Publications by authors named "Ruth Wittoek"

30 Publications

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Core outcome measurement instrument selection for physical function in hand osteoarthritis using the OMERACT Filter 2.1 process.

Semin Arthritis Rheum 2021 Sep 15. Epub 2021 Sep 15.

Departments of Rheumatology and Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.

Objective: Physical function is one of the Outcome Measures in Rheumatology (OMERACT) core outcome domains for hand osteoarthritis studies. Our aim was to select appropriate instrument(s) to measure this domain, as part of the development of a core outcome measurement set.

Methods: Following the OMERACT Filter 2.1 instrument selection process, the (function subscale of) the Australian/Canadian Hand Osteoarthritis Index (AUSCAN), Functional Index for Hand Osteoarthritis (FIHOA) and Michigan Hand Outcomes Questionnaire (MHQ) were assessed for domain match, feasibility, truth and discrimination. Data gathered from available literature, working group and patient surveys, and additional analyses in two hand osteoarthritis cohorts were used to inform a consensus process. Results were summarized in Summary of Measurements Properties tables and reviewed by the OMERACT technical advisory group.

Results: MHQ passed the assessment of domain match and feasibility by the working group and patient research partners. For AUSCAN important limitations in feasibility were noted, but domain match was good. FIHOA did not pass the assessment and was not taken through the follow-up assessment. Based on published literature, reliability and construct/longitudinal validity of both MHQ and AUSCAN fulfilled OMERACT standards. While clinical trial discrimination and thresholds of meaning were good for AUSCAN, results for MHQ were ambiguous.

Conclusion: MHQ was provisionally endorsed as OMERACT core outcome measure for the core domain physical function. While AUSCAN may have better metric properties than MHQ, it received provisional endorsement as a second measure of function due to important feasibility issues. A research agenda to merit full endorsement was set.
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http://dx.doi.org/10.1016/j.semarthrit.2021.08.014DOI Listing
September 2021

Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study.

Ann Rheum Dis 2021 Aug 18. Epub 2021 Aug 18.

Rheumatology, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico, Mexico.

Objectives: This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range.

Methods: Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort.

Results: 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups.

Conclusions: Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.
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http://dx.doi.org/10.1136/annrheumdis-2021-219931DOI Listing
August 2021

Methotrexate treatment in hand osteoarthritis refractory to usual treatments: A randomised, double-blind, placebo-controlled trial.

Semin Arthritis Rheum 2021 Aug 6;51(4):831-838. Epub 2021 May 6.

Department of Rheumatology, Pasteur Hospital, Nice University Hospital, Cote d'Azur University, Nice F-06000, France; Department of Rheumatology, University of Cote d'Azur, Nice Hospital, Laboratory LAMHESS, EA6312, IBV CNRS IMR 7277 INSERM U1091 UNS, France.

Objective: To examine the effect of methotrexate (MTX) on pain and structural progression in symptomatic erosive hand osteoarthritis (HOA).

Methods: This 1-year prospective, single-centre, randomised, double-blind, placebo-controlled study (www.ClinicalTrial.gov, NCT01068405) followed up patients with symptomatic erosive HOA. Patients were randomised into two groups based on the drug that was administered: 10 mg methotrexate (MTX) per week or a placebo. The primary endpoint was the change in pain (determined using a visual analogue scale [VAS]) from baseline to 3 months. The secondary endpoints were pain VAS score at 12 months, clinical features (pain VAS score and function), radiographic features (the anatomical radiographic Verbruggen-Veys [VV] score and Gent University Score System), and magnetic resonance imaging (MRI) at 12 months.

Results: Sixty-four patients with HOA were randomised into either the placebo or MTX group. At 3 months, there was no significant difference in the mean decrease in the pain VAS score (mm) (MTX: 21.1 [standard deviation, 27.4], placebo: 11.7 [24.3]; p = 0.2). At 12 months, according to the VV score, erosive joints progressed significantly more to a remodelling phase in the MTX group than in the placebo group (27% vs 15%; p = 0.03). Joints with space loss appeared to be eroding less in the MTX group compared to the placebo group (8% vs 29%; p = 0.2). Synovitis on MRI at baseline could be associated with the erosive structural evolution of non-erosive joints (p = 0.02).

Conclusions: Weekly doses of 10-mg MTX showed no superiority over the placebo in terms of pain relief at 3 or 12 months.

Clinical Trial Registration Number: This study was registered at www.ClinicalTrial.gov (NCT01068405).
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http://dx.doi.org/10.1016/j.semarthrit.2021.04.016DOI Listing
August 2021

Ultrasonography of Inflammatory and Structural Lesions in Hand Osteoarthritis: An OMERACT Agreement and Reliability Study.

Arthritis Care Res (Hoboken) 2021 Jun 16. Epub 2021 Jun 16.

The Parker Institute, Copenhagen University Hospital Bispebjerg-Frederiksberg, Frederiksberg, Denmark.

Objective: To standardize and assess the reliability of ultrasonographic assessment of inflammatory and structural lesions in patients with hand osteoarthritis (OA).

Methods: The Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group selected synovial hypertrophy (SH), joint effusion (JE), and power Doppler (PD) signals as the main inflammatory lesions in hand OA, and suggested osteophytes in the scapho-trapezio-trapezoid (STT) and cartilage defects in the proximal interphalangeal (PIP) joints as novel additions to previous structural scoring systems. A complementary imaging atlas provided detailed examples of the scores. A reliability exercise of static images was performed for the inflammatory features, followed by a patient-based exercise with six sonographers testing inflammatory and structural features in twelve hand OA patients. We used Cohen's kappa (κ) for intra-reader and Light's κ for inter-reader reliability for all features except PD, in which Prevalence-Adjusted Bias-Adjusted Kappa (PABAK) was applied. Percentage agreement was also assessed.

Results: The web-based reliability exercise demonstrated substantial intra- and inter-reader reliability for all inflammatory features (κ>0.64). In the patient-based exercise, intra- and inter-reader reliability varied: SH κ=0.73 and 0.45; JE κ=0.70 and 0.55; PD PABAK=0.90 and 0.88; PIP cartilage κ=0.56 and 0.45; STT osteophytes κ=0.62 and 0.36. Percentage close agreement was high for all features (>85%).

