Désirée M F M van der Heijde

Leiden University Medical Centre, Leyden, South Holland, Netherlands

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Publications (27)135.23 Total impact

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    ABSTRACT: 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.
    Journal of Rheumatology Supplement 09/2014; 92:9-14.
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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 (r(s)=0.83 and r(s)=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; · 9.27 Impact Factor
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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; · 4.44 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. · 9.27 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. · 4.44 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. · 9.27 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. · 3.17 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. · 2.05 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. · 9.27 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. · 9.27 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. · 7.87 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. · 3.17 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. · 3.17 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. · 3.17 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. · 3.17 Impact Factor
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    ABSTRACT: To examine the baseline demographic and disease characteristics that might influence improvement as measured by the Assessment in Ankylosing Spondylitis Response Criteria (ASAS 20) in patients with ankylosing spondylitis (AS). A multicenter Phase 3 study was performed to compare the safety and efficacy of 24 weeks of etanercept 25 mg subcutaneous injection twice weekly (n = 138) and placebo (n = 139) in patients with AS. The ASAS 20 was measured at multiple time points. Using a significance level of 0.05, a repeated measures logistic regression model was used to determine which baseline factors influenced response in the etanercept-treated patients during the 24-week double blind portion of the trial. The following baseline factors were used in the model: demographic and disease severity variables, concomitant medications, extra-articular manifestations, and HLA-B27 status. The predictive capability of the model was then tested on the patients receiving placebo after they had received open-label etanercept treatment. Baseline factors that were significant predictors of an ASAS 20 response in etanercept-treated patients were C-reactive protein (CRP), back pain score, and Bath Ankylosing Spondylitis Functional Index (BASFI) score. Although clinical response to etanercept was seen at all levels of baseline disease activity, responses were consistently more likely with higher CRP levels or back pain scores and less likely with increased BASFI scores at baseline. Higher CRP values and back pain scores and lower BASFI scores at baseline were significant predictors of a higher ASAS 20 response in patients with AS receiving etanercept but predictive value was of insufficient magnitude to determine treatment in individual patients.
    The Journal of Rheumatology 10/2005; 32(9):1751-4. · 3.17 Impact Factor
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    ABSTRACT: To compare the benefits of initiating treatment with methotrexate (MTX) and infliximab (anti-tumor necrosis factor alpha [anti-TNFalpha] monoclonal antibody) with those of MTX treatment alone in patients with rheumatoid arthritis (RA) of < or =3 years' duration. RA patients were eligible if they had active disease and no prior treatment with MTX or a TNFalpha inhibitor. One thousand forty-nine patients were randomly assigned in a 4:5:5 ratio to 3 treatment groups: MTX-placebo, MTX-3 mg/kg infliximab, and MTX-6 mg/kg infliximab. MTX dosages were rapidly escalated to 20 mg/week, and infliximab or placebo infusions were given at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. At week 54, the median percentage of American College of Rheumatology improvement (ACR-N) was higher for the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than for the MTX-placebo group (38.9% and 46.7% versus 26.4%, respectively; P < 0.001 for both comparisons). Patients in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups also showed less radiographic progression than those receiving MTX alone (mean +/- SD changes in van der Heijde modification of the total Sharp score at week 54: 0.4 +/- 5.8 and 0.5 +/- 5.6 versus 3.7 +/- 9.6, respectively; P < 0.001 for each comparison). In addition, physical function improved significantly more in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than in the MTX-placebo group. Infliximab therapy was associated with a significantly higher incidence of serious infections, especially pneumonia. For patients with active RA in its early stages, combination therapy with MTX and infliximab provides greater clinical, radiographic, and functional benefits than treatment with MTX alone.
    Arthritis & Rheumatology 11/2004; 50(11):3432-43. · 7.87 Impact Factor
