Maarten Boers

VU University Medical Center, Amsterdamo, North Holland, Netherlands

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Publications (445)2484.62 Total impact

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    ABSTRACT: Residual subclinical synovitis can still be present in joints of rheumatoid arthritis (RA) patients despite clinical remission and has been linked to ongoing radiological damage. The aim of the present study was to assess subclinical synovitis by positron emission tomography (PET; macrophage tracer 11 C-(R)-PK11195) in early RA patients with minimal disease activity without clinically apparent synovitis (MDA); and its relationship with clinical outcome and magnetic resonance imaging (MRI), respectively. Baseline PET and MRI of hands/wrists were performed in 25 early MDA RA patients (DAS 44 < 1.6; no tender/swollen joints) on combined DMARD therapy. PET tracer uptake (semi-quantitative score: 0–3) and MRI synovitis and bone marrow edema (OMERACT RAMRIS) were assessed in MCP, PIP and wrist joints (22 joints/patient; cumulative score). Eleven of 25 patients (44 %) showed enhanced tracer uptake in ≥ 1 joint. Fourteen of these 25 (56 %) patients developed a flare within 1 year: 8/11 (73 %) with a positive, and 6/14 (43 %) with a negative PET. In the latter, in 5/6 patients flare was located outside the scan region. Median cumulative PET scores of patients with a subsequent flare in the hands or wrists were significantly higher than those of patients without a flare (1.5 [IQR 0.8–5.3] vs 0.0 [IQR 0.0–1.0], p = 0.04); significance was lost when all flares were considered (1.0 [IQR 0.0–4.0] vs 0.0 [IQR 0.0–1.0], p = 0.10). No difference in cumulative MRI scores was observed between both groups. Positive PET scans were found in almost half of early RA patients with MDA. Patients with a subsequent flare in hand or wrist had higher cumulative PET scores but not MRI scores, suggesting that subclinical arthritis on PET may predict clinical flare in follow-up.
    Arthritis Research & Therapy 12/2015; 17(1). DOI:10.1186/s13075-015-0770-7 · 3.75 Impact Factor
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    ABSTRACT: Objectives: To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naïve patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX). Methods: In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology-European League Against Rheumatism (OMERACT-EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT-EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2-5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy. Results: Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2-5): -0.7 (95% CIs -1.2 to -0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8. Conclusions: In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment. Trial registration number: NCT00767325.
    Annals of the rheumatic diseases 11/2015; DOI:10.1136/annrheumdis-2015-207709 · 10.38 Impact Factor
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    ABSTRACT: Objective: The Outcome Measures in Rheumatology (OMERACT) polymyalgia rheumatica (PMR) working group aims to develop a core set of outcome measures to be used in clinical trials for PMR. Previous reports from OMERACT 11 included a qualitative study of the patient experience and a preliminary literature review. Methods: A 3-round Delphi survey of clinicians and patients with PMR was undertaken to identify a candidate core domain set for PMR research. Additionally, a literature review of outcome measures and their respective measurement instruments was undertaken. Meetings of patient research partners and clinicians were convened to review face validity of the provisional core domain set, which was subsequently presented and discussed at the OMERACT 12 congress. Results: Of the 60 clinicians taking part in round 1, 55 took part in round 2 and 51 in round 3. Of the 55 patients who took part in round 1, 46 and 35 took part in subsequent rounds. In total, 91% of participants in round 3 deemed the resulting draft core domain set reasonable. The literature review identified 28 studies for full review. Measurement instruments for each proposed domain were identified. Clinicians are highly aware of glucocorticoid-related adverse effects, but there is relatively little evidence about their true prevalence and severity, especially in PMR. Conclusion: A provisional core domain set, presented for clinical trials in PMR, comprises acute phase markers, physical function, death, glucocorticoid-related adverse events, and development of giant cell arteritis. Measurement instruments are suggested that may cover each domain, but these require formal validation for clinical trials in PMR.
