Author
C.T. Chou
Other affiliations: National Yang-Ming University
Bio: C.T. Chou is an academic researcher from Taipei Veterans General Hospital. The author has contributed to research in topics: Medicine & Immunology. The author has an hindex of 5, co-authored 5 publications receiving 3381 citations. Previous affiliations of C.T. Chou include National Yang-Ming University.
Papers
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Charité1, Leiden University2, Maastricht University3, Dokuz Eylül University4, Ruhr University Bochum5, University of Córdoba (Spain)6, University of Paris7, Sun Yat-sen University8, Ege University9, University of Alberta10, Ghent University11, University of Copenhagen12, Fırat University13, Barking, Havering and Redbridge University Hospitals NHS Trust14, Chung Shan Medical University15
TL;DR: The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial spondyloarthritis in those with chronic back pain.
Abstract: Objective: To validate and refine two sets of candidate criteria for the classification/diagnosis of axial spondyloarthritis (SpA). Methods: All Assessment of SpondyloArthritis international Society (ASAS) members were invited to include consecutively new patients with chronic (⩾3 months) back pain of unknown origin that began before 45 years of age. The candidate criteria were first tested in the entire cohort of 649 patients from 25 centres, and then refined in a random selection of 40% of cases and thereafter validated in the remaining 60%. Results: Upon diagnostic work-up, axial SpA was diagnosed in 60.2% of the cohort. Of these, 70% did not fulfil modified New York criteria and, therefore, were classified as having “non-radiographic” axial SpA. Refinement of the candidate criteria resulted in new ASAS classification criteria that are defined as: the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature (“imaging arm”) or the presence of HLA-B27 plus at least two SpA features (“clinical arm”). The sensitivity and specificity of the entire set of the new criteria were 82.9% and 84.4%, and for the imaging arm alone 66.2% and 97.3%, respectively. The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI (sensitivity 85.1%, specificity 65.1%) and slightly better than that of the modified Amor criteria (sensitivity 82.9, specificity 77.5%). Conclusion: The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain. Trial registration number: NCT00328068.
2,704 citations
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TL;DR: The new ASAS classification criteria for peripheral SpA performed well in patients presenting with peripheral arthritis, enthesitis and/or dactylitis, particularly regarding sensitivity.
Abstract: Objective To evaluate new classifi cation criteria for peripheral spondyloarthritis (SpA) in patients with SpA with peripheral manifestations only. Methods In this Assessment of SpondyloArthritis international Society (ASAS) study, two prespecifi ed sets of criteria were compared against the European Spondylarthropathy Study Group (ESSG) and Amor criteria in newly referred consecutive patients with undiagnosed peripheral arthritis, and/or enthesitis, and/ or dactylitis that usually began before 45 years of age. The clinical diagnosis (SpA vs no SpA) made by the ASAS rheumatologist served as reference standard. Results In all, 24 ASAS centres included 266 patients, with a fi nal diagnosis of SpA being made in 66.2%. After adjustments a fi nal set of criteria showed the best balance between sensitivity (77.8%) and specifi city (82.9%): arthritis and/or enthesitis and/or dactylitis plus (A) one or more of the following parameters: psoriasis, infl ammatory bowel disease, preceding infection, human leucocyte antigen B27, uveitis, sacroiliitis on imaging, or (B) two or more other parameters: arthritis, enthesitis, dactylitis, infl ammatory back pain in the past, family history of SpA. The new criteria performed better than modifi ed versions of the ESSG (sensitivity 62.5%, specifi city 81.1%) and the Amor criteria (sensitivity 39.8%, specifi city 97.8%), particularly regarding sensitivity. In the entire ASAS population of 975 patients the combined use of ASAS criteria for axial SpA and ASAS criteria for peripheral SpA also had a better balance (sensitivity 79.5%, specifi city 83.3%) than the modifi ed ESSG (sensitivity 79.1%, specifi city 68.8%) and Amor criteria (sensitivity 67.5%, specifi city 86.7%), respectively. Conclusions The new ASAS classifi cation criteria for peripheral SpA performed well in patients presenting with peripheral arthritis, enthesitis and/or dactylitis.
