The Value of Adding MRI to a Clinical Treat-to-Target Strategy in Rheumatoid Arthritis Patients in Clinical Remission: Clinical and Radiographic Outcomes from the Imagine-RA Randomized Controlled Trial

Signe Møller-Bisgaard¹, Kim Hørslev-Petersen², Bo Jannik Ejbjerg³, Merete Lund Hetland¹, Daniel Glinatsi⁴, 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 Balding⁵, Anne Grethe Jurik¹⁹, Henrik S Thomsen⁵ and Mikkel Østergaard²⁰, 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, ⁵Department of Radiology, Copenhagen University Hospital 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, Aarhus University Hospital, Aarhus, Denmark, ²⁰Center 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: Monday, October 22, 2018

Title: Rheumatoid Arthritis – Diagnosis, Manifestations, and Outcomes Poster II: Diagnosis and Prognosis

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Targeting MRI remission in rheumatoid arthritis (RA) patients in clinical remission may improve clinical outcome and halt joint damage progression.

The purpose of the trial was to determine whether a treat-to-target (T2T) strategy based on structured MRI assessments targeting absence of osteitis/bone marrow edema (BME) would lead to improved clinical and radiographic outcomes, compared with a conventional T2T strategy in RA patients in clinical remission.

Methods: The IMAGINE-RA study was a 2-year investigator-initiated, randomized, open-label multicentre study. Two hundred RA patients in clinical remission (defined as: DAS28-CRP<3.2 and no swollen joints) receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were randomly assigned 1:1 to a conventional DAS28-CRP guided T2T strategy, targeting DAS28-CRP<3.2 and no swollen joints or an MRI guided T2T strategy based on the same clinical T2T strategy and MRI targeting absence of BME. Patients were followed every 4 months over a 2-year follow-up period. In the MRI T2T arm contrast-enhanced MRI of the dominant hand 2^nd-5^th metacarpophalangeal joints and wrist was performed ahead of the clinical visit and evaluated for presence/absence of BME. Treatment was escalated according to a predefined treatment algorithm if target was not reached, starting with increments in csDMARD mono/combination therapy and then adding biologic DMARDs. The co-primary endpoints were 1) proportion of patients achieving DAS28-CRP remission (DAS28-CRP<2.6) and 2) proportion of patients with no radiographic progression (change in total Sharp/vdHeijde score≤0) 24 months from baseline. Secondary outcomes included various clinical, functional, radiographic and MRI variables. Pearson’s chi-square statistics and repeated-measures logistic regression models were used to assess primary and secondary outcomes.

Results: Primary and secondary clinical and radiographic outcomes at 24 months are presented in the table. 76 patients in the MRI T2T arm and 95 patients in conventional T2T arm completed the study. Of them 64 patients (85%) in the MRI T2T arm and 83 patients (88%) in the conventional T2T arm reached the primary clinical endpoint (chi-square=0.324, p=0.569) and 49 patients (66%) in the MRI T2T arm and 58 (62%) in the conventional T2T arm reached the primary radiographic endpoint (chi-square=0.265, p=0.606). ACR/EULAR remission rates, swollen joint count, patient VAS global and HAQ favoured the MRI T2T arm (p<0.038).

