Rheumatoid Arthritis: Ostergaard M

Ostergaard M, Szkudlarek M. · No affiliation provided · Scand J Rheumatol. · Pubmed #12737323 No free full text.

Abstract: Implementing the modern treatment strategy in rheumatoid arthritis (RA), i.e. early initiation and optimal adjustments of aggressive therapies, requires methods for early diagnosis and sensitive monitoring of the disease process. In rheumatoid arthritis clinical trials and routine management, conventional radiography is the pivotal method for diagnosing and monitoring structural joint damage. However, it is insensitive to bone damage at its earliest stages and totally incapable of capturing the primary feature of rheumatoid disease, the synovitis. In comparison with radiography, magnetic resonance imaging (MRI) offers assessment of bone damage with improved sensitivities to early pathology and to change. In addition, detailed assessment of soft tissue changes, including synovitis and tenosynovitis, is possible and MRI findings are of prognostic value for the long-term radiological outcome. Ultrasonography (US) is less validated than MRI, but available data suggests that US offers comparable information on both inflammatory and destructive changes in RA finger and toe joints. Issues of reliability, standardization and documentation limit its value in clinical trials, This article reviews current knowledge on conventional radiography, computed tomography, MRI and US for assessment of peripheral joints in RA. The rationale is provided for MRI being the new gold standard for assessment of RA joints and US becoming a routine bedside tool for improved joint assessments and injections by rheumatologists. Pursuing the goal of improving patient care and disease outcome, rheumatologists can no longer afford to ignore MRI and US as means to measure disease activity and joint damage in rheumatoid arthritis.

McQueen FM, Ostergaard M. · Department of Molecular Medicine and Pathology, University of Auckland, New Zealand. · Best Pract Res Clin Rheumatol. · Pubmed #17870031 No free full text.

Abstract: New imaging modalities are assuming an increasingly important role in the investigation and management of rheumatoid arthritis. It is now possible to obtain information about all tissues within the joint in three dimensions using tomographic techniques such as magnetic resonance imaging (MRI) and high-resolution computerized tomography. Erosions are very clearly depicted using these modalities and MRI also allows imaging of soft tissues with assessment of joint inflammation. High-resolution ultrasound is a convenient clinical technique for the assessment of erosions, synovitis and tenosynovitis in real-time and facilitates diagnostic and therapeutic interventions such as joint aspiration and injection. Exciting experimental modalities are also being developed with the potential to provide not just morphological but functional imaging. Techniques such as positron emission tomography (PET) and single photon emission tomography (SPECT) can reveal actively metabolizing bone and the proliferation of synovial cells via radioactive labeling. Bioluminescence and fluorescence reflectance imaging are other approaches that allow imaging, and potentially the delivery of therapeutic agents, at a molecular level.

Keeling SO, Landewe R, van der Heijde D, Bathon J, Boers M, Garnero P, Geusens P, El-Gabalawy H, Inman RD, Kraus VB, Kvien TK, Mease PJ, Ostergaard M, Ritchlin C, Syversen SW, Maksymowych WP. · Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. · J Rheumatol. · Pubmed #17343310 No free full text.

Abstract: OBJECTIVE: A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker extensively studied in RA, was then used to test these criteria. Our objectives were: (1) To assess the strength of evidence in support of CRP as a soluble biomarker reflecting structural damage in RA according to the draft validation criteria. (2) To assess the strength of recommendation for inclusion of individual criteria in the draft set. METHODS: A systematic literature review was conducted to elicit evidence in support of each specific criterion composing the 14-criteria draft set. A summary of the key literature findings per criterion was presented to both the working group and to participants in a special interest soluble biomarker group at OMERACT 8. Participants at OMERACT 8 were asked to rate the strength of evidence and the strength of the recommendation in support of each individual criterion on a 0-10 numerical rating scale. Working group members not present at OMERACT voted by a Web-based survey. RESULTS: Minimal data were extracted from the literature pertaining to those criteria listed under the category of truth. Ratings for strength of evidence were moderate to low (< 7) for CRP as a biomarker reflecting structural damage in RA; this was true for all criteria except those listed under the category of feasibility and 2 listed under the category of discrimination pertaining to assay reproducibility and evidence regarding sources of variability. Ratings for strength of recommendation for inclusion of each of the 14 criteria in the draft set were high (> 7) except for those criteria listed under the category of truth. CONCLUSION: The draft criteria serve as a useful template in the evaluation of the strength of evidence in support of a particular soluble biomarker as reflecting structural damage in RA.

Conaghan PG, McQueen FM, Peterfy CG, Lassere MN, Ejbjerg B, Bird P, O'Connor PJ, Haavardsholm E, Edmonds JP, Emery P, Genant HK, Ostergaard M, Anonymous00379. · Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK. · J Rheumatol. · Pubmed #16331788 No free full text.

