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Supplementary file 1. MRI scanning protocol
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Detailed MR-scan protocol
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MR imaging was performed on an MSK-extreme 1.5T extremity MR imaging system (GE,
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Wisconsin, USA) using a 145mm coil for the foot and a 100mm coil for the hand. The patient
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was positioned in a chair beside the scanner, with the hand or foot fixed in the coil with
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cushions.
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In the hand, the following sequences were acquired before contrast injection: T1-weighted
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fast spin-echo (FSE) sequence in the coronal plane (repetition time (TR) 575 ms, echo time
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(TE) 11.2 ms, acquisition matrix 388×288, echo train length (ETL) 2). After intravenous
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injection of gadolinium contrast (gadoteric acid, Guerbet, Paris, France, standard dose of 0.1
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mmol/kg) the following sequences were obtained: T1-weighted FSE sequence with frequency
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selective fat saturation (fatsat) in the coronal plane (TR/TE 700/9.7ms, acquisition matrix
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364×224, ETL 2), T1-weighted FSE sequence with frequency selective fat saturation in the
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axial plane (wrist: TR/TE 540/7.7 ms; acquisition matrix 320x192; ETL 2 and
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metacarpophalangeal joints: TR/TE 570/7.7 ms; acquisition matrix 320x192; ETL 2).
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The obtained sequences of the forefoot were post-gadolinium sequences which included: T1-
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weighted FSE fatsat sequence in the axial plane (TR/TE 700/9.5ms; acquisition matrix
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364x224, ETL 2) and: T1-weighted FSE fatsat sequence in the coronal plane (perpendicular
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to the axis of the metatarsals) (TR/TE 540/7.5ms; acquisition matrix 320x192, ETL 2).
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Field-of-view was 100mm for the hand and 140mm for the foot. Coronal sequences of the
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hand had 18 slices with a slice thickness of 2mm and a slice gap of 0.2mm. Coronal
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sequences of the foot had 20 slices with a slice thickness of 3mm and a slice gap of 0.3mm.
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All axial sequences had a slice thickness of 3mm and a slice gap of 0.3mm with 20 slices for
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the wrist, 16 for the metacarpophalangeal joints and 14 for the foot.
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According to the RAMRIS-method, T2-weighted fat suppressed sequences, or when this
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sequence is not available a short tau inversion recovery (STIR) sequence, should be used to
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assess BME. Previously, three studies have demonstrated that a contrast enhanced T1-
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weigthed fat suppressed sequence has a strong correlation with T2-weighted fat suppressed
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sequences.1–3 A T2-weighted image shows increased water signal and a contrast-enhanced
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T1-weighted sequence shows increased water content and the increased perfusion and
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interstitial leakage. A strong correlation has been shown in arthritis patients but also in
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patients without inflammatory diseases such as bone bruises, intraosseous ganglions, bone
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infarcts and even nonspecific cases.2,3 We used the contrast enhanced T1-weighted fat
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suppressed sequence as it allowed a shorter scan time and has a higher signal to noise ratio.
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MR scoring
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All bones, joints and tendons were scored semi-quantitatively. Similar to the RAMRIS
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method synovitis score was scored based on the volume of enhancing tissue in the synovial
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compartment (none, mild, moderate, severe (range 0-3)). Erosions were scored, according to
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RAMRIS, based on the affected volume of the bone on a score from 0-10 (no erosions, 0-
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10%, 10-20%, etc.). Similar to method described by Haavardsholm et al the tenosynovitis-
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score was based on the thickness of peritendinous effusion or synovial proliferation with
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contrast enhancement (normal, <2mm, 2-5mm, >5mm (range 0-3)).4,5 BME was depicted on
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a contrast enhanced T1-weigthed fat suppressed sequence and also scored on a 0-3 scale
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based on the affected volume of the bone (no BME, >0-33%, >33-66%, >66%), The scores of
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all joints were summed and the total BME, synovitis and tenosynovitis scored were summed
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as well, yielding the total MRI-inflammation-score.
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REFERENCES
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1. Stomp W, Krabben A, Heijde D van der, et al. Aiming for a shorter rheumatoid arthritis
MRI protocol: can contrast-enhanced MRI replace T2 for the detection of bone marrow
oedema? Eur Radiol 2014;24:2614–22. doi:10.1007/s00330-014-3272-0.
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2. Schmid MR, Hodler J, Vienne P, et al. Bone Marrow Abnormalities of Foot and Ankle:
STIR versus T1-weighted Contrast-enhanced Fat-suppressed Spin-Echo MR Imaging.
Radiology 2002;224:463–9. doi:10.1148/radiol.2242011252.
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3. Mayerhoefer ME, Breitenseher MJ, Kramer J, et al. STIR vs. T1-weighted fat-suppressed
gadolinium-enhanced MRI of bone marrow edema of the knee: Computer-assisted
quantitative comparison and influence of injected contrast media volume and acquisition
parameters. J Magn Reson Imaging 2005;22:788–93. doi:10.1002/jmri.20439.
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4. Østergaard M, Edmonds J, McQueen F, et al. An introduction to the EULAR–OMERACT
rheumatoid arthritis MRI reference image atlas. Ann Rheum Dis 2005;64:i3–7.
doi:10.1136/ard.2004.031773.
