An MRI-guided Treatment Strategy to Prevent Disease Progression in Patients With Rheumatoid Arthritis

Study Overview
=================
Brief Summary
-----------------
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).

Detailed Description
-----------------
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.

Official Title
-----------------
Does an MRI-guided Treatment Strategy Reduce Disease Activity and Progression in Patients With Rheumatoid Arthritis (RA): a Randomised Controlled Trial

Conditions
-----------------
Arthritis, Arthritis, Rheumatoid, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases, Connective Tissue Diseases, Autoimmune Diseases

Intervention / Treatment
-----------------
* Procedure: Magnetic resonance imaging (MRI)
* Other: Conventional biochemical and clinical examinations


Participation Criteria
=================
Eligibility Criteria
-----------------
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 Maximum inclusion dose is defined as: MTX 25 mg/week (or maximum tolerated dose if 25 mg/week is not tolerated), SSZ 2g/day (or maximum tolerated dose if 2 g/day is not tolerated) and HCQ 200 mg/day (or maximum tolerated dose if 200 mg/day is not tolerated) Exclusion Criteria: Previous or current biological treatment Known intolerance to methotrexate treatment which means that the patient is not able to tolerate a minimum of MTX 7.5 mg (minimum dose). DMARD 3-drug therapy at maximum tolerated/maximum inclusion dose* I.m, intra-articular or i.v glucocorticoid administration ≤ 6 weeks prior to inclusion Oral glucocorticoid administration > 5 mg/day Changes in oral glucocorticoid dose < 3 months prior to inclusion Myocrisin treatment Affected liver enzymes > 2 x the upper limit of normal at the time of screening Current and/or imminent wish to become pregnant Contra-indications for TNF-alpha-inhibiting treatment Contra-indications for MRI Known alcohol/drug abuse Inability to give informed consent Inability to cooperate with the study programme due to physical or mental reasons

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional biochemical and clinical examinations<br>Biochemical and clinical examinations | Other: Conventional biochemical and clinical examinations<br>* 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<br>|
| Experimental: Conventional biochemical and clinical examinations and MRI.<br>Biochemical and clinical examinations and MRI. | Procedure: Magnetic resonance imaging (MRI)<br>* 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)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DAS28 remission (<2.6) |  | 24 month | 
| No radiographic progression (assessed by the Sharp/vdHeijde method). |  | 24 month | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Arthritis, Rheumatoid/drug therapy, Arthritis, Rheumatoid/pathology, Disease Progression, Longitudinal Studies, Prospective Studies, Imaging, Magnetic Resonance, Remission Induction, Synovitis/immunology, Synovitis/pathology, Wrist Joint/pathology, Wrist Joint/physiopathology