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

NCT ID: NCT01656278

Last Updated: 2017-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2017-05-31

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.

Conditions

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Conventional biochemical and clinical examinations

Biochemical and clinical examinations

Group Type: ACTIVE_COMPARATOR

Conventional biochemical and clinical examinations

Intervention Type: 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

Conventional biochemical and clinical examinations and MRI.

Biochemical and clinical examinations and MRI.

Group Type: EXPERIMENTAL

Magnetic resonance imaging (MRI)

Intervention Type: 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)

Interventions

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)

Intervention Type: PROCEDURE

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

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

King Christian X´Hospital for Rheumatic Diseases

OTHER

Sponsor Role: collaborator

Slagelse Hospital

OTHER

Sponsor Role: collaborator

Glostrup University Hospital, Copenhagen

OTHER

Sponsor Role: collaborator

Abbott

INDUSTRY

Sponsor Role: collaborator

Professor of Rheumatology, MD, DMSci, Kim Horslev-Petersen

OTHER

Sponsor Role: lead

Responsible Party

Professor of Rheumatology, MD, DMSci, Kim Horslev-Petersen

Professor of Rheumatology, MD, DMSci

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Kim Hørslev-Petersen, Professor

Role: PRINCIPAL_INVESTIGATOR

King Christian X´Hospital for Rheumatic Diseases

Signe Møller-Bisgaard, MD

Role: STUDY_DIRECTOR

Dep. of Rheumatology, Rigshospitalet, Glostrup

Mikkel Østergaard, Professor

Role: STUDY_CHAIR

Dep. of Rheumatology, Rigshospitalet, Glostrup

Bo Ejbjerg, MD, PhD

Role: STUDY_CHAIR

Dep. of Rheumatology Slagelse Hospital

Merete Hetland, MD, PhD, DMSci

Role: STUDY_CHAIR

Dep. of Rheumatology, Rigshospitalet, Glostrup

Locations

Dep. of Rheumatology Aarhus Hospital

Aarhus, , 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 King Christian X´Hospital for Rheumatic Diseases

Gråsten, , 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, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 34474649 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32929463 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30721294 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25896862 (View on PubMed)

Other Identifiers

IMAGINE-RA

Identifier Type: -

Identifier Source: org_study_id