1,276 citations
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University of Queensland1, Hanyang University2, Eulji University3, Cedars-Sinai Medical Center4, National Institutes of Health5, University of Texas Health Science Center at Houston6, French Institute of Health and Medical Research7, Sir Charles Gairdner Hospital8, University of Western Australia9, Oslo University Hospital10, National Institute for Health and Welfare11, Danube University Krems12, King Abdulaziz University13, Second Military Medical University14, Ghent University Hospital15, National Autonomous University of Mexico16, University of California17, University of Otago18, Toronto Western Hospital19, Central University, India20, Nuffield Orthopaedic Centre21, Norfolk and Norwich University Hospital22, University of Cambridge23, University Health Network24, University of Toronto25, Memorial University of Newfoundland26, University of Alberta27, VU University Medical Center28, National Yang-Ming University29, Taipei Veterans General Hospital30, Military University Nueva Granada31, Universidade Nova de Lisboa32, Spanish National Research Council33, University of Bristol34, National Institute for Health Research35
Abstract: The association of endoplasmic reticulum aminopeptidase 2 (ERAP2) with ankylosing spondylitis (AS) was recently described in the large International Genetics of AS Consortium Immunochip study. Variants in ERAP2 have also been associated with inflammatory bowel disease, psoriasis, acute anterior uveitis and birdshot chorioretinopathy. Subsequent investigation demonstrated an association of ERAP2 with AS which was present when one conditioned on one of the two independent haplotypes of ERAP1 associated with AS or when HLA-B27-negative patients were analysed separately. These two analyses provide analogous evidence for the association of ERAP2 with AS in HLA-B27-negative cases because of the genetic interaction between HLA-B27 and the AS-associated ERAP1 variants in AS cases. ERAP1 and ERAP2 are located on chromosome 5q15 in the opposite orientation. The locus is challenging to analyse because of the strong linkage disequilibrium (LD) across the locus and the epistasis between ERAP1 and HLA-B alleles associated with AS. We therefore sought to investigate the association of ERAP2 with AS in HLA-B27-positive patients. This is of clinical importance because functional studies have demonstrated that the strongly AS-protective variant rs2248374 causes a functional ERAP2 protein knockout, because its G allele causes a loss of ERAP2 protein expression. There is also a variant of ERAP2 which changes its enzyme catalytic activity and specificity (rs2549782, K392A). Because this is in almost complete LD with rs2248374 (1000 Genomes D′=1.00, r2=0.90), it is almost never translated in vivo. Further, the very strong LD between these markers means that analysis of rs2549782 for association would yield results almost identical to the results for rs2248374 presented below. Therefore, it is of relevance to determine whether the association of ERAP2 with HLA-B27-negative disease is also found in HLA-B27-positive cases, since ERAP inhibition may offer a novel therapeutic for AS...
77 citations
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University of Queensland1, Ghent University2, Dokuz Eylül University3, Taipei Veterans General Hospital4, University of Alberta5, Erciyes University6, St George's Hospital7, Charité8, Universidad de La Sabana9, Leiden University Medical Center10, Chung Shan Medical University11, Queensland University of Technology12
TL;DR: In a clinical setting of referred back pain patients suspected to have axial SpA, genetic data was unable to use genetic data to construct a predictive model better than that based on existing clinical data.
