An MRI Guided Treat-to-Target Strategy in Rheumatoid Arthritis Patients in Clinical Remission Improved MRI Inflammation but Not Damage Progression - Results from the Imagine-RA Randomized Controlled Trial

Signe Møller-Bisgaard¹, Kim Hørslev-Petersen², Bo Jannik Ejbjerg³, Daniel Glinatsi⁴, Merete Lund Hetland¹, Lykke Ørnbjerg¹, Jakob M. Møller⁵, Mikael Boesen⁶, Robin Christensen⁷, Kristian Stengaard-Pedersen⁸, Ole Rintek Madsen⁹, Bente Jensen¹⁰, Jan Alexander Villadsen¹¹, Ellen-Margrethe Hauge⁸, Philip Bennett¹², Oliver Hendricks², Karsten Asmussen¹³, Marcin Ryszard Kowalski¹⁴, Hanne Lindegaard¹⁵, Sabrina Mai Nielsen⁷, Henning Bliddal¹⁶, Niels Steen Krogh¹⁷, Torkell Ellingsen¹⁵, Agente Nielsen¹⁸, Lone Balding¹⁹, Anne Grethe Jurik²⁰, Henrik S Thomsen¹⁹ and Mikkel Østergaard²¹, ¹Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Copenhagen, Denmark, ²King Christian 10th Hospital for Rheumatic Diseases, University of Southern Denmark, Institute of Regional Health Research, Graasten, Denmark, ³Department of Rheumatology, Zealand University Hospital, Køge, Denmark, ⁴Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Rigshospitalet, Centre for Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark, ⁵Dept. of Radiology, Copenhagen University Hospitals, Herlev and Gentofte, Copenhagen, Denmark, ⁶Department of Radiology, Bispebjerg-Frederiksberg Hospital, Copenhagen, Copenhagen, Denmark, ⁷Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg, Denmark, ⁸Department of Rheumatology, Aarhus University Hospital, Department of Clinical Medicine, Aarhus, Denmark, ⁹Department of Rheumatology, Copenhagen University Hospital, Herlev and Gentofte, Hellerup, Denmark, ¹⁰Department of Rheumatology, Frederiksberg Hospital, Copenhagen, Denmark, Copenhagen, Denmark, ¹¹Department of Rheumatology, Silkeborg Hospital, Silkeborg, Denmark, ¹²Department of Rheumatology, Copenhagen University Hospital, Herlev and Gentofte, Copenhagen, Denmark, ¹³Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark, ¹⁴Department of Rheumatology, Sygehus Vendsyssel, Hjørring, Hjørring, Denmark, ¹⁵Department of Rheumatology, Odense University Hospital, Odense, Denmark, ¹⁶The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark, ¹⁷The DANBIO Registry, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark, ¹⁸Department of Radiology, Silkeborg Hospital, Silkeborg, Denmark, ¹⁹Department of Radiology, Copenhagen University Hospital Herlev and Gentofte, Copenhagen, Denmark, ²⁰Department of Radiology, Aarhus University Hospital, Aarhus, Denmark, ²¹Center for Rheumatology and Spine Diseases, Rigshospitalet Glostrup Copenhagen Center for Arthritis Research, Copenhagen, Denmark

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: MRI, remission and rheumatoid arthritis (RA)

Session Information

Date: Sunday, October 21, 2018

Title: 3S082 ACR Abstract: Imaging of Rheumatic Diseases I: MRI & CT (863–868)

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Magnetic Resonance Imaging (MRI) bone marrow edema (BME)/osteitis and MRI synovitis have been identified as predictors of structural damage progression in rheumatoid arthritis RA^1,2. Targeting MRI remission may reduce inflammation and halt damage progression.

The purpose was to investigate whether a 2-year treat-to-target (T2T) strategy targeting MRI remission (defined as absence of BME) suppresses MRI-determined measures of disease activity and structural joint damage in RA patients in clinical remission.

Methods: In the two year investigator initiated, randomized, open label multicentre IMAGINE-RA study, 200 RA patients in clinical remission (defined as DAS28-CRP<3.2 and no swollen joints) receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDSs) were randomized 1:1 to a conventional DAS28-CRP guided T2T treatment strategy targeting DAS28<3.2 and no swollen joints or an MRI guided T2T treatment strategy applying the same clinical T2T strategy and in addition targeting absence of MRI BME. Patients were followed every 4 months over a 2-year follow-up period. In all patients contrast-enhanced MRIs of the 2^nd-5^th metacarpophalangeal (MCP) joints and wrist of the dominant hand were performed at baseline, 12 and 24 months. In the MRI T2T arm MRI was performed every 4 months ahead of the clinical visit and assessed for presence/absence of BME by one blinded evaluator so the result was available for the investigator at the visit. In the conventional T2T arm MRI findings were blinded to the investigator. If treatment target was not met treatment was escalated according to a predefined treatment algorithm starting with increment in csDMARD and then adding biologic DMARDs. MRIs (0,12 and 24 months) were evaluated according to the RAMRIS scoring system, with known chronology by one blinded experienced reader. Pearson´s chi-square statistics and repeated-measures logistic regression models were used to assess outcomes.