Abstract: Magnetic resonance imaging (MRI) has now been used extensively in cross-sectional and observational studies as well as in controlled clinical trials to assess disease activity and joint damage in rheumatoid arthritis (RA). MRI measurements or scores for erosions, bone edema, and synovitis have been developed and validated by several groups. The OMERACT criteria require that outcome measures demonstrate adequate validity, discriminative power, and feasibility if they are to be useful in clinical trials. Specific performance targets for these criteria depend on the scientific, regulatory, logistical, and financial context of the study in question. We review the extent to which MRI assessments of joint erosion, bone edema, and synovitis fulfil these criteria, particularly as they relate to proof-of-concept RA clinical trials.

Ostergaard M, Ejbjerg B. · Department of Rheumatology, Copenhagen University Hospital at Herlev, Denmark. · Semin Musculoskelet Radiol. · Pubmed #15643570 No free full text.

Abstract: Early diagnosis, followed by early initiation and optimal adjustments of aggressive therapies, are acknowledged as essential to optimize long-term clinical and radiological outcome in rheumatoid arthritis (RA). This requires sensitive methods for detection and monitoring of the primary feature of RA--the synovitis. In comparison with conventional methods, magnetic resonance imaging (MRI) offers assessment of the rheumatoid synovium with improved sensitivity to early pathology and to change. Various aspects such as volume, vascularity, and edema can be assessed by different metrological approaches. MRI findings are of prognostic value to the long-term radiological outcome. This article reviews current knowledge on MRI for assessment of the synovium in RA, focusing on the validity of MRI measures of synovitis. Future perspectives and suggested research priorities are described. The rationale is provided for MRI becoming the new gold standard for assessment of RA joints and for MRI assessments of synovitis being reliable and valid measures of rheumatoid disease activity.

Conaghan P, Edmonds J, Emery P, Genant H, Gibbon W, Klarlund M, Lassere M, McGonagle D, McQueen F, O'Connor P, Peterfy C, Shnier R, Stewart N, Ostergaard M. · Rheumatology Research Unit, University of Leeds, UK. · J Rheumatol. · Pubmed #11361206 No free full text.

Abstract: Complementing the 3 papers that precede it, this paper explains the rationale for the activities of an OMERACT working party on magnetic resonance imaging (MRI) evaluation of rheumatoid arthritis (RA), sets out provisional recommendations for the acquisition and scoring of MRI of the hand and wrist in RA, and delineates some of the many residual problems that need to be addressed.

Ostergaard M. · Danish Research Centre of Magnetic Resonance, Hvidovre Hospital, Copenhagen. · Dan Med Bull. · Pubmed #10514940 No free full text.

This publication has no abstract.

Ostergaard M, Halberg P. · H:S Hvidovre Hospital, reumatologisk afdeling. · Ugeskr Laeger. · Pubmed #9989192 No free full text.

Abstract: Intra-articular glucocorticosteroid injections are widely used in mono- or oligoarticular flares of patients with rheumatoid arthritis and other aseptic inflammatory joint diseases, as well as in osteoarthritis. Rapid and pronounced, but usually temporary, suppression of local joint inflammation may be achieved with only minor systemic effect. In osteoarthritis the effect is brief and transient. Triamcinolone hexacetonide provides the longest clinical effect, but since this drug may cause local tissue necrosis when injected outside a synovial cavity it should be used only by experienced clinicians. The risk of glucocorticoid-induced cartilage damage is discussed. The risk is probably less than that of untreated joint inflammation. Nevertheless, it is recommended that injections into the same joint are limited, for instance to one injection every six weeks and no more than three or four in one year. Furthermore, indications and contraindications should be carefully considered prior to each injection. Intra-articular glucocorticoid therapy may be of considerable clinical value in the management of aseptic arthritis, if administered on correct indications using a correct technique.

Szkudlarek M, Court-Payen M, Strandberg C, Klarlund M, Klausen T, Ostergaard M. · The Danish Research Center of Magnetic Resonance, University of Copenhagen Hvidovre Hospital, Denmark. · Arthritis Rheum. · Pubmed #11592362 links to  free full text

