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Abstract Number: 1045

Dynamic Contrast-Enhanced Magnetic Resonance Imaging of the Wrist in Rheumatoid Arthritis Patients Treated with Methotrexate, Intra-Articular Glucocorticoid and Adalimumab/Placebo

Mette Bjørndal Axelsen1, Merete L. Hetland2, Kim Hørslev-Petersen3, Kristian Stengaard-Pedersen4, Peter Junker5, Jan Pødenphant6, Jakob M. Møller7, Henning Bliddal8, Olga Kubassova9, Mikael Boesen10 and Mikkel Østergaard11, 1Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Copenhagen, Denmark, 2Copenhagen University Hospital Glostrup, Copenhagen, Denmark, 3Institute of Regional Health Services Research, University of Southern Denmark, Graasten, Denmark, 4Arhus University Hospital, Aarhus, Denmark, 5Odense University Hospital, Odense, Denmark, 6Copenhagen University at Gentofte, Hellerup, Denmark, 7Department of Radiology, Copenhagen University Hospital in Herlev, Copenhagen, Denmark, 8Department of Rheumatology, The Parker Institute, Copenhagen University Hospital at Frederiksberg, Copenhagen, Denmark, 9Image Analysis Ltd., Leeds, United Kingdom, 10The Parker Institute, Department of Rheumatology, Copenhagen University Hospital at Frederiksberg, Copenhagen, Denmark, 11Dept of Rheumatology RM, Copenhagen University Hospital at Glostrup, Copenhagen, Denmark

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Magnetic resonance imaging (MRI), outcome measures and rheumatoid arthritis (RA)

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Session Information

Session Title: Imaging of Rheumatic Diseases: Magnetic Resonance Imaging, Computed Tomography and X-ray

Session Type: Abstract Submissions (ACR)

Background/Purpose: To validate parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in an early rheumatoid arthritis (RA) clinical trial by comparison with clinical parameters of disease activity, and by investigating the sensitivity to change during a 2-year-follow-up.

Methods: 14 early RA patients diagnosed according to the ACR1987 criteria within 6 months of inclusion and with a DAS28 ≥3.2 (9/5 women/men, median aged 37 [range 27–69] years, disease duration 82 [42–129] days) were randomized 1:1 to treatment with methotrexate (MTX) and adalimumab or MTX and placebo. Any swollen joints were injected with triamcinolone (max 4 joints/4 ml per visit) in a 2-year-follow-up. If continuous disease activity was present, treatment was intensified. Conventional MRI and DCE-MRI of the right wrist were performed at baseline, and after 6, 12 and 24 months using a 0.6 Tesla MRI-unit. A 3-slice dynamic sequence was obtained at the time of injection of the contrast agent (Gadoteric acid 0.2 mL/kg). DCE-MRI parameters: TR 33ms, TE 4.2ms, flip angle 25°, FOV 200 mm2, matrix 108×192, slice thickness 3 mm.

On DCE-MR images, the wrist were manually delineated using the image software Dynamika version 4.6.0 (Image analysis Ltd., Leeds, UK, www.imageanalysis.org) and for these regions of interest (ROI) the number of enhancing voxels (Nvoxel), the initial rate of enhancement (IRE), the maximum enhancement (ME), the IRE×Nvoxel and ME×Nvoxel were extracted by the software and compared to clinical parameters of disease activity.

Results:
Table 1. Clinical and MRI data at baseline and at follow-up visits.

 

Baseline

6 months

12 months

24 months

DAS28(CRP)

4.75 (3.5–6.1)

2.2 (1.8–2.8)***

2.0 (1.7–3.9)***

2.1 (1.7–3.3)***

CRP (mg/mL)

14 (7–116)

7 (7–11)**

7 (7–47)*

7 (7–31)*

Patient´s VAS pain

48 (12–82)

11 (2–37)***

22 (1-72)*

15 (0–72)***

Patient´s VAS global

54 (19–98)

22 (3–45)***

24 (0–75)*

21 (0­–67)***

Patient´s VAS fatique

46 (9–90)

18 (2–83)NS

30 (0–85)NS

24.5 (0–68)*

Health Assessment Questionnaire

1.0 (0.0–1.875)

0.130 (0­–1)***

0.125 (0.0–1.00)**

0.13 (0.0–1.0)**

VAS doctor

51 (15–76)

5 (0–16)***

2 (0–26)***

3 (0–33)***

Swollen Joint Count 28

3 (1–7)

0 (0–1)***

0 (0–1)

0 (0–0)

Tender Joint Count 28

5 (2–17)

0 (0–2)***

0 (0–2)

0 (0–3)

Number of Enhancing voxels (Nvoxel)

548 (0–3786)

73 (0–1763) NS

181 (0–1694)NS

74 (0–617)NS

Maximum Enhancement (ME)

1.21 (0–1.39)

1.17 (0.00–1.32)NS

1.19 (0–1.39)NS

1.23 (0–1.51)NS

Initial Rate of Enhancement (IRE) (%/s)

0.45 (0.0–1.20)

0.35 (0–0.9)NS

0.40 (0.0–1.0)NS

0.6 (0.0–1.7)NS

ME×Nvoxel

666 (0–5251)

85 (0–2329)NS

215 (0–2350)NS

90 (0–929)NS

IRE×Nvoxel (%/s)

246 (0–4543)

26(0–1587)NS

63 (0–1694)NS

44 (0–1049)NS

Values are presented as medians (minimum–maximum). VAS: visual analog scale. Change from baseline: Wilcoxon Signed Ranks Test, *: p<0.05, **: p<0.01, ***: p<0.005, NS: not significant.

All clinical parameters decreased during follow-up, while there were no statistically significant changes for the DCE-MRI parameters, which may reflect lack of power. Furthermore, it should be emphasized that only 3 of the examined wrist joints were clinically affected at baseline.

Conclusion: DCE-MRI is a promising outcome measure in clinical trials, but MRI at baseline must include clinically involved joints.


Disclosure:

M. B. Axelsen,

Abbott Laboratories,

2;

M. L. Hetland,

Roche,

5,

Pfizer Inc,

5,

MSD,

5,

Bristol-Myers Squibb,

5,

UCB Nordic,

5,

Abbott Laboratories,

5;

K. Hørslev-Petersen,

Abbott Immunology Pharmaceuticals,

2;

K. Stengaard-Pedersen,

Pfizer Inc,

5,

Roche Pharmaceuticals,

5,

Abbott Immunology Pharmaceuticals,

5,

Grünenthal,

5,

Danish Association against Rheumatism,

5;

P. Junker,
None;

J. Pødenphant,
None;

J. M. Møller,
None;

H. Bliddal,
None;

O. Kubassova,

Image Analysis Ltd.,

4;

M. Boesen,

Image Analysis,

5;

M. Østergaard,

Abbott Laboratories,

2,

Centocor, Inc.,

5,

Merck Pharmaceuticals,

5,

Mundipharma,

8,

Novo,

8,

Pfizer Inc,

5,

Roche Pharmaceuticals,

5,

UCB Nordic,

5.

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