Abstract: Objective Spondyloarthritis (SpA) is often diagnosed late in the course of the disease and improved methods for early diagnosis are required. We have tested the ability of genetic profiling to diagnose axial SpA (axSpA) as a whole group, or ankylosing spondylitis (AS) alone, in a cohort of chronic back pain patients. Methods 282 patients were recruited from centres in the United Kingdom, Germany, Taiwan, Canada, Columbia and Turkey as part of the ASAS classification criteria for axSpA study (ASAS cohort). Subjects were classified according to the ASAS axSpA criteria, and the modified New York Criteria for AS. Patients were genotyped for ~200,000 immune-mediated disease SNPs using the Illumina Immunochip. Results We first established the predictive accuracy of genetic data comparing 9,638 healthy controls and 4,428 AS cases from the homogenous International Genetics of AS (IGAS) Consortium Immunochip study which showed excellent predictive power (AUC=0.91). Genetic risk scores had lower predictive power (AUC=0.83) comparing ASAS cohort axSpA cases meeting the ASAS imaging criteria with IGAS controls. Comparing genetic risk scores showed moderate discriminatory capacity between IGAS AS and ASAS imaging positive cases (AUC 0.67±0.05), indicating that significant differences in genetic makeup exist between the cohorts. Conclusion In a clinical setting of referred back pain patients suspected to have axial SpA we were unable to use genetic data to construct a predictive model better than that based on existing clinical data. Potential confounding factors include significant heterogeneity in the ASAS cohort, possibly reflecting the disease heterogeneity of axSpA, or differences between centres in ascertainment or classification performance.
23 citations
01 Jan 2016
TL;DR: In this paper, the ability of genetic profiling to diagnose axial SpA ( axSpA ) as a whole group, or ankylosing spondylitis ( AS ) alone, in a cohort of chronic back pain patients was tested.
Abstract: OBJECTIVES - Spondyloarthritis ( SpA ) is often diagnosed late in the course of the disease and improved methods for early diagnosis are required. We have tested the ability of genetic profiling to diagnose axial SpA ( axSpA ) as a whole group, or ankylosing spondylitis ( AS ) alone, in a cohort of chronic back pain patients. METHODS - 282 patients were recruited from centres in the United Kingdom, Germany, Taiwan, Canada, Columbia and Turkey as part of the ASAS classification criteria for axSpA study (ASAS cohort). Subjects were classified according to the ASAS axSpA criteria, and the modified New York Criteria for AS. Patients were genotyped for ~200,000 immune-mediated disease SNPs using the Illumina Immunochip. RESULTS
We first established the predictive accuracy of genetic data comparing 9,638 healthy controls and 4,428 AS cases from the homogenous International Genetics of AS ( IGAS ) Consortium Immunochip study which showed excellent predictive power (AUC=0.91). Genetic risk scores had lower predictive power (AUC=0.83) comparing ASAS cohort axSpA cases meeting the ASAS imaging criteria with IGAS controls. Comparing genetic risk scores showed moderate discriminatory capacity between IGAS AS and ASAS imaging positive cases (AUC 0.67+/-0.05), indicating that significant differences in genetic makeup exist between the cohorts. CONCLUSIONS - In a clinical setting of referred back pain patients suspected to have axial SpA we were unable to use genetic data to construct a predictive model better than that based on existing clinical data. Potential confounding factors include significant heterogeneity in the ASAS cohort, possibly reflecting the disease heterogeneity of axSpA, or differences between centres in ascertainment or classification performance.
17 citations
Cited by
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TL;DR: Intensified research efforts and global initiatives are clearly needed to address the burden of low back pain as a public health problem, where health and other systems are often fragile and not equipped to cope with this growing burden.
2,114 citations
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TL;DR: The new ASAS classification criteria for peripheral SpA performed well in patients presenting with peripheral arthritis, enthesitis and/or dactylitis, particularly regarding sensitivity.