Abstract: OBJECTIVE: To evaluate the effectiveness of power Doppler ultrasonography (PDUS) for assessing inflammatory activity in the metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA), using dynamic magnetic resonance imaging (MRI) as a reference method. METHODS: PDUS and dynamic MRI were performed on 54 MCP joints of 15 patients with active RA and on 12 MCP joints of 3 healthy controls. PDUS was performed with a LOGIQ 500 unit by means of a 7-13-MHz linear array transducer. Later the same day, MRI was performed with a 1.0T MR unit. A series of 24 coronal T1-weighted images of the second through the fifth MCP joints was obtained, with intravenous injection of gadolinium diethylenetriaminepentaacetic acid after the fourth image (dynamic MRI). From the MR images, the rate of early synovial enhancement (RESE; defined as the relative enhancement per second during the first 55 seconds postinjection) was calculated and compared with the flow signal on PDUS, which was scored as present or absent. RESULTS: In RA patients, flow signal on PDUS was detected in 17 of 54 MCP joints examined. Postcontrast MR images revealed an RESE of > or = 1.0%/second in 18 of 54 RA MCP joints. PDUS showed no flow in 47 of 48 MCP joints with an RESE of <1.0%/second and revealed flow in 16 of 18 MCP joints with an RESE of > or = 1.0%/second. Using dynamic MRI as a reference, PDUS had a sensitivity of 88.8% and a specificity of 97.9%. CONCLUSION: PDUS was reliable for assessing inflammatory activity in the MCP joints of RA patients, using dynamic MRI as the standard. PDUS and clinical assessment of joint swelling/tenderness were only weakly correlated.

Ostergaard M, Klarlund M, Lassere M, Conaghan P, Peterfy C, McQueen F, O'Connor P, Shnier R, Stewart N, McGonagle D, Emery P, Genant H, Edmonds J. · Department of Rheumatology and Danish Research Centre of Magnetic Resonance, Hvidovre Hospital, University of Copenhagen. · J Rheumatol. · Pubmed #11361204 No free full text.

Abstract: Magnetic resonance imaging (MRI) allows direct visualization of inflammation and destruction in rheumatoid arthritis (RA) joints. However, MRI scoring methods have not yet been standardized or appropriately validated. Our aim was to examine interreader agreement for a simple system of scoring RA changes on MRI among 5 centers that had not undertaken intergroup calibration. MRI of RA wrist and metacarpophalangeal (MCP) joints were scored by experienced readers in 5 centers in different countries. In substudy 1, 5 sets of 2nd-5th MCP joints from UK [Technique A: 1.5 T, coronal and axial T1 and T2 spin-echo, -/+ fat saturation (FS), -/+ iv gadolinium (Gd)] were scored for synovitis (score 0-3) and bone lesions (0-3). In substudy 2, we evaluated 19 sets of 2nd-5th MCP joints [10 sets from UK (Technique A) and 9 sets from the US (Technique B: 1.5 T; coronal T1 spin-echo and T2* gradient-echo + FS, no Gd)] and 19 wrist joints [9 from the US (Technique B) and 10 from Denmark (Technique C: 1.0 T; coronal and axial T1 spin-echo, no FS, -/+ Gd)]. Synovitis (0-3), bone lesions (0-3), and joint space narrowing (JSN, 0-3) were scored in each MCP joint and in 3 different regions of the wrist. Bone erosions and lesions in each bone were scored 0-5. Substudy 1 served to test and redesign the score sheets. In substudy 2, the scores of synovitis and bone lesions by the 5 groups were the same or differed by only one grade in 73% and 85% of joints, respectively. On MRI that included 2 imaging planes and iv Gd (Techniques A and C), these rates were 86% (synovitis) and 97% (bone lesions). Corresponding intraclass correlation coefficients (quadratic weighted kappas) were 0.44-0.68, mean 0.58 (synovitis), and 0.44-0.69, mean 0.62 (bone lesion), i.e., in the moderate to good range. Unweighted kappa values were in the low to moderate range, generally lowest for JSN (< 0.20), better for synovitis and bone erosions, and best for bone lesions, being generally highest for MRI with 2 planes pre- and post-Gd and in MCPjoints compared with wrists. These preliminary results suggest that the basic interpretation of MRI changes in RA wrist and MCP joints is relatively consistent among readers from different countries and medical backgrounds, but that further training, calibration, and standardization of imaging protocols and grading schemes will be necessary to achieve acceptable intergroup reproducibility in assessing synovitis and bone destruction in RA multicenter studies.

Ostergaard M, Hansen MS, Stoltenberg MB, Gideon P, Jensen KE, Klarlund M, Lorenzen I. · H:S Hvidovre Hospital, reumatologisk afdeling. · Ugeskr Laeger. · Pubmed #10962915 No free full text.

Abstract: To evaluate MRI for assessment of inflammation, destruction and prognosis in rheumatoid arthritis (RA), 26 RA patients, randomized to disease-modifying anti-rheumatic drug (DMARD) therapy alone or in combination with oral prednisolone, were followed for one year with contrast-enhanced MRI of the dominant wrist (months zero, three, six and 12), conventional radiography and clinical and biochemical examinations. Significant synovial membrane volume reductions were observed in both groups, earliest in the DMARD + prednisolone group. The rate of erosive progression on MRI was highly correlated with baseline and area-under-curve (AUC)-values of synovial membrane volume, but not with baseline or AUC-values of local or global clinical or biochemical parameters, nor with +/- prednisolone. MRI was more sensitive than radiography as regards detection of progressive bone destruction (22 versus 12 new bone erosions). MRI may prove valuable as marker of joint disease activity and destruction and, perhaps, prognosis in RA.