Conclusion: With ultrasound, substantial to excellent intra-reader reliability was found for inflammatory features of hand OA. Inter-reader reliability was moderate, but overall high close agreement between readers suggest that better reliability is achievable after further training. Assessment of osteophytes in the STT joint and cartilage in the PIP joints achieved less good reliability and the latter is not endorsed.
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http://dx.doi.org/10.1002/acr.24734DOI Listing
June 2021

Topographical analysis of structural lesions between dominant and non-dominant hands in erosive osteoarthritis.

Rheumatol Int 2021 Mar 27;41(3):617-623. Epub 2021 Jan 27.

Department Rheumatology, Université de Lorraine, CHRU-Nancy, 54000, Nancy, France.

Key Messages: No difference between both hands was observed for clinical and radiographical presentations in EHOA patients. A bilateral and symmetrical relationship was found between hand joints.

Highlights: EHOA have symmetrical distribution and specific association in structural lesions. This study aims to analyse the preferential topographical distribution of clinical and structural lesions between the dominant and non-dominant hands in erosive hand osteoarthritis (EHOA) patients. Both hands were assessed via radiography in EHOA patients. A comparative analysis of the clinical features and structural lesions between the dominant and non-dominant hands was performed. The structural lesions were assessed according to the anatomical radiographic score of Verbruggen-Veys (VV). Next, a principal component analysis was performed to describe and highlight the relationships observed between the joints. Sixty patients were included in this study: there were 57 women, and the mean age was 66.1 (± 7.6) years. For the distal interphalangeal (DIP) joints, nodes were observed more frequently on the dominant hand (4 vs 3; p = 0.005). No difference in structural lesions was observed between the two hands except for the 2nd proximal interphalangeal (PIP) (p = 0.045). A principal component analysis with varimax rotation described relationships between the 2nd PIP, 3rd PIP, 4th PIP, 4th DIP and 5th DIP joints in both hands. No significant differences between dominant and non-dominant hands were observed for clinical and structural lesions in our sample of EHOA patients. A bilateral and symmetrical injury was observed in most EHOA joints. Trial registration Clinical trial registration number: NCT01068405.
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http://dx.doi.org/10.1007/s00296-020-04784-1DOI Listing
March 2021

MRI-based Synthetic CT in the Detection of Structural Lesions in Patients with Suspected Sacroiliitis: Comparison with MRI.

Radiology 2021 02 22;298(2):343-349. Epub 2020 Dec 22.

From the Departments of Radiology (L.B.O.J., M.C., N.H.) and Rheumatology (D.E., F.V.d.B., P.C., P.J., R.W.), Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium; VIB Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Ghent University, Ghent, Belgium (D.E., F.v.d.B., P.C., P.J., R.W.); and Department of Radiology & Diagnostic Imaging, University of Alberta Hospital, Edmonton, Canada (J.L.J.).

Background Evaluation of structural lesions in the sacroiliac (SI) joints can improve the accuracy for diagnosis of spondyloarthritis. However, structural lesions, such as erosions, are difficult to assess on routine T1-weighted MRI scans. Purpose To determine the diagnostic performance of MRI-based synthetic CT (sCT) in the depiction of erosions, sclerosis, and ankylosis of the SI joints compared with T1-weighted MRI, with CT as the reference standard. Materials and Methods A prospective study (clinical trial registration no. B670201837885) was performed from February 2019 to November 2019. Adults were referred from a tertiary hospital rheumatology outpatient clinic with clinical suspicion of inflammatory sacroiliitis. MRI and CT of the SI joints were performed on the same day. SCT images were generated from MRI scans using a commercially available deep learning-based image synthesis method. Two readers independently recorded if structural lesions (erosions, sclerosis, and ankylosis) were present on T1-weighted MRI, sCT, and CT scans in different reading sessions, with readers blinded to clinical information and other images. Diagnostic performance of sCT and T1-weighted MRI scans were analyzed using generalized estimating equation models, with consensus results of CT as the reference standard. Results Thirty participants were included (16 men, 14 women; mean age, 40 years ± 10 [standard deviation]). Diagnostic accuracy of sCT was higher than that of T1-weighted MRI for erosion (94% vs 86%, = .003), sclerosis (97% vs 81%, < .001), and ankylosis (92% vs 84%, = .04). With sCT, specificity for erosion detection (96% [95% CI: 90, 98] vs 89% [95% CI: 81, 94], = .01] and sensitivity for detection of sclerosis [94% [95% CI: 87, 97] vs 20% [95% CI: 10, 35], < .001] and ankylosis (93% [95% CI: 78, 98] vs 70% [95% CI: 47, 87], = .001) were improved. Conclusion With CT as the reference standard, synthetic CT of the sacroiliac joints has better diagnostic performance in the detection of structural lesions in individuals suspected of having sacroiliitis compared with routine T1-weighted MRI. © RSNA, 2020 See also the editorial by Fritz in this issue.
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http://dx.doi.org/10.1148/radiol.2020201537DOI Listing
February 2021

Development of classification criteria for hand osteoarthritis: comparative analyses of persons with and without hand osteoarthritis.

RMD Open 2020 06;6(2)

Rheumatology, Leiden University Medical Center, Leiden, Netherlands.

Objectives: Further knowledge about typical hand osteoarthritis (OA) characteristics is needed for the development of new classification criteria for hand OA.

Methods: In a cross-sectional multi-centre international study, a convenience sample of patients from primary and secondary/tertiary care with a physician-based hand OA diagnosis (n = 128) were compared with controls with hand complaints due to inflammatory or non-inflammatory conditions (n = 70). We examined whether self-reported, clinical, radiographic and laboratory findings were associated with hand OA using logistic regression analyses. Discrimination between groups was assessed by calculating the area under receiver operating curves (AUC).

Results: Strong associations with hand OA were observed for radiographic osteophytes (OR = 1.62, 95% CI 1.40 to 1.88) and joint space narrowing (JSN) (OR = 1.57, 95% CI 1.36 to 1.82) in the distal interphalangeal (DIP) joints with excellent discrimination (AUC = 0.82 for both). For osteophytes and JSN, we found acceptable discrimination between groups in the proximal interphalangeal joints (AUC = 0.77 and 0.78, respectively), but poorer discrimination in the first carpometacarpal joints (AUC = 0.67 and 0.63, respectively). Painful DIP joints were associated with hand OA, but were less able to discriminate between groups (AUC = 0.67). Age and family history of OA were positively associated with hand OA, whereas negative associations were found for pain, stiffness and soft tissue swelling in metacarpophalangeal joints, pain and marginal erosions in wrists, longer morning stiffness, inflammatory biomarkers and autoantibodies.

