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OBJECTIVE: Quality of care (QoC) delivery in rheumatoid arthritis (RA) continues to suffer from various challenges (eg, delay in diagnosis and referral) that can lead to poor patient outcomes. This study aimed to identify good practice interventions that address these challenges in RA care in North America. METHODS: The study was conducted in three steps: (1) literature review of existing publications and guidelines (April 2005 to April 2021) on QoC in RA; (2) in-person visits to >50 individual specialists and health care professionals across nine rheumatology centers in the United States and Canada to identify challenges in RA care and any corresponding good practice interventions; and (3) collation and organization of findings of the two previous methods by commonalities to identify key good practice interventions, followed by further review by RA experts to ensure key challenges and gaps in RA care were captured. RESULTS: Several challenges and eight good practice interventions were identified in RA care. The interventions were prioritized based on the perceived positive impact on the challenges in care and ease of implementation. High-priority interventions included the use of technology to improve care, streamlining specialist treatment, and facilitating comorbidity assessment and care. Other interventions included enabling patient access to optimal medication regimens and improving patient self-management strategies. CONCLUSION: Learnings from the study can be implemented in other rheumatology centers throughout North America to improve RA care. Although the study was completed before the COVID-19 pandemic, the findings remain relevant.
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The discovery of toll-like receptors (TLRs) and the subsequent recognition that endogenous nucleic acids (NAs) could serve as TLR ligands have led to essential insights into mechanisms of healthy immune responses as well as pathogenic mechanisms relevant to systemic autoimmune and inflammatory diseases. In systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis, NA-containing immune complexes serve as TLR ligands, with distinct implications depending on the additional immune stimuli available. Plasmacytoid dendritic cells (pDCs), the robust producers of type I interferon (IFN-I), are providing critical insights relevant to TLR-mediated healthy immune responses and tissue repair, as well as generation of inflammation, autoimmunity and fibrosis, processes central to the pathogenesis of many autoimmune diseases. In this review, we describe recent data characterizing the role of platelets and NA-binding chemokines in modulation of TLR signaling in pDCs, as well as implications for how the IFN-I products of pDCs contribute to the generation of inflammation and wound healing responses by monocyte/macrophages. Chemokine modulators of TLR-mediated B cell tolerance mechanisms and interactions between TLR signaling and metabolic pathways are also considered. The modulators of TLR signaling and their contribution to the pathogenesis of systemic autoimmune diseases suggest new opportunities for identification of novel therapeutic targets.
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Enfermedades Autoinmunes , Autoinmunidad , Células Dendríticas , Inflamación , Interferón Tipo I , Transducción de Señal , Receptores Toll-Like , Humanos , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Animales , Inflamación/inmunología , Receptores Toll-Like/metabolismo , Enfermedades Autoinmunes/inmunología , Interferón Tipo I/metabolismo , Plaquetas/inmunología , Plaquetas/metabolismo , Linfocitos B/inmunología , Linfocitos B/metabolismo , Tolerancia Inmunológica , Inmunomodulación , Quimiocinas/metabolismoRESUMEN
The discovery of interferon in the 1950s represents much more than the identification of the first cytokine and the key mediator of antiviral host defense. Defining the molecular nature and complexity of the type I interferon family, as well as its inducers and molecular mechanisms of action, was the work of investigators working at the highest level and producing insights of great consequence. Current knowledge of receptor-ligand interactions, cell signaling, and transcriptional regulation derives from studies of type I interferon. It is on the shoulders of the giants who produced that knowledge that others stand and have revealed critical mechanisms of the pathogenesis of systemic lupus erythematosus and other autoimmune diseases. The design of novel therapeutics is informed by the advances in investigation of type I interferon, with the potential for important impact on patient management.
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Interferón Tipo I , Lupus Eritematoso Sistémico , Animales , Humanos , Interferón Tipo I/inmunología , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Transducción de SeñalRESUMEN
The Advances in Targeted Therapies meets annually, convening experts in the field of rheumatology to both provide scientific updates and identify existing scientific gaps within the field. To review the major unmet scientific needs in rheumatology. The 23rd annual Advances in Targeted Therapies meeting convened with more than 100 international basic scientists and clinical researchers in rheumatology, immunology, infectious diseases, epidemiology, molecular biology and other specialties relating to all aspects of immune-mediated inflammatory diseases. We held breakout sessions in five rheumatological disease-specific groups including: rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpa), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and vasculitis, and osteoarthritis (OA). In each group, experts were asked to identify and prioritise current unmet needs in clinical and translational research. An overarching theme across all disease states is the continued need for clinical trial design innovation with regard to therapeutics, endpoint and disease endotypes. Within RA, unmet needs comprise molecular classification of disease pathogenesis and activity, pre-/early RA strategies, more refined pain profiling and innovative trials designs to deliver on precision medicine. Continued scientific questions within PsA include evaluating the genetic, immunophenotypic, clinical signatures that predict development of PsA in patients with psoriasis, and the evaluation of combination therapies for difficult-to-treat disease. For axSpA, there continues to be the need to understand the role of interleukin-23 (IL-23) in pathogenesis and the genetic relationship of the IL-23-receptor polymorphism with other related systemic inflammatory diseases (eg, inflammatory bowel disease). A major unmet need in the OA field remains the need to develop the ability to reliably phenotype and stratify patients for inclusion in clinical trials. SLE experts identified a number of unmet needs within clinical trial design including the need for allowing endpoints that reflect pharmacodynamic/functional outcomes (eg, inhibition of type I interferon pathