Désirée M F M van der Heijde

Leiden University Medical Centre, Leyden, South Holland, Netherlands

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Publications (32)162.05 Total impact

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    ABSTRACT: Rheumatoid arthritis (RA) that is negative for anticitrullinated protein antibodies (ACPA) is a subentity of RA, characterized by less severe disease. At the individual level, however, considerable differences in the severity of joint destruction occur. We performed a study on genetic factors underlying the differences in joint destruction in ACPA-negative patients. A genome-wide association study was done with 262 ACPA-negative patients with early RA included in the Leiden Early Arthritis Clinic and related to radiographic joint destruction over 7 years. Significant single-nucleotide polymorphisms (SNP) were evaluated for association with progression of radiographic joint destruction in 253 ACPA-negative patients with early RA included in the Better Anti-Rheumatic Farmaco Therapy (BARFOT) study. According to the Bonferroni correction of the number of tested SNP, the threshold for significance was p < 2 × 10(-7) in phase 1 and 0.0045 in phase 2. In both cohorts, joint destruction was measured by Sharp/van der Heijde method with good reproducibility. Thirty-three SNP associated with severity of joint destruction (p < 2 × 10(-7)) in phase 1. In phase 2, rs2833522 (p = 0.0049) showed borderline significance. A combined analysis of both the Leiden and BARFOT datasets of rs2833522 confirmed this association with joint destruction (p = 3.57 × 10(-9)); the minor allele (A) associated with more severe damage (for instance, after 7 yrs followup, patients carrying AA had 1.22 times more joint damage compared to patients carrying AG and 1.50 times more joint damage than patients carrying GG). In silico analysis using the ENCODE and Ensembl databases showed presence of H3K4me3 histone mark, transcription factors, and long noncoding RNA in the region of rs2833522, an intergenic SNP located between HUNK and SCAF4. Rs2833522 might be associated with the severity of joint destruction in ACPA-negative RA.
    The Journal of Rheumatology 06/2015; 72(Suppl 3). DOI:10.3899/jrheum.140741 · 3.19 Impact Factor
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    ABSTRACT: Back and joint pain are the most common extraintestinal symptoms reported by patients with inflammatory bowel disease (IBD). We assessed the impact of back/joint pain, illness perceptions and coping on quality of life (QOL) and work productivity in patients with IBD. Our cohort included 155 IBD patients with and 100 without arthropathy. Arthropathy was defined as daily back pain for ≥ three months and/or peripheral joint pain and/or joint swelling over the last year. At baseline and at 12 months, patients completed questionnaires on the extent of back/joint pain, IBD disease activity, illness perceptions, coping, QOL, and work productivity. The impact of back/joint pain, illness perceptions and coping on QOL and work productivity was determined, using linear mixed models. In total, 204 IBD patients (72% Crohn's disease, 40% male, mean age 44±14 years) completed questionnaires at both time points. At both time points, IBD patients with back/joint pain reported a significantly lower QOL and work productivity compared to IBD patients without back/joint pain. Predictors of low QOL were back/joint pain (ß -1.04, 95% CI -1.40,-0.68), stronger beliefs about the illness consequences (ß-0.39, 95% CI -0.59,-0.18) and emotional impact of IBD (ß -0.47, 95% CI -0.66,-0.28), and the coping strategy "decreasing activity" (ß -0.26, 95% CI-0.48,-0.03). Predictors of work productivity were back/joint pain (ß 0.22, 95% CI 0.07,0.37) and illness consequences (ß 0.14, 95% CI 0.06,0.22). Back/joint pain, illness perceptions and coping are significant predictors of QOL and work productivity, after controlling for disease activity. Copyright © 2014 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Journal of Crohn s and Colitis 12/2014; 9(3). DOI:10.1093/ecco-jcc/jju025 · 6.23 Impact Factor
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    ABSTRACT: Objective: To review the available literature on the likelihood of having cardiovascular (CV) risk factors and on developing CV comorbidities in patients with gout and/or asymptomatic hyperuricemia as an evidence base for generating multinational clinical practice recommendations in the 3e (Evidence, Expertise, Exchange) Initiative in Rheumatology. Methods: A systematic literature search was carried out using MEDLINE, EMBASE, and The Cochrane Library, and abstracts presented at the 2010/2011 meetings of the American College of Rheumatology (ACR) and the European League Against Rheumatism, searching for CV risk factors and new CV comorbidities in patients with asymptomatic hyperuricemia and/or a diagnosis of gout. Trials that fulfilled predefined inclusion criteria were systematically reviewed. Results: A total of 66 out of 8918 identified publications were included in this review. After assessment of the risk of bias, 32 articles with a high risk of bias were excluded. Data could not be pooled because of clinical and statistical heterogeneity. In general, both for asymptomatic hyperuricemia and for gout the hazard ratios for CV comorbidities were only modestly increased (1.5 to 2.0) as were the hazard ratios for CV risk factors, ranging from 1.4 to 2.0 for hypertension and from 1.0 to 2.4 for diabetes. Conclusion: Unlike the common opinion that patients with gout or hyperuricemia are at higher risk of developing CV disease, the actual risk to develop CV disease is either rather weak (for hyperuricemia) or poorly investigated (for gout).
    Journal of Rheumatology Supplement 09/2014; 92:9-14. DOI:10.3899/jrheum.140457
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    ABSTRACT: To assess the sequence and type of active joints in a cohort of newly diagnosed juvenile idiopathic arthritis (JIA) patients with full access to current treatment at first visit and during a follow-up period of 5-years, in order to identify an index joint/group of joints for magnetic resonance imaging in JIA. Patient charts of all consecutive newly diagnosed JIA patients with a follow-up duration of at least 5 years were analyzed. Patients were derived from two tertiary pediatric rheumatology centers. Patient characteristics and data concerning the presence of joints with arthritis and the use of medication were recorded. Findings from 95 JIA patients [39 (41 %) oligoarticular and 56 (59 %) polyarticular] were analyzed. At first visit, distribution of active joints among patients was as follows: knee (n = 70, 74 %), ankle (n = 55, 58 %), elbow (n = 23, 24 %), wrist (n = 23, 24 %), metacarpophalangeal (MCP) (n = 20, 21 %), proximal interphalangeal (PIP) (n = 13, 14 %), hip (n = 6, 6 %), shoulder (n = 5, 5 %), and distal interphalangeal (DIP) (n = 4, 4 %) joints. After a follow-up period of 5 years, the cumulative percentage of patients with specific joint involvement changed into: knee (n = 88, 93 %), ankle (n = 79, 83 %), elbow (n = 43, 45 %), wrist (n = 38, 40 %), MCP (n = 36, 38 %), PIP (n = 29, 31 %), shoulder (n = 20, 21 %), hip (n = 17, 19 %), and DIP (n = 9, 10 %) joints. Despite changes in treatment strategies over the years, the knee remains the most commonly involved joint at onset and during follow-up in JIA, followed by the ankle, elbow, and wrist. For the evaluation of outcome with MRI, the knee appears the most appropriate joint in JIA.
    Rheumatology International 08/2014; 35(2). DOI:10.1007/s00296-014-3108-x · 1.52 Impact Factor
  • Robert Hemke · Andrea S Doria · Nikolay Tzaribachev · Mario Maas · Désirée M F M van der Heijde · Marion A J van Rossum ·
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    ABSTRACT: Recent advances in magnetic resonance imaging (MRI) techniques have substantially improved the evaluation of joint pathologies in juvenile idiopathic arthritis (JIA). Because of the current availability of highly effective antirheumatic therapies and the unique and useful features of MRI, there is a growing need for an accurate and reproducible MRI assessment scoring system for JIA, such as the rheumatoid arthritis MRI Scoring (RAMRIS) for patients with rheumatoid arthritis (RA). To effectively evaluate the efficacy of treatment in clinical research trials, we need to develop and validate scoring methods to accurately measure joint outcomes, standardize imaging protocols for data acquisition and interpretation, and create imaging atlases to differentiate physiologic and pathologic joint findings in childhood and adolescence. Such a standardized, validated, JIA-MRI scoring method could be used as an outcome measure in clinical trials.
    The Journal of Rheumatology 11/2013; 41(2). DOI:10.3899/jrheum.131081 · 3.19 Impact Factor
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    ABSTRACT: Background: Anticitrullinated peptide antibodies (ACPA) and acute phase reactants may be increased before arthritis becomes clinically detectable, suggesting that the processes underlying rheumatoid arthritis (RA) start preclinically. Whether local inflammation occurs in the preclinical phase is unknown. Therefore, we studied the small joints of ACPA positive arthralgia patients for local subclinical inflammation. Methods: Imaging was performed using 1.5 T extremity MRI. Painful hand or foot joints of 21 ACPA positive arthralgia patients without clinical arthritis were imaged. For comparison, hand and foot joints of 22 ACPA positive RA patients and 19 symptom free controls were studied. Within ACPA positive arthralgia patients, painful and symptom free joint regions were imaged. Scoring was performed according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) method. Analyses were performed on joint region level and focused on inflammation (synovitis plus bone marrow oedema). Results: The mean combined inflammation scores of the metacarpophalangeal/proximal interphalangeal joints of controls, painful joints of ACPA positive arthralgia patients and ACPA positive RA patients were 0.1, 0.7 and 3.7, respectively (p<0.001). Likewise, the mean combined inflammation scores of the wrist were 0.9, 2.3 and 10.3, respectively (p<0.001) and that of the metatarsophalangeal joints 0.5, 0.9 and 3.8, respectively (p=0.10). At the MCP joints, the combined inflammation score was significantly correlated with C reactive protein and erythrocyte sedimentation rate levels (rs=0.83 and rs=0.78, respectively) Conclusions: The present data suggest that local subclinical inflammation occurs in ACPA positive arthralgia patients.
    Annals of the rheumatic diseases 01/2013; 72(9). DOI:10.1136/annrheumdis-2012-202628 · 10.38 Impact Factor
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    Maria H E Vossen · Alfons A den Broeder · Femke Hendriks-Roelofs · Désirée M F M van der Heijde · Monique Reijnierse ·
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    ABSTRACT: Objective: To assess characteristics of deployment of MRI of the SI joints (MR-SI) in patients with suspected axial spondyloarthritis (SpA) before and after a targeted intervention. Methods: In a retrospective chart review study, all MR-SI performed in the period 1 April 2004 to 31 December 2010 were collected. Inclusion criteria were complete patient data and MR-SI ordered by a rheumatologist for suspicion of axial SpA. MR-SI reports were graded as normal, suspected sacroiliitis or sacroiliitis. In April 2007 an intervention was made to improve deployment. Rheumatologists were provided with data on ordering behaviour, patient characteristics and MRI outcomes. An introduction on the effect of pretest chance on positive and negative predictive value was given; the burden for patients and costs was illustrated. An alternative behavioural strategy was offered in the form of a simple diagnostic algorithm. Percentages of MRIs and positive MRI for sacroiliitis were compared before and after intervention. Results: From April 2004 to April 2007, 198 MR-SIs were performed, of which 166 (83.9%) were normal, 5 (2.5%) were suspicious and 27 (13.6%) were positive. After the intervention, patients displayed significantly more SpA features. More optimal patient selection resulted in 79 MR-SI requests, a decrease of 60.1%. Fifty-seven (72.2%) reports were normal, 0 were suspicious and 22 (27.8%) were positive. Conclusion: A simple, one-time, five-step feedback intervention resulted in a 60% reduction in MR-SI requests with a doubling of the percentage of MR-SI positive for sacroiliitis. This approach may benefit future research in areas with diagnostic uncertainty and suboptimal testing.
