Pernille Bøyesen

Publications (20)115.88 Total impact

• Article: Ultrasonographic assessment of osteophytes in 127 patients with hand osteoarthritis: exploring reliability and associations with MRI, radiographs and clinical joint findings.

  Alexander Mathiessen, Ida Kristin Haugen, Barbara Slatkowsky-Christensen, Pernille Bøyesen, Tore K Kvien, Hilde Berner Hammer
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  ABSTRACT: OBJECTIVE: To investigate the reliability of ultrasonographic assessment of osteophytes and explore the concordance of osteophytes detected by ultrasound, MRI, conventional radiography (CR) and clinical joint examination in patients with hand osteoarthritis (HOA).METHODS: The study included 127 HOA patients (116 women, mean age 68.6 years (SD 5.8)) with ultrasound, CR and clinical examination of both hands and MRI of dominant hand. Osteophytes were assessed by all imaging modalities on 0-3 scales, whereas clinical bony enlargement was assessed as absent/present. An ultrasound atlas of ostephytes was developed, and the intra and inter-reader reliability of scoring ultrasound osteophytes on still images using the atlas as reference was examined. The reliability for ultrasound readings was examined with κ and percentage exact agreement (PEA) and percentage close agreement (PCA), and the sensitivity, specificity and PEA/PCA of ultrasound was calculated in comparison with MRI, CR and clinical examination.RESULTS: Ultrasound had high sensitivity (0.83) and specificity (0.75) in detecting osteophytes compared with MRI, with excellent PCA (96.1%). Moderate/large osteophytes (grade 2-3) were demonstrated more often by ultrasound (n=401) than by MRI (n=288) in 851 interphalangeal joints. Ultrasound detected more osteophytes (53.2%) than CR (30.0%) and clinical examination (36.9%). Intra and inter-reader reliability of ultrasound was excellent (PEA >88%, PCA 100% and weighted kappa >0.91).CONCLUSION: Ultrasound can reliably assess osteophytes in patients with HOA. Good agreement was found between osteophytes detected by ultrasound and MRI, while ultrasound was more sensitive than CR and clinical examination, which could be due to a multiplanar joint demonstration by ultrasound.
  Annals of the rheumatic diseases 04/2012; · 8.11 Impact Factor
• Article: Comparison of features by MRI and radiographs of the interphalangeal finger joints in patients with hand osteoarthritis.

  Ida K Haugen, Pernille Bøyesen, Barbara Slatkowsky-Christensen, Sølve Sesseng, Jessica Bijsterbosch, Désirée van der Heijde, Tore K Kvien
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  ABSTRACT: To examine the construct validity of MRI in the detection of structural hand osteoarthritis features with conventional radiography (CR) as reference and explore the association between radiographic severity and MRI-defined pathology. 106 hand osteoarthritis patients (97 women, mean age 68.9 years (SD 5.6)) had 1.0T contrast-enhanced MRI and CR of the dominant hand. The 2nd-5th interphalangeal joints were scored according to the preliminary Oslo hand osteoarthritis MRI score and Kellgren-Lawrence (KL) scale and Osteoarthritis Research Society International atlas for radiographs. The authors compared the number of joints with structural features by MRI and CR (Wilcoxon signed-rank test) and examined concordance at the individual joint level. The OR of MRI features in joints with doubtful (KL grade 1), mild (2) and moderate/severe (≥3) radiographic osteoarthritis was estimated by generalised estimating equations (KL grade 0 as reference). MRI detected approximately twice as many joints with erosions and osteophytes compared with CR (p<0.001), but identification of joint space narrowing, cysts and malalignment was similar. The sensitivity of MRI was very high for osteophytes (1.00) and erosions (0.95), while specificity was lower (0.22 and 0.63). The prevalence of most MRI features increased with radiographic severity, but synovitis was more frequent in joints with mild osteoarthritis (OR2.1, 95% CI 1.4 to 3.2) than in moderate/severe osteoarthritis (OR1.4, 95% CI 1.0 to 2.2). MRI detected more osteophytes and erosions than CR, suggesting that erosive osteoarthritis may be more common than indicated by CR. Synovitis was most common in mild osteoarthritis. Whether this is due to burn-out of inflammation in late disease must be investigated further.
  Annals of the rheumatic diseases 03/2012; 71(3):345-50. · 8.11 Impact Factor
• Source

  Available from: Ida Kristin Haugen

  Article: Imaging modalities in hand osteoarthritis--and perspectives of conventional radiography, magnetic resonance imaging, and ultrasonography.

