An MRI-guided Treatment Strategy to Prevent Disease Progression in Patients With Rheumatoid Arthritis (IMAGINE-RA)
Does an MRI-guided Treatment Strategy Reduce Disease Activity and Progression in Patients With Rheumatoid Arthritis (RA): a Randomised Controlled Trial
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Real)
Estágio
- Não aplicável
Contactos e Locais
Locais de estudo
-
-
-
Aarhus, Dinamarca, 8600
- Dep. of Rheumatology Aarhus Hospital
-
Copenhagen, Dinamarca, 2000
- Dep. of Rheumatology Frederiksberg Hospital
-
Copenhagen, Dinamarca, 2600
- Dep. of Rheumatology Glostrup Hospital
-
Copenhagen, Dinamarca, 2900
- Dep. of Rheumatology Gentofte Hospital
-
Graasten, Dinamarca, 6300
- Dep. of Rheumatology King Christian X´Hospital for Rheumatic Diseases
-
Hjørring, Dinamarca, DK-9800
- Department of Rheumatology University Hospital Vendsyssel
-
Odense, Dinamarca, 5000
- Dep. of rheumatology Odense Hospital
-
Silkeborg, Dinamarca, 8600
- Dep. of Rheumatology Silkeborg Hospital
-
Slagelse, Dinamarca, 4200
- Dep. of Rheumatology Slagelse Hospital
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Solteiro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Comparador Ativo: Conventional biochemical and clinical examinations
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
|
|
Experimental: Conventional biochemical and clinical examinations and MRI.
Biochemical and clinical examinations and 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)
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
|---|---|
|
DAS28 remission (<2.6)
Prazo: 24 month
|
24 month
|
|
No radiographic progression (assessed by the Sharp/vdHeijde method).
Prazo: 24 month
|
24 month
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
No radiographic progression (Sharp/vdHeijde score).
Prazo: 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.
|
24 month
|
|
No MRI erosion (RAMRIS) score
Prazo: 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.
|
24 month
|
|
MRI synovitis (RAMRIS) score
Prazo: 24 months
|
MRI synovitis (RAMRIS) score at 12 and 24 months
|
24 months
|
|
MRI bone marrow oedema (RAMRIS) score
Prazo: 24 months
|
MRI bone marrow oedema (RAMRIS) score at 12 and 24 months
|
24 months
|
|
HAQ score
Prazo: 24 month
|
Changes in HAQ score from 0-12 and 0-24 months
|
24 month
|
|
SF-36 score
Prazo: 24 month
|
Changes in SF-36 score from 0-12 and 0-24 months
|
24 month
|
|
EQ-5D score
Prazo: 24 month
|
Changes in EQ-5D score from 0-12 and 0-24 months
|
24 month
|
|
ACR/EULAR 2011 remission
Prazo: 24 month
|
ACR/EULAR 2011 remission at 12 and 24 months
|
24 month
|
|
DAS28
Prazo: 24 month
|
DAS28 at 12 and 24 month
|
24 month
|
|
DAS28 remission (<2.6) at 12 months
Prazo: 24 months
|
24 months
|
|
|
biomarker analyses
Prazo: 24 month
|
24 month
|
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Dynamic MRI
Prazo: 24 month
|
Dynamic MRI variable (including initial rate of enhancement (IRE) and maximum enhancement (ME)).
|
24 month
|
Colaboradores e Investigadores
Colaboradores
Investigadores
- Investigador principal: Kim Hørslev-Petersen, Professor, King Christian X´Hospital for Rheumatic Diseases
- Diretor de estudo: Signe Møller-Bisgaard, MD, Dep. of Rheumatology, Rigshospitalet, Glostrup
- Cadeira de estudo: Mikkel Østergaard, Professor, Dep. of Rheumatology, Rigshospitalet, Glostrup
- Cadeira de estudo: Bo Ejbjerg, MD, PhD, Dep. of Rheumatology Slagelse Hospital
- Cadeira de estudo: Merete Hetland, MD, PhD, DMSci, Dep. of Rheumatology, Rigshospitalet, Glostrup
Publicações e links úteis
Publicações Gerais
- 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.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- IMAGINE-RA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .