Biomarkers in the era of targeted therapy in giant cell arteritis and polymyalgia rheumatica:is it possible to replace acute-phase reactants?

Research into giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) has become more important in the last few decades. Physicians are facing several challenges in managing the diagnosis, treatment, and relapses of GCA and PMR patients. The search for biomarkers could provide elements to guide a physician’s decision. In this review, we aim to summarize the scientific publications about biomarkers in GCA and PMR in the past decade. The first point raised by this review is the number of clinical situations in which biomarkers could be useful: differential diagnosis of either GCA or PMR, diagnosis of underlying vasculitis in PMR, prediction of relapse or complications, disease activity monitoring, choice, and modification of treatments. The second point raised by this review is the large number of biomarkers studied, from common markers like C-reactive protein, erythrocyte sedimentation rate, or elements of blood count to inflammatory cytokines, growth factors, or immune cell subpopulations. Finally, this review underlines the heterogeneity between the studies and proposes points to consider in studies evaluating biomarkers in general and particularly in the case of GCA and PMR.</p

Reliability Exercise of Ultrasound Salivary Glands in Sjögren's Disease:An International Web Training Initiative

INTRODUCTION: Major salivary gland ultrasonography (SGUS) demonstrated its good metric properties as an outcome measure for diagnosing primary Sjögren's disease (SD). The objective was to assess SGUS reliability among sonographers with different levels of experience, using web training.METHODS: Sonographers from expert centers participated in the reliability exercise. Before exercises, training was done by videoconferencing. Reliability of the two most experienced sonographers (MES) was assessed and then compared to other sonographers. Intra-reader and inter-reader reliability of SGUS items were assessed by computing Cohen's κ coefficients.RESULTS: All sets were read twice by all 14 sonographers within a 4-month interval. Intra-reader reliability of MES was almost perfect for homogeneity, substantial for Outcome Measures in Rheumatology (OMERACT) scoring system (OMERACTss). Among LES (less experienced sonographers), reliability was moderate to almost perfect for homogeneity, fair to moderate for OMERACTss, and fair to almost perfect for binary OMERACTss. Inter-reader reliability between MES was almost perfect for homogeneity, substantial for diagnosis, moderate for OMERACTss, and substantial for binary OMERACTss. Compared to MES, reliabilities of LES were moderate to almost perfect for both homogeneity and diagnosis, only fair to moderate for OMERACTss, but increased in binary OMERACTss.CONCLUSIONS: Videoconferencing training sessions in an international reliability exercise could be an excellent tool to train experienced and less-experienced sonographers. SGUS homogeneity items is useful to distinguish normal from abnormal salivary glands parenchyma independently of diagnosis. Structural damage evaluations by OMERACT scoring system is a new comprehensive score to diagnose patients with SD and could be easily used by sonographers in a binary method.</p

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Effets pharmacodynamiques et pharmacocinétiques des biothérapies dans les maladies auto-immunes et inflammatoires

Polymyalgia rheumatica (PMR) is an inflammatory rheumatism affecting people over50 years of age. Polymyalgia rheumatica is sometimes associated with giant cell arteritis.Strong inflammation and a quick response to glucocorticoids are common marks of thedisease. PMR pathophysiology is poorly understood. Genetic predisposition, high levels of interleukin-6 (IL-6) in the serum, a decrease of B cell and an activation of T cells are the main elements identified. Bone turnover is affected by the strong inflammation and is responsible for fracture with high mortality and morbidity. In this thesis, we report some elements for PMR pathophysiology (increased IL-6, decreased B cells, large consequences of inflammation, no auto-antibody signature) and their connections to each other. We try to determine the abnormalities in patients resistant to glucocorticoids and prognostic factors to an innovative treatment: an anti-interleukin-6 receptor antibody, tocilizumab. We studied theeffect of tocilizumab on the immunological manifestations observed in PMR patients. Wealso studied bone remodeling and its evolution under therapy in PMR and we developed a modelling for pharmacokinetic and pharmacodynamic of tocilizumab. New leads for research are suggested, for example the characterization of the immune infiltration in the shoulder of PMR patients.La pseudo-polyarthrite rhizomélique, est un rhumatisme inflammatoire qui touche les sujets de plus de 50 ans. Elle est parfois associée à une vascularite (l’artérite à cellules géantes). La pseudo-polyarthrite rhizomélique est caractérisée par une forte inflammation et une réponse rapide aux corticoïdes. La physiopathologie de la maladie est mal connue. Une prédisposition chez les patients porteurs de certains allèles génétiques, un taux élevé d’interleukine-6 (IL-6) dans le sang, une diminution des lymphocytes B et une activation des lymphocytes T font partie des quelques éléments identifiés. L’inflammation est aussi responsable d’une altération du remodelage osseux qui peut entrainer des fractures responsables d’une mortalité et d’une morbidité importantes. Dans cette thèse nous rapportons des éléments de physiopathologie (augmentation de l’IL-6,diminution des lymphocytes B, conséquences de l’inflammation, absence de signature auto-anticorps) et leurs connexions. Nous avons également cherché à déterminer les anomalies présentes chez les patients avec une maladie résistante aux corticoïdes, des facteurs pronostiques de réponse au tocilizumab (un anticorps anti-récepteur de l’IL-6) et son effet sur ces anomalies. Enfin nous avons analysé le remodelage osseux et son évolution sous traitement et mis en place une modélisation pharmacocinétique et pharmacodynamique du tocilizumab. Ce travail de thèse ouvre de nouvelles perspectives de recherche, entre autres sur l’immunologie au sein du tissu péri-articulaire

Biotherapies’ mode of action and pharmacology in inflammatory and autoimmune diseases : tocilizumab and polymyalgia rheumatica