  Ida K Haugen, Pernille Bøyesen
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  ABSTRACT: Hand osteoarthritis (OA) is very frequent in middle-aged and older women and men in the general population. Currently, owing to high feasibility and low costs, conventional radiography (CR) is the method of choice for evaluation of hand OA. CR provides a two-dimensional picture of bony changes, such as osteophytes, erosions, cysts, and sclerosis, and joint space narrowing as an indirect measure of cartilage loss. There are several standardized scoring methods for evaluation of radiographic hand OA. The scales have shown similar reliability, validity, and sensitivity to change, and no conclusion about the preferred instrument has been drawn. Patients with hand OA may experience pain, stiffness, and physical disability, but the associations between radiographic findings and clinical symptoms are weak to moderate and vary across studies. OA is, indeed, recognized to involve the whole joint, and modern imaging techniques such as ultrasound (US) and magnetic resonance imaging (MRI) could be valuable tools for better evaluation of hand OA. Standardized scoring methods have been proposed for both modalities. Several studies have examined the validity of US features in hand OA, whereas knowledge of the validity of MRI is more limited. However, both synovitis (detected by either US or MRI) and MRI-defined bone marrow lesions have been associated with pain, indicating that treatment of inflammation is important for pain management in hand OA. Both US and MRI have shown better sensitivity than CR in detection of erosions, and this may indicate that erosive hand OA may be more common than previously thought.
  Arthritis research & therapy 12/2011; 13(6):248. · 4.27 Impact Factor
• Article: Associations between MRI-defined synovitis, bone marrow lesions and structural features and measures of pain and physical function in hand osteoarthritis.

  Ida Kristin Haugen, Pernille Bøyesen, Barbara Slatkowsky-Christensen, Sølve Sesseng, Désirée van der Heijde, Tore K Kvien
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  ABSTRACT: To explore associations between MRI features and measures of pain and physical function in hand osteoarthritis (OA). Eighty-five patients (77 women) with mean (SD) age of 68.8 (5.6) years underwent contrast-enhanced MRI of the interphalangeal joints (dominant hand) and clinical joint assessment. One investigator read the MRIs for presence/severity of osteophytes, joint space narrowing, erosions, bone attrition, cysts, malalignment, synovitis, flexor tenosynovitis, bone marrow lesions (BMLs) and ligament discontinuity according to the proposed Oslo hand OA MRI score. Pain and physical function were assessed by joint palpation (tenderness yes/no), self-reported questionnaires (Australian/Canadian (AUSCAN) hand index, Functional Index of hand osteoarthritis (FIHOA), Arthritis Impact Measurement Scale-2 (AIMS-2) hand/finger) and grip strength. Logistic regression with generalised estimating equations was used to explore associations between the presence of MRI features and joint tenderness, and linear regression for associations between the burden of MRI abnormalities and patient-reported outcomes and grip strength (adjusted for age and sex). MRI features with p<0.25 were introduced into a multivariate model. The final model included features with p≤0.10 (backward selection). MRI-defined moderate/severe synovitis (OR=2.4; p<0.001), BMLs (OR=1.5; p=0.06), erosions (OR=1.4; p=0.05), attrition (OR=2.5; p<0.001) and osteophytes (OR=1.4; p=0.10) were associated with joint tenderness independently of each other (final model adjusted for age and sex). The sum score of MRI-defined attrition was associated with FIHOA (B=0.58; p=0.005), while the sum score of osteophytes was associated with grip strength (B=-0.39; p<0.001). No significant associations were found with AUSCAN pain/physical function or AIMS-2 hand/finger subscales. MRI-defined synovitis, BMLs, erosions and attrition were associated with joint tenderness. Synovitis and BMLs may be targets for therapeutic interventions in hand OA.
  Annals of the rheumatic diseases 11/2011; 71(6):899-904. · 8.11 Impact Factor
• Article: The OMERACT Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) is reliable and sensitive to change: results from an OMERACT workshop.

