Clinical trial NCT01656278: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Keywords: Arthritis, Rheumatoid/drug therapy
Arthritis, Rheumatoid/pathology
Disease Progression
Longitudinal Studies
Prospective Studies
Imaging, Magnetic Resonance
Remission Induction
Synovitis/immunology
Synovitis/pathology
Wrist Joint/pathology
Wrist Joint/physiopathology
Lead sponsor: King Christian X´Hospital for Rheumatic Diseases
Sponsor class: OTHER
Collaborators: name: King Christian X´Hospital for Rheumatic Diseases
name: Slagelse Hospital
name: Glostrup University Hospital, Copenhagen
name: Abbott
First posted: 2012-08-02
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: DAS28 remission (<2.6)
timeFrame: 24 month
measure: No radiographic progression (assessed by the Sharp/vdHeijde method).
timeFrame: 24 month
Secondary outcomes:
measure: No radiographic progression (Sharp/vdHeijde score).
timeFrame: 24 month
measure: No MRI erosion (RAMRIS) score
timeFrame: 24 month
measure: MRI synovitis (RAMRIS) score
timeFrame: 24 months
measure: MRI bone marrow oedema (RAMRIS) score
timeFrame: 24 months
measure: HAQ score
timeFrame: 24 month
measure: SF-36 score
timeFrame: 24 month
measure: EQ-5D score
timeFrame: 24 month
measure: ACR/EULAR 2011 remission
timeFrame: 24 month
measure: DAS28
timeFrame: 24 month
measure: DAS28 remission (<2.6) at 12 months
timeFrame: 24 months
measure: biomarker analyses
timeFrame: 24 month
Other outcomes:
measure: Dynamic MRI
timeFrame: 24 month
Locations:
city: Aarhus
country: Denmark
facility: Dep. of Rheumatology Aarhus Hospital
city: Copenhagen
country: Denmark
facility: Dep. of Rheumatology Frederiksberg Hospital
city: Copenhagen
country: Denmark
facility: Dep. of Rheumatology Glostrup Hospital
city: Copenhagen
country: Denmark
facility: Dep. of Rheumatology Gentofte Hospital
city: Graasten
country: Denmark
facility: Dep. of Rheumatology King Christian X´Hospital for Rheumatic Diseases
city: Hjørring
country: Denmark
facility: Department of Rheumatology University Hospital Vendsyssel
city: Odense
country: Denmark
facility: Dep. of rheumatology Odense Hospital
city: Silkeborg
country: Denmark
facility: Dep. of Rheumatology Silkeborg Hospital
city: Slagelse
country: Denmark
facility: Dep. of Rheumatology Slagelse Hospital
Study officials:
affiliation: King Christian X´Hospital for Rheumatic Diseases
name: Kim Hørslev-Petersen, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Rheumatology, Rigshospitalet, Glostrup
name: Signe Møller-Bisgaard, MD
role: STUDY_DIRECTOR
affiliation: Dep. of Rheumatology, Rigshospitalet, Glostrup
name: Mikkel Østergaard, Professor
role: STUDY_CHAIR
affiliation: Dep. of Rheumatology Slagelse Hospital
name: Bo Ejbjerg, MD, PhD
role: STUDY_CHAIR
affiliation: Dep. of Rheumatology, Rigshospitalet, Glostrup
name: Merete Hetland, MD, PhD, DMSci
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.