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Jrheum.190333.Full.Pdf J Rheumatol First Release June 1 2019; J Rheumatol 2019;46:xxx-xxx; doi:10.3899/jrheum.190333 Canadian Rheumatology Association Meeting Fairmont The Queen Elizabeth Montreal, Quebec, Canada February 27 – March 2, 2019 The 73rd Annual Meeting of The Canadian Rheumatology Association was held at the Fairmont The Queen Elizabeth, Montreal, Quebec, Canada February 27 – March 2, 2019. The program consisted of presentations covering original research, symposia, awards, and lectures. Highlights of the meeting include the following 2019 Award Winners: Distinguished Rheumatologist, Edward Keystone; Distinguished Investigator, Diane Lacaille; Teacher-Educator, Shirley Tse; Emerging Investigator, Glen Hazlewood; Best Abstract on SLE Research by a Trainee – Ian Watson Award, Alexandra Legge; Best Abstract on Clinical or Epidemiology Research by a Trainee – Phil Rosen Award, Lauren King; Best Abstract on Basic Science Research by a Trainee, Remy Pollock; Best Abstract for Research by an Undergraduate Student, Andrea Carboni-Jimènez; Best Abstract on Research by a Rheumatology Resident, May Choi; Best Abstract by a Medical Student, Leonardo Calderon; Best Abstract by a Post-Graduate Research Trainee, Carolina Munoz-Grajales; Best Abstract by a Rheumatology Post-Graduate Research Trainee, Andre Luquini; Best Abstract on Quality Care Initiatives in Rheumatology, Cheryl Barnabe and Ines Colmegna; Best Abstract on Research by Young Faculty, Bindee Kuriya; Practice Reflection Award, Gold, Jason Kur; Practice Reflection Award, Silver, May Choi. Lectures and other events included Keynote Lecture by Andre Picard: Quirky Past, Uncertain Future: The State of Medicare in Canada; Keynote Address by Diane Lacaille, Distinguished Investigator Awardee: Time to Re-Label Comorbidities in RA – Coexisting or Complications; State of the Art Lecture by Mark Roberts: Myositis and its Mimics; Dunlop-Dottridge Lecture by Gilles Boire: The 4-H of Biomarkers in Arthritis: A lot of Help, Potential Harm, Some Hype, Increasing Hope; and the Great Debate: Be it Resolved that Competency-based Medical Education will Result in Improved Quality of Care for Patients vs the “Old Way” of Training Rheumatologists. Arguing for: Mercedes Chan and Marie-Paule Morin, and against: Beth Hazel and Heather McDonald-Blumer. Topics including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, psoriatic arthritis, spondyloarthritis, vasculitis, osteoarthritis, fibromyalgia, and their respective diagnoses, treatments, and outcomes are reflected in the abstracts, which we are pleased to publish in this issue of The Journal. Personal non-commercial use only. The Journal of Rheumatology Copyright © 2019. All rights reserved. Introduction 1 Downloaded on September 27, 2021 from www.jrheum.org The 4-H of Biomarkers in Arthritis: A Lot of Help, Occasional Harm, Some Hype, Increasing Hope Gilles Boire and Hugues Allard-Chamard ABSTRACT. (Gilles Boire): It was both a pleasure and an honor to present the 2019 Dunlop-Dottridge Lecture. My co-author and I will now discuss benefits and pitfalls of biomarkers developed through emerging techniques, evaluated through the experiential perspective of a seasoned clinician, as they apply to the quest for biomarker identification in rheumatic diseases. (J Rheumatol 2019;46:xxxx; doi:10.3899/jrheum.190375) Key Indexing Terms: BIOLOGICAL MARKERS GENETIC PREDISPOSITION TO DISEASE ENVIRONMENT AUTOIMMUNE DISEASES OUTCOMES Thousands of papers on biomarkers in rheumatology are indicative of a patient’s feelings, well-being, or functions, are published each year, and the numbers are increasing steadily. not considered biomarkers. A biomarker may consist of a After decades of relatively simple biomarkers such as auto - single variable or be composite when exploiting input from 2 antibodies and single proteins, we are on the verge of a multiple variables . In rheumatology, biomarkers contribute 3 revolution that is already transforming other areas of to various clinical objectives (Table 1) . medicine: the availability of next-generation biomarkers Biomarkers may give mechanistic, clinical, or therapeutic 4 resulting from the combination of high throughput techniques information . They come under various forms, such as allowing the collection of thousands to millions of variables proteins (frequently antibodies), genetic and epigenetic traits, at the same time, and their simultaneous analysis by compu- imaging results, histological findings, cellular responses, 3 tational tools, yielding various scores, signatures, or subsets gene expression, or microbiome characterization . Their to be used for pathogenic studies, biologically based sources are diverse, ranging from fluids (blood, serum, diagnosis, prognosis, and selection of optimal drug regimens. plasma, urine, saliva, synovial fluid), isolated blood cells, While heralding a new era in rheumatology, these complex skin, gums, membranes and organs, feces, imaging, and even 3 biomarkers raise challenges and risks that need to be carefully digital (such as those obtained from a smart watch) . addressed before their implementation. We will first concen- The ideal biomarker is safe and easy to measure, sensitive trate on the uses and misuses of current biomarkers to illus- and specific, reproducible, consistent across gender and race, trate how the next generation of composite biomarkers will actionable such that it can inform clinical management, and 3,4 positively and unfortunately, potentially negatively alter our cost-efficient . Many biomarkers are co-correlated and thus approach to disease pathogenesis, diagnosis, and treatments. their concomitant usage does not add much to the infor- mation generated by a single one [e.g., erythrocyte sedimen- The ABC of Biomarkers tation rate and C-reactive protein (CRP) to evaluate RA Biomarkers are objectively measured characteristics that disease activity]. evaluate physiological or pathogenic processes, as well as potential indicators of therapeutic responses1. Variables Current Uses (HELP) and Misuses (HARM) of Biomarkers Current biomarkers are best used to support clinical From the Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke; Department of Medicine, Centre decisions, especially to support or invalidate hypotheses intégré universitaire de Santé et de Services Sociaux de l’Estrie - Centre resulting from careful collection of signs and symptoms. Hospitalier Universitaire de Sherbrooke (CIUSSS de l’Estrie-CHUS), Antibodies are often considered the rheumatologists’ area of Sherbrooke, Quebec, Canada. expertise. It is thus appropriate to use them to illustrate the H. Allard-Chamard, MD, PhD, Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, and Department good and the bad sides of current biomarkers. of Medicine, CIUSSS de l’Estrie-CHUS, currently Research Fellow in • HELP Medicine, Ragon Institute of Massachusetts General Hospital, For example, a 72-year-old woman is referred for presumed Massachusetts Institute of Technology, and Department of Medicine, Harvard University; G. Boire, MD, MSc, Department of Medicine, polymyalgia rheumatica. She presents with a few weeks of Faculty of Medicine and Health Sciences, Université de Sherbrooke, and shoulder and hip pain and limitation, the CRP is increased, Department of Medicine, CIUSSS de l’Estrie-CHUS. but you note swelling and tenderness in some small joints of Address correspondence to Dr. G. Boire, 3001 12th Ave. North, Division of Rheumatology, Room 3853, Sherbrooke, Quebec J1H 5N4, Canada. both hands and in wrists. You think of rheumatoid arthritis E-mail: [email protected] (RA). If anti-CCP [anticyclic citrullinated peptide] and Personal non-commercial use only. The Journal of Rheumatology Copyright © 2019. All rights reserved. 2 The Journal of Rheumatology 2019; 46: doi:10.3899/jrheum.190333 Downloaded on September 27, 2021 from www.jrheum.org Table 1. Current uses of biomarkers in rheumatology. Purpose Examples of Biomarkers Susceptibility/risk factor assessment HLA-B27, smoking, obesity Diagnostics Periarticular erosions in at least 3 joints in a patient with arthritis to diagnose RA; presence of intracellular sodium urate crystals in polymorphonuclear cells during synovioanalysis to diagnose gout Monitoring CRP during polymyalgia rheumatica treatment; swollen joint counts in RA patients Prognostics (relates to natural history of the disease) High-titer anti-CCP antibodies; persistent depressive symptoms in RA patients Predictive (relates to benefit or harm from a specific TPMT genotype and risk of azathioprine toxicity; therapy) seropositivity in RA patients and degree of response to rituximab Pharmacodynamic/response Blood levels of anti-TNF drugs; CRP Safety ALT levels; neutrophil counts Surrogate endpoints Bone densitometry changes and prediction of fragility fracture risk; remission according to SDAI and prevention of progression of radiographic erosions in RA Development of drug target Cytokine expresion in serum and synovial membrane RA: rheumatoid arthritis; CRP: C-reactive protein; CCP: cyclic citrullinated peptide; TPMT: thiopurine methyltransferase; TNF: tumor necrosis factor; ALT: alanine aminotransferase; SDAI: Simple Disease Activity Index. rheumatoid factor are both strongly positive, you feel very ated vasculitis (AAV). However, if the patient also has a heart comfortable with the diagnosis. murmur and low complement levels, features not typical of Similarly, seeing a
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