Conclusions: Differences in symptoms, clinical findings, radiographic changes and laboratory tests were found in patients with hand OA versus controls. Radiographic OA features, especially in DIP joints, were best suited to discriminate between groups.
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http://dx.doi.org/10.1136/rmdopen-2020-001265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425183PMC
June 2020

Assessment of structural lesions, synovitis and bone marrow lesions in erosive hand osteoarthritis on MRI (0.3T) compared to the radiographic anatomical Verbruggen-Veys score.

PLoS One 2020 23;15(6):e0234972. Epub 2020 Jun 23.

Department Rheumatology, University Hospital of Nancy, Nancy, France.

Objective: To evaluate prevalence of structural lesions, synovitis and bone marrow lesions (BMLs) on MRI performed with a 0.3T imaging system in patients with erosive hand osteoarthritis (EHOA) and to compare them to the anatomic radiographic Verbruggen-Veys score (VV).

Design: For this Cross-sectional study, fifty-five EHOA patients were studied with 0.3T contrast-enhanced MRI and radiography (RX) of their dominant hand. Structural lesions were scored according to the OMERACT Hand Osteoarthritis MRI Scoring System as follows: osteophytes and erosions were graded from 0 to 3. On joint destruction lesion synovitis and BMLs were graded from 0 to 1. And on MRI, we evaluated the presence of several structural features: N: normal, O: osteophytic lesions, E: erosive lesions, E/O: osteophytic and erosive lesions and D: joint destruction. RX was scored according to the VV system. Relations between MRI features and VV stages were analysed.

Results: MRI identified more structural lesions than RX (77.3% versus 74.8%) and particularly more erosive lesions (E or E/O) than VV Phase E (33.5% versus 20.2%). E/O and D were mostly found on MRI. Synovitis and BMLs were significantly associated with E/O and D with the following odds ratios (ORs): 8.4 (95% CI 1.8-13.6); OR: 13.7 (95% CI 2.9-21.0); OR: 15.7 (95% CI 3.2-23.5); OR: 38.5 (95% CI 9.5-57.0), respectively.

Conclusion: MRI 0.3T appears completely relevant for EHOA lesion analysis. First, MRI shows more erosive lesions than RX in EHOA; second, it allows for the analysis of synovitis and BMLs to be associated with more specific structural MRI features (E/O and D).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234972PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310719PMC
September 2020

Influence of non-steroidal anti-inflammatory drugs on the inflammatory sonographic features in erosive hand osteoarthritis: an intervention study.

Rheumatol Adv Pract 2020 28;4(1):rkaa002. Epub 2020 Jan 28.

Department of Internal Medicine, Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium.

Objective: The aim was to examine whether inflammatory US features in erosive hand OA patients change when discontinuing intake of NSAIDs before US examination in a non-randomized study.

Methods: Patients ( = 99) were allocated to the NSAIDs or control group according to their intake at baseline. US was performed at baseline (T0) and 2 weeks after discontinuation of NSAIDs (T1). Inflammatory features (i.e. synovial proliferation, effusion and power Doppler signal) were scored using a semi-quantitative scale (from zero to three). Pain levels were scored on a numerical rating scale. Binomial mixed models were fitted for US features, and odds ratios of having a US score of at least two at most one for synovial proliferation and effusion, and zero at least one for power Doppler were calculated.

Results: At baseline, both groups [NSAIDs group ( = 47) control group ( = 52)] were comparable for numerical rating scale pain, disease duration, number of radiographically affected joints, BMI and US baseline data, but not for age ( = 0.005). At T1, more synovial proliferation and power Doppler signal was seen compared with T0 in the NSAIDs group ( = 0.018 and 0.031, respectively). However, the interaction term time*NSAIDs was not found to be significant for any variable. The numerical rating scale pain at T1 was higher compared with baseline, although statistically non-significant.

Conclusion: No significant changes in inflammatory US features were seen in patients with erosive hand OA after withdrawal of NSAIDs for 2 weeks. This study suggests that an NSAID-free period is not necessary before assessing inflammatory disease activity in erosive hand OA.
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http://dx.doi.org/10.1093/rap/rkaa002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032542PMC
January 2020

Report from the Hand Osteoarthritis Working Group at OMERACT 2018: Update on Core Instrument Set Development.

J Rheumatol 2019 09 15;46(9):1183-1187. Epub 2019 Jan 15.

From the Department of Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium; Department of Rheumatology, and Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Division of Academic Rheumatology, University of Nottingham; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; National Institute for Health Research (NIHR), Leeds Biomedical Research Centre, Leeds, UK; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway; Department of Rheumatology, Sorbonne Université, INSERM, Saint-Antoine Hospital AP-HP, DHU i2B, Paris, France; Department of Medicine, Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Objective: To evaluate hand osteoarthritis tools for core instrument set development.

Methods: For OMERACT 2018, a systematic literature review and advances in instrument validation were presented.

Results: Visual analog and numerical rating scales were considered valuable for pain and patient's global assessment, despite heterogeneous phrasing and missing psychometric evidence for some aspects. The Modified Intermittent and Constant Osteoarthritis Pain scale was lacking evidence. The Michigan Hand Outcomes Questionnaire had advantages above other pain/function questionnaires. The Hand Mobility in Scleroderma scale was valid, although responsiveness was questioned. Potential joint activity instruments were evaluated.

Conclusion: The development of the core instrument set is progressing, and a research agenda was also developed.
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http://dx.doi.org/10.3899/jrheum.181003DOI Listing
September 2019

RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients.

Nat Commun 2019 01 2;10(1). Epub 2019 Jan 2.

Department of Rheumatology, Faculty of Medicine and Health Sciences, Laboratory for Molecular Immunology and Inflammation, Ghent University, C. Heymanslaan 10, 9000, Ghent, Belgium.

Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). RORγt, the key Thelper17 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and γδ-T cells, but their contribution to SpA is still unclear. Here we describe the presence of particular RORγtT-betPLZF iNKT and γδ-hi T cell subsets in healthy peripheral blood. RORγt iNKT and γδ-hi T cells show IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of SpA patients where they act as major IL-17 secretors. SpA derived iNKT and γδ-T cells showed unique and Th17-skewed phenotype and gene expression profiles. Strikingly, RORγt inhibition blocked γδ17 and iNKT17 cell function while selectively sparing IL-22 subsets. Overall, our findings highlight a unique diversity of human RORγt T cells and underscore the potential of RORγt antagonism to modulate aberrant type 17 responses.
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http://dx.doi.org/10.1038/s41467-018-07911-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315029PMC
January 2019

Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1α and anti-interleukin-1β dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis.

Ann Rheum Dis 2019 03 14;78(3):413-420. Epub 2018 Dec 14.

Immunology Development, AbbVie, North Chicago, Illinois, USA.

Objective: To assess the efficacy, safety, pharmacokinetics and pharmacodynamics of the anti-interleukin (IL)-1α/β dual variable domain immunoglobulin lutikizumab (ABT-981) in erosive hand osteoarthritis (HOA).

Methods: Patients with ≥1 erosive and ≥3 tender and/or swollen hand joints were randomised to placebo or lutikizumab 200 mg subcutaneously every 2 weeks for 24 weeks. The primary endpoint was change in Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain subdomain score from baseline to 16 weeks. At baseline and week 26, subjects had bilateral hand radiographs and MRI of the hand with the greatest number of baseline tender and/or swollen joints. Continuous endpoints were assessed using analysis of covariance models, with treatment and country as main factors and baseline measurements as covariates.

Results: Of 132 randomised subjects, 1 received no study drug and 110 completed the study (placebo, 61/67 (91%); lutikizumab, 49/64 (77%)). AUSCAN pain was not different among subjects treated with lutikizumab versus placebo at week 16 (least squares mean difference, 1.5 (95% CI -1.9 to 5.0)). Other clinical and imaging endpoints were not different between lutikizumab and placebo. Lutikizumab significantly decreased serum high-sensitivity C reactive protein levels, IL-1α and IL-1β levels, and blood neutrophils. Lutikizumab pharmacokinetics were consistent with phase I studies and not affected by antidrug antibodies. Injection site reactions and neutropaenia were more common in the lutikizumab group; discontinuations because of adverse events occurred more frequently with lutikizumab (4/64) versus placebo (1/67).

Conclusion: Despite adequate blockade of IL-1, lutikizumab did not improve pain or imaging outcomes in erosive HOA compared with placebo.
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http://dx.doi.org/10.1136/annrheumdis-2018-213336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390132PMC
March 2019

Etanercept in patients with inflammatory hand osteoarthritis (EHOA): a multicentre, randomised, double-blind, placebo-controlled trial.

Ann Rheum Dis 2018 12 3;77(12):1757-1764. Epub 2018 Oct 3.

Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.

Objective: Hand osteoarthritis is a prevalent disease with limited treatment options. Since joint inflammation is often present, we investigated tumour necrosis factor (TNF) as treatment target in patients with proven joint inflammation in a proof-of-concept study.

Methods: This 1-year, double-blind, randomised, multicentre trial (NTR1192) enrolled patients with symptomatic erosive inflammatory hand osteoarthritis. Patients flaring after non-steroidal anti-inflammatory drug washout were randomised to etanercept (24 weeks 50 mg/week, thereafter 25  mg/week) or placebo. The primary outcome was Visual Analogue Scale (VAS) pain at 24 weeks. Secondary outcomes included clinical and imaging outcomes (radiographs scored using Ghent University Scoring System (GUSS, n=54) and MRIs (n=20)).

Results: Of 90 patients randomised to etanercept (n=45) or placebo (n=45), respectively, 12 and 10 discontinued prematurely. More patients on placebo discontinued due to inefficacy (6 vs 3), but fewer due to adverse effects (1 vs 6). The mean between-group difference (MD) in VAS pain was not statistically significantly different (-5.7 (95% CI -15.9 to 4.5), p=0.27 at 24 weeks; - 8.5 (95% CI -18.6 to 1.6), p=0.10 at 1  year; favouring etanercept). In prespecified per-protocol analyses of completers with pain and inflammation at baseline (n=61), MD was -11.8 (95% CI -23.0 to -0.5) (p=0.04) at 1  year. Etanercept-treated joints showed more radiographic remodelling (delta GUSS: MD 2.9 (95% CI 0.5 to 5.4), p=0.02) and less MRI bone marrow lesions (MD -0.22 (95% CI -0.35 to -0.09), p = 0.001); this was more pronounced in joints with baseline inflammation.

Conclusion: Anti-TNF did not relieve pain effectively after 24 weeks in erosive osteoarthritis. Small subgroup analyses showed a signal for effects on subchondral bone in actively inflamed joints, but future studies to confirm this are warranted.
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http://dx.doi.org/10.1136/annrheumdis-2018-213202DOI Listing
December 2018

Repetitive Knee Bending and Synovitis in Individuals at Risk of and With Knee Osteoarthritis: Data From the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium.

Arthritis Care Res (Hoboken) 2019 10;71(10):1372-1378

Ghent University, Ghent, Belgium.

Objective: To investigate associations between engagement in knee bending (stair climbing, kneeling, squatting, heavy lifting, getting in/out of a squatting position) and synovitis prevalence on noncontrast magnetic resonance imaging (MRI) in individuals at risk of and with knee osteoarthritis.

Methods: We included baseline data from 594 participants (mean ± SD age 61.5 ± 8.9 years, 61% had Kellgren/Lawrence grade ≥2; 59% were female; mean ± SD body mass index was 30.7 ± 4.8 kg/m ) of the Osteoarthritis Biomarker Consortium Foundation for the National Institutes of Health project. Knee bending activities were queried by a standard questionnaire, and the severity of Hoffa synovitis and effusion synovitis (surrogate outcomes of synovitis) were graded using the MRI OsteoArthritis Knee Scoring system. Logistic regression was used, unadjusted and adjusted, for metabolic syndrome, physical activity level, and sex. A grade ≥1 defined synovitis prevalence, with a grade ≥2 cutoff implemented in sensitivity analyses.