Ostergaard M, Hansen M, Stoltenberg M, Gideon P, Klarlund M, Jensen KE, Lorenzen I. · The Danish Research Center of Magnetic Resonance, Hvidovre University Hospital. · Arthritis Rheum. · Pubmed #10323447 links to  free full text

Abstract: OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease-modifying antirheumatic drug (DMARD) therapy alone (11 patients) or DMARDs in combination with oral prednisolone (15 patients), were followed up for 1 year with contrast-enhanced MRI of the dominant wrist (months 0, 3, 6, and 12), conventional radiography (months 0 and 12), and clinical and biochemical examinations. Bone erosion (by MRI and radiography) and synovial membrane volumes (by MRI) were assessed. RESULTS: Significant synovial membrane volume reductions were observed after 3 and 6 months in the DMARD + prednisolone group, and after 6 and 12 months in the DMARD-alone group (P < 0.01-0.02, by Wilcoxon-Pratt analysis). The rate of erosive progression on MRI was highly correlated with baseline scores and, particularly, with area under the curve (AUC) values of synovial membrane volume (Spearman's sigma = 0.69, P < 0.001), but not with baseline or AUC values of local or global clinical or biochemical parameters, or with prednisolone treatment. In none of 5 wrists with baseline volumes <5 cm3, but in 8 of 10 wrists with baseline volumes > or =10 cm3, erosive progression was found by MRI and/or radiography, indicating a predictive value of synovial membrane volumes. MRI was more sensitive than radiography for the detection of progressive bone destruction (22 versus 12 new bone erosions). CONCLUSION: MRI-determined synovial membrane volumes are closely related to the rate of progressive joint destruction. Quantitative MRI assessment of synovitis may prove valuable as a marker of joint disease activity and a predictor of progressive joint destruction in RA.

McGonagle D, Tan AL, Møller Døhn U, Ostergaard M, Benjamin M. · University of Leeds, and Chapel Allerton Hospital, Leeds, UK. · Arthritis Rheum. · Pubmed #19333927 No free full text.

Abstract: OBJECTIVE: The microanatomic basis for formation of erosions in inflammatory arthritis is incompletely understood but is thought to be related to bare areas and the associated cartilage-synovium junction. The purpose of this study was to test the hypothesis that erosion-prone sites are associated with microdamage in macroscopically normal joints. METHODS: Histologic evaluation of erosion-prone sites was performed on 20 collateral ligaments (CLs) from the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of 5 normal cadavers. In addition, the MCP joints (n = 17) and PIP joints (n = 3) of 20 patients with rheumatoid arthritis (RA) were assessed by computed tomography (CT) to ascertain whether the topography of erosion formation in patients with RA corresponded to the cadaveric findings. RESULTS: Absence of a bare area was noted in cadaveric tissue at the periligamentous erosion-prone regions, especially in the distal MCP joints and both distal and proximal PIP joints. Nevertheless, these sites exhibited soft-tissue pathologic features and bony microdamage/cyst formation. Other significant findings included the presence of pannus without inflammatory changes in the regions in which a bare area was absent, and the replacement of bare area regions with fibrovascular synovial tissue in joints without inflammatory changes. The sites of cadaveric tissue microdamage corresponded to CT-determined erosion formation in the MCP and PIP joints of patients with RA, in whom erosions adjacent to the CLs were more common than dorsal or volar erosions. CONCLUSION: Periarticular erosion formation may not necessarily depend on the presence of a bare area and has a propensity to occur adjacent to ligaments in which bone microdamage is common. These findings suggest that periligamentous locations prone to microdamage may critically influence the topography of erosion formation in inflammatory arthritis.

Emery P, Van Vollenhoven R, Ostergaard M, Choy E, Combe B, Graninger W, Krueger K, Matucci-Cerinic M, Navarro F, van Riel P, Settas L, Steinfeld S. · University of Leeds, Leeds, UK. · Ann Rheum Dis. · Pubmed #19286904 No free full text.

This publication has no abstract.

Sennels H, Sørensen S, Ostergaard M, Knudsen L, Hansen M, Skjødt H, Peters N, Colic A, Grau K, Jacobsen S. · Department of Clinical Biochemistry, Hvidovre Hospital, Copenhagen University Hospital, Hvidovre, Denmark. · Scand J Rheumatol. · Pubmed #18612923 No free full text.