    The Journal of Rheumatology 11/2015; DOI:10.3899/jrheum.141179 · 3.19 Impact Factor

  • Value in Health 11/2015; 18(7):A353. DOI:10.1016/j.jval.2015.09.652 · 3.28 Impact Factor

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    ABSTRACT: Purpose: The purpose of this study is to evaluate the efficacy of (18)F-FDG-PET as first-line diagnostic investigation, prior to performing a direct laryngoscopy with biopsy under general anesthesia, in patients suspected of recurrent laryngeal carcinoma after radiotherapy. Patients and methods: 150 patients suspected of recurrent T2-4 laryngeal carcinoma at least two months after prior (chemo)radiotherapy with curative intent for resectable disease were randomized to direct laryngoscopy (CWU: conventional workup strategy) or to (18)F-FDG-PET only followed by direct laryngoscopy if PET was assessed 'positive' or 'equivocal' (PWU: PET based workup strategy), to compare the effectiveness of these strategies. Primary endpoint was the number of indications for direct laryngoscopies classified as unnecessary based on absence of recurrence, both on direct laryngoscopy and on six month follow up. Safety endpoints comprised resectability of recurrent lesions and completeness of surgical margins following salvage laryngectomy. Results: Intention-to-treat analyses were performed on all randomized patients (CWU: n=74, PWU: n=76). Tumor recurrence was similar in both groups: 45 patients (30%; 21 CWU, 24 PWU) within six months. In 53 patients in the CWU arm (72%, 95% CI: 60-81) unnecessary direct laryngoscopies were performed compared to 22 in the PWU arm (29%, 95% CI: 19-40) (p<0·0001). The percentage of salvage laryngectomies (resectability) and positive surgical margins were similar between CWU and PWU (81%, 63% respectively, p=0·17, and 29%, 7%, respectively, p=0.20). The prevalence of the combination of local unresectability and positive margins is in the CWU group 24% and in the PWU group 8%. No difference (p=0.32) in disease specific survival between both groups was found. Conclusion: In patients with suspected laryngeal carcinoma after radiotherapy, PET as the first diagnostic procedure can reduce the need for direct laryngoscopy by more than 50% without jeopardizing quality of treatment.
    Radiotherapy and Oncology 10/2015; DOI:10.1016/j.radonc.2015.10.010 · 4.36 Impact Factor
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    ABSTRACT: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of linked multisystem life- and organ-threatening diseases. The Outcome Measures in Rheumatology (OMERACT) vasculitis working group has been at the forefront of outcome development in the field and has achieved OMERACT endorsement of a core set of outcomes for AAV. Patients with AAV report as important some manifestations of disease not routinely collected through physician-completed outcome tools; and they rate common manifestations differently from investigators. The core set includes the domain of patient-reported outcomes (PRO). However, PRO currently used in clinical trials of AAV do not fully characterize patients' perspectives on their burden of disease. The OMERACT vasculitis working group is addressing the unmet needs for PRO in AAV. Current activities of the working group include (1) evaluating the feasibility and construct validity of instruments within the PROMIS (Patient-Reported Outcome Measurement Information System) to record components of the disease experience among patients with AAV; (2) creating a disease-specific PRO measure for AAV; and (3) applying The International Classification of Functioning, Disability and Health to examine the scope of outcome measures used in AAV. The working group has developed a comprehensive research strategy, organized an investigative team, included patient research partners, obtained peer-reviewed funding, and is using a considerable research infrastructure to complete these interrelated projects to develop evidence-based validated outcome instruments that meet the OMERACT filter of truth, discrimination, and feasibility. The OMERACT vasculitis working group is on schedule to achieve its goals of developing validated PRO for use in clinical trials of AAV.
    The Journal of Rheumatology 09/2015; 42(11). DOI:10.3899/jrheum.141143 · 3.19 Impact Factor
  • Lilian H D van Tuyl · Maarten Boers ·
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    ABSTRACT: Patient-reported outcomes (PROs) are abundant in rheumatology and their numbers continue to increase. But which of the available measures are most important? Core outcome sets-including groups of domains and instruments for measuring them-have been defined for many rheumatic diseases, with the aim that all these outcomes should be measured in every clinical trial. The subgroup of PROs included in these core sets is, therefore, undoubtedly important. This Review summarizes the PROs included in core outcome sets developed for use in clinical trials across a wide range of rheumatic diseases. Three PROs are commonly utilized across the majority of rheumatic conditions: pain, physical functioning and the patient global assessment of disease activity. However, additional research is needed to fully understand the role of the patient global assessment of disease activity, to distinguish specific domains within the broad concept of health-related quality of life, and to work towards consensus on the choice between generic and disease-specific instruments in various contexts.