Results: The prevalence of grade ≥1 Hoffa synovitis and effusion synovitis equaled 59% (n = 353) and 62% (n = 366), respectively. Adjusted for confounders, kneeling for ≥30 minutes during a single day was associated with grade ≥1 Hoffa synovitis prevalence (odds ratio [OR] 1.65 [95% confidence interval (95% CI) 1.11-2.47]). Participants engaging in this activity ≤1 day per week had greater odds for prevalent Hoffa synovitis than those who did not perform the activity (OR 1.88 [95% CI 1.11-3.18]). No other significant associations were found. Sensitivity analyses yielded similar findings.

Conclusion: In this selected sample with a preponderance of grade ≥1 Hoffa and/or effusion synovitis on noncontrast MRI, only prolonged kneeling was associated with Hoffa synovitis prevalence. Replication in other samples is warranted.
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http://dx.doi.org/10.1002/acr.23760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421112PMC
October 2019

2018 update of the EULAR recommendations for the management of hand osteoarthritis.

Ann Rheum Dis 2019 01 28;78(1):16-24. Epub 2018 Aug 28.

Instituto de Salud Musculoesquelética, Madrid, Spain.

Since publication of the European League Against Rheumatism (EULAR) recommendations for management of hand osteoarthritis (OA) in 2007 new evidence has emerged. The aim was to update these recommendations. EULAR standardised operating procedures were followed. A systematic literature review was performed, collecting the evidence regarding all non-pharmacological, pharmacological and surgical treatment options for hand OA published to date. Based on the evidence and expert opinion from an international task force of 19 physicians, healthcare professionals and patients from 10 European countries formulated overarching principles and recommendations. Level of evidence, grade of recommendation and level of agreement were allocated to each statement. Five overarching principles and 10 recommendations were agreed on. The overarching principles cover treatment goals, information provision, individualisation of treatment, shared decision-making and the need to consider multidisciplinary and multimodal (non-pharmacological, pharmacological, surgical) treatment approaches. Recommendations 1-3 cover different non-pharmacological treatment options (education, assistive devices, exercises and orthoses). Recommendations 4-8 describe the role of different pharmacological treatments, including topical treatments (preferred over systemic treatments, topical non-steroidal anti-inflammatory drugs (NSAIDs) being first-line choice), oral analgesics (particularly NSAIDs to be considered for symptom relief for a limited duration), chondroitin sulfate (for symptom relief), intra-articular glucocorticoids (generally not recommended, consider for painful interphalangeal OA) and conventional/biological disease-modifying antirheumatic drugs (discouraged). Considerations for surgery are described in recommendation 9. The last recommendation relates to follow-up. The presented EULAR recommendations provide up-to-date guidance on the management of hand OA, based on expert opinion and research evidence.
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http://dx.doi.org/10.1136/annrheumdis-2018-213826DOI Listing
January 2019

Diet-induced weight loss alone or combined with exercise in overweight or obese people with knee osteoarthritis: A systematic review and meta-analysis.

Semin Arthritis Rheum 2019 04 21;48(5):765-777. Epub 2018 Jun 21.

Department of Rehabilitation Sciences, Ghent University Hospital Campus, Corneel Heymanslaan 10, Building 3B3, 9000 Ghent, Belgium. Electronic address:

Objectives: The purposes were to (i) determine the effect of diet-only treatments and combined diet and exercise treatments on pain and physical function and (ii) explore the effect of these treatments on inflammatory biomarkers in overweight and obese adults with knee osteoarthritis.

Methods: Five electronic databases were searched until March 2017. Randomised controlled trials investigating the effect of non-surgical non-pharmacological weight loss treatment, with or without exercise, on self-reported pain and/or physical function and/or inflammatory biomarkers were selected. Two review authors independently extracted data and assessed risk of bias for each study. Standardised mean differences (SMD) of outcomes were pooled as appropriate, using a random effects approach.

Results: 2676 articles were identified, 19 met review criteria and 9 met criteria for meta-analyses. Diet-only treatments did not reduce pain (SMD -0.13; 95% confidence interval, CI: -0.37, 0.10; I = 49%) while a combination of diet and exercise treatments did reduce pain moderately (SMD -0.37; 95%CI: -0.69, -0.04; I = 54%). Physical function improved moderately with diet treatments (SMD -0.30; 95%CI: -0.52, -0.08; I = 47%) and combined diet and exercise treatments (SMD -0.32; 95%CI: -0.56, -0.08; I = 24%). Of the inflammatory markers assessed, only IL-6 reduced with diet-only treatments (SMD -0.23; 95%CI: -0.45, -0.02; I = 0%).

Conclusion: Overall, moderate pain-relief is achievable with a combination of diet and exercise, but potentially not with diet-only treatments. Findings support that either diet-only treatments or combined diet and exercise treatments moderately improve physical function. Overall, treatment effects on inflammatory biomarkers are questionable.
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http://dx.doi.org/10.1016/j.semarthrit.2018.06.005DOI Listing
April 2019

To be or not to be rheumatologist: survey among Belgian medical students and internal medicine trainees: what do certified rheumatologists think about the current rheumatology training program?

Clin Rheumatol 2017 Dec 15;36(12):2805-2812. Epub 2017 May 15.

Department Rheumatology, University Hospital Ghent, De Pintelaan 185, 9000, Ghent, Belgium.

In several countries, there have been increasing concerns over the years that fewer medical students or trainees choose rheumatology as a specialty. The aim of this three-step survey is to study the motivational factors for students and trainees in internal medicine to choose for rheumatology as a future career option and the idea among experienced rheumatologists about the needs for changes in the training program. An online survey was distributed among students in medical training (in the final 3 years) and trainees in internal medicine from the Ghent University and University Hospital. Questions concerned the level of clinical exposure to rheumatology and the motivation about becoming rheumatologist. Next, experienced rheumatologists were asked about the needs to change the current training. Descriptive data are shown and chi-squared tests were calculated to assess differences between groups (based on gender and exposure). Logistic regression was performed to study associations between demographic variables and choosing rheumatology as career. Only a minority of students (17%) and about half of trainees (45%) were ever exposed to rheumatology. Only 11% of students and 17% of trainees considered becoming rheumatologist. There was no difference in choice based on gender but previous exposure seemed to play an important role, and especially during the pre-specialty years. Univariate logistic regression identified the year of training and exposure as predictors for choosing rheumatology. Multivariate analysis only retained exposure as significantly associated (odds ratio (95% CI) = 2.88 (1.51-12.58)). Rheumatology is considered to be a fascinating discipline among Belgian students and trainees. Exposure during pre-specialty years is the strongest predictor for choosing rheumatology as future career option.
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http://dx.doi.org/10.1007/s10067-017-3673-yDOI Listing
December 2017

Hand-related physical function in rheumatic hand conditions: a protocol for developing a patient-reported outcome measurement instrument.