  Pernille Bøyesen, Fiona M McQueen, Frédérique Gandjbakhch, Siri Lillegraven, Laura Coates, Charlotte Wiell, Espen A Haavardsholm, Philip G Conaghan, Charles G Peterfy, Paul Bird, Mikkel Ostergaard
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  ABSTRACT: The aim of this multireader exercise was to assess the reliability and sensitivity to change of the psoriatic arthritis magnetic resonance imaging score (PsAMRIS) in PsA patients followed for 1 year. MRI was acquired from 12 patients with PsA before initiation of treatment and after 12 months. MR images were scored according to PsAMRIS (for synovitis, tenosynovitis, periarticular inflammation, bone marrow edema, bone erosion, and bone proliferation) under standardized conditions, in unknown chronological order. Intraobserver/interobserver reliability was examined by intraclass correlation coefficients (ICC) and sensitivity to change by standardized response means (SRM). The interobserver reliability of PsAMRIS was high for synovitis, tenosynovitis, periarticular inflammation, and bone edema status and change scores (interobserver ICC 0.87-0.97). The intraobserver reliability was moderate to high (ICC 0.60-0.98) for status and change scores, except for change in periarticular inflammation (ICC 0.33). PsAMRIS sensitivity to change was moderate for synovitis, tenosynovitis, and periarticular inflammation (SRM 0.5-0.8), while poor (SRM 0.1-0.3) for bone marrow edema, erosion, and bone proliferation. Rare occurrence and minimal change contributed to poor SRM and change-score ICC for bone parameters. This multireader exercise, performed under standardized conditions, confirmed PsAMRIS to have high interobserver and intraobserver reliability for hand PsA. Measures of inflammation were sensitive to change, implying that PsAMRIS may be a valuable tool for monitoring change in inflammation during PsA clinical trials.
  The Journal of Rheumatology 09/2011; 38(9):2034-8. · 3.69 Impact Factor
• Article: Development and preliminary validation of a magnetic resonance imaging joint space narrowing score for use in rheumatoid arthritis: potential adjunct to the OMERACT RA MRI scoring system.

  Mikkel Ostergaard, Pernille Bøyesen, Iris Eshed, Frédérique Gandjbakhch, Siri Lillegraven, Paul Bird, Violaine Foltz, Annelies Boonen, Marissa Lassere, Kay-Geert Hermann, Allen Anandarajah, Uffe Møller Døhn, Jane Freeston, Charles G Peterfy, Harry K Genant, Espen A Haavardsholm, Fiona M McQueen, Philip G Conaghan
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  ABSTRACT: To develop and validate a magnetic resonance imaging (MRI) method of assessment of joint space narrowing (JSN) in rheumatoid arthritis (RA). Phase A: JSN was scored 0-4 on MR images of 5 RA patients and 3 controls at 15 wrist sites and 2nd-5th metacarpophalangeal (MCP) joints by 8 readers (7 once, one twice), using a preliminary scoring system. Phase B: Image review, discussion, and consensus on JSN definition, and revised scoring system. Phase C: MR images of 15 RA patients and 4 controls were scored using revised system by 5 readers (4 once, one twice), and results compared with radiographs [Sharp-van der Heijde (SvdH) method]. Phase A: Intraobserver agreement: intraclass correlation coefficient (ICC) = 0.99; smallest detectable difference (SDD, for mean of readings) = 2.8 JSN units (4.9% of observed maximal score). Interobserver agreement: ICC = 0.93; SDD = 6.4 JSN units (9.9%). Phase B: Agreement was reached on JSN definition (reduced joint space width compared to normal, as assessed in a slice perpendicular to the joint surface), and revised scoring system (0-4 at 17 wrist sites and 2nd-5th MCP; 0: none; 1: 1-33%; 2: 34-66%; 3: 67-99%; 4: ankylosis). Phase C: Intraobserver agreement: ICC = 0.90; SDD = 6.8 JSN units (11.0%). Interobserver agreement: ICC = 0.92 and SDD = 6.2 JSN units (8.7%). The correlation (ICC) with the SvdH radiographic JSN score of the wrist/hand was 0.77. Simplified approaches evaluating fewer joint spaces demonstrated similar reliability and correlation with radiographic scores. An MRI scoring system of JSN in RA wrist and MCP joints was developed and showed construct validity and good intra- and interreader agreements. The system may, after further validation in longitudinal data sets, be useful as an outcome measure in RA.
  The Journal of Rheumatology 09/2011; 38(9):2045-50. · 3.69 Impact Factor
• Article: Update on research and future directions of the OMERACT MRI inflammatory arthritis group.

  Philip G Conaghan, Fiona M McQueen, Paul Bird, Charles G Peterfy, Espen A Haavardsholm, Frédérique Gandjbakhch, Pernille Bøyesen, Laura Coates, Bo Ejbjerg, Iris Eshed, [......], Jane Freeston, Siri Lillegraven, Marissa Lassere, Charlotte Wiell, Allen Anandarajah, Anne Duer-Jensen, Philip O'Connor, Harry K Genant, Paul Emery, Mikkel Ostergaard
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  ABSTRACT: The OMERACT Magnetic Resonance Imaging (MRI) Task Force has developed and evolved the psoriatic arthritis MRI score (PsAMRIS) over the last few years, and at OMERACT 10, presented longitudinal evaluation by multiple readers, using PsA datasets obtained from extremity MRI magnets. Further evaluation of this score will require more PsA imaging datasets. As well, due to improved image resolution since the development of the original rheumatoid arthritis MRI scoring system (RAMRIS), the Task Force has worked on semiquantitative assessment of joint space narrowing, and developed a reliable method as a potential RAMRIS addendum, although responsiveness will need to be evaluated. One of the strengths of MRI is the ability to detect subclinical synovitis, so the group worked on obtaining low disease activity/clinical remission datasets from a number of international centers and presented cross-sectional findings. Subsequent longitudinal evaluation of this unique resource will be a major continuing focus for the group.
  The Journal of Rheumatology 09/2011; 38(9):2031-3. · 3.69 Impact Factor
• Article: Synovitis and osteitis are very frequent in rheumatoid arthritis clinical remission: results from an MRI study of 294 patients in clinical remission or low disease activity state.