    Nature Reviews Rheumatology 09/2015; DOI:10.1038/nrrheum.2015.116 · 9.85 Impact Factor
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    ABSTRACT: Objective: To evaluate the content validity and measurement properties of the Patient-Reported Outcome Measurement Information System (PROMIS) physical function item bank and a 20-item short form in patients with RA in comparison with the HAQ disability index (HAQ-DI) and 36-item Short Form Health Survey (SF-36) physical functioning scale (PF-10). Methods: The content validity of the instruments was evaluated by linking their items to the International Classification of Functioning, Disability and Health (ICF) core set for RA. The measures were administered to 690 RA patients enrolled in the Dutch Rheumatoid Arthritis Monitoring registry. Measurement precision was evaluated using item response theory methods and construct validity was evaluated by correlating physical function scores with other clinical and patient-reported outcome measures. Results: All 207 health concepts identified in the physical function measures referred to activities that are featured in the ICF. Twenty-three of 26 ICF RA core set domains are featured in the full PROMIS physical function item bank compared with 13 and 8 for the HAQ-DI and PF-10, respectively. As hypothesized, all three physical function instruments were highly intercorrelated (r 0.74-0.84), moderately correlated with disease activity measures (r 0.44-0.63) and weakly correlated with age (rs 0.07-0.14). Item response theory-based analysis revealed that a 20-item PROMIS physical function short form covered a wider range of physical function levels than the HAQ-DI or PF-10. Conclusion: The PROMIS physical function item bank demonstrated excellent measurement properties in RA. A content-driven 20-item short form may be a useful tool for assessing physical function in RA.
    Rheumatology (Oxford, England) 07/2015; DOI:10.1093/rheumatology/kev265 · 4.48 Impact Factor
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    Maarten Boers · Alfonso J Cruz Jentoft ·
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    ABSTRACT: Following a newly developed concept of health, this viewpoint suggests that the concept of frailty can usefully be defined as: the weakening of health, i.e. the resilience or capacity to cope, and to maintain and restore one's integrity, equilibrium, and sense of wellbeing in three domains: physical, mental, and social.
    Calcified Tissue International 07/2015; 97(5). DOI:10.1007/s00223-015-0038-x · 3.27 Impact Factor
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    ABSTRACT: The Dutch-Flemish PROMIS Group translated the adult PROMIS Pain Interference item bank into Dutch-Flemish. The aims of the current study were to calibrate the parameters of these items using an item response theory (IRT) model, to evaluate the cross-cultural validity of the Dutch-Flemish translations compared to the original English items, and to evaluate their reliability and construct validity. The 40 items in the bank were completed by 1085 Dutch chronic pain patients. Before calibrating the items, IRT model assumptions were evaluated using confirmatory factor analysis (CFA). Items were calibrated using the graded response model (GRM), an IRT model appropriate for items with more than two response options. To evaluate cross-cultural validity, differential item functioning (DIF) for language (Dutch vs. English) was examined. Reliability was evaluated based on standard errors and Cronbach's alpha. To evaluate construct validity correlations with scores on legacy instruments (e.g., the Disabilities of the Arm, Shoulder and Hand Questionnaire) were calculated. Unidimensionality of the Dutch-Flemish PROMIS Pain Interference item bank was supported by CFA tests of model fit (CFI = 0.986, TLI = 0.986). Furthermore, the data fit the GRM and showed good coverage across the pain interference continuum (threshold-parameters range: -3.04 to 3.44). The Dutch-Flemish PROMIS Pain Interference item bank has good cross-cultural validity (only two out of 40 items showing DIF), good reliability (Cronbach's alpha = 0.98), and good construct validity (Pearson correlations between 0.62 and 0.75). A computer adaptive test (CAT) and Dutch-Flemish PROMIS short forms of the Dutch-Flemish PROMIS Pain Interference item bank can now be developed.
    PLoS ONE 07/2015; 10(7):e0134094. DOI:10.1371/journal.pone.0134094 · 3.23 Impact Factor
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    ABSTRACT: To investigate the longitudinal relationship between disease activity and self-reported physical activity (PA) in patients with early rheumatoid arthritis during the first year of treatment with combination therapy. PA was measured with the Short QUestionnaire to ASsess Health-enhancing physical activity (SQUASH) at baseline, 13 weeks, 26 weeks, and 52 weeks after start of treatment in context of the COBRA-light trial. The reported PA classified patients as meeting or not meeting the World Health Organization (WHO) PA guideline (cut off: 150 minutes of moderate-intense activity per week). Other measurements included the Disease Activity Score (DAS). Since both treatment arms showed equal effect, these were analysed as one group with simple before-after analyses and generalized estimating equations (GEE). In these analyses, 140 patients (86% of trial population; 66% women, mean age 52 years) with complete data were included. At entry, 69% of these patients met the WHO PA guideline, increasing to 90% at week 13, and remaining stable at 89% after one year (p<0.001). Mean DAS improved from 4.0 to 1.8 during the first year of treatment (p<0.001). In GEE analyses, DAS decreases were significantly associated with PA increases (p=0.008). Patients with clinically relevant responses (expressed as DAS remission, EULAR good or ACR70 response) showed higher PA levels compared to non-responders, regardless of the definition of response, for both the WHO and Dutch PA guideline. Early RA patients on combination therapy improve both disease activity and physical activity, a beneficial effect persisting for at least one year. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    07/2015; 74(Suppl 2). DOI:10.1002/acr.22668
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    ABSTRACT: To describe the expression and diagnostic use of 14-3-3η autoantibodies in early rheumatoid arthritis (RA). 14-3-3η autoantibody levels were measured using an electrochemiluminescent multiplexed assay in 500 subjects (114 disease-modifying antirheumatic drug-naive patients with early RA, 135 with established RA, 55 healthy, 70 autoimmune, and 126 other non-RA arthropathy controls). 14-3-3η protein levels were determined in an earlier analysis. Two-tailed Student t tests and Mann-Whitney U tests compared differences among groups. Receiver-operator characteristic (ROC) curves were generated and diagnostic performance was estimated by area under the curve (AUC), as well as specificity, sensitivity, and likelihood ratios (LR) for optimal cutoffs. Median serum 14-3-3η autoantibody concentrations were significantly higher (p < 0.0001) in patients with early RA (525 U/ml) when compared with healthy controls (235 U/ml), disease controls (274 U/ml), autoimmune disease controls (274 U/ml), patients with osteoarthritis (259 U/ml), and all controls (265 U/ml). ROC curve analysis comparing early RA with healthy controls demon-strated a significant (p < 0.0001) AUC of 0.90 (95% CI 0.85-0.95). At an optimal cutoff of ≥ 380 U/ml, the ROC curve yielded a sensitivity of 73%, a specificity of 91%, and a positive LR of 8.0. Adding 14-3-3η autoantibodies to 14-3-3η protein positivity enhanced the identification of patients with early RA from 59% to 90%; addition of 14-3-3η autoantibodies to anticitrullinated protein antibodies (ACPA) and/or rheumatoid factor (RF) increased identification from 72% to 92%. Seventy-two percent of RF- and ACPA-seronegative patients were positive for 14-3-3η autoantibodies. 14-3-3η autoantibodies, alone and in combination with the 14-3-3η protein, RF, and/or ACPA identified most patients with early RA.
    The Journal of Rheumatology 07/2015; 42(9). DOI:10.3899/jrheum.141385 · 3.19 Impact Factor
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    ABSTRACT: Treatment options for rheumatoid arthritis (RA) include pharmacological interventions, physical therapy treatments and balneotherapy. To evaluate the benefits and harms of balneotherapy in patients with RA. A systematic review POPULATION: Studies were eligible if they were randomised controlled trials consisting of participants with definitive or classical RA. We searched various databases up to December 2014.Balneotherapy had to be the intervention under study, and had to be compared with another intervention or with no intervention. We considered pain, improvement, disability, tender joints, swollen joints and adverse events among the main outcome measures. We excluded studies when only laboratory variables were reported as outcome measures.Two review authors independently selected trials, performed data extraction and assessed risk of bias. This review includes nine studies involving 579 participants. Most studies showed an unclear risk of bias in most domains. We found no statistically significant differences on pain or improvementbetween mud packs versus placebo (1 study; n=45; hand RA; very low level of evidence).Concerning the effectiveness of additional radon in carbon dioxide baths, we found no statistically significant differences between groups for all outcomes at three-month follow-up (2 studies;n=194; low to moderate level of evidence). We noted some benefit of additional radon at six months in pain (moderate level of evidence). One study (n=148) compared balneotherapy (seated immersion) versus hydrotherapy (exercises in water), land exercises or relaxation therapy. We found no statistically significant differences in pain or in physical disability (very low level of evidence) between groups. We found no statistically significant differences in pain intensity at eight weeks, but some benefit of mineral baths in overall improvement at eight weekscompared toCyclosporin A (1 study; n=57; low level of evidence). Overall evidence is insufficient to show that balneotherapy is more effective than no treatment; that one type of bath is more effective than another or that one type of bath is more effective than exercise or relaxation therapy. We were not able to assess any clinical relevant impact of balneotherapy over placebo, no treatment or other treatments.