Abstract: OBJECTIVE: To determine whether circulating levels of osteopontin (OPN), osteoprotegerin (OPG), total soluble receptor activator of nuclear factor-kappa B ligand (total sRANKL), and high-sensitivity C-reactive protein (hsCRP) change in patients with rheumatoid arthritis (RA) during immunosuppressive therapy. METHODS: Twenty-five active RA patients were randomized to treatment with either etanercept alone or in combination with methotrexate (MTX). The treatment response after 16 weeks was assessed using the European League Against Rheumatism (EULAR) response criteria. Blood samples were taken before the start of and every fourth week during the study. OPN, OPG, and total sRANKL were measured by enzyme-linked immunosorbent assays (ELISAs) and hsCRP by highly sensitive turbidometry. RESULTS: At baseline, OPN and hsCRP were significantly (p<0.001) elevated compared to healthy persons. Compared to baseline only hsCRP levels decreased significantly (p<0.05 to p<0.001) in the EULAR responders through the study. OPN remained significantly (p<0.05) elevated at 16 weeks in patients with a low disease activity score (DAS< or =3.2). Total sRANKL increased significantly (p<0.05) from baseline to week 12. No statistically significant changes were observed in the non-responders. CONCLUSION: Active RA patients showed increased circulating levels of hsCRP and OPN, but only hsCRP decreased during etanercept therapy. Our findings suggest that OPN, OPG, total sRANKL, and hsCRP reflect different aspects of the inflammatory process in RA.

Knudsen LS, Klarlund M, Skjødt H, Jensen T, Ostergaard M, Jensen KE, Hansen MS, Hetland ML, Nielsen HJ, Johansen JS. · Department of Rheumatology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark. · J Rheumatol. · Pubmed #18597410 No free full text.

Abstract: OBJECTIVE: To determine plasma interleukin 6 (pIL-6), plasma vascular endothelial growth factor (pVEGF), and serum (s) YKL-40 in patients with early rheumatoid arthritis (RA) and unclassified polyarthritis (PA), and investigate their relationship with radiographic outcome. METHODS: pIL-6 and pVEGF were determined by ELISA and sYKL-40 by an in-house radioimmunoassay in 51 patients with early RA and 21 with PA. Patients were followed with clinical and biochemical measurement every month for 2 years. Conventional radiographs of hands, wrists, and forefeet were scored according to the Larsen method, and magnetic resonance imaging of 2nd to 5th metacarpophalangeal joints of the dominant hand were evaluated for presence or absence of bone erosions. RESULTS: Baseline pIL-6, pVEGF, sYKL-40, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were elevated in RA patients compared to healthy persons (p < 0.001), but were not in patients with PA. Patients with early RA had higher pIL-6 (p = 0.007), pVEGF (p = 0.02), and sYKL-40 (p = 0.024) compared to PA patients. pIL-6, sYKL-40, CRP, and ESR but not pVEGF decreased in patients that responded to treatment after 2 years. The mean value of pIL-6 during the first and second year were higher in patients with early RA with progression in bone erosions (n = 14) compared to early RA patients without progression (n = 30; first year 8.4 vs 2.8 ng/l, p = 0.04; second year 6.1 vs 3.6 ng/l, p = 0.03). CONCLUSION:Plasma IL-6 was the only biomarker related to treatment response and progressive erosive disease in patients with early RA, but it may not give additional information compared to CRP in relation to disease activity and treatment response.

Linde L, Sørensen J, Ostergaard M, Hørslev-Petersen K, Hetland ML. · Department of Rheumatology, Copenhagen University Hospital, Hvidovre, Denmark. · J Rheumatol. · Pubmed #18484697 No free full text.

Abstract: OBJECTIVE: To compare validity, reliability, and responsiveness of generic and disease specific health-related quality of life (HRQOL) instruments in rheumatoid arthritis (RA). METHODS: Two samples of patients completed the Medical Outcomes Study Short Form-36 Health Survey (SF-36), EuroQol (EQ)-5D, 15D, Rheumatoid Arthritis Quality of Life Scale (RAQoL), Health Assessment Questionnaire (HAQ), and visual analog scales (VAS) for pain, fatigue, and global RA. Validity (convergent, discriminant, and known-groups) was evaluated in a cross-section of 200 patients. Reliability was evaluated by agreement (intraclass correlation coefficient; baseline to 2 weeks) and internal consistency (Cronbach's alpha); and responsiveness by the standardized response mean stratified on improvement, status quo, or deterioration in health status after 6 months in 150 patients followed longitudinally. Followup questionnaires (at 2 weeks and 6 months) included questions about changes in health status since baseline. RESULTS: The cross-sectional sample included 77% women, median age 57 years (range 19-87), disease duration 6 years (0-58), with Disease Activity Score 28-joint count (DAS28) of 3.10 (1.21-6.47). The longitudinal sample included 80% women, median age 60 years (22-82). Validity: all instruments discriminated between low, moderate, and high DAS28. Reliability: RAQoL and HAQ displayed good repeatability (ICC > 0.95) and internal consistency (Cronbach's alpha > 0.90). Responsiveness: SF-36 bodily pain scale and VAS pain were responsive to both improvement and deterioration. CONCLUSION: All instruments were valid measures for HRQOL in RA. The RAQoL and HAQ displayed the best reliability, while the SF-36 bodily pain scale and VAS pain were the most responsive. The choice of instrument should depend on the study objectives.