  Frédérique Gandjbakhch, Philip G Conaghan, Bo Ejbjerg, Espen A Haavardsholm, Violaine Foltz, Andrew K Brown, Uffe Møller Døhn, Marissa Lassere, Jane Freeston, Pernille Bøyesen, Paul Bird, Bruno Fautrel, Merete Lund Hetland, Paul Emery, Pierre Bourgeois, Kim Hørslev-Petersen, Tore K Kvien, Fiona McQueen, Mikkel Ostergaard
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  ABSTRACT: In rheumatoid arthritis (RA), radiographic progression may occur despite clinical remission. This may be explained by subclinical inflammation. Magnetic resonance imaging (MRI) provides a greater sensitivity than clinical examination and radiography for assessing disease activity. Our objective was to determine the MRI characteristics of RA patients in clinical remission or low disease activity (LDA) state. Databases from 6 cohorts were collected from 5 international centers. RA patients in clinical remission according to Disease Activity Score28-C-reactive protein (DAS28-CRP < 2.6; n = 213) or LDA-state (2.6 ≤ DAS28-CRP < 3.2; n = 81) with available MRI data were included. MRI were assessed according to the OMERACT RA MRI scoring system (RAMRIS). Patient characteristics: 70% women, median age 55 (interquartile range, IQR 43-63) years, disease duration 2.3 (IQR 0.7-5.1) years, DAS28-CRP 2.2 (IQR 1.8-2.6), Simplified Disease Activity Index, SDAI, 3.9 (IQR 1.9-6.5), Clinical Disease Activity Index, CDAI, 3.1 (IQR 1.5- 5.8), rheumatoid factor/anti-cyclic citrullinated peptide positivity 57%/54%, presence of radiographic erosions: 66%. Wrist and metacarpophalangeal MRI (MCP-MRI) data were available for 287 and 241 patients, respectively. MRI inflammatory activity in wrist and/or MCP joints was observed in the majority [synovitis: 95%, bone edema (osteitis): 35%] of patients. The median (IQR) RAMRIS score was 6 (3-9) for synovitis and 0 (0-2) for osteitis. Synovitis and osteitis were not less frequent in DAS28 clinical remission (synovitis/osteitis 96%/35%) than LDA (91/36). A trend towards lower frequencies of osteitis in patients in SDAI and CDAI remission was observed. Subclinical inflammation was identified by MRI in the majority of RA patients in clinical remission or LDA state. This may explain structural progression in such patients. Further work is required to understand the place of modern imaging in future remission criteria.
  The Journal of Rheumatology 09/2011; 38(9):2039-44. · 3.69 Impact Factor
• Article: Tenosynovitis of the extensor carpi ulnaris tendon predicts erosive progression in early rheumatoid arthritis.

  Siri Lillegraven, Pernille Bøyesen, Hilde Berner Hammer, Mikkel Østergaard, Till Uhlig, Sølve Sesseng, Tore K Kvien, Espen A Haavardsholm
  Annals of the rheumatic diseases 04/2011; 70(11):2049-50. · 8.11 Impact Factor
• Article: MRI in early rheumatoid arthritis: synovitis and bone marrow oedema are independent predictors of subsequent radiographic progression.