    European journal of physical and rehabilitation medicine 07/2015; · 1.90 Impact Factor
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    ABSTRACT: During OMERACT 12, a workshop was held with the aim to endorse a core set of domains for 3 settings: clinical trials of symptom and structure modification and observational studies. Additional goals were to endorse a core set of contextual factors for these settings, and to define preliminary instruments for each core domain. Finally, an agenda for future research in hand osteoarthritis (OA) was to be proposed. Literature reviews of preliminary instruments for each core domain of the proposed core set for hand OA in the settings described above. Literature review of radiographic scoring methods and modern imaging in hand OA were also performed. Proposed contextual factors for a core set were identified through 2 Delphi exercises with participation of hand OA experts, patient partners, and OMERACT participants. Results from Delphi exercises and systematic literature reviews were presented and discussed. It was agreed that a preliminary core domain set for the setting clinical trials of symptom modification should contain at least "pain, physical function, patient global assessment, joint activity and hand strength." The settings clinical trial of structure modification and observational studies would in addition include structural damage. Preliminary instruments for the proposed domains were agreed on. A list of prioritized contextual factors was defined and endorsed for further research. A research agenda was proposed for domain instrument validation according to the OMERACT Filter 2.0. Preliminary core sets for clinical trials of symptom and structure modification and observational studies in hand osteoarthritis, including preliminary instruments and contextual factors, were agreed upon during OMERACT 12.
    The Journal of Rheumatology 07/2015; 42(11). DOI:10.3899/jrheum.141017 · 3.19 Impact Factor
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    ABSTRACT: Background The Animated Activity Questionnaire (AAQ) measures activity limitations in hip and knee osteoarthritis (HKOA), and demonstrated good validity and reliability [1]. The AAQ shows stylized video animations of different levels of activity performance. Patients are asked to choose which video best matches their own performance. Accordingly, for international studies, the AAQ should show minimal Differential Item Functioning (DIF) across countries, which means that patients from different countries with the same level of activity limitations should have the same score on each item. Objectives To evaluate cross-cultural validity of the AAQ. Methods In 7 European countries patients were asked to complete the AAQ. An example of an item of the AAQ is shown on: Ordinal logistic regression was used to evaluate DIF across languages (Dutch versus 6 other languages). As a criterion for uniform DIF we used an odds ratio outside the interval 0.53–1.89. An significant interaction term (p-value <0.05) between translation item score and original Dutch score was considered as non-uniform DIF. Analyses were adjusted for sex, age, and affected joint. Results Data available were from: Netherlands (N=279), Denmark (N=109), France (N=121), Italy (N=203), United Kingdom (N=142), Norway (N=62), and Spain (N=37). Compared to Dutch, none of the 17 items showed DIF in Danish and French; uniform DIF occurred in 1 item for Norwegian versus Dutch and English versus Dutch; for Spanish versus Dutch 1 item showed uniform DIF, and 1 item showed non-uniform DIF; for Italian versus Dutch 3 items showed uniform DIF, and 3 items showed non-uniform DIF. Conclusions Cross-cultural validity of the AAQ looks promising. Further analyses with more data per country are needed and currently collected. Since minimal translation is needed for the AAQ, cross-cultural differences will mainly be based on cultural differences. The AAQ seems to have great potential for international use in research and daily clinical practice. References Acknowledgements Funding: EULAR Patient Reported Outcome research grant. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases; 06/2015