Hetland ML, Ejbjerg B, Hørslev-Petersen K, Jacobsen S, Vestergaard A, Jurik AG, Stengaard-Pedersen K, Junker P, Lottenburger T, Hansen I, Andersen LS, Tarp U, Skjødt H, Pedersen JK, Majgaard O, Svendsen AJ, Ellingsen T, Lindegaard H, Christensen AF, Vallø J, Torfing T, Narvestad E, Thomsen HS, Ostergaard M, Anonymous00063. · Department of Rheumatology, Copenhagen University Hospital, Hvidovre, Denmark. · Ann Rheum Dis. · Pubmed #18388160 No free full text.

Abstract: OBJECTIVE: To identify predictors of radiographic progression in a 2-year randomised, double-blind, clinical study (CIMESTRA) of patients with early rheumatoid arthritis (RA). METHODS: Patients with early RA (n = 130) were treated with methotrexate, intra-articular betamethasone and ciclosporin/placebo-ciclosporin. Baseline magnetic resonance imaging (MRI) of the wrist (wrist-only group, n = 130) or MRI of wrist and metacarpophalangeal (MCP) joints (wrist+MCP group, n = 89) (OMERACT RAMRIS), x-ray examination of hands, wrists and forefeet (Sharp/van der Heijde Score (TSS)), Disease Activity Score (DAS28), anti-cyclic citrullinated peptide antibodies (anti-CCP), HLA-DRB1-shared epitope (SE) and smoking status were assessed. Multiple regression analysis was performed with delta-TSS (0-2 years) as dependent variable and baseline DAS28, TSS, MRI bone oedema score, MRI synovitis score, MRI erosion score, anti-CCP, smoking, SE, age and gender as explanatory variables. RESULTS: Baseline values: median DAS28 5.6 (range 2.4-8.0); anti-CCP positive 61%; radiographic erosions 56%. At 2 years: DAS28 2.0 (0.5-5.7), in DAS remission: 56%, radiographic progression 26% (wrist+MCP group, similar for wrist-only group). MRI bone oedema score was the only independent predictor of delta-TSS (wrist+MCP group: coefficient = 0.75 (95% CI 0.55 to 0.94), p<0.001; wrist-only group: coefficient = 0.59 (95% CI 0.40 to 0.77), p<0.001). Bone oedema score explained 41% of the variation in the progression of TSS (wrist+MCP group), 25% in wrist-only group (Pearson's r = 0.64 and r = 0.50, respectively). Results were confirmed by sensitivity analyses. CONCLUSION: In a randomised controlled trial aiming at remission in patients with early RA, baseline RAMRIS MRI bone oedema score of MCP and wrist joints (and of wrist only) was the strongest independent predictor of radiographic progression in hands, wrists and forefeet after 2 years. MRI synovitis score, MRI erosion score, DAS28, anti-CCP, SE, smoking, age and gender were not independent risk factors. TRIAL REGISTRATION NUMBER: NCT00209859.

Holm B, Jacobsen S, Skjodt H, Klarlund M, Jensen T, Hetland ML, Ostergaard M. · Department of Physiotherapy, Copenhagen University Hospital at Hvidovre, Copenhagen, Denmark. · Phys Ther. · Pubmed #18276936 links to  free full text

Abstract: BACKGROUND AND PURPOSE: The purpose of this study was to translate the German Keitel Functional Test (KFT) into Danish and test it for reliability, concurrent and predictive validity, and responsiveness in patients with rheumatoid arthritis (RA). METHODS: Translation of the KFT was performed according to international recommendations, and the translated version was tested twice by 2 observers for intraobserver and interobserver reliability, with a 1-week interval between assessments, in 20 patients with RA with stable disease activity. Validity was investigated by studying 2 patient groups: (1) 15 patients with long-lasting (median=6 years) active RA, tested before and after 2, 6, and 14 weeks of anti-tumor necrosis factor alpha (TNF-alpha) inhibitor therapy, and (2) 35 patients with early (median=0.25 year) RA, tested at years 0, 0.5, 1, and 2. Twenty-three patients in the early RA group also were tested at year 7. KFT, conventional clinical and biochemical markers of disease activity, and Health Assessment Questionnaire (HAQ) were used. RESULTS: The translated KFT showed good intraobserver reliability (intraclass correlation coefficients [ICC]=.90 and .95, coefficient of variation [CV]=3.5%) and interobserver reliability (ICC=.99 and .92, CV=3.5%), and the KFT correlated with several measures of disease activity and, most closely, with the HAQ. The KFT was, in contrast to clinical disease activity measures, not sensitive to changes over time. Only baseline KFT data were significantly related to functional changes over a long period of time as measured by the KFT, and only in the early RA group. DISCUSSION AND CONCLUSION: The Danish translation of the KFT showed good reliability, acceptable concurrent validity, very poor responsiveness, and inconclusive results concerning predictive validity. The results of this study do not support the use of the KFT for monitoring function in clinical practice, as an outcome measure in clinical trials, or as a predictor of functional changes.