  Pernille Bøyesen, Espen A Haavardsholm, Mikkel Ostergaard, Désirée van der Heijde, Sølve Sesseng, Tore K Kvien
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  ABSTRACT: To determine whether MRI and conventional (clinical and laboratory) measures of inflammation can predict 3-year radiographic changes measured by the van der Heijde Sharp score in patients with early rheumatoid arthritis (RA). 55 patients with RA with disease duration <1 year participated in this 3-year follow-up study. Patients were evaluated at baseline, 3, 6, 12 and 36 months by swollen and tender joint count, disease activity score based on 28-joint count, erythrocyte sedimentation rate (ESR), C reactive protein, MRI measures of synovitis, bone marrow oedema and tenosynovitis of the dominant wrist, as well as conventional x-rays of the hands and wrists. All measures of inflammation decreased during the follow-up period. ESR, MRI synovitis and MRI bone marrow oedema were independent predictors of 3-year radiographic progression adjusted for age, sex and anti-citrullinated protein antibodies. The 1-year cumulative measures of MRI synovitis and bone marrow oedema provided an improved explanation of variation (adjusted R(2)) in radiographic change compared with the baseline MRI values (adjusted R(2)=0.32 and 0.20 vs 0.11 and 0.04, respectively). Both baseline and 1-year cumulative measures of MRI synovitis and bone marrow oedema independently predicted 3-year radiographic progression. These results confirm that MRI synovitis and MRI bone marrow oedema precede radiographic progression in patients with early RA.
  Annals of the rheumatic diseases 03/2011; 70(3):428-33. · 8.11 Impact Factor
• Article: Hand osteoarthritis and MRI: development and first validation step of the proposed Oslo Hand Osteoarthritis MRI score.

  Ida K Haugen, Siri Lillegraven, Barbara Slatkowsky-Christensen, Espen A Haavardsholm, Sølve Sesseng, Tore K Kvien, Désirée van der Heijde, Pernille Bøyesen
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  ABSTRACT: MRI scoring systems for hand osteoarthritis (HOA) are currently not available. The present work proposes the Oslo HOA MRI (OHOA-MRI) score and examines the intrareader and inter-reader reliability. Relevant HOA features were included in the initial version of the OHOA-MRI score after literature review and informal group discussions. After a training session and two calibration exercises (with three readers), features with low reliability and/or low prevalence were excluded, and feature definitions/gradings were improved. In the reliability exercise 3 readers independently evaluated MRI scans of distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints in 10 patients with HOA according to the final proposed score. The reading was repeated after 1 week. Intraclass correlation coefficients (ICCs), percentage exact agreement/percentage close agreement (PEA/PCA) and smallest detectable difference were calculated. The final proposed OHOA-MRI score includes assessment of synovitis, flexor tenosynovitis, erosions, osteophytes (OPs), joint space narrowing (JSN) and bone marrow lesions (BMLs) on a 0-3 scale, and absence/presence of cysts, malalignment (frontal/sagittal plane), collateral ligaments (CLs) and BMLs at CL insertion sites. Inter-reader reliability was very good for synovitis, erosions, OPs, JSN, malalignment (frontal) and BMLs (ICCs ≥ 0.83, PCA ≥ 89%), and good for flexor tenosynovitis (ICC 0.64, PCA 80%) and CL presence (ICC 0.79, PEA 63%). Cysts, malalignment (sagittal) and BMLs at CL insertion sites showed high PEA (≥ 85%), but poor to moderate ICCs (0.00-0.59). Intrareader reliability was similar. The reliability was generally highest in PIP joints. The proposed OHOA-MRI score could reliably assess HOA features. However, further validation is needed.
  Annals of the rheumatic diseases 03/2011; 70(6):1033-8. · 8.11 Impact Factor
• Article: Prediction of MRI erosive progression: a comparison of modern imaging modalities in early rheumatoid arthritis patients.

  Pernille Bøyesen, Espen A Haavardsholm, Désirée van der Heijde, Mikkel Østergaard, Hilde Berner Hammer, Sølve Sesseng, Tore K Kvien
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  ABSTRACT: To examine the associations between modern imaging modalities and joint damage measured as 1-year MRI erosive progression, in early rheumatoid arthritis (RA) patients. 84 RA patients with disease duration of less than 1 year were included in this inception cohort. Patients were evaluated at baseline, 3, 6 and 12 months by core measures of disease activity, MRI and ultrasound grey-scale (USGS) of inflammation, conventional radiography and digital x-ray radiogrammetry (DXR) bone mineral density (BMD) of cortical hand bone. 53 of the 79 patients (67%) who completed the follow-up had MRI erosive progression (dependent variable). USGS and MRI bone marrow oedema (BME) were in multivariate analyses independent predictors of 1-year MRI erosive progression. There was a trend towards higher MRI synovitis score and 3-month DXR BMD loss in patients developing MRI erosions. On an individual level, USGS inflammation, MRI synovitis and MRI BME also somewhat better predicted outcome than rheumatoid factor, anticitrullinated protein antibodies and disease activity score 28. USGS inflammation and MRI BME were independent predictors of MRI erosive progression in early RA patients on a group level. The exact prognosis of the individual patients could not be determined by imaging alone.
  Annals of the rheumatic diseases 11/2010; 70(1):176-9. · 8.11 Impact Factor
• Article: High disease activity is a predictor of cortical hand bone loss in post-menopausal patients with established rheumatoid arthritis: a 5-year multicentre longitudinal study.