	MRI T2T	Conventional T2T	Difference between groups (95% CI)	P value*
Primary endpoints
Radiographic:
No radiographic progression, n (%)	49 (66.2%)	58 (62.4%)	OR, 1.19 (0.04 to 39.47)	0.922
Clinical:
DAS28-CRP remission (DAS28<2.6), n (%)	64 (85.3%)	83 (88.3%)	OR, 1.03 (0.31 to 3.43)	0.958
Secondary endpoints
Clinical
ACR-EULAR Boolean remission, n (%)	37 (49.3%)	30 (31.9%)	OR, 4.19 (1.30 to 13.57)	0.017
SDAI remission (SDAI≤3.3), n (%)	48 (64.0%)	56 (62.2%)	OR, 1.67 (0.59 to 4.71)	0.336
CDAI remission (CDAI≤2.8), n (%)	53 (69.7%)	59 (64.8%)	OR, 2.75 (0.90 to 8.36)	0.075
DAS28-CRP	1.9 (0.1)	2.1 (0.1)	-0.2 (-0.3 to 0.0)	0.093
Morning stiffness, min	13.1 (3.2)	10.1 (2.9)	3.0 (-5.4 to 11.4)	0.486
Tender joint count (0-28)	0.2 (0.1)	0.5 (0.1)	-0.2 (-0.6 to 0.1)	0.171
Swollen joint count (0-28)	0.0 (0.1)	0.3 (0.1)	-0.3 (-0.5 to -0.0)	0.038
Patient VAS global (0-100)	15.5 (1.8)	21.2 (1.6)	-5.7 (-10.4 to -0.9)	0.019
Patient VAS pain (0-100)	14.2 (1.7)	18.7 (1.6)	-4.5 (-9.0 to 0.0)	0.052
Patient VAS fatigue (0-100)	21.8 (1.9)	24.4 (1.7)	-2.6 (-7.7 to 2.4)	0.311
Physician VAS global (0-100)	4.7 (0.8)	6.9 (0.8)	-2.3 (-4.4 to -0.1)	0.041
Radiographic
Change in TSS	1.0 (0.3)	1.3 (0.3)	-0.3 (-1.1 to 0.6)	0.559
Function and quality of life
Change in HAQ	-0.052 (0.024)	0.091 (0.023)	-0.143 (-0.209 to -0.078)	<0.001
Patient with normal function (HAQ≤0.5), n(%)	61 (80.3%)	75 (79.8%)	OR, 0.73 (0.08 to 7.14)	0.790
Change in SF-36 PCS	1.1 (1.0)	-0.2 (0.9)	1.3 (-1.3 to 4.0)	0.330
Change in SF-36 MCS	-0.5 (1.0)	-0.9 (0.9)	0.5 (-2.1 to 3.0)	0.727
Change in EQ-5D	0.040 (0.015)	0.019 (0.013)	0.021 (-0.017 to 0.060)	0.279
95% CI, 95% confidence interval; ACR=American College of Rheumatology; CDAI=Clinical Disease Activity Index; CRP=C-reactive protein; DAS28-CRP=Disease activity score in 28 joints based on four variables, including CRP; EQ-5D=EuroQol-5 dimensions; EULAR=European League Against Rheumatism; HAQ=Health Assessment Questionnaire; MCS= Mental Component Summary score; MRI=Magnetic Resonance Imaging; PCS=Physical Component Summary score; RAMRIS=RA magnetic resonance imaging scoring system; SDAI=Simplified Disease Activity Index; SF-36=Short Form 36 item questionnaire; T2T=treat-to-target; TSS=Total Sharp/van der Heijde score; VAS=Visual Analogue Scale. 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, with the minimum being 86 patients in the MRI T2T arm (range 86-98) and 91 (range 91-99) in the conventional T2T arm.

Conclusion: Targeting absence of MRI BME in addition to a conventional T2T strategy in RA patients in clinical remission had no effect on the probability of achieving DAS28-CRP remission or halt radiographic progression. However, more patients achieved ACR/EULAR remission and positive effect on physical function was seen when MRI was used for treatment guidance.

Clinicaltrials.gov Identifier: NCT01656278

Disclosure: S. Møller-Bisgaard, None; K. Hørslev-Petersen, None; B. J. Ejbjerg, None; M. L. Hetland, None; D. Glinatsi, 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, Hetland ML, Glinatsi D, 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. The Value of Adding MRI to a Clinical Treat-to-Target Strategy in Rheumatoid Arthritis Patients in Clinical Remission: Clinical and Radiographic Outcomes from the Imagine-RA Randomized Controlled Trial [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/the-value-of-adding-mri-to-a-clinical-treat-to-target-strategy-in-rheumatoid-arthritis-patients-in-clinical-remission-clinical-and-radiographic-outcomes-from-the-imagine-ra-randomized-controlled-tria/. Accessed .

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