Døhn UM, Ejbjerg BJ, Hasselquist M, Narvestad E, Court-Payen M, Szkudlarek M, Møller J, Thomsen HS, Ostergaard M. · Department of Rheumatology, Copenhagen University Hospital at Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. · Ann Rheum Dis. · Pubmed #17606464 No free full text.

Abstract: OBJECTIVES: To investigate intramodality and intermodality agreements of CT and MRI erosion volumes in metacarpophalangeal (MCP) joints in rheumatoid arthritis (RA), and to compare the volumes with erosion scores for CT, MRI and radiography. METHODS: In total, 17 patients with RA and four healthy controls underwent unilateral CT, MRI and radiography of second to fifth MCP joints in one hand. Erosion volumes (using OSIRIS software) and scores were determined from CT, MRI and radiography (scores only). RESULTS: CT, MRI and radiography detected 77, 62 and 12 erosions, respectively. On CT, the mean erosion volume was 26 mm(3) (median 10; range 0 to 248) and 30 mm(3) (18; 1 to 163) on MRI. Total erosion volumes (per patient/control) were 97 mm(3) (29; 0 to 485) on CT and 90 mm(3) (46; 0 to 389) on MRI. For volumes, Spearman correlation coefficients were 0.96 to 0.99 (CT vs CT), 0.95 to 0.98 (MRI vs MRI) and 0.64 to 0.89 (CT vs MRI), all p<0.01. MRI erosion volumes correlated with the Outcome Measures in Rheumatology Clinical Trials/Rheumatoid Arthritis Magnetic Resonance Imaging Score (OMERACT RAMRIS) erosion scores (0.91 to 0.99; p<0.01) and the Sharp/van der Heijde erosion score (0.49 to 0.63; p<0.01). CONCLUSION: Very high intramodality and high intermodality agreements of CT and MRI erosion volumes were found, encouraging further testing in longitudinal studies. A close correlation with CT and MRI erosion volumes supports the OMERACT RAMRIS erosion score as a valid measure of joint destruction in RA.

McQueen FM, Gao A, Ostergaard M, King A, Shalley G, Robinson E, Doyle A, Clark B, Dalbeth N. · Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Sciences, University of Auckland, Park Rd, Private Bag 92019 Auckland, New Zealand. · Ann Rheum Dis. · Pubmed #17491098 No free full text.

Abstract: OBJECTIVES: MRI bone oedema has been observed in early and advanced RA and may represent a cellular infiltrate (osteitis) in subchondral bone. We studied MRI scans from RA patients undergoing surgery, seeking to identify regions of bone oedema and examine its histopathological equivalent in resected bone. METHODS: Preoperative contrast-enhanced MRI scans were obtained in 11 RA patients scheduled for orthopaedic surgery to the hands/wrists or feet. In 9, MRI scans were scored by 2 readers for bone oedema (RAMRIS system). Its distribution with respect to surgical site was investigated. In 4 patients, 7 bone samples were examined for a cellular infiltrate, and this was compared with MRI bone oedema, scored for spatial extent and intensity. RESULTS: Inter-reader intraclass correlation coefficients for bone oedema were 0.51 (all sites) and 0.98 (bone samples for histology). Bone oedema was observed at 60% of surgical sites vs 38% of non-surgical sites. High-grade bone oedema (score >/=50% maximum) was strongly associated with the surgical field (OR 9.3 (3.5 to 24.2), p<0.0001). Bone oedema scores correlated with pain (r = 0.67, p = 0.048) and CRP (r = 0.86, p = 0.01). In 4 of the 7 bone samples, there was concordance between bone oedema and subchondral osteitis. In 3, there was no MRI bone oedema, and osteitis was "slight". CONCLUSION: High-grade MRI bone oedema was common within the field of intended surgery and associated with pain. There was concordance between the presence and severity of MRI bone oedema and osteitis on histology, with an MRI threshold effect due to differences in image resolution.

