Author
Piet L. C. M. van Riel
Other affiliations: Radboud University Nijmegen Medical Centre
Bio: Piet L. C. M. van Riel is an academic researcher from Radboud University Nijmegen. The author has contributed to research in topics: Rheumatoid arthritis & Arthritis. The author has an hindex of 65, co-authored 286 publications receiving 22585 citations. Previous affiliations of Piet L. C. M. van Riel include Radboud University Nijmegen Medical Centre.
Papers published on a yearly basis
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Medical University of Vienna1, University of Amsterdam2, Leiden University Medical Center3, Leeds Teaching Hospitals NHS Trust4, Chapel Allerton Hospital5, Humboldt State University6, Oregon Health & Science University7, Utrecht University8, VU University Medical Center9, University of Montpellier10, University of Belgrade11, Erasmus University Rotterdam12, University of Paris-Sud13, Charles University in Prague14, Radboud University Nijmegen Medical Centre15, University of Cologne16, Weston Education Centre17, Tufts University18
TL;DR: These recommendations intend informing rheumatologists, patients, national rheumology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.
Abstract: In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at
4,730 citations
Harvard University1, Broad Institute2, Monash University3, Kyoto University4, Genentech5, Vanderbilt University6, New York University7, NewYork–Presbyterian Hospital8, Second Military Medical University9, University of Queensland10, University of Toronto11, University of Groningen12, University of Tartu13, Beijing Jiaotong University14, Icahn School of Medicine at Mount Sinai15, Radboud University Nijmegen16, Medisch Spectrum Twente17, Leiden University18, University of Paris19, French Institute of Health and Medical Research20, University of Alabama at Birmingham21, GlaxoSmithKline22, University of Cambridge23, University of Amsterdam24, Hanyang University25, Spanish National Research Council26, Complutense University of Madrid27, Umeå University28, Boston University29, Council on Education for Public Health30, McGill University31, National Health Service32, University of Manchester33, University of Pittsburgh34, University of California, San Francisco35, Karolinska Institutet36, North Shore-LIJ Health System37, University of Chicago38, University of Tokyo39
TL;DR: A genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries provides empirical evidence that the genetics of RA can provide important information for drug discovery, and sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis.
Abstract: A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2, 3, 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci6 and pathway analyses7, 8, 9—as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes—to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
1,910 citations
Medical University of Vienna1, Maastricht University2, Leiden University3, Paris Descartes University4, University of Leeds5, Pierre-and-Marie-Curie University6, Utrecht University7, Humboldt State University8, University of Montpellier9, University of Genoa10, University of Santiago, Chile11, Autonomous University of Madrid12, University of Glasgow13, Charles University in Prague14, Radboud University Nijmegen15, King's College London16, Sapienza University of Rome17, Karolinska Institutet18, Oregon Health & Science University19, Tufts University20, Charité21
TL;DR: In this article, the authors present a set of recommendations for the treatment of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects.
Abstract: Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-a-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.
1,372 citations
Brigham and Women's Hospital1, Massachusetts Institute of Technology2, Harvard University3, National Institutes of Health4, University of Toronto5, University of Manchester6, Celera Corporation7, Leiden University8, Karolinska Institutet9, University of Texas at Austin10, Radboud University Nijmegen Medical Centre11, University of California, San Francisco12, VU University Amsterdam13, University of Leeds14, University of Oxford15, University of Aberdeen16, The Feinstein Institute for Medical Research17, Karolinska University Hospital18, University of Groningen19, University of California, Davis20, King's College21, University of Amsterdam22, University of Sheffield23, Hoffmann-La Roche24, University Health Network25, North Shore-LIJ Health System26, Broad Institute27
TL;DR: Seven new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 × 10−8) in an analysis of all 41,282 samples, and an additional 11 SNPs replicated at P < 0.05, suggesting that most represent genuine rhearatoid arthritisrisk alleles.
Abstract: To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 x 10(-8)) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.
1,277 citations
TL;DR: Investigations assessing the impact of anti-TNF agents on intermediary metabolism suggest that TNF-alpha blockade may improve insulin resistance and lipid profiles in patients with chronic inflammatory diseases.