Abstract: Objective To evaluate new classifi cation criteria for peripheral spondyloarthritis (SpA) in patients with SpA with peripheral manifestations only. Methods In this Assessment of SpondyloArthritis international Society (ASAS) study, two prespecifi ed sets of criteria were compared against the European Spondylarthropathy Study Group (ESSG) and Amor criteria in newly referred consecutive patients with undiagnosed peripheral arthritis, and/or enthesitis, and/ or dactylitis that usually began before 45 years of age. The clinical diagnosis (SpA vs no SpA) made by the ASAS rheumatologist served as reference standard. Results In all, 24 ASAS centres included 266 patients, with a fi nal diagnosis of SpA being made in 66.2%. After adjustments a fi nal set of criteria showed the best balance between sensitivity (77.8%) and specifi city (82.9%): arthritis and/or enthesitis and/or dactylitis plus (A) one or more of the following parameters: psoriasis, infl ammatory bowel disease, preceding infection, human leucocyte antigen B27, uveitis, sacroiliitis on imaging, or (B) two or more other parameters: arthritis, enthesitis, dactylitis, infl ammatory back pain in the past, family history of SpA. The new criteria performed better than modifi ed versions of the ESSG (sensitivity 62.5%, specifi city 81.1%) and the Amor criteria (sensitivity 39.8%, specifi city 97.8%), particularly regarding sensitivity. In the entire ASAS population of 975 patients the combined use of ASAS criteria for axial SpA and ASAS criteria for peripheral SpA also had a better balance (sensitivity 79.5%, specifi city 83.3%) than the modifi ed ESSG (sensitivity 79.1%, specifi city 68.8%) and Amor criteria (sensitivity 67.5%, specifi city 86.7%), respectively. Conclusions The new ASAS classifi cation criteria for peripheral SpA performed well in patients presenting with peripheral arthritis, enthesitis and/or dactylitis.
1,276 citations
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TL;DR: A comprehensive handbook on the most relevant aspects for the assessments of spondyloarthritis, covering classification criteria, MRI and x rays for sacroiliac joints and the spine, a complete set of all measurements relevant for clinical trials and international recommendations for the management of SpA are provided.
Abstract: The field of spondyloarthritis (SpA) has experienced major progress in the last decade, especially with regard to new treatments, earlier diagnosis, imaging technology and a better definition of outcome parameters for clinical trials. In the present work, the Assessment in SpondyloArthritis international Society (ASAS) provides a comprehensive handbook on the most relevant aspects for the assessments of spondyloarthritis, covering classification criteria, MRI and x rays for sacroiliac joints and the spine, a complete set of all measurements relevant for clinical trials and international recommendations for the management of SpA. The handbook focuses at this time on axial SpA, with ankylosing spondylitis (AS) being the prototype disease, for which recent progress has been faster than in peripheral SpA. The target audience includes rheumatologists, trial methodologists and any doctor and/or medical student interested in SpA. The focus of this handbook is on practicality, with many examples of MRI and x ray images, which will help to standardise not only patient care but also the design of clinical studies.
1,227 citations
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TL;DR: This Review focuses on the recent advances that have been made regarding the transcriptional control of TH 17 cell plasticity and stability, as well as the effector functions of TH17 cells, and highlights the mechanisms of IL-17 signalling in mesenchymal and barrier epithelial tissues.
Abstract: Following the discovery of T helper 17 (TH17) cells, the past decade has witnessed a major revision of the TH subset paradigm and substantial progress has been made in deciphering the molecular mechanisms of T cell lineage commitment and function. In this Review, we focus on the recent advances that have been made regarding the transcriptional control of TH17 cell plasticity and stability, as well as the effector functions of TH17 cells, and we highlight the mechanisms of IL-17 signalling in mesenchymal and barrier epithelial tissues. We also discuss the emerging clinical data showing that IL-17-specific and IL-23-specific antibody treatments are remarkably effective for treating many immune-mediated inflammatory diseases.
1,174 citations
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Leiden University Medical Center1, Ruhr University Bochum2, Ghent University Hospital3, Universidade Nova de Lisboa4, University of Zurich5, Paris Descartes University6, Sorbonne7, Semmelweis University8, VU University Medical Center9, University of Toronto10, University College London11, University of Leeds12, Erciyes University13, University of Lisbon14, University of Texas at Austin15, Charité16, Ghent University17, University of São Paulo18
TL;DR: The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA and three overarching principles and 13 recommendations deal with surgery and spinal fractures.
Abstract: To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6-8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.
1,147 citations