  Mari Hoff, Pernille Bøyesen, Glenn Haugeberg, Marijn Vis, Anthony D Woolf, Espen A Havaardsholm, Ben A C Dijkmans, Tore K Kvien, Till Uhlig, Willem F Lems
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  ABSTRACT: The objective of this study was to examine 5-year change in cortical hand BMD in female RA patients with established disease. Further, possibly baseline predictors of 5-year loss in digital X-ray radiogrammetry (DXR)-BMD were studied. This 5-year multicentre, longitudinal study included patients from Amsterdam (the Netherlands), Truro (UK) and Oslo (Norway). At baseline, 50 patients were consecutively included per centre. Inclusion criteria were: female sex, age 50-70 years and disease duration >or=5 years. This study presents 5-year follow-up data for 85 of these 150 patients (29 patients from Amsterdam; 26 from Truro; and 30 from Oslo). Clinical examination, blood test and radiographs were taken at baseline and 5-year follow-up. Cortical hand BMD was measured by DXR from hand radiographs. The mean (95% CI) baseline DXR-BMD for all patients was 0.46 (0.44, 0.48) g/cm(2) and the median 5-year DXR-BMD change was -6.7% (-11.2, -2.82%). Five-year DXR-BMD loss was associated with baseline measurements of age, RF, CRP, HAQ and 28-joint disease activity score (DAS-28) in univariate linear regression analyses. DAS-28 at baseline was an independent predictor of 5-year DXR-BMD loss in multivariate linear regression analyses corrected for centre, age and use of bone-protective agents. High disease activity measured by DAS-28 was an independent predictor of cortical hand bone loss over 5 years in established, destructive RA. This finding supports that increased disease activity leads to localized bone loss in long-standing RA and underlines the importance of tight control and aggressive anti-inflammatory treatment in these patients.
  Rheumatology (Oxford, England) 05/2010; 49(9):1676-82. · 4.24 Impact Factor
• Article: Biomarkers in early rheumatoid arthritis: longitudinal associations with inflammation and joint destruction measured by magnetic resonance imaging and conventional radiographs.

  Silje W Syversen, Espen A Haavardsholm, Pernille Bøyesen, Guro L Goll, Cecilie Okkenhaug, Per Ivar Gaarder, Désirée van der Heijde, Tore K Kvien
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  ABSTRACT: To examine associations between a panel of soluble biomarkers and progressive joint destruction assessed by magnetic resonance imaging (MRI) and conventional radiographs as well as longitudinal associations with disease activity assessed clinically and by MRI in early rheumatoid arthritis (RA) patients. 84 early RA patients were evaluated at baseline, 3, 6 and 12 months with clinical examination, serum and urine sampling, MRI scans of the dominant wrist and conventional radiographs of the hands. A panel of biomarkers (sCTX-I, uCTX-II, sOPG, sYKL-40, sCOMP and sMMP-3) was assessed by ELISA. MRI images and conventional radiographs were scored according to the RA MRI score (RAMRIS) and the van der Heijde modified Sharp score (SHS), respectively. Longitudinal associations between biomarkers and MRI inflammation and disease activity score (DAS28) and association with the progression of damage were examined with adjustments for known predictors. The baseline sCTX-I level predicted progression in joint destruction assessed by MRI and conventional radiographs, whereas the uCTX-II level was a predictor of progression in SHS but not RAMRIS. Consistent associations, both with MRI inflammation (synovitis and bone marrow oedema) and DAS28 were found for sYKL-40 and sMMP-3 in addition to C-reactive protein at baseline and in longitudinal analyses. Associations remained significant in multivariate analyses. Levels of sCTX-I and uCTX-II were significant predictors of progressive joint destruction, whereas sMMP-3 and sYKL-40 were merely markers of joint inflammation. The clinical value of these markers for use in individual patients is limited due to a considerable overlap in levels of patients with progression and no progression.
  Annals of the rheumatic diseases 03/2010; 69(5):845-50. · 8.11 Impact Factor
• Article: Bone erosions at the distal ulna detected by ultrasonography are associated with structural damage assessed by conventional radiography and MRI: a study of patients with recent onset rheumatoid arthritis.

