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

Not Applicable

Completed

• Conditions: Rheumatic Diseases; Autoimmune Diseases; Connective Tissue Diseases; Arthritis, Rheumatoid; Musculoskeletal Diseases; Arthritis; Joint Diseases
• Interventions: Other: Conventional biochemical and clinical examinations; Procedure: Magnetic resonance imaging (MRI)

• Registration Number: NCT01656278
• Lead Sponsor: Professor of Rheumatology, MD, DMSci, Kim Horslev-Petersen

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.

Study Timeline

• Study Start: 2012-03
• Study First Submitted: 2012-07-05
• Study First Submitted QC: 2012-07-31
• Study First Posted: 2012-08-02
• Primary Completion: 2017-05
• Study Completion: 2017-05
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-22
• Last Update Posted: 2017-06-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conventional biochemical and clinical examinations	Conventional biochemical and clinical examinations	Biochemical and clinical examinations
Conventional biochemical and clinical examinations and MRI.	Magnetic resonance imaging (MRI)	Biochemical and clinical examinations and MRI.

Primary Outcome Measures

Name	Time	Method
DAS28 remission (<2.6)	24 month
No radiographic progression (assessed by the Sharp/vdHeijde method).	24 month

Secondary Outcome Measures

Name	Time	Method
DAS28	24 month	DAS28 at 12 and 24 month
MRI synovitis (RAMRIS) score	24 months	MRI synovitis (RAMRIS) score at 12 and 24 months
MRI bone marrow oedema (RAMRIS) score	24 months	MRI bone marrow oedema (RAMRIS) score at 12 and 24 months
SF-36 score	24 month	Changes in SF-36 score from 0-12 and 0-24 months
ACR/EULAR 2011 remission	24 month	ACR/EULAR 2011 remission at 12 and 24 months
HAQ score	24 month	Changes in HAQ score from 0-12 and 0-24 months
biomarker analyses	24 month
No MRI erosion (RAMRIS) score	24 month	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.
EQ-5D score	24 month	Changes in EQ-5D score from 0-12 and 0-24 months
No radiographic progression (Sharp/vdHeijde score).	24 month	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.
DAS28 remission (<2.6) at 12 months	24 months

Trial Locations

Locations (9)

Dep. of Rheumatology Aarhus Hospital; 🇩🇰 Aarhus, Denmark

Dep. of Rheumatology King Christian X´Hospital for Rheumatic Diseases; 🇩🇰 Graasten, Denmark

Dep. of Rheumatology Frederiksberg Hospital; 🇩🇰 Copenhagen, Denmark

Dep. of Rheumatology Glostrup Hospital; 🇩🇰 Copenhagen, Denmark

Dep. of Rheumatology Gentofte Hospital; 🇩🇰 Copenhagen, Denmark

Dep. of rheumatology Odense Hospital; 🇩🇰 Odense, Denmark

Department of Rheumatology University Hospital Vendsyssel; 🇩🇰 Hjørring, Denmark

Dep. of Rheumatology Silkeborg Hospital; 🇩🇰 Silkeborg, Denmark

Dep. of Rheumatology Slagelse Hospital; 🇩🇰 Slagelse, Denmark