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    ABSTRACT: Background Guidelines suggest treatment in rheumatoid arthritis (RA) should be targeted at remission, in close consultation with the patient. Our recent qualitative study of the patient perspective on remission in RA identified reduction or absence of a) certain symptoms and b) impact of the disease on daily life, as well as c) a return to normal life as important themes. Objectives The current study aimed to determine the relative importance of the many aspects of remission identified within these three themes to produce a short list of the most important aspects to inform future research. Methods RA patients from the Netherlands, the United Kingdom (UK), Austria, Denmark, France, and the United States (US) were asked to complete a survey that contained all 26 domains of remission identified in our qualitative study. Patients were asked to rate domains for importance (“not important”, “important”, or “essential” to characterise a period of remission) and if important or essential, whether this domain needs to be `'less”, ‘almost gone’, or ‘gone’ to reflect remission. In addition, respondents were asked to determine their personal top 3 of most important/essential domains that characterise remission. First, frequency of a particular domain mentioned in the top 3 was calculated. Second, domains that >30% of patients identified as “not important” were removed. The remaining domains were sorted on the percentage of patients that evaluated a particular domain as “essential”. Results Data from 274 RA patients were collected (54 Netherlands, 33 UK, 51 Austria, 43 Denmark, 43 France, and 50 US), including 75% females, mean (SD) age 57 (13) years, disease duration 12 (9) years (range 0 to 50). 38% reported they were currently in remission and 41% reported erosive disease. The most often mentioned domains in the top 3 were: pain (n=188,67%), fatigue (n=91,33%) and independence (n=53,19%). Domains that were most frequently rated as “essential” to characterise a period of remission were: pain (n=163,60%), being mobile (n=142,52%), physical function (n=140,51%), being independent (n=129,47%) and fatigue (n=113,41%). Pain needed to be less (13%), almost gone (42%) or gone (45%) to reflect remission. Similar patterns were seen for fatigue (23%,40%,37%), independence (16%,31%,53%), mobility (16%,35%,49%) and physical functioning (14%,29%,57%). Conclusions The most important domains of RA disease activity that need to be improved in order to reflect remission from a patient perspective are pain, fatigue, independence, mobility and physical functioning. Measurement of these domains in low disease activity will be a next challenge. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):435.3-436. DOI:10.1136/annrheumdis-2015-eular.2238 · 10.38 Impact Factor
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    ABSTRACT: Background The Dutch cardiovascular risk management (CV-RM) guideline considers rheumatoid arthritis (RA) an independent risk factor for cardiovascular disease (CVD), for which CV-RM is necessary. Objectives To investigate the effect of CV-RM interventions (blood pressure lowering therapy and lipid-lowering therapy) on the 10-year CV risk in patients with RA. Methods Consecutive RA patients visiting Reade, a large outpatient rheumatology clinic, were included in this study. CV risk screening was performed at baseline, after one and two years, and included a lifestyle questionnaire, physical examination, laboratory investigations and assessment of the 10-year CV risk. The Dutch CVRM guideline classifies a risk <10% as low, between 10% and 20% as intermediate and a risk ≥20% as high (1). Patients with a history of CVD were classified as high risk. The results of the CV screening were communicated to the general practitioner, who decided whether or not to start preventive medication. Results In total, 350 patients were included in the Amsterdam CV-RM cohort at the time of analysis. Seventy-two patients had undergone two rescreening's. Of those patients, 76% were female, the mean age at baseline was 62 years and 5 had a history of CVD. After two years, the overall 10-year risk increased significantly from 21.7% to 26.2% (p<0.01). Five new cases of CVD occurred, all in the high risk group. At baseline, 42 patients (58%) had a high CV risk, which increased to 55 (76%) at the second rescreening after correction for age (figure 1a). During follow-up a total of 44 patients had an indication to use antihypertensive therapy. However, only 25 of them used or started antihypertensives whereas in 19 patients antihypertensive therapy wasn't given at all (figure 1b). In both groups (treated versus not treated), 10-year CV risk increased. However, the increase in CV risk was lower in the group that started antihypertensive therapy in the first year (3.6% vs. 6.9%) (figure 1c). The indication for lipid lowering therapy was present in 49 patients. Eighteen used or started statins whereas 31 patients did not receive lipid lowering treatment despite having an indication. In the statin starters, the average increase in 10-year CV risk was 2.7%, versus 8.6% in patients that had an indication for statin use but did not receive lipid lowering therapy. Conclusions Despite implementing CV-RM in RA patients, we found an unexpected overall increase in 10-year CV risk. This might be a reflection of undertreatment of both hypertension and dyslipidemia as many patients who had an indication to use preventive medications do not receive adequate treatment, despite of repeated screening. Obviously, CV-RM guidelines are poorly performed in RA patients and need to be optimized. References Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):192.1-192. DOI:10.1136/annrheumdis-2015-eular.3765 · 10.38 Impact Factor
