlled trial. Trials. 2015 Apr 21;16:178. doi: 10.1186/s13063-015-0693-2. |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D001172 | Arthritis, Rheumatoid |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D018450 | Disease Progression |
| D013585 | Synovitis |
| ID | Term |
|---|---|
| D017437 | Skin and Connective Tissue Diseases |
| D007154 | Immune System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D009682 | Magnetic Resonance Spectroscopy |
| D012149 | Restraint, Physical |
| ID | Term |
|---|---|
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
| D032763 | Behavior Control |
| D013812 | Therapeutics |
| D007103 | Immobilization |
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