Døhn UM, Skjødt H, Hetland ML, Vestergaard A, Møller JM, Knudsen LS, Ejbjerg BJ, Thomsen HS, Ostergaard M. · Department of Rheumatology, Copenhagen University Hospital at Hvidovre, Kettegaard Allé 30, 2650, Hvidovre, Denmark. · Clin Rheumatol. · Pubmed #17332974 No free full text.

Abstract: The aim of this study is to investigate the course of magnetic resonance imaging (MRI) signs of inflammatory and destructive changes in rheumatoid arthritis (RA) wrist and metacarpophalangeal (MCP) joints during etanercept treatment. MRI of the non-dominant wrist and second to fifth MCP joints was performed in five clinical active RA patients before and 4 and 16 weeks after initiation of etanercept treatment. MRI was evaluated according to the EULAR-OMERACT RA MRI reference image atlas. The median 28-joint count disease activity score (DAS28; erythrocyte sedimentation rate based) was 5.6 (range 5.0-6.8) at baseline and 3.5 (1.5-4.1) at week 16 (decreased in all patients compared to baseline, Wilcoxon-Pratt, p < 0.05). The median MRI synovitis score was 18 (14-21), 18 (10-20) and 16 (10-20) at baseline, week 4 and 16, respectively (decreased in all patients compared to baseline, Wilcoxon-Pratt, p < 0.05), while corresponding MRI bone oedema scores were 4 (0-13), 3 (0-9) and 1 (0-3; NS). The median MRI bone erosion score was 27 (11-111; NS) at all time points. Four patients had identical total bone erosion scores at baseline and week 16, whereas one patient showed a reduced score. In conclusion, one patient showed erosive regression, while no patient showed erosive progression on MRI during 16 weeks of etanercept therapy; even though clinical and MRI signs of joint inflammation remained. This small study supports that erosive progression judged by MRI is minimal in RA patients treated with etanercept, even in joints with persistent inflammation.

Jensen TW, Ostergaard M. · Department of Endocrinology at Copenhagen University Hospital, Hvidovre, Denmark. · Nat Clin Pract Rheumatol. · Pubmed #16932647 No free full text.

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Linde L, Hetland ML, Ostergaard M. · Department of Rheumatology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark. · Scand J Rheumatol. · Pubmed #16641042 No free full text.

Abstract: OBJECTIVES: To assess the drug survival and reasons for discontinuation of intramuscular methotrexate (imMTX) in rheumatological patients who had switched to imMTX from oral methotrexate (oMTX). METHODS: Data from 212 consecutive patients who switched from oMTX to imMTX therapy at our outpatient clinic between April 1997 and January 2004 were collected retrospectively through survey of case records. Data included reason for discontinuation of oMTX, disease activity parameters, duration of imMTX therapy, and, in patients who withdrew, the reason for discontinuation of imMTX. RESULTS: The main reasons for switching from oMTX to imMTX were lack of efficacy (66%) and adverse events (28%). After 6 months, 114 patients (54%) were still receiving imMTX therapy, and their median serum C-reactive protein (CRP) and the percentage of patients who had received glucocorticoids during the previous 6 weeks had decreased (p<0.001). The median survival of imMTX therapy was 7.5 months (interquartile range 3-17). Twenty per cent of the patients received imMTX for more than 24 months. Of the 212 patients, 41% and 9% stopped imMTX therapy because of lack of efficacy and adverse events, respectively. Of the patients who had stopped oMTX because of adverse events, 22% also withdrew from imMTX because of adverse events. CONCLUSION: Half of the patients benefited from switching from oral to intramuscular methotrexate for at least 6 months, but only a minority adhered to the treatment for years. Lack of efficacy was the most frequent reason for discontinuation, while adverse events were rare.

Wakefield RJ, Balint PV, Szkudlarek M, Filippucci E, Backhaus M, D'Agostino MA, Sanchez EN, Iagnocco A, Schmidt WA, Bruyn GA, Bruyn G, Kane D, O'Connor PJ, Manger B, Joshua F, Koski J, Grassi W, Lassere MN, Swen N, Kainberger F, Klauser A, Ostergaard M, Brown AK, Machold KP, Conaghan PG, Anonymous00384. · Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK. · J Rheumatol. · Pubmed #16331793 No free full text.

Abstract: Ultrasound (US) has great potential as an outcome in rheumatoid arthritis trials for detecting bone erosions, synovitis, tendon disease, and enthesopathy. It has a number of distinct advantages over magnetic resonance imaging, including good patient tolerability and ability to scan multiple joints in a short period of time. However, there are scarce data regarding its validity, reproducibility, and responsiveness to change, making interpretation and comparison of studies difficult. In particular, there are limited data describing standardized scanning methodology and standardized definitions of US pathologies. This article presents the first report from the OMERACT ultrasound special interest group, which has compared US against the criteria of the OMERACT filter. Also proposed for the first time are consensus US definitions for common pathological lesions seen in patients with inflammatory arthritis.