An MRI-guided Treatment Strategy to Prevent Disease Progression in Patients With Rheumatoid Arthritis (IMAGINE-RA)

• ClinicalTrials.gov Identifier: NCT01656278
• Recruitment Status: Completed
• First Posted: August 2, 2012
• Last Update Posted: June 23, 2017
• Sponsor: Professor of Rheumatology, MD, DMSci, Kim Horslev-Petersen
• Collaborators: King Christian X´Hospital for Rheumatic Diseases; Slagelse Hospital; Glostrup University Hospital, Copenhagen; Abbott
• Information provided by (Responsible Party): Professor of Rheumatology, MD, DMSci, Kim Horslev-Petersen, King Christian X´Hospital for Rheumatic Diseases

Tracking Information

• First Submitted Date: July 5, 2012
• First Posted Date: August 2, 2012
• Last Update Posted Date: June 23, 2017
• Actual Study Start Date: March 2012
• Actual Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 31, 2012)

• DAS28 remission (<2.6) [ Time Frame: 24 month ]
• No radiographic progression (assessed by the Sharp/vdHeijde method). [ Time Frame: 24 month ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 31, 2012)

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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: July 31, 2012)

Dynamic MRI [ Time Frame: 24 month ]

Dynamic MRI variable (including initial rate of enhancement (IRE) and maximum enhancement (ME)).

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: An MRI-guided Treatment Strategy to Prevent Disease Progression in Patients With Rheumatoid Arthritis
• Official Title: Does an MRI-guided Treatment Strategy Reduce Disease Activity and Progression in Patients With Rheumatoid Arthritis (RA): a Randomised Controlled Trial
• 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 Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment

Condition

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

Study Arms

• Active Comparator: Conventional biochemical and clinical examinations
  Biochemical and clinical examinations
  Intervention: Other: Conventional biochemical and clinical examinations
• Experimental: Conventional biochemical and clinical examinations and MRI.
  Biochemical and clinical examinations and MRI.
  Intervention: Procedure: Magnetic resonance imaging (MRI)

Publications *

• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 31, 2012): 200
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 2017
• Actual Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark

Administrative Information

• NCT Number: NCT01656278
• Other Study ID Numbers: IMAGINE-RA
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Professor of Rheumatology, MD, DMSci, Kim Horslev-Petersen, King Christian X´Hospital for Rheumatic Diseases
• Original Responsible Party: Same as current
• Current Study Sponsor: Professor of Rheumatology, MD, DMSci, Kim Horslev-Petersen
• Original Study Sponsor: Same as current

Collaborators

• King Christian X´Hospital for Rheumatic Diseases
• Slagelse Hospital
• Glostrup University Hospital, Copenhagen
• Abbott

Investigators

• Principal Investigator: Kim Hørslev-Petersen, Professor; King Christian X´Hospital for Rheumatic Diseases
• Study Director: Signe Møller-Bisgaard, MD; Dep. of Rheumatology, Rigshospitalet, Glostrup
• Study Chair: Mikkel Østergaard, Professor; Dep. of Rheumatology, Rigshospitalet, Glostrup
• Study Chair: Bo Ejbjerg, MD, PhD; Dep. of Rheumatology Slagelse Hospital
• Study Chair: Merete Hetland, MD, PhD, DMSci; Dep. of Rheumatology, Rigshospitalet, Glostrup

• PRS Account: King Christian X´Hospital for Rheumatic Diseases
• Verification Date: June 2017