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    ABSTRACT: Objectives To determine the long term effects of initial glucocorticoid therapy on joint damage in patients with early rheumatoid arthritis (RA). Methods Randomised controlled trials assessing the efficacy of glucocorticoid treatment during one or two years in RA including follow up measurements after the original study duration were identified. Lead authors of these studies were invited to provide data on patient characteristics, disease activity, co treatment, and (erosive) joint damage. A comprehensive dataset with individual patient data was created and used for analyses, and data up to five years after the start of trials was analysed. Results Original study data and follow up measurements after the trial duration were shared by authors from five studies. Of the 838 patients entering these studies, 413 had been allocated to a treatment strategy including glucocorticoids. In total, 79% percent of the patients had at least one follow up radiograph scored between 3 and 5 years follow up after start of the original trial. Radiological progression over five years was significantly lower in glucocorticoid users (p=0.001). When analysing exclusively the time period after trials, initial glucocorticoid users and controls showed similar radiological progression rates. Conclusions Addition of glucocorticoid therapy to treatment in early RA is effective in decreasing radiological damage. This beneficial effect can still be identified after five years of follow up, mainly reflecting the initially obtained advantage. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):736.1-736. DOI:10.1136/annrheumdis-2015-eular.6215 · 10.38 Impact Factor
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    ABSTRACT: Background Large pivotal randomised controlled trials (RCTs) in rheumatoid arthritis (RA) increasingly employ “adaptive” designs that allow early dropout in the comparator group (effectively placebo). Such designs frequently result in unbalanced and high dropout rates that compromise inference from meta-analysis, especially on adverse events. Objectives To evaluate and compare risk of serious adverse effects associated with treatment of currently EMA and/or FDA approved biologics and targeted synthetic DMARDs for RA based on data from randomised trials with an explicit goal of adjusting for the skewed dropout between groups1. Methods Through a systematic literature search, RA RCTs evaluating biologics or targeted synthetic DMARDs were identified. Major outcome was risk of serious adverse events (SAEs) adjusted for follow-up time based on the number of subjects experiencing an event and person-years – expressed as rate ratios with 95% confidence intervals. If person-years were not reported, it was estimated by assuming a linear dropout rate from baseline to follow-up. A network meta-analysis was performed with a mixed effects Poisson regression model (with study as a random and treatment as a fixed effect). As a sensitivity analysis, we explored the effect of dose (recommended/low/high), as well as the impact of concomitant use of conventional synthetic DMARDs (y/n), and adjusted for these factors in the model. Results From 176 identified RCTs meeting our eligibility criteria, 46 RCTs did not report data on SAEs and 15 were unpublished. Thus, the meta-analysis included 115 trials (319 trial-arms; 47,327 patients; approx. 