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5. Haavardsholm EA, Østergaard M, Ejbjerg BJ, et al. Introduction of a novel magnetic
resonance imaging tenosynovitis score for rheumatoid arthritis: reliability in a multireader
longitudinal study. Ann Rheum Dis 2007;66:1216–20. doi:10.1136/ard.2006.068361.
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Supplementary file 2. Patient characteristics at baseline presentation, comparing patients
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with known HAQ-scores to patients with unknown HAQ-scores.
Patient characteristic
Patients with
known HAQscores
N=204
Patients with
unknown HAQscores
N=37
Age in years, mean (SD)
44.3 (12.9)
42.5 (10.8)
Female sex, n (%)
187 (77.6)
31 (83.8)
Family history of RA, n (%)
71 (29.5)
8 (21.6)
Symptom duration in weeks, median (IQR)
18.4 (9.7–48.2)
13.4 (9.7–26.3)
Presence of morning stiffness ≥60 minutes * ‡, n (%)
80 (33.2)
18 (48.6)
BMI in kg/m2, median (IQR)
26.1 (23.6–29.9)
26.0 (22.2–32.7)
68-TJC, median * (IQR)
6 (3 – 10)
7 (3 – 15)
Current smoker, n (%)
54 (22.4)
9 (24.3)
ACPA-positive (>7 U/mL), n (%)
32 (13.3)
7 (18.9)
IgM-RF-positive (>3.5 IU/mL), n (%)
51 (21.2)
8 (21.6)
Increased CRP (>10 mg/L), n (%)
53 (22.0)
8 (21.6)
Baseline VAS pain score, median (IQR)
5 (3 – 7)
6 (4.5 – 7)
MRI-inflammation score, mean (SD)
4.5 (5.7)
4.0 (5.2)
First quartile (N=44)
<0.25
n/a
Second quartile (N=62)
0.25 – 0.50
n/a
Third quartile (N=51)
0.63 –0.88
n/a
Fourth quartile (N=47)
≥1.0
n/a
Autoantibody status
Baseline HAQ-score
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Symptoms were noted by rheumatologists as reported by the patients.
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*
Missing data were as follows: Morning stiffness (27), 68-TJC (4).
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‡
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Legend:
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ACPA = anti-citrullinated peptide antibody; BMI = body mass index; CRP = C-reactive
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protein; ESR = erythrocyte sedimentation rate; HAQ = Health Assessment Questionnaire;
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IgM-RF = immunoglobulin M rheumatoid factor; IQR = interquartile range; RA =
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rheumatoid arthritis; SD = standard deviation; TJC = tender joint count.
The presence of symptoms refers to the presence of symptoms at the baseline visit.
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Supplementary file 3. Frequency table and cumulative percentages of HAQ-scores in the
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studied population.
HAQ-score
Number of patients
Cumulative percentages
0.00
31
15.1
0.13
13
21.5
0.25
25
33.7
0.38
18
42.4
0.50
19
52.2
0.63
14
59.0
0.75
12
64.9
0.88
25
77.1
1.0
13
83.4
1.1
8
87.3
1.2
10
92.2
1.4
4
94.1
1.5
5
96.6
1.6
4
98.5
1.9
2
99.5
2.0
1
100.0
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Legend:
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Table showing the distribution of HAQ-scores in the studied population. As the HAQ-score is
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a semi-quantitative score, the groups could not fit exactly equal number. This table indicates
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the cut-offs points for creating four groups with equal numbers to be on HAQ-scores of 0.25,
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0.63 and 1.0. The lowest quartile contains patients with HAQ-scores <0.25 with N=44. The
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second quartile contains HAQ-scores 0.25–0.50 (N=62). Patients in the third quartile had
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HAQ-scores 0.63–0.88 (N=51). Finally, the quartile with the highest HAQ-scores contains
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HAQ-scores ≥ 1.0. (N=47).
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Supplementary file 4. Kaplan-Meier One Minus Survival plot showing cumulative
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progression to rheumatoid arthritis (according to the 2010 classification criteria) for CSA-
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patients, that were divided in four groups based on their baseline HAQ-score.
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Legend:
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Patients were appointed into quartiles according to their total HAQ-score to create four
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subgroups with equal numbers, see supplementary file 3. Each line represents one HAQ-score
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quartile and cumulative progression to rheumatoid arthritis according to the 2010
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classification criteria. The lowest quartile contains patients with HAQ-scores <0.25 (with
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N=44) was the reference group Hazard ratios for developing RA for the quartile containing
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HAQ-scores 0.20–0.50 (N=62) was 0.67 (95%CI 0.17–2.7). For the quartile (N=51)
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containing HAQ-scores between 0.63–0.88 HR 2.0 (95%CI=0.60–6.4). For the quartile that
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contained HAQ-scores ≥1.0 (N=47) it was 2.7 (95%CI 0.85–8.5), compared to the lowest
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quartile.
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Supplementary file 5. Line plot showing changes in HAQ-score for individual CSA-patients
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that converted to clinical arthritis
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Legend:
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Line plot showing intra-individual change in HAQ-scores over time for 25 patients. Each line
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represents an individual patient and shows time-interval and change in HAQ from CSA-
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baseline (left dot) to progression to clinical arthritis(right dot).
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