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

Arthritis, Rheumatoid Clinical Trial

— IMAGINE-RA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01656278
• Other study ID #: IMAGINE-RA
• Status: Completed
• Phase: N/A
• First received: July 5, 2012
• Last updated: June 22, 2017
• Start date: March 2012
• Est. completion date: May 2017

Study information

• Verified date: June 2017
• Source: King Christian X´Hospital for Rheumatic Diseases
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: May 2017
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Autoimmune Diseases
• Collagen Diseases
• Connective Tissue Diseases
• Disease Progression
• Joint Diseases
• Musculoskeletal Diseases
• Rheumatic Diseases

Intervention

Procedure:
• 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)

Other:
• 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

Locations

Country	Name	City	State
Denmark	Dep. of Rheumatology Aarhus Hospital	Aarhus
Denmark	Dep. of Rheumatology Frederiksberg Hospital	Copenhagen
Denmark	Dep. of Rheumatology Gentofte Hospital	Copenhagen
Denmark	Dep. of Rheumatology Glostrup Hospital	Copenhagen
Denmark	Dep. of Rheumatology King Christian X´Hospital for Rheumatic Diseases	Graasten
Denmark	Department of Rheumatology University Hospital Vendsyssel	Hjørring
Denmark	Dep. of rheumatology Odense Hospital	Odense
Denmark	Dep. of Rheumatology Silkeborg Hospital	Silkeborg
Denmark	Dep. of Rheumatology Slagelse Hospital	Slagelse

Sponsors (5)

Lead Sponsor	Collaborator
Professor of Rheumatology, MD, DMSci, Kim Horslev-Petersen	Abbott, Glostrup University Hospital, Copenhagen, King Christian X´Hospital for Rheumatic Diseases, Slagelse Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Dynamic MRI	Dynamic MRI variable (including initial rate of enhancement (IRE) and maximum enhancement (ME)).	24 month
Primary	DAS28 remission (<2.6)		24 month
Primary	No radiographic progression (assessed by the Sharp/vdHeijde method).		24 month
Secondary	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
Secondary	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
Secondary	MRI synovitis (RAMRIS) score	MRI synovitis (RAMRIS) score at 12 and 24 months	24 months
Secondary	MRI bone marrow oedema (RAMRIS) score	MRI bone marrow oedema (RAMRIS) score at 12 and 24 months	24 months
Secondary	HAQ score	Changes in HAQ score from 0-12 and 0-24 months	24 month
Secondary	SF-36 score	Changes in SF-36 score from 0-12 and 0-24 months	24 month
Secondary	EQ-5D score	Changes in EQ-5D score from 0-12 and 0-24 months	24 month
Secondary	ACR/EULAR 2011 remission	ACR/EULAR 2011 remission at 12 and 24 months	24 month
Secondary	DAS28	DAS28 at 12 and 24 month	24 month
Secondary	DAS28 remission (<2.6) at 12 months		24 months
Secondary	biomarker analyses		24 month