30,045 person-years): abatacept (16), adalimumab (36), anakinra (2), certolizumab (16), etanercept (27), golimumab (21), infliximab (17), rituximab (13), and tocilizumab (29), tofacitinib (36), and placebo/control (106) arms. The risk of SAEs was statistically significantly higher (P<0.05) for certolizumab compared with: placebo/control, abatacept, adalimumab, etanercept, golimumab, rituximab, and tofacitinib (see table). The risk for SAEs was statistically significantly lower for etanercept compared to tocilizumab. Confidence in the estimates was downgraded because of indirectness (lack of head-2-head trials) and risk of bias due to selective outcome reporting (i.e. low quality evidence). Conclusions This network meta-analysis of available RCTs (accounting for person-years) provides empirical evidence that certolizumab is associated with an increased risk of SAEs compared with placebo/control, several biologics, and tofacitinib for RA; although our confidence in the estimates is limited (i.e. the true effects may be substantially different). References Acknowledgements This study was supported by unrestricted grants from The Oak Foundation and indirectly by The Danish Health and Medicines Authority Disclosure of Interest S. Tarp Grant/research support from: paid to institute: AbbVie and Roche, Speakers bureau: paid to institute: Pfizer and MSD, D. Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Actelion, Amgen, BMS, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Speakers bureau: AbbVie, Actelion, UCB, G. Luta: None declared, M. Boers: None declared, U. Tarp Grant/research support from: paid to the institute: MSD, Speakers bureau: Pfizer, UCB, Roche, MSD, K. Asmussen Consultant for: MSD, Pfizer, AbbVie, Novartis, UCB, H. Bliddal Grant/research support from: AbbVie, BMS, AstraZeneca, Daiichi Sankyo, GSK, Grünenthal, Lilly, MSD, Mundipharma, Nycomed, NOVO, Piere Fabre, Pfizer, Roche, Sanofi Aventis, Schering-Plough, Takeda, Wyeth, Consultant for: AbbVie, Hospira, Celgene AstraZeneca, Grünenthal, Lilly, Mundipharma, Nycomed, Pfizer, Roche, Wyeth, B. Brock Grant/research support from: paid to institution: Novo, Consultant for: Novo, Allergen, Speakers bureau: Pfizer, A. Dossing: None declared, T. Jørgensen Grant/research support from: paid to institute: Roche, AbbVie, S. Thirstrup Employee of: works as a regulatory consultant at NDA Regulatory Services Ltd, but does not receive fees directly from pharmaceutical companies, R. Christensen Grant/research support from: paid to institute AbbVie, Janssen, MSD, MundiPharma, Roche, Consultant for: paid to institute AbbVie, BMS, Eli Lilly, MSD, Norpharma, Pfizer, Roche, Speakers bureau: paid to institute AbbVie, Bayer HealthCare Pharmaceuticals, BMS, Janssen, MSD, MundiPharma, Novartis, Pfizer, Roche, Wyeth
    Annals of the Rheumatic Diseases; 06/2015

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  • 2001-2015
    • VU University Medical Center
      • • Department of Epidemiology and Biostatistics
      • • Department of Rheumatology
      • • Department of Surgery
      • • Department of Nuclear Medicine and PET Research
      Amsterdamo, North Holland, Netherlands
    • St George Hospital
      Sydney, New South Wales, Australia
  • 1998-2015
    • VU University Amsterdam
      • • Department of Epidemiology and Biostatistics
      • • Department of Ophthalmology
      Amsterdamo, North Holland, Netherlands
  • 2013
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands
  • 2012
    • University of Guelph
      XIA, Ontario, Canada
  • 2011
    • Boston University
      • Arthritis Center
      Boston, MA, United States
  • 1999-2010
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2008
    • University of Otago
      • Department of Medicine (Dunedin)
      Taieri, Otago, New Zealand
  • 2007
    • Erasmus MC
      • Department of General Practice
      Rotterdam, South Holland, Netherlands
  • 1988-2007
    • Leiden University Medical Centre
      • Department of Rheumatology
      Leyden, South Holland, Netherlands
  • 2006
    • Centraal Bureau voor de Statistiek
      's-Gravenhage, South Holland, Netherlands
  • 2003-2006
    • University of Ottawa
      • Department of Epidemiology and Community Medicine
      Ottawa, Ontario, Canada
  • 2001-2004
    • Academisch Medisch Centrum Universiteit van Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2002
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
    • University of Leuven
      Louvain, Flemish, Belgium
  • 1993-2002
    • Maastricht University
      • • Department of Internal Medicine
      • • Department of Epidemiology
      Maestricht, Limburg, Netherlands
    • The Ottawa Hospital
      • Department of Medicine
      Ottawa, Ontario, Canada
  • 1995
    • The University of Western Ontario
      • Department of Medicine
      London, Ontario, Canada
  • 1994-1995
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 1993-1995
    • American College of Rheumatology
      Atlanta, Georgia, United States
  • 1991
    • Diakonessen Hospital Utrecht
      Utrecht, Utrecht, Netherlands
  • 1988-1991
    • Leiden University
      Leyden, South Holland, Netherlands
  • 1990
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands