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

Signe Møller-Bisgaard*, Kim Hørslev-Petersen, Bo Ejbjerg, Merete Lund Hetland, Lykke Midtbøll Ørnbjerg, Daniel Glinatsi, Jakob Møller, Mikael Boesen, Robin Christensen, Kristian Stengaard-Pedersen, Ole Rintek Madsen, Bente Jensen, Jan Alexander Villadsen, Ellen Margrethe Hauge, Philip Bennett, Oliver Hendricks, Karsten Asmussen, Marcin Kowalski, Hanne Lindegaard, Sabrina Mai Nielsen & 8 others Henning Bliddal, Niels Steen Krogh, Torkell Ellingsen, Agnete H. Nielsen, Lone Balding, Anne Grethe Jurik, Henrik S. Thomsen, Mikkel Østergaard

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Importance: Whether using magnetic resonance imaging (MRI) to guide treatment in patients with rheumatoid arthritis (RA) improves disease activity and slows joint damage progression is unknown.

Objective: To determine whether an MRI-guided treat-to-target strategy vs a conventional clinical treat-to-target strategy improves outcomes in patients with RA in clinical remission.

Design, Setting, and Participants: Two-year, randomized, multicenter trial conducted at 9 hospitals in Denmark. Two hundred patients with RA in clinical remission (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] <3.2 and no swollen joints) were enrolled between April 2012 and June 2015. The final follow-up visit was April 2017.

Interventions: Patients were randomly allocated (1:1) to an MRI-guided vs a conventional treat-to-target strategy. In the MRI-guided group, the treatment goal was absence of MRI bone marrow edema combined with clinical remission, defined as DAS28-CRP of 3.2 or less and no swollen joints. In the conventional group, the treatment goal was clinical remission.

Main Outcomes and Measures: Co-primary outcomes were proportions of patients achieving DAS28-CRP remission (DAS28-CRP <2.6) and with no radiographic progression (no increase in total van der Heijde-modified Sharp score) at 24 months. Significance testing for the primary outcome was based on 1-sided testing. Secondary outcomes were clinical and MRI measures of disease activity, physical function, and quality of life.

Results: Of 200 patients randomized (133 women [67%]; mean [SD] age, 61.6 [10.5] years; median baseline DAS28-CRP, 1.9 [interquartile range, 1.7-2.2]; van der Heijde-modified Sharp score, 18.0 [interquartile range, 7.0-42.5]), 76 patients (76%) in the MRI-guided group and 95 (95%) in the conventional group completed the study. Of these, 64 (85%) vs 83 (88%), respectively, reached the primary clinical end point (risk difference, -4.8% [1-sided 95% CI, -13.6% to + ∞; 1-sided P = .19]) and 49 (66%) vs 58 (62%), respectively, reached the primary radiographic end point (risk difference, 4.7% [1-sided 95% CI, -7.0% to + ∞; 1-sided P = .25). Of 10 key secondary end points, 8 were null and 2 showed statistically significant benefit for the MRI treat-to-target group. Seventeen patients (17%) in the MRI-guided treat-to-target group and 6 patients (6%) in the conventional treat-to-target group experienced serious adverse events.

Conclusions and Relevance: Among patients with RA in clinical remission, an MRI-guided treat-to-target strategy compared with a conventional treat-to-target strategy did not result in improved disease activity remission rates or reduce radiographic progression. These findings do not support the use of an MRI-guided strategy for treating patients with RA.

Trial Registration: ClinicalTrials.gov Identifier: NCT01656278.

Original languageEnglish
JournalJAMA - Journal of the American Medical Association
Volume321
Issue number5
Pages (from-to)461-472
ISSN0098-7484
DOIs
Publication statusPublished - 5. Feb 2019

Fingerprint

Randomized Controlled Trials
Joints
Denmark
Multicenter Studies
Quality of Life
Outcome Assessment (Health Care)
Exercise

Keywords

  • Aged
  • Antirheumatic Agents/adverse effects
  • Arthritis, Rheumatoid/diagnostic imaging
  • Bone Marrow/diagnostic imaging
  • Disease Progression
  • Edema/diagnostic imaging
  • Female
  • Humans
  • Joints/diagnostic imaging
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Osteitis/diagnostic imaging
  • Outcome and Process Assessment (Health Care)
  • Radiography
  • Remission Induction