    Rheumatology (Oxford, England) 01/2013; 52(5). DOI:10.1093/rheumatology/kes405 · 4.48 Impact Factor
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    ABSTRACT: The aim of this study was to define characteristic MRI findings in the spine of patients with axial spondyloarthritis (SpA) and provide a definition of a positive spinal MRI for inflammation and structural changes. Technical details of spinal MRI and the description of spinal lesions of both inflammation and structural changes were discussed in consecutive meetings of 10 experts of the Assessment in SpondyloArthritis international Society (ASAS). The discussions aimed at a broad consensus on definitions of 'a positive spinal MRI' for both types of lesions and were backed up by a systematic literature search. A total of six different types of lesions were described for inflammation--anterior/posterior spondylitis, spondylodiscitis, arthritis of costovertebral joints, arthritis of zygoapophyseal joints and enthesitis of spinal ligaments--and another four for structural changes--fatty deposition, erosions, syndesmophytes and ankylosis. In the literature review, four relevant papers were identified. Anterior/posterior spondylitis and fat depositions at vertebral edges were considered as the most typical findings in SpA. Based on expert consensus and taking the literature review into consideration, a positive spinal MRI for inflammation was defined as the presence of anterior/posterior spondylitis in ≥3 sites. Evidence of fatty deposition at several vertebral corners was found to be suggestive of axial SpA, especially in younger adults. ASAS members (n=56) approved these definitions by voting in January 2010. This consensus statement gives clear descriptions of disease-related spinal lesions and of definitions of a positive spinal MRI for inflammatory lesions (spondylitis) and structural changes (fat deposition). These definitions can be used to describe findings of spinal MRI in patients with SpA in daily practice and clinical studies.
    Annals of the rheumatic diseases 05/2012; 71(8):1278-88. DOI:10.1136/ard.2011.150680 · 10.38 Impact Factor
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    Rosaline van den Berg · Ewa Stanislawska-Biernat · Désirée M F M van der Heijde ·
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    ABSTRACT: To give an overview of the recommendations for the use of anti-TNF-α therapy in AS in 23 countries worldwide. The recommendations were collected, translated and a summary was checked by Assessment of SpondyloArthritis International Society (ASAS) members from the respective countries. The recommendations were compared with the ASAS recommendations (2006) on three aspects: patient selection for initiation of treatment (diagnosis, disease activity, previous treatment and contraindications), assessment of disease and assessment of response. The majority of the recommendations are similar to the ASAS recommendation with regard to patient selection, assessment of disease and treatment response. Additional objective assessments of disease activity are required in eight countries, leading to a more strict indication to start anti-TNF-α therapy. CONCLUSION; Most national recommendations follow the international ASAS recommendations, suggesting that the latter are widely implemented. This might contribute to comparable access with anti-TNF-α treatment across countries. This article shows that general consensus exists about the use of anti-TNF-α therapy in AS across the world, although some countries require additional objective signs of inflammation and/or more pre-treatment, which limits access.
    Rheumatology (Oxford, England) 12/2011; 50(12):2270-7. DOI:10.1093/rheumatology/ker270 · 4.48 Impact Factor
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    ABSTRACT: Human leucocyte antigen shared epitope (SE) alleles are associated with joint destruction, the presence of anticitrullinated protein antibodies (ACPA) and the ACPA fine specificity repertoire in rheumatoid arthritis (RA). A large variation in joint destruction is seen within the ACPA-positive patient population, and it is conceivable that certain ACPA reactivities contribute to radiological damage. The authors investigated whether ACPA fine specificities, which are formed under the influence of SE alleles, associate with the extent of radiographic joint damage. Antibodies recognising six citrullinated epitopes were determined in sera of 330 ACPA-positive RA patients genotyped for SE alleles. The association between SE alleles, ACPA fine specificity and radiographic joint damage was assessed using radiographic follow-up data. A second cohort of 154 RA patients with 5 and 10-year radiographic follow-up was used for replication. SE alleles predisposed to the recognition of certain citrullinated epitopes. However, none of the ACPA fine specificities studied influenced radiographic joint damage. Importantly, although SE alleles associated with radiographic damage in the total RA population, this association was no longer detectable after stratification for the presence of ACPA. SE alleles are instrumental in shaping the ACPA repertoire. However, ACPA fine specificities formed under the influence of SE alleles do not seem to affect joint destruction.
    Annals of the rheumatic diseases 06/2011; 70(8):1461-4. DOI:10.1136/ard.2010.146506 · 10.38 Impact Factor
  • Robert B M Landewé · Désirée M F M van der Heijde ·
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    ABSTRACT: Spondyloarthritis (SpA) is an umbrella term for a group of rheumatic diseases characterised by inflammation of the sacroiliac (SI) joints and vertebral column; today, differentiation is made between axial SpA and peripheral SpA. Ankylosing spondylitis (Bechterew's disease) is the most typical form of axial SpA whereby sacroiliitis can be found on X-rays of the SI joints. Axial SpA can, however, also be present without radiographic evidence of sacroiliitis. A range of SpA-related symptoms can also manifest themselves outside the musculoskeletal system, for example, uveitis, psoriasis and inflammatory intestinal diseases. Tumour necrosis factor (TNF)-α inhibitors play an important role in the treatment of SpA. New classification criteria have recently been established in which MRI of the SI joints and the presence of the HLA-B27 tissue antigen are key. Axial and peripheral SpA should be recognized early in order to be able to successfully treat these conditions.
    Nederlands tijdschrift voor geneeskunde 01/2011; 155(30-31):A3680.
  • Rosanne Koevoets · Cornelia F Allaart · Désireé M F M van der Heijde · Tom W J Huizinga ·

    The Journal of Rheumatology 12/2010; 37(12):2632-3. DOI:10.3899/jrheum.100552 · 3.19 Impact Factor
  • Rosaline van den Berg · Désirée M F M van der Heijde ·
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    ABSTRACT: The Assessment of SpondyloArthritis International Society (ASAS) group has recently developed criteria to classify patients with axial SpA with or without radiographic sacroiliitis, and criteria to classify patients with peripheral SpA. The ASAS axial criteria consist of 2 arms and can be applied in patients with back pain (>3 months almost every day). In one arm, imaging (radiographs and magnetic resonance imaging [MRI]) has an important role, in the other arm--HLA-B27. MRI can detect active inflammation and structural damage associated with SpA. According to the ASAS axial SpA criteria, patients with chronic back pain aged less than 45 years at onset can be classified as having axial SpA if sacroiliitis on imaging (radiographs or MRI) plus 1 further SpA feature are present, or if HLA-B27 plus 2 further SpA features are present. The ASAS peripheral criteria can be applied in patients with peripheral arthritis (usually asymmetric arthritis predominantly involving the lower limbs), enthesitis, or dactylitis. Patients can be classified as having peripheral SpA if 1 of the following features is present: uveitis, HLA-B27, preceding genitourinary or gastrointestinal infection, psoriasis, inflammatory bowel disease, sacroiliitis on imaging (radiographs or MRI), or if 2 of the following features besides the entry feature are present: arthritis, enthesitis, dactylitis, inflammatory back pain, or a positive family history of SpA.
    Polskie archiwum medycyny wewnȩtrznej 11/2010; 120(11):452-7. · 2.12 Impact Factor
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    ABSTRACT: The presence of anti-citrullinated protein antibodies (ACPA) is a powerful predictive factor for the development and progression of rheumatoid arthritis (RA). The ACPA response has been shown to consist of various isotypes, but the consequences of differences in isotype distribution have not been extensively investigated. To investigate the relationship between ACPA isotypes, disease progression and radiological outcome. ACPA isotypes were determined in sera of anti-cyclic citrullinated peptide 2-positive patients by enzyme-linked immunosorbent assay (ELISA). To investigate whether the ACPA response continues to evolve during disease development, the ACPA isotype profile during progression of undifferentiated arthritis (UA) to RA was studied. The association of disease progression with ACPA isotype use was assessed using long-term radiographic follow-up data from patients with RA in two independent cohorts. The ACPA isotype distribution did not expand during disease progression from UA to RA, but was relatively stable over time. In both RA cohorts, the baseline ACPA isotype profile was a significant predictor of disease severity, with more isotypes indicating a higher risk of radiographic damage (odds ratio for every additional isotype: 1.4 (95% CI 1.1 to 1.9) p<0.001). ACPA isotypes supplied additional prognostic information to ACPA status alone, even after correction for other predictive factors. The magnitude of the ACPA isotype profile at baseline reflects the risk of future radiographic damage. These results indicate that the presence and the constitution of the ACPA response are relevant to the disease course of RA.