BMJ Open 2016 12 14;6(12):e011174. Epub 2016 Dec 14.

The Parker Institute, Bispebjerg & Frederiksberg Hospital, Copenhagen, Denmark.

Introduction: There is no consensus about what constitutes the most appropriate patient-reported outcome measurement (PROM) instrument for measuring physical function in patients with rheumatic hand conditions. Existing instruments lack psychometric testing and vary in feasibility and their psychometric qualities. We aim to develop a PROM instrument to assess hand-related physical function in rheumatic hand conditions.

Methods And Analysis: We will perform a systematic search to identify existing PROMs to rheumatic hand conditions, and select items relevant for hand-related physical function as well as those items from the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) item bank that are relevant to patients with rheumatic hand conditions. Selection will be based on consensus among reviewers. Content validity of selected items will be established through the use of focus groups. If patients deem necessary, we will develop new items based on the patients' input. We will examine whether it is valid to score all selected and developed items on the same scale as the original items from the PROMIS PF item bank. Our analyses will follow the methods used for calibrating the original PROMIS PF item bank in US samples, which were largely based on the general PROMIS approach.

Ethics And Dissemination: This study will be carried out in accordance with the Helsinki Declaration. Ethics approvals will be obtained where necessary, and signed informed consent will be obtained from all participants. We aim to disseminate the results of the study through publication in international peer-reviewed journals and at international conferences.
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http://dx.doi.org/10.1136/bmjopen-2016-011174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5168653PMC
December 2016

Translation of clinical problems in osteoarthritis into pathophysiological research goals.

RMD Open 2016 26;2(1):e000224. Epub 2016 May 26.

Laboratory of Tissue Homeostasis and Disease, Department of Development and Regeneration, KU Leuven and Division of Rheumatology , Skeletal Biology and Engineering Research Center, University Hospitals Leuven , Leuven , Belgium.

Osteoarthritis (OA) accounts for more disability among the elderly than any other disease and is associated with an increased mortality rate. The prevalence in Europe will rise in the future since this continent has a strongly ageing population and an obesity epidemic; obesity and age both being major risk factors for OA. No adequate therapeutic options, besides joint replacement, are available, although they are greatly needed and should be acquired by adequate research investments. However, the perspective on OA from a researcher's point of view is not always aligned with the perspective of a patient with OA. Researchers base their views on OA mainly on abnormalities in structure and function while patients consider OA as a collection of symptoms. In this viewpoint paper, we discuss the possibility of translating the most important clinical problems into pathophysiological research goals to facilitate the translation from bench to bedside and vice versa. This viewpoint is the outcome of a dialogue within the 'European League Against Rheumatism study group on OA' and People with Arthritis/Rheumatism across Europe (PARE) representatives.
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http://dx.doi.org/10.1136/rmdopen-2015-000224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885448PMC
June 2016

Sustained response to tocilizumab in a patient with relapsing polychondritis with aortic involvement: a case based review.

Clin Rheumatol 2015 Jan 16;34(1):189-93. Epub 2014 May 16.

Department of Rheumatology, University Hospital of Ghent, De Pintelaan 185, 9000, Ghent, Belgium,

This paper presents a case with refractory relapsing polychondritis (RPC), complicated with severe aortic involvement, which is successfully treated with tocilizumab. Previous treatments consisted of methotrexate, corticosteroids, cyclosporine, cyclophosphamide, infliximab, and etanercept. With these treatments, the patient had recurrent episodes of fever, polyarthritis, tenosynovitis, subcutaneous nodules, and progressive cardiac disease. One year after the start of treatment with tocilizumab, there is resolution of all symptoms, normalization of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and the dose of prednisolone is tapered down to 2 mg/day. We have reviewed the English literature for reports of patients with refractory RPC, successfully treated with tocilizumab. We found five additional case reports. In one case report, a patient with refractory RPC complicated with aortitis was successfully treated with tocilizumab. In three case reports, patients with refractory RPC complicated with laryngotracheal involvement were successfully treated with tocilizumab. All cases had, like our patient, failed conventional treatment. We also reviewed the literature for reports of the effect of biologicals on cardiac involvement in RPC. Current literature is presented and discussed.
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http://dx.doi.org/10.1007/s10067-014-2670-7DOI Listing
January 2015

Predictors of functional impairment and pain in erosive osteoarthritis of the interphalangeal joints: comparison with controlled inflammatory arthritis.

Arthritis Rheum 2012 May;64(5):1430-6

University Hospital Ghent, Ghent, Belgium.

Objective: To compare levels of pain and functional limitation in patients with erosive osteoarthritis (OA) of the interphalangeal finger joints with those in patients with nonerosive OA and patients with controlled inflammatory arthritis affecting the hands, and to explore predictors of functional impairment in erosive OA.

Methods: A cross-sectional study including 270 patients with OA of the hands who were referred to rheumatology clinics was performed. A group of patients with inflammatory arthritis (rheumatoid arthritis or psoriatic arthritis) with a low Disease Activity Score in 28 joints (<3.2; n = 79) was examined. Levels of functional impairment (measured by the Functional Index for Hand OA [FIHOA] and Australian/Canadian OA Hand Index [AUSCAN]) and pain were compared between the groups. Predictors of functional impairment in erosive OA were evaluated by generalized linear models.