Cite this

Møller-Bisgaard, Signe ; Hørslev-Petersen, Kim ; Ejbjerg, Bo ; Hetland, Merete Lund ; Ørnbjerg, Lykke Midtbøll ; Glinatsi, Daniel ; Møller, Jakob ; Boesen, Mikael ; Christensen, Robin ; Stengaard-Pedersen, Kristian ; Madsen, Ole Rintek ; Jensen, Bente ; Villadsen, Jan Alexander ; Hauge, Ellen Margrethe ; Bennett, Philip ; Hendricks, Oliver ; Asmussen, Karsten ; Kowalski, Marcin ; Lindegaard, Hanne ; Nielsen, Sabrina Mai ; Bliddal, Henning ; Krogh, Niels Steen ; Ellingsen, Torkell ; Nielsen, Agnete H. ; Balding, Lone ; Jurik, Anne Grethe ; Thomsen, Henrik S. ; Østergaard, Mikkel. / 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. In: JAMA - Journal of the American Medical Association. 2019 ; Vol. 321, No. 5. pp. 461-472.
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title = "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",
abstract = "Importance: Whether using magnetic resonance imaging (MRI) to guide treatment in patients with rheumatoid arthritis (RA) improves disease activity and slows joint damage progression is unknown.Objective: To determine whether an MRI-guided treat-to-target strategy vs a conventional clinical treat-to-target strategy improves outcomes in patients with RA in clinical remission.Design, Setting, and Participants: Two-year, randomized, multicenter trial conducted at 9 hospitals in Denmark. Two hundred patients with RA in clinical remission (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] <3.2 and no swollen joints) were enrolled between April 2012 and June 2015. The final follow-up visit was April 2017.Interventions: Patients were randomly allocated (1:1) to an MRI-guided vs a conventional treat-to-target strategy. In the MRI-guided group, the treatment goal was absence of MRI bone marrow edema combined with clinical remission, defined as DAS28-CRP of 3.2 or less and no swollen joints. In the conventional group, the treatment goal was clinical remission.Main Outcomes and Measures: Co-primary outcomes were proportions of patients achieving DAS28-CRP remission (DAS28-CRP <2.6) and with no radiographic progression (no increase in total van der Heijde-modified Sharp score) at 24 months. Significance testing for the primary outcome was based on 1-sided testing. Secondary outcomes were clinical and MRI measures of disease activity, physical function, and quality of life.Results: Of 200 patients randomized (133 women [67{\%}]; mean [SD] age, 61.6 [10.5] years; median baseline DAS28-CRP, 1.9 [interquartile range, 1.7-2.2]; van der Heijde-modified Sharp score, 18.0 [interquartile range, 7.0-42.5]), 76 patients (76{\%}) in the MRI-guided group and 95 (95{\%}) in the conventional group completed the study. Of these, 64 (85{\%}) vs 83 (88{\%}), respectively, reached the primary clinical end point (risk difference, -4.8{\%} [1-sided 95{\%} CI, -13.6{\%} to + ∞; 1-sided P = .19]) and 49 (66{\%}) vs 58 (62{\%}), respectively, reached the primary radiographic end point (risk difference, 4.7{\%} [1-sided 95{\%} CI, -7.0{\%} to + ∞; 1-sided P = .25). Of 10 key secondary end points, 8 were null and 2 showed statistically significant benefit for the MRI treat-to-target group. Seventeen patients (17{\%}) in the MRI-guided treat-to-target group and 6 patients (6{\%}) in the conventional treat-to-target group experienced serious adverse events.Conclusions and Relevance: Among patients with RA in clinical remission, an MRI-guided treat-to-target strategy compared with a conventional treat-to-target strategy did not result in improved disease activity remission rates or reduce radiographic progression. These findings do not support the use of an MRI-guided strategy for treating patients with RA.Trial Registration: ClinicalTrials.gov Identifier: NCT01656278.",
keywords = "Aged, Antirheumatic Agents/adverse effects, Arthritis, Rheumatoid/diagnostic imaging, Bone Marrow/diagnostic imaging, Disease Progression, Edema/diagnostic imaging, Female, Humans, Joints/diagnostic imaging, Magnetic Resonance Imaging, Male, Middle Aged, Osteitis/diagnostic imaging, Outcome and Process Assessment (Health Care), Radiography, Remission Induction",
author = "Signe M{\o}ller-Bisgaard and Kim H{\o}rslev-Petersen and Bo Ejbjerg and Hetland, {Merete Lund} and {\O}rnbjerg, {Lykke Midtb{\o}ll} and Daniel Glinatsi and Jakob M{\o}ller and Mikael Boesen and Robin Christensen and Kristian Stengaard-Pedersen and Madsen, {Ole Rintek} and Bente Jensen and Villadsen, {Jan Alexander} and Hauge, {Ellen Margrethe} and Philip Bennett and Oliver Hendricks and Karsten Asmussen and Marcin Kowalski and Hanne Lindegaard and Nielsen, {Sabrina Mai} and Henning Bliddal and Krogh, {Niels Steen} and Torkell Ellingsen and Nielsen, {Agnete H.} and Lone Balding and Jurik, {Anne Grethe} and Thomsen, {Henrik S.} and Mikkel {\O}stergaard",
year = "2019",
month = "2",
day = "5",
doi = "10.1001/jama.2018.21362",
language = "English",
volume = "321",
pages = "461--472",
journal = "J A M A: The Journal of the American Medical Association",
issn = "0098-7484",
publisher = "American Medical Association",
number = "5",