Results: MRI outcomes of inflammation and damage at 24 months are presented in the table. The MRI T2T arm showed statistically significant reductions at 24 months in all inflammatory endpoints (osteitis, tenosynovitis and total inflammation score, p<0.018), except synovitis, (p=0.074), compared to the conventional T2T arm. No differences between treatment strategies were seen in damage progression.

MRI outcomes at 24 months
	MRI T2T	Conventional T2T	Difference between groups (95% CI)	P value*
MRI
Inflammation
Change in osteitis (RAMRIS) score	-1.8 (0.6)	-0.1 (0.5)	-1.8 (-3.2 to -0.3)	0.018
Change in synovitis (RAMRIS) score	-0.5(0.3)	0.3 (0.3)	-0.8 (-1.8 to o.1)	0.074
Change in tenosynovit (RAMRIS) score	-0.9 (0.3)	0.3 (0.3)	-1.2 (-2.1 to -0.3)	0.007
Change in total inflammation (RAMRIS) score	-2.9 (1.0)	0.7 (1.0)	-3.6 (-6.4 to -0.8)	0.013
Damage
Change in erosion (RAMRIS) score	0.5 (0.2)	0.6 (0.2)	-0.1 (-0.6 to 0.4)	0.663
Change in JSN (RAMRIS) score	0.1 (0.2)	0.4 (0.1)	-0.3 (-0.7 to 0.2)	0.236
Change in total damage (RAMRIS) score	0.6 (0.3)	1.0 (0.3)	-0.3 (-1.2 to 0.5)	0.395
No progression in erosion (RAMRIS), n (%)	59 (79.7%)	70 (75.3%)	OR, 1.06 (0.02 to 66.59)	0.976
95% CI, 95% confidence interval; JSN=joint space narrowing; MRI=Magnetic Resonance Imaging; RAMRIS=RA magnetic resonance imaging scoring system; T2T=treat-to-target; total damage score=sum score of MRI erosion and JSN; total inflammation score=sum score of MRI synovitis, osteitis and tenosynovitis. Data are presented as least square means (SE) unless otherwise stated. Analyses are based on full analysis set (patients having a baseline visit and at least one follow-up visit) with no data imputation to replace missing data. *P values are based on repeated-measures logistic regression models. For some of the variables, fewer patients were included in the analyses due to missing data in the MRI T2T arm (range 85-89) and in the conventional T2T arm (range 90-95).

Conclusion: An MRI T2T strategy, aiming to eliminate MRI BME, was more effective than a conventional T2T strategy in reducing MRI inflammation but not MRI damage progression. The reduced inflammatory load caused by the MRI T2T strategy may reduce long-term structural joint damage and improve patient-reported outcomes, but more than two years follow-up data are needed to clarify this.

Clinicaltrials.gov Identifier: NCT01656278

References:

Hetland et al, Ann Rheum Dis 2009;68(3) 2. Boyesen et al, Ann Rheum Dis 2011;70(3)

Disclosure: S. Møller-Bisgaard, None; K. Hørslev-Petersen, None; B. J. Ejbjerg, None; D. Glinatsi, None; M. L. Hetland, None; L. Ørnbjerg, None; J. M. Møller, None; M. Boesen, None; R. Christensen, None; K. Stengaard-Pedersen, None; O. Rintek Madsen, None; B. Jensen, None; J. A. Villadsen, None; E. M. Hauge, None; P. Bennett, None; O. Hendricks, None; K. Asmussen, None; M. Ryszard Kowalski, None; H. Lindegaard, None; S. M. Nielsen, None; H. Bliddal, None; N. S. Krogh, None; T. Ellingsen, None; A. Nielsen, None; L. Balding, None; A. G. Jurik, None; H. S. Thomsen, None; M. Østergaard, None.

To cite this abstract in AMA style:

Møller-Bisgaard S, Hørslev-Petersen K, Ejbjerg BJ, Glinatsi D, Hetland ML, Ørnbjerg L, Møller JM, Boesen M, Christensen R, Stengaard-Pedersen K, Rintek Madsen O, Jensen B, Villadsen JA, Hauge EM, Bennett P, Hendricks O, Asmussen K, Ryszard Kowalski M, Lindegaard H, Nielsen SM, Bliddal H, Krogh NS, Ellingsen T, Nielsen A, Balding L, Jurik AG, Thomsen HS, Østergaard M. An MRI Guided Treat-to-Target Strategy in Rheumatoid Arthritis Patients in Clinical Remission Improved MRI Inflammation but Not Damage Progression – Results from the Imagine-RA Randomized Controlled Trial [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/an-mri-guided-treat-to-target-strategy-in-rheumatoid-arthritis-patients-in-clinical-remission-improved-mri-inflammation-but-not-damage-progression-results-from-the-imagine-ra-randomized-controlled-t/. Accessed .

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