  Hilde B Hammer, Espen A Haavardsholm, Pernille Bøyesen, Tore K Kvien
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  ABSTRACT: Ultrasonography (US) is a sensitive tool for detecting erosions in patients with RA. The wrist is usually involved in the RA process, where the distal ulna with its superficial localization is easily accessible for US examination. In this longitudinal study, we wanted to examine the presence, localization and development of erosions at the distal ulna by US in patients with recent onset RA, and to analyse whether erosions at this localization are associated with joint damage in hands assessed by conventional radiography (CR) and MRI. Seventy patients with recent onset RA (median disease duration 106 days) were examined by US of the distal ulna, in addition to hand radiography [assessed by van der Heijde-modified Sharp score (vdHSS)] and MRI of the wrist [assessed by RA MRI scoring (RAMRIS) erosion score]. Twelve months later 58 patients were re-assessed. US detected erosions at the distal ulna in 11% of the patients at baseline and 24% at follow-up (the majority of erosions were at the ulnar side). Logistic regression analyses showed the presence of erosions at baseline to be associated with baseline RAMRIS erosion score (P < 0.001), and at follow-up to RAMRIS erosion score (P = 0.02) and vdHSS (P = 0.008). A significant number of patients had US erosions at the distal ulna at baseline, with increased prevalence after 1 year. The US-detected erosions were associated with structural joint damage in hands assessed by both MRI and CR. US of the distal ulna could thus give useful clinical information.
  Rheumatology (Oxford, England) 09/2009; 48(12):1530-2. · 4.24 Impact Factor
• Article: Testing an OMERACT MRI scoring system for peripheral psoriatic arthritis in cross-sectional and longitudinal settings.

  Fiona McQueen, Marissa Lassere, Anne Duer-Jensen, Charlotte Wiell, Philip G Conaghan, Frédérique Gandjbakhch, Kay-Geert A Hermann, Paul Bird, Pernille Bøyesen, Charles Peterfy, Bo Ejbjerg, Espen A Haavardsholm, Laura Coates, Mikkel Ostergaard
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  ABSTRACT: Magnetic resonance imaging (MRI) is increasingly used to measure articular inflammation and damage in patients with psoriatic arthritis (PsA). We evaluated the reliability of a new OMERACT PsA MRI scoring system, PsAMRIS, in PsA fingers. In 2 separate studies, MRI scans were obtained from patients with clinical evidence of synovitis or dactylitis of the fingers. For the first cross-sectional study, images were obtained at one timepoint. For the second longitudinal study, images were obtained at 2 timepoints, 6 weeks apart. Scans were scored using PsAMRIS in an international multireader setting, for synovitis, tenosynovitis, periarticular inflammation, bone edema, bone erosions, and bone proliferation. Global status scores from both datasets revealed moderate to high reliability for scoring most features, although reliability was poor for periarticular inflammation in the cross-sectional study. Change scores that reflected inflammatory activity also exhibited moderate to good reliability in the longitudinal exercise, despite there being very little absolute change in MRI synovitis or tenosynovitis observed in this dataset. At the distal interphalangeal joints, reliability for change scores was acceptable only for synovitis and tenosynovitis. Further development and testing of the PsAMRIS is planned to improve its performance as a clinical and research tool to identify and measure pathology in peripheral joint PsA.
  The Journal of Rheumatology 09/2009; 36(8):1811-5. · 3.69 Impact Factor
• Article: The OMERACT MRI inflammatory arthritis group: advances and future research priorities.

  Philip G Conaghan, Paul Bird, Fiona McQueen, Charles Peterfy, Pernille Bøyesen, Frédérique Gandjbakhch, Anne Duer-Jensen, Espen A Haavardsholm, Bo Ejbjerg, Charlotte Wiell, Laura Coates, Kay-Geert A Hermann, Philip O'Connor, Marissa Lassere, Jane E Freeston, Allen Anandarajah, Harry Genant, Paul Emery, Mikkel Ostergaard
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  ABSTRACT: The OMERACT magnetic resonance imaging (MRI) in inflammatory arthritis group previously developed the rheumatoid arthritis MRI score (RAMRIS) for use in clinical studies, evaluated the use of extremity MRI, and initiated development of a psoriatic arthritis MRI score (PsAMRIS). At OMERACT 9 the group looked at clarifications of applying the RAMRIS, and presented data from a study examining how the contrast agent gadolinium affects RAMRIS outcomes. Much of the group's effort has been aimed at the iterative development of its PsA score, and reported exercises examining this score demonstrated encouraging results, allowing subsequent presentation of a preliminary PsAMRIS. The large amount of data presented were followed by discussions with the wider audience highlighting constructive suggestions for future research priorities, including further feasibility studies, understanding imaging remission, and further improvements to PsAMRIS.
  The Journal of Rheumatology 09/2009; 36(8):1803-5. · 3.69 Impact Factor
• Article: The OMERACT psoriatic arthritis magnetic resonance imaging scoring system (PsAMRIS): definitions of key pathologies, suggested MRI sequences, and preliminary scoring system for PsA Hands.

