Overview

This trial is active, not recruiting.

Conditions arthritis, arthritis, rheumatoid, joint diseases, musculoskeletal diseases, rheumatic diseases, connective tissue diseases, autoimmune diseases
Treatments magnetic resonance imaging (mri), conventional biochemical and clinical examinations
Sponsor Professor of Rheumatology, MD, DMSci, Kim Horslev-Petersen
Collaborator King Christian X´Hospital for Rheumatic Diseases
Start date March 2012
End date June 2017
Trial size 200 participants
Trial identifier NCT01656278, IMAGINE-RA

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Treatment algorithm based on conventional biochemical and clinical examinations
conventional biochemical and clinical examinations
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
(Experimental)
Treatment algorithm based on conventional biochemical and clinical examinations and MRI.
magnetic resonance imaging (mri)
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)

Primary Outcomes

Measure
DAS28 remission (<2.6)
time frame: 24 month
No radiographic progression (assessed by the Sharp/vdHeijde method).
time frame: 24 month

Secondary Outcomes

Measure
No radiographic progression (Sharp/vdHeijde score).
time frame: 24 month
No MRI erosion (RAMRIS) score
time frame: 24 month
MRI synovitis (RAMRIS) score
time frame: 24 months
MRI bone marrow oedema (RAMRIS) score
time frame: 24 months
HAQ score
time frame: 24 month
SF-36 score
time frame: 24 month
EQ-5D score
time frame: 24 month
ACR/EULAR 2011 remission
time frame: 24 month
DAS28
time frame: 24 month
DAS28 remission (<2.6) at 12 months
time frame: 24 months
biomarker analyses
time frame: 24 month

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Does an MRI-guided Treatment Strategy Reduce Disease Activity and Progression in Patients With Rheumatoid Arthritis (RA): a Randomised Controlled Trial
Principal investigator Kim Hørslev-Petersen, Professor
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.
Trial information was received from ClinicalTrials.gov and was last updated in December 2015.
Information provided to ClinicalTrials.gov by King Christian X´Hospital for Rheumatic Diseases.