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    ABSTRACT: Radiologic progression in rheumatoid arthritis (RA) is considered the consequence of persistent inflammatory activity. To determine whether a change in disease activity is related to a change in radiologic progression in individual patients, we investigated the longitudinal relationship between inflammatory disease activity and subsequent radiologic progression. The databases of the University Medical Center Nijmegen (UMCN) cohort and the Maastricht Combination Therapy in RA (COBRA) followup study cohort were analyzed. The UMCN cohort included 185 patients with early RA who were followed up for up to 9 years. Patients were assessed every 3 months for disease activity and every 3 years for radiologic damage. The COBRA cohort included 152 patients with early RA who were followed up for up to 6 years. Patients were assessed at least every year for disease activity and every 12 months for radiologic damage. Disease activity was assessed with the Disease Activity Score (DAS) (original DAS in the UMCN cohort, DAS28 in the COBRA cohort). Radiologic damage was measured by the Sharp/van der Heijde score in both cohorts. Data were analyzed with longitudinal regression analysis (generalized estimating equations [GEE]), using autoregression for longitudinal associations and radiologic damage as the dependent variable. Time, time(2) baseline predictors for radiologic progression and their interactions with time, as well as DAS/DAS28 (actual values or interval means and interval SDs of the means) were subsequently modeled as explanatory variables. Data analyzed by GEE showed a decrease in radiologic progression over time (regression coefficient for time(2) -1.0 [95% confidence interval -1.4, -0.6] in the UMCN cohort and -0.4 [95% confidence interval -0.8, 0.0] in the COBRA cohort). After adjustment for time effects and baseline predictors of radiologic progression and their interactions with time, a positive longitudinal relationship was indicated by autoregressive GEE between the mean interval DAS and radiologic progression in the UMCN cohort (regression coefficient 5.4 [95% confidence interval 2.1, 8.6]), and between the DAS28 and radiologic progression in the COBRA cohort (regression coefficient 1.4 [95% confidence interval 0.8, 2.0]). In the UMCN cohort, the SD of the mean interval DAS was independently longitudinally related to the radiologic progression over the same periods (regression coefficient 20.2 [95% confidence interval 7.2, 33.3]). In both cohorts, the longitudinal relationships between (fluctuations in) disease activity and radiologic progression were found selectively in rheumatoid factor (RF)-positive patients. Radiologic progression is not linear in individual patients. Fluctuations in disease activity are directly related to changes in radiologic progression, which supports the hypothesis that disease activity causes radiologic damage. This relationship might only exist in RF-positive patients.
    Arthritis & Rheumatology 08/2004; 50(7):2082-93. · 7.87 Impact Factor
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    ABSTRACT: To select the most appropriate radiologic scoring method for the evaluation of radiographic progression in ankylosing spondylitis (AS) in clinical trials. The validity of the currently available methods, the Bath Ankylosing Spondylitis Radiology Index (BASRI), the Stoke Ankylosing Spondylitis Spine Score (SASSS), and the modified SASSS (M-SASSS), was tested according to the aspects of the Outcome Measures in Rheumatology Clinical Trials filter: truth, discrimination (reliability and sensitivity to change), and feasibility, using radiographs of 133 patients at 4 different time points (baseline, 1 year, 2 years, and 4 years). One observer scored these sets in chronological order. To assess interobserver reliability, a second observer scored radiographs of 20 patients at the 4 different time points. After 4 years, 9% and 8% of patients showed changes >0 in the sacroiliac (SI) joints and hips, respectively. Independent of the method chosen, approximately 40% of patients showed changes in both the lumbar and cervical spine. Therefore, it was concluded that, for the assessment of progression, SI joints and hips are of minor importance. The intraclass correlation coefficient (ICC) varied from 0.87 to 0.98 and ICCs for intraobserver scores varied from 0.96 to 0.99. Concerning progression scores, only the ICC for the M-SASSS measured after 2 years remained acceptable (0.82). The intraobserver scores for progression after 2 years of followup were an ICC of 0.93 for the BASRI, an ICC of 0.79 for the SASSS, and an ICC of 0.95 for the M-SASSS. Concerning sensitivity to change, it was found that the M-SASSS classified the highest percentage of patients with a change >0. The M-SASSS is the most appropriate method by which to score the radiographic progression in AS patients in clinical trials.
    Arthritis & Rheumatology 08/2004; 50(8):2622-32. · 7.87 Impact Factor

Publication Stats

2k Citations
135.23 Total Impact Points


  • 2013
    • Leiden University Medical Centre
      • Department of Rheumatology
      Leyden, South Holland, Netherlands
  • 2005–2012
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, Germany
  • 2011
    • Academisch Medisch Centrum Universiteit van Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2003–2005
    • Maastricht University
      • Interne Geneeskunde
      Maastricht, Provincie Limburg, Netherlands
  • 2004
    • Radboud University Medical Centre (Radboudumc)
      Nymegen, Gelderland, Netherlands
  • 2002
    • VU University Medical Center
      Amsterdamo, North Holland, Netherlands