637 citations
Cited by
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Medical University of Vienna1, Boston University2, Arthritis Research UK3, Johns Hopkins University4, University of California, San Francisco5, Humboldt University of Berlin6, University of Toronto7, National Jewish Health8, Brigham and Women's Hospital9, Paris Descartes University10, University of Leeds11, Catholic University of the Sacred Heart12, Erasmus University Rotterdam13, University of Colorado Denver14, Leiden University15, University of California, San Diego16, University of Massachusetts Medical School17, University of Michigan18, University of Washington19, McGill University Health Centre20, University of Pittsburgh21, Ministry of Health (New Zealand)22, New York University23, University of Manchester24, University of Amsterdam25, University of Kansas26, Women's College Hospital27
TL;DR: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features.
Abstract: Objective The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classifi cation criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classifi cation criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated infl ammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/ or erosive disease—this being the appropriate current paradigm underlying the disease construct ‘RA’. Results In the new criteria set, classifi cation as ‘defi nite RA’ is based on the confi rmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). Conclusion This new classifi cation system redefi nes the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defi ning the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct ‘RA’.
7,120 citations
Medical University of Vienna1, Boston University2, Arthritis Research UK3, Johns Hopkins University4, University of California, San Francisco5, Charité6, University of Toronto7, National Jewish Health8, Harvard University9, University of Paris10, University of Leeds11, Catholic University of the Sacred Heart12, Erasmus University Rotterdam13, University of Colorado Denver14, Leiden University15, University of California, San Diego16, University of Massachusetts Medical School17, University of Michigan18, University of Washington19, McGill University20, University of Pittsburgh21, Ministry of Health (New Zealand)22, New York University23, University of Manchester24, University of Amsterdam25
TL;DR: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features.
Abstract: Objective The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease—this being the appropriate current paradigm underlying the disease construct ‘RA’. Results In the new criteria set, classification as ‘definite RA’ is based on the confirmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). Conclusion This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct ‘RA’.
5,964 citations
TL;DR: The Modified DAS that included 28-joint counts were able to discriminate between high and low disease activity (as indicated by clinical decisions of rheumatologists) and are as valid as disease activity scores that include more comprehensive joint counts.
Abstract: Objective. The development and validation of Modified Disease Activity Scores (DAS) that include different 28-joint counts.
Methods. These scores were developed by canonical discriminant analyses and validated for criterion, correlational, and construct validity. The influence of disease duration on the composition of the DAS was also investigated.
Results. No influence of disease duration was found. The Modified DAS that included 28-joint counts were able to discriminate between high and low disease activity (as indicated by clinical decisions of rheumatologists).
Conclusion. The Modified DAS are as valid as disease activity scores that include more comprehensive joint counts.
5,718 citations
Massachusetts Institute of Technology1, Broad Institute2, University of California, Los Angeles3, University of British Columbia4, Baylor College of Medicine5, Howard Hughes Medical Institute6, University of Washington7, Ludwig Institute for Cancer Research8, University of California, San Francisco9, University of Connecticut10, University of Zagreb11, University of Texas at Austin12, Washington University in St. Louis13, University of Queensland14, Harvard University15, Cold Spring Harbor Laboratory16, University of Southern California17, University of California, Santa Cruz18, Simon Fraser University19, Morgridge Institute for Research20, University of Texas at Dallas21, National Institutes of Health22
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
5,037 citations
Medical University of Vienna1, University of Amsterdam2, Leiden University Medical Center3, Chapel Allerton Hospital4, Leeds Teaching Hospitals NHS Trust5, Humboldt State University6, Oregon Health & Science University7, Utrecht University8, VU University Medical Center9, University of Montpellier10, University of Belgrade11, Erasmus University Rotterdam12, University of Paris-Sud13, Charles University in Prague14, Radboud University Nijmegen Medical Centre15, University of Cologne16, Weston Education Centre17, Tufts University18
TL;DR: These recommendations intend informing rheumatologists, patients, national rheumology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.
Abstract: In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at
4,730 citations