}

Møller-Bisgaard, S, Hørslev-Petersen, K, Ejbjerg, B, Hetland, ML, Ørnbjerg, LM, Glinatsi, D, Møller, 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 & Østergaard, M 2019, '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 - Journal of the American Medical Association, vol. 321, no. 5, pp. 461-472. https://doi.org/10.1001/jama.2018.21362

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. / Møller-Bisgaard, Signe; Hørslev-Petersen, Kim; Ejbjerg, Bo; Hetland, Merete Lund; Ørnbjerg, Lykke Midtbøll; Glinatsi, Daniel; Møller, Jakob; Boesen, Mikael; Christensen, Robin; Stengaard-Pedersen, Kristian; Madsen, Ole Rintek; Jensen, Bente; Villadsen, Jan Alexander; Hauge, Ellen Margrethe; Bennett, Philip; Hendricks, Oliver; Asmussen, Karsten; Kowalski, Marcin; Lindegaard, Hanne; Nielsen, Sabrina Mai; Bliddal, Henning; Krogh, Niels Steen; Ellingsen, Torkell; Nielsen, Agnete H.; Balding, Lone; Jurik, Anne Grethe; Thomsen, Henrik S.; Østergaard, Mikkel.

In: JAMA - Journal of the American Medical Association, Vol. 321, No. 5, 05.02.2019, p. 461-472.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - 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

AU - Møller-Bisgaard, Signe

AU - Hørslev-Petersen, Kim

AU - Ejbjerg, Bo

AU - Hetland, Merete Lund

AU - Ørnbjerg, Lykke Midtbøll

AU - Glinatsi, Daniel

AU - Møller, Jakob

AU - Boesen, Mikael

AU - Christensen, Robin

AU - Stengaard-Pedersen, Kristian

AU - Madsen, Ole Rintek

AU - Jensen, Bente

AU - Villadsen, Jan Alexander

AU - Hauge, Ellen Margrethe

AU - Bennett, Philip

AU - Hendricks, Oliver

AU - Asmussen, Karsten

AU - Kowalski, Marcin

AU - Lindegaard, Hanne

AU - Nielsen, Sabrina Mai

AU - Bliddal, Henning

AU - Krogh, Niels Steen

AU - Ellingsen, Torkell

AU - Nielsen, Agnete H.

AU - Balding, Lone

AU - Jurik, Anne Grethe

AU - Thomsen, Henrik S.

AU - Østergaard, Mikkel

PY - 2019/2/5

Y1 - 2019/2/5

N2 - Importance: Whether using magnetic resonance imaging (MRI) to guide treatment in patients with rheumatoid arthritis (RA) improves disease activity and slows joint damage progression is unknown.Objective: To determine whether an MRI-guided treat-to-target strategy vs a conventional clinical treat-to-target strategy improves outcomes in patients with RA in clinical remission.Design, Setting, and Participants: Two-year, randomized, multicenter trial conducted at 9 hospitals in Denmark. Two hundred patients with RA in clinical remission (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] <3.2 and no swollen joints) were enrolled between April 2012 and June 2015. The final follow-up visit was April 2017.Interventions: Patients were randomly allocated (1:1) to an MRI-guided vs a conventional treat-to-target strategy. In the MRI-guided group, the treatment goal was absence of MRI bone marrow edema combined with clinical remission, defined as DAS28-CRP of 3.2 or less and no swollen joints. In the conventional group, the treatment goal was clinical remission.Main Outcomes and Measures: Co-primary outcomes were proportions of patients achieving DAS28-CRP remission (DAS28-CRP <2.6) and with no radiographic progression (no increase in total van der Heijde-modified Sharp score) at 24 months. Significance testing for the primary outcome was based on 1-sided testing. Secondary outcomes were clinical and MRI measures of disease activity, physical function, and quality of life.Results: Of 200 patients randomized (133 women [67%]; mean [SD] age, 61.6 [10.5] years; median baseline DAS28-CRP, 1.9 [interquartile range, 1.7-2.2]; van der Heijde-modified Sharp score, 18.0 [interquartile range, 7.0-42.5]), 76 patients (76%) in the MRI-guided group and 95 (95%) in the conventional group completed the study. Of these, 64 (85%) vs 83 (88%), respectively, reached the primary clinical end point (risk difference, -4.8% [1-sided 95% CI, -13.6% to + ∞; 1-sided P = .19]) and 49 (66%) vs 58 (62%), respectively, reached the primary radiographic end point (risk difference, 4.7% [1-sided 95% CI, -7.0% to + ∞; 1-sided P = .25). Of 10 key secondary end points, 8 were null and 2 showed statistically significant benefit for the MRI treat-to-target group. Seventeen patients (17%) in the MRI-guided treat-to-target group and 6 patients (6%) in the conventional treat-to-target group experienced serious adverse events.Conclusions and Relevance: Among patients with RA in clinical remission, an MRI-guided treat-to-target strategy compared with a conventional treat-to-target strategy did not result in improved disease activity remission rates or reduce radiographic progression. These findings do not support the use of an MRI-guided strategy for treating patients with RA.Trial Registration: ClinicalTrials.gov Identifier: NCT01656278.