  Mikkel Ostergaard, Fiona McQueen, Charlotte Wiell, Paul Bird, Pernille Bøyesen, Bo Ejbjerg, Charles Peterfy, Frédérique Gandjbakhch, Anne Duer-Jensen, Laura Coates, Espen A Haavardsholm, Kay-Geert A Hermann, Marissa Lassere, Philip O'Connor, Paul Emery, Harry Genant, Philip G Conaghan
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  ABSTRACT: This article describes a preliminary OMERACT psoriatic arthritis magnetic resonance image scoring system (PsAMRIS) for evaluation of inflammatory and destructive changes in PsA hands, which was developed by the international OMERACT MRI in inflammatory arthritis group. MRI definitions of important pathologies in peripheral PsA and suggestions concerning appropriate MRI sequences for use in PsA hands are also provided.
  The Journal of Rheumatology 09/2009; 36(8):1816-24. · 3.69 Impact Factor
• Article: Monitoring anti-TNFalpha treatment in rheumatoid arthritis: responsiveness of magnetic resonance imaging and ultrasonography of the dominant wrist joint compared with conventional measures of disease activity and structural damage.

  E A Haavardsholm, M Østergaard, H B Hammer, P Bøyesen, A Boonen, D van der Heijde, T K Kvien
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  ABSTRACT: To evaluate the responsiveness of magnetic resonance imaging (MRI) and ultrasonography (US) compared with conventional measures of disease activity and structural damage in patients with rheumatoid arthritis (RA) during the first year of treatment with anti-tumour necrosis factor alpha (TNFalpha). A cohort of patients with RA (N = 36, median age 53 years, disease duration 7.6 years and disease activity score (DAS28) 5.7) was evaluated by core measures of disease activity, US (one wrist), MRI (one wrist) and conventional radiography (CR, both hands and wrists) at initiation of treatment with anti-TNFalpha agents and after 3, 6 and 12 months. Responsiveness was assessed by standardised response means (SRM). Accepted thresholds were applied to classify responsiveness as trivial, low, moderate or good. MRI synovitis (SRM between -0.79 and -0.92) and the MRI total inflammation score comprising synovitis, tenosynovitis and bone marrow oedema (SRM between -1.05 and -1.24) were highly responsive. Moderate to high responsiveness was found for MRI tenosynovitis and bone marrow oedema, all the composite indices (DAS28, simplified disease activity index (SDAI) and clinical disease activity index (CDAI)) and the 28-swollen joint count. US displayed low to moderate responsiveness. The MRI erosion score displayed low responsiveness but was more responsive than CR measures at 3 and 6 months follow-up. MRI and CR measures of annual progression rates of damage performed similarly and were highly responsive. The most responsive measure of inflammation when evaluating anti-TNFalpha medication was a composite measure comprising MRI synovitis, tenosynovitis and bone marrow oedema, and this may be a promising outcome measure in clinical studies.
  Annals of the rheumatic diseases 12/2008; 68(10):1572-9. · 8.11 Impact Factor
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  Available from: Espen Haavardsholm

  Article: A high serum level of eotaxin (CCL 11) is associated with less radiographic progression in early rheumatoid arthritis patients.

  Silje W Syversen, Guro L Goll, Espen A Haavardsholm, Pernille Bøyesen, Tor Lea, Tore K Kvien
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  ABSTRACT: Prognosis in rheumatoid arthritis (RA) is difficult to assess. The aim of this study was to examine whether serum levels of a spectrum of cytokines were predictive of radiographic progression in early RA patients. A total of 82 early RA patients (disease duration < 1 year) were followed for 12 months. Clinical assessments, X-rays of hands and magnetic resonance imaging (MRI) of the dominant wrist were assessed at baseline and after 3, 6 and 12 months. The X-rays were scored according to the van der Heijde modified Sharp score (vdHSS). Cytokine analyses were performed with multiplex technology. Associations between cytokines and radiographic progression were examined by logistic regression. In all, 49% of the patients developed radiographic progression. The median (interquartile range (IQR)) baseline eotaxin level (pg/ml) was significantly lower in patients with (193 (119 to 247)) than without progression (265 (166 to 360)). In the univariate logistic regression analyses, eotaxin was negatively associated to radiographic progression, and this association was maintained in the multivariate model with an odds ratio (OR) (95% confidence interval (CI)) for progression of 0.58 (0.41 to 0.82) per 50 pg/ml increase in eotaxin level. None of the other measured cytokines showed any association to radiographic progression. This study raises the hypothesis that high serum levels of eotaxin predict less radiographic progression in early RA patients.
  Arthritis research & therapy 01/2008; 10(2):R28. · 4.27 Impact Factor