Results: Of 270 patients with hand OA, 167 (61.9%) were classified as having erosive OA. Despite a higher percentage of patients taking analgesics (almost 60%), patients with erosive OA had worse functional outcome and pain scores than patients with controlled inflammatory arthritis or nonerosive OA. Pain scores remained significantly higher in patients with erosive OA after correction for potential confounders. FIHOA and AUSCAN function scores showed a trend toward more disability in patients with erosive OA. Female sex and the number of radiographic affected joints (consisting of joints in the erosive and remodeled radiographic phases) were the strongest predictors of functional impairment in erosive OA. Whether the carpometacarpal joints were affected did not influence functional status in patients with erosive OA.

Conclusion: Our findings indicate that patients with erosive OA have more functional impairment and significantly more pain compared to patients with controlled inflammatory arthritis affecting the hands. This highlights the significant clinical burden of erosive OA and warrants the search for new treatment strategies.
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http://dx.doi.org/10.1002/art.33502DOI Listing
May 2012

Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: a double blind, randomised trial on structure modification.

Ann Rheum Dis 2012 Jun 29;71(6):891-8. Epub 2011 Nov 29.

Rheumatology Department, Ghent University Hospital, Ghent, Belgium.

Background: Adalimumab blocks the action of tumor necrosis factor-α and reduces disease progression in rheumatoid arthritis and psoriatic arthritis. The effects of adalimumab in controlling progression of structural damage in erosive hand osteoarthritis (HOA) were assessed.

Methods: Sixty patients with erosive HOA on radiology received 40 mg adalimumab or placebo subcutaneously every two weeks during a 12-month randomized double-blind trial. Response was defined as the reduction in progression of structural damage according to the categorical anatomic phase scoring system. Furthermore, subchondral bone, bone plate erosion, and joint-space narrowing were scored according to the continuous Ghent University Score System (GUSSTM).

Results: The disease appeared to be active since 40.0% and 26,7% of patients out of the placebo and adalimumab group, respectively, showed at least one new interphalangeal (IP) joint that became erosive during the 12 months follow-up. These differences were not significant and the overall results showed no effect of adalimumab. Risk factors for progression were then identified and the presence of palpable soft tissue swelling at baseline was recognized as the strongest predictor for erosive progression. In this subpopulation at risk, statistically significant less erosive evolution on the radiological image (3.7%) was seen in the adalimumab treated group compared to the placebo group (14.5%) (P = 0.009). GUSSTM scoring confirmed a less rapid rate of mean increase in the erosion scores during the first 6 months of treatment in patients in adalimumab-treated patients.

Conclusion: Palpable soft tissue swelling in IP joints in patients with erosive HOA is a strong predictor for erosive progression. In these joints adalimumab significantly halted the progression of joint damage compared to placebo.
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http://dx.doi.org/10.1136/ard.2011.149849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371224PMC
June 2012

Reliability and construct validity of ultrasonography of soft tissue and destructive changes in erosive osteoarthritis of the interphalangeal finger joints: a comparison with MRI.

Ann Rheum Dis 2011 Feb 15;70(2):278-83. Epub 2010 Nov 15.

Department of Rheumatology, University Hospital Ghent, Gent, Belgium.

Objectives: To study the reliability and construct validity of ultrasound in interphalangeal finger joints affected by erosive osteoarthritis (EOA) and non-EOA with MRI as the reference method.

Methods: 252 joints were examined by ultrasound, conventional radiography and clinical examination. Ultrasound was performed using a high-frequency linear transducer (12 × 18 MHz). On the same day, magnetic resonance images of 112 joints were obtained on a 3.0 T magnetic resonance unit. The ultrasound and MRI images were re-read independently by other readers unaware of the diagnosis, clinical and other imaging findings. Interobserver reliability was calculated by the percentage of exact agreement obtained and κ statistics. With MRI as the reference method, the sensitivity and specificity of ultrasound in detecting structural (bone erosions and osteophytes) and soft tissue (effusion and grey-scale synovitis) changes in EOA were calculated.

Results: Ultrasound and MRI were found to be more sensitive in detecting erosions than conventional radiography in EOA. A high agreement between ultrasound and MRI in the assessment of bone erosions (77.7%), osteophytes (75.9%) and synovitis (86.5%) was present. A high percentage of inflammatory changes was found in EOA, and in smaller amount in non-EOA, both confirmed by MRI. Good interobserver reliability of ultrasound was obtained for all variables (all median κ > 0.8).

Conclusion: Grey-scale ultrasound proved to be a reliable and valid imaging technique to assess erosions and soft tissue changes, compared with MRI as a reference method in EOA.
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http://dx.doi.org/10.1136/ard.2010.134932DOI Listing
February 2011

Structural and inflammatory sonographic findings in erosive and non-erosive osteoarthritis of the interphalangeal finger joints.

Ann Rheum Dis 2010 Dec 6;69(12):2173-6. Epub 2010 Aug 6.

Department of Rheumatology, University Hospital Gent, De Pintelaan, Gent, Belgium.

Objective: The objectives were: (1) to determine if ultrasound (US) can detect more erosions in erosive osteoarthritis (EOA) of the interphalangeal (IP) joints than conventional radiography (CR); and (2) to explore the frequency of structural and inflammatory findings in EOA and non-EOA.

Methods: Structural changes and the anatomical phase were scored on CR in IP joints of 31 patients with EOA and 7 patients with non-EOA. Structural and inflammatory changes were scored by US. The frequency of sonographic findings was compared between the anatomical phases and between EOA and non-EOA by generalised estimation equation (GEE) modelling.

Results: US detected 68 of 72 (94.4%) erosions seen on CR. US detected 45 additional erosive joints in EOA. The frequency of joint effusion and power Doppler signal was similar in EOA compared to non-EOA (p = 0.91 and p = 0.68, respectively). Statistically significantly more synovitis was present in full erosive phase compared to non-erosive phases in EOA (p=0.04). No differences in inflammatory findings were found between non-erosive phases in EOA and non-EOA.

Conclusion: US is capable of detecting erosions in radiographic non-erosive phases. The highest frequency of synovitis is present in erosive joints but inflammatory findings are common in all anatomical phases of EOA and non-EOA.
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http://dx.doi.org/10.1136/ard.2010.128504DOI Listing
December 2010

Morbid anatomy of 'erosive osteoarthritis' of the interphalangeal finger joints: an optimised scoring system to monitor disease progression in affected joints.

Ann Rheum Dis 2010 May 29;69(5):862-7. Epub 2009 Nov 29.

Department of Rheumatology, 0K12 IB - Ghent University Hospital, De Pintelaan, 185, B-9000 Gent, Belgium.

Objectives: To develop and validate a quantitative radiographic scoring system, the Ghent University Scoring System (GUSS), with better ability to detect progression over a shorter period of time in erosive osteoarthritis (OA) of the interphalangeal (IP) finger joints compared with the existing anatomic phase scoring system.

Methods: Thirty IP finger joints showing erosive features at baseline or follow-up were selected from 18 patients with erosive hand OA. Posteroanterior radiographs of these joints obtained at baseline, 6 and 12 months--totalling 90 images--were used for the study. All joints were first scored according to the original anatomic phase scoring system. Erosive progression and signs of repair or remodelling were then scored by indicating the proportion of normal subchondral bone, subchondral plate and joint space on an 11-point rating scale (range 0-100 with 10 unit increases). Inter- and intrareader reproducibility was studied using intraclass correlation coefficients (ICCs). Based on the within-variance of two readers, the smallest detectable change (SDC) was calculated and allowed identification of joints with changes above the SDC as 'progressors'.

Results: Longitudinal inter-reader ICC scores rated well for all variables and the total score (ICC 0.86-0.93). To identify 'real' change over background noise, a change of at least 40 units on the total score (range 0-300) over 12 months (SDC 0-12:36.0), and 50 units over 6 months (SDC 0-6:47.6) had to be present. 60% of the 30 joints were identified as 'progressors' over 6 months compared with 33.3% with the classical anatomical scoring system, and 70% versus 56.6%, respectively, over 12 months.

Conclusion: GUSS, is a reliable method to score radiographic change over time in erosive IP OA and detects more progression over a shorter period of time than the classical scoring system.
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http://dx.doi.org/10.1136/ard.2009.112714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925149PMC
May 2010

Clinical assessment in the spondyloarthropathies.

Adv Exp Med Biol 2009 ;649:1-16

Department of Rheumatology, University Hospital Ghent, Ghent, Belgium.

In order to measure disease activity, progression and response to therapy, it is important to use accurate, reliable and feasible outcome measures that can ideally be used in longitudinal cohorts, clinical trials and clinical practice. With emerging therapies, the focus on the methodology of outcome assessment has increased to ensure that discriminant and responsive instruments are used. This chapter reviews available measures of three major areas of disease impact in the spondyloarthropathies (disease activity, structural damage and functioning) and discusses the relevance for use in clinical practice. First, the outcome measures available for the assessment of different domains in ankylosing spondylitis, composite-indices and response criteria for use in clinical trials and clinical practice in ankylosing spondylitis are discussed. Secondly, the performance of these in psoriatic arthritis and more disease-specific instruments in psoriatic arthritis are discussed.
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http://dx.doi.org/10.1007/978-1-4419-0298-6_1DOI Listing
September 2009

Decrease of disease activity under ineffective therapy in DMARD-naive patients with early rheumatoid arthritis: role of antibody profiles and carriage of the HLA shared epitope in predicting decrease of disease activity.

J Rheumatol 2007 Oct;34(10):1992-6

Ghent University, Gent, Belgium.

Objective: To evaluate whether the baseline presence of rheumatoid arthritis (RA)-associated biomarkers could define subgroups of patients that are more prone to show a spontaneous decrease of RA disease activity. In a previous placebo-controlled phase II trial that failed to show any superiority of the experimental compound versus placebo, a remarkable decrease of such disease activity was observed despite the lack of effective treatment.

Methods: A subgroup of 83 disease modifying antirheumatic drug-naive RA patients with disease duration < 3 years was analyzed. Rheumatoid factor (RF), anti-citrullinated protein/peptide antibodies (ACPA), and HLA shared epitope (SE) were determined at baseline.

Results: RF-positive patients tended to have higher levels of disease activity at baseline compared to RF-negative patients [Disease Activity Score (DAS) 6.12 vs 5.65, p = 0.02 at screening], but the decrease in disease activity was similar in both subgroups (DAS -1.23 vs -1.07). In contrast, ACPA-positive patients showed similar baseline disease activity scores compared to ACPA-negative patients, but tended to show a smaller decrease of disease activity than patients without ACPA (Delta DAS -1.53 vs -0.79, p = 0.013). Presence of the HLA-SE seemed not to have any effect on the baseline DAS or on the spontaneous decrease of DAS.

Conclusion: The predictive value of baseline RA-associated biomarkers for spontaneous decrease of disease activity under placebo or ineffective treatment is limited. Yet the data analyzed here might be useful for the design of future placebo-controlled trials in RA.
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October 2007

Osteochondral repair in synovial joints.

Curr Opin Rheumatol 2007 May;19(3):265-71

Ghent University Hospital, Department of Rheumatology, Ghent, Belgium.

Purpose Of Review: One of the major challenges in rheumatology remains the induction of osteochondral repair in synovial joints. Remarkable progress has been made in controlling the inflammatory pathways of chronic synovitis and tissue damage in rheumatoid arthritis and spondyloarthropathy. Here, we provide an overview of the current knowledge on the mechanisms involved in osteochondral repair in degenerative joint diseases, as well as in immune mediated inflammatory arthritides, with special emphasis on tumor necrosis factor alpha and IL-1.

Recent Findings: Homeostasis of articular cartilage and subchondral bone are essential for maintaining the integrity of osteochondral structures within synovial joints. This is achieved by the regulation of a delicate balance between anabolic and catabolic signals. In articular cartilage one cell type, the chondrocyte, is responsible for regulation of homeostasis. In bone, however, two distinct cell types, osteoblasts and osteoclasts, are responsible for anabolic and catabolic pathways, respectively. In inflammatory joint disorders, this tight regulation is profoundly dysregulated, with tumor necrosis factor alpha acting as an important catalyst of a disturbed homeostasis, together with IL-1. Targeting these cytokines may restore the intrinsic repair capacity of osteochondral structures.

Summary: To restore catabolic cytokine balances appears to be a suitable strategy to promote osteochondral repair.
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http://dx.doi.org/10.1097/BOR.0b013e3280be58ffDOI Listing
May 2007
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