AB - Importance: Whether using magnetic resonance imaging (MRI) to guide treatment in patients with rheumatoid arthritis (RA) improves disease activity and slows joint damage progression is unknown.Objective: To determine whether an MRI-guided treat-to-target strategy vs a conventional clinical treat-to-target strategy improves outcomes in patients with RA in clinical remission.Design, Setting, and Participants: Two-year, randomized, multicenter trial conducted at 9 hospitals in Denmark. Two hundred patients with RA in clinical remission (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] <3.2 and no swollen joints) were enrolled between April 2012 and June 2015. The final follow-up visit was April 2017.Interventions: Patients were randomly allocated (1:1) to an MRI-guided vs a conventional treat-to-target strategy. In the MRI-guided group, the treatment goal was absence of MRI bone marrow edema combined with clinical remission, defined as DAS28-CRP of 3.2 or less and no swollen joints. In the conventional group, the treatment goal was clinical remission.Main Outcomes and Measures: Co-primary outcomes were proportions of patients achieving DAS28-CRP remission (DAS28-CRP <2.6) and with no radiographic progression (no increase in total van der Heijde-modified Sharp score) at 24 months. Significance testing for the primary outcome was based on 1-sided testing. Secondary outcomes were clinical and MRI measures of disease activity, physical function, and quality of life.Results: Of 200 patients randomized (133 women [67%]; mean [SD] age, 61.6 [10.5] years; median baseline DAS28-CRP, 1.9 [interquartile range, 1.7-2.2]; van der Heijde-modified Sharp score, 18.0 [interquartile range, 7.0-42.5]), 76 patients (76%) in the MRI-guided group and 95 (95%) in the conventional group completed the study. Of these, 64 (85%) vs 83 (88%), respectively, reached the primary clinical end point (risk difference, -4.8% [1-sided 95% CI, -13.6% to + ∞; 1-sided P = .19]) and 49 (66%) vs 58 (62%), respectively, reached the primary radiographic end point (risk difference, 4.7% [1-sided 95% CI, -7.0% to + ∞; 1-sided P = .25). Of 10 key secondary end points, 8 were null and 2 showed statistically significant benefit for the MRI treat-to-target group. Seventeen patients (17%) in the MRI-guided treat-to-target group and 6 patients (6%) in the conventional treat-to-target group experienced serious adverse events.Conclusions and Relevance: Among patients with RA in clinical remission, an MRI-guided treat-to-target strategy compared with a conventional treat-to-target strategy did not result in improved disease activity remission rates or reduce radiographic progression. These findings do not support the use of an MRI-guided strategy for treating patients with RA.Trial Registration: ClinicalTrials.gov Identifier: NCT01656278.

KW - Aged

KW - Antirheumatic Agents/adverse effects

KW - Arthritis, Rheumatoid/diagnostic imaging

KW - Bone Marrow/diagnostic imaging

KW - Disease Progression

KW - Edema/diagnostic imaging

KW - Female

KW - Humans

KW - Joints/diagnostic imaging

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Osteitis/diagnostic imaging

KW - Outcome and Process Assessment (Health Care)

KW - Radiography

KW - Remission Induction

U2 - 10.1001/jama.2018.21362

DO - 10.1001/jama.2018.21362

M3 - Journal article

VL - 321

SP - 461

EP - 472

JO - J A M A: The Journal of the American Medical Association

JF - J A M A: The Journal of the American Medical Association

SN - 0098-7484

IS - 5

ER -