La pseudo-polyarthrite rhizomélique, est un rhumatisme inflammatoire qui touche les sujets de plus de 50 ans. Elle est parfois associée à une vascularite (l’artérite à cellules géantes). La pseudo-polyarthrite rhizomélique est caractérisée par une forte inflammation et une réponse rapide aux corticoïdes. La physiopathologie de la maladie est mal connue. Une prédisposition chez les patients porteurs de certains allèles génétiques, un taux élevé d’interleukine-6 (IL-6) dans le sang, une diminution des lymphocytes B et une activation des lymphocytes T font partie des quelques éléments identifiés. L’inflammation est aussi responsable d’une altération du remodelage osseux qui peut entrainer des fractures responsables d’une mortalité et d’une morbidité importantes. Dans cette thèse nous rapportons des éléments de physiopathologie (augmentation de l’IL-6,diminution des lymphocytes B, conséquences de l’inflammation, absence de signature auto-anticorps) et leurs connexions. Nous avons également cherché à déterminer les anomalies présentes chez les patients avec une maladie résistante aux corticoïdes, des facteurs pronostiques de réponse au tocilizumab (un anticorps anti-récepteur de l’IL-6) et son effet sur ces anomalies. Enfin nous avons analysé le remodelage osseux et son évolution sous traitement et mis en place une modélisation pharmacocinétique et pharmacodynamique du tocilizumab. Ce travail de thèse ouvre de nouvelles perspectives de recherche, entre autres sur l’immunologie au sein du tissu péri-articulaire.Polymyalgia rheumatica (PMR) is an inflammatory rheumatism affecting people over50 years of age. Polymyalgia rheumatica is sometimes associated with giant cell arteritis.Strong inflammation and a quick response to glucocorticoids are common marks of thedisease. PMR pathophysiology is poorly understood. Genetic predisposition, high levels of interleukin-6 (IL-6) in the serum, a decrease of B cell and an activation of T cells are the main elements identified. Bone turnover is affected by the strong inflammation and is responsible for fracture with high mortality and morbidity. In this thesis, we report some elements for PMR pathophysiology (increased IL-6, decreased B cells, large consequences of inflammation, no auto-antibody signature) and their connections to each other. We try to determine the abnormalities in patients resistant to glucocorticoids and prognostic factors to an innovative treatment: an anti-interleukin-6 receptor antibody, tocilizumab. We studied theeffect of tocilizumab on the immunological manifestations observed in PMR patients. Wealso studied bone remodeling and its evolution under therapy in PMR and we developed a modelling for pharmacokinetic and pharmacodynamic of tocilizumab. New leads for research are suggested, for example the characterization of the immune infiltration in the shoulder of PMR patients

Effets pharmacodynamiques et pharmacocinétiques des biothérapies dans les maladies auto-immunes et inflammatoires

Polymyalgia rheumatica (PMR) is an inflammatory rheumatism affecting people over50 years of age. Polymyalgia rheumatica is sometimes associated with giant cell arteritis.Strong inflammation and a quick response to glucocorticoids are common marks of thedisease. PMR pathophysiology is poorly understood. Genetic predisposition, high levels of interleukin-6 (IL-6) in the serum, a decrease of B cell and an activation of T cells are the main elements identified. Bone turnover is affected by the strong inflammation and is responsible for fracture with high mortality and morbidity. In this thesis, we report some elements for PMR pathophysiology (increased IL-6, decreased B cells, large consequences of inflammation, no auto-antibody signature) and their connections to each other. We try to determine the abnormalities in patients resistant to glucocorticoids and prognostic factors to an innovative treatment: an anti-interleukin-6 receptor antibody, tocilizumab. We studied theeffect of tocilizumab on the immunological manifestations observed in PMR patients. Wealso studied bone remodeling and its evolution under therapy in PMR and we developed a modelling for pharmacokinetic and pharmacodynamic of tocilizumab. New leads for research are suggested, for example the characterization of the immune infiltration in the shoulder of PMR patients.La pseudo-polyarthrite rhizomélique, est un rhumatisme inflammatoire qui touche les sujets de plus de 50 ans. Elle est parfois associée à une vascularite (l’artérite à cellules géantes). La pseudo-polyarthrite rhizomélique est caractérisée par une forte inflammation et une réponse rapide aux corticoïdes. La physiopathologie de la maladie est mal connue. Une prédisposition chez les patients porteurs de certains allèles génétiques, un taux élevé d’interleukine-6 (IL-6) dans le sang, une diminution des lymphocytes B et une activation des lymphocytes T font partie des quelques éléments identifiés. L’inflammation est aussi responsable d’une altération du remodelage osseux qui peut entrainer des fractures responsables d’une mortalité et d’une morbidité importantes. Dans cette thèse nous rapportons des éléments de physiopathologie (augmentation de l’IL-6,diminution des lymphocytes B, conséquences de l’inflammation, absence de signature auto-anticorps) et leurs connexions. Nous avons également cherché à déterminer les anomalies présentes chez les patients avec une maladie résistante aux corticoïdes, des facteurs pronostiques de réponse au tocilizumab (un anticorps anti-récepteur de l’IL-6) et son effet sur ces anomalies. Enfin nous avons analysé le remodelage osseux et son évolution sous traitement et mis en place une modélisation pharmacocinétique et pharmacodynamique du tocilizumab. Ce travail de thèse ouvre de nouvelles perspectives de recherche, entre autres sur l’immunologie au sein du tissu péri-articulaire

Against the dryness—an innovative 3D acini model to test new drugs in primary Sjögren’s syndrome

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Manifestations ostéo-articulaires secondaires à une piqûre, griffure, morsure ou à germes inhabituels ou émergents

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