    Annals of the rheumatic diseases 06/2010; 69(6):1110-6. DOI:10.1136/ard.2009.116384 · 10.38 Impact Factor
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    ABSTRACT: Autoantigen-specific immunotherapy by mucosal tolerance induction via the intranasal route is an attractive therapeutic option for the treatment of autoimmune diseases, including rheumatoid arthritis (RA). Human cartilage glycoprotein-39 (HC gp-39) has been identified as a potential key autoantigen in RA. Based on animal studies, intranasal administration of the autoantigen is hypothesised to induce immunological tolerance in patients with RA and to ameliorate disease activity. In a phase I/IIA clinical trial in patients with RA, intranasal application of HC gp-39 was safe and well tolerated. To investigate the efficacy of intranasally administered fully human, recombinant HC gp-39 (Org 39141) by a large clinical study. In a 13-week multicentre, double-blind, randomised, placebo-controlled, parallel-group, dose-finding, proof-of-concept trial, patients with RA (disease-modifying antirheumatic drug (DMARD) naive or after washout of DMARD treatment) were randomised to receive either intranasal applications of placebo or HC gp-39 in doses of 30, 150, 300 or 600 microg, once a week. The primary efficacy variable was the 28 joint count Disease Activity Score (DAS28). During the treatment period the DAS28 decreased similarly for all treatment groups-including placebo-indicating lack of efficacy of intranasal HC gp-39 treatment in the current setting. Safety variables were similar for all study groups. It was concluded that with the treatment protocol used (dose levels and frequency of dosing), intranasal treatment with Org 39141 was safe but did not result in more clinical improvement than in placebo-treated patients.
    Annals of the rheumatic diseases 09/2009; 69(9):1655-9. DOI:10.1136/ard.2009.117234 · 10.38 Impact Factor
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    ABSTRACT: To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis (RA) treated with methotrexate (MTX) versus those treated with infliximab plus MTX. Patients who had not previously been treated with MTX with active RA were randomly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. Radiographic joint damage was assessed using the modified Sharp/van der Heijde score (SHS). The relationship between disease activity measures at baseline and week 14, as well as those averaged over time, were examined in relation to the change in SHS from baseline through week 54. C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and swollen joint count were associated with greater joint damage progression in the MTX-only group, while none of these parameters was associated with progression in the infliximab plus MTX group. Mean changes in SHS among patients in the highest CRP (> or = 3 mg/dl) and ESR (> or = 52 mm/hour) tertiles in the MTX-only group were 5.62 and 5.89, respectively, compared with 0.73 and 1.12 in the infliximab plus MTX group (P < 0.001). Patients with greater joint damage at baseline (SHS > or = 10.5) showed less progression with infliximab plus MTX compared with MTX alone (-0.39 versus 4.11; P < 0.001). Patients receiving MTX alone who had persistently active disease at week 14 showed greater radiographic progression of joint damage than those taking MTX plus infliximab. High CRP level, high ESR, or persistent disease activity was associated with greater radiographic progression in the group taking MTX alone, while little radiographic progression was seen in patients receiving both MTX and infliximab, regardless of the abnormal levels of these traditional predictors.
    Arthritis & Rheumatology 04/2006; 54(3):702-10. DOI:10.1002/art.21678 · 7.76 Impact Factor
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    ABSTRACT: Magnetic resonance imaging (MRI) of the sacroiliac (SI) joints and the spine is increasingly important in the assessment of inflammatory activity and structural damage in clinical trials with patients with ankylosing spondylitis (AS). We investigated inter-reader reliability and sensitivity to change of several scoring systems to assess disease activity and change in disease activity in patients with AS. Twenty sets of consecutive MRI, derived from a randomized clinical trial comparing an active drug with placebo and selected on the basis of the presence of activity at baseline, were presented electronically to 7 experienced readers from different countries (Europe, Canada). Readers scored the MRI by 3 different methods including: a global score (grading activity per SI joint); a more comprehensive global score (grading activity per SI joint per quadrant); and a detailed scoring system [Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system], which scores 6 images, divided into quadrants, with additional scores for "depth" and "intensity." A fourth and a fifth scoring system were constructed afterwards. The fourth method included the SPARCC score minus the additional scores for "depth" and "intensity," and the fifth method included the SPARCC slice with the maximum score. Inter-reader reliability was investigated by calculating intraclass correlation coefficients (ICC) for all readers together and for all possible reader pairs. Sensitivity to change was investigated by calculating standardized response means (SRM) on change scores that were made positive. Overall inter-reader ICC per method were between 0.47 and 0.58 for scoring status, and between 0.40 and 0.53 for scoring change. ICC per possible reader pairs showed much more fluctuation per method, with lowest observed values close to zero (no agreement) and highest observed values over 0.80 (excellent agreement). In general, agreement of status scores was somewhat better than agreement of change scores, and agreement of the comprehensive SPARCC scoring system was somewhat better than agreement of the more condensed systems. Sensitivity to change differed per reader, but in general was somewhat better for the comprehensive SPARCC system. This experiment under "real life," far from optimal conditions demonstrates the feasibility of scoring exercises for method comparison, provides evidence for the reliability and sensitivity to change of scoring systems to be used in assessing activity of SI joints in clinical trials, and sets the conditions for further validation research in this field.
    The Journal of Rheumatology 11/2005; 32(10):2050-5. · 3.19 Impact Factor
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    Kay-Geert A Hermann · Robert B M Landewé · Jürgen Braun · Désirée M F M van der Heijde ·
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    ABSTRACT: Depiction of inflammatory lesions by magnetic resonance imaging (MRI) in ankylosing spondylitis (AS) is possible both by short-tau inversion recovery (STIR) imaging and by gadolinium-enhanced T1-weighted imaging with fat saturation (T1/Gd). The aim of this prospective study was to investigate whether Gd-enhanced sequences add relevant information compared to STIR imaging alone in the detection of active spinal lesions. MRI of the spine was performed in 48 patients with AS, who participated in a clinical trial of tumor necrosis factor blocking drugs, by STIR and T1/Gd at baseline and after 6 months. Images were evaluated separately for the 2 techniques by 2 readers blinded for true time sequence and treatment. The ASspiMRI-a scoring method was used, in which 23 vertebral units are graded for inflammation from 0 to 6 (total score 0 to 138). Mean scorings of both techniques within readers were in the same range (reader 1: STIR 7.8, T1/Gd 7.7; reader 2: STIR 4.4, T1/Gd 4.7). Intraclass correlation coefficients comparing STIR and T1/Gd where high for both status scores (reader 1: 0.88; reader 2: 0.90) and change scores (both readers: 0.88). Bland and Altman analysis for both sequences showed homogeneous interreader variability along the entire spectrum of scorings, for both status scores and change scores. Smallest detectable change for status scores was 6.2 for STIR and 6.7 for T1/Gd, and for change scores 6.5 and 6.3, respectively. Standardized response means were comparable for both methods (range: 0.80-1.09). In conclusion, both STIR and T1/Gd sequences measure inflammation of the spine, as well as change of inflammation, with a high level of agreement between the 2 sequences. For future clinical randomized trials with MRI of the spine as outcome measure, STIR could be considered for use as the sole imaging technique.
    The Journal of Rheumatology 11/2005; 32(10):2056-60. · 3.19 Impact Factor
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    ABSTRACT: Agreement on response criteria in rheumatoid arthritis (RA) has allowed better standardization and interpretation of clinical trial reports. With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. The threshold for MDA is between high disease activity and remission and, by definition, anyone in remission will also be in MDA. True remission is still rare in RA; in addition, the American College of Rheumatology definition is difficult to apply in the context of trials. Participants at OMERACT 6 in 2002 agreed on a conceptual definition of minimal disease activity (MDA): "that state of disease activity deemed a useful target of treatment by both the patient and the physician, given current treatment possibilities and limitations." To prepare for a preliminary operational definition of MDA for use in clinical trials, we asked rheumatologists to assess 60 patient profiles describing real RA patients seen in routine clinical practice. Based on their responses, several candidate definitions for MDA were designed and discussed at the OMERACT 7 in 2004. Feedback from participants and additional on-site analyses in a cross-sectional database allowed the formulation of 2 preliminary, equivalent definitions of MDA: one based on the Disease Activity Score 28 (DAS28) index, and one based on meeting cutpoints in 5 out the 7 WHO/ILAR core set measures. Researchers applying these definitions first need to choose whether to use the DAS28 or the core set definition, because although each selects a similar proportion in a population, these are not always the same patients. In both MDA definitions, an initial decision node places all patients in MDA who have a tender joint count of 0 and a swollen joint count of 0, and an erythrocyte sedimentation rate (ESR) no greater than 10 mm. If this condition is not met: * The DAS28 definition places patients in MDA when DAS28 < or = 2.85; * The core set definition places patients in MDA when they meet 5 of 7 criteria: (1) Pain (0-10) < or = 2; (2) Swollen joint count (0-28) < or = 1; (3) Tender joint count (0-28) < or = 1; (4) Health Assessment Questionnaire (HAQ, 0-3) < or = 0.5; (5) Physician global assessment of disease activity (0-10) < or = 1.5; (6) Patient global assessment of disease activity (0-10) < or = 2; (7) ESR < or = 20. This set of 2 definitions gained approval of 73% of the attendees. These (and other) definitions will now be subject to further validation in other databases.
    The Journal of Rheumatology 11/2005; 32(10):2016-24. · 3.19 Impact Factor
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    ABSTRACT: Magnetic resolution imaging (MRI) is a promising tool in the assessment of inflammation and structural damage in clinical trials in ankylosing spondylitis (AS). The ASAS/OMERACT MRI in AS working group, a collaborative initiative of rheumatologists and musculoskeletal radiologists with a special interest in this field, collected data on all available scoring methods for both sacroiliac (SI) joints and spine, and tested them with respect to the OMERACT filter. These data were presented together with the technical specifications of all methods at the OMERACT 7 conference. In addition, the results of 2 separate experiments on the inter-reader reliability of scoring methods to assess activity in SI joints, and on the comparison of STIR sequence versus T1 post-gadolinium (Gd) sequence for the spine, were presented. Thereafter, 8 groups discussed these data and proposed a research agenda, each on a different topic. This information was reported back to all participants and a prioritized research agenda was compiled by voting. Research on scoring methods for assessing disease activity, in both the spine and SI joints, was considered most important. Research on assessing structural damage was considered less important. The specific process and results of this initiative are discussed.
    The Journal of Rheumatology 11/2005; 32(10):2042-7. · 3.19 Impact Factor

Publication Stats

2k Citations
162.05 Total Impact Points


  • 2010-2014
    • Leiden University Medical Centre
      • Department of Rheumatology
      Leyden, South Holland, Netherlands
  • 2010-2013
    • Leiden University
      Leyden, South Holland, Netherlands
  • 2011
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Academic Medical Center
      Amsterdamo, North Holland, Netherlands
  • 2000-2009
    • Maastricht University
      • Interne Geneeskunde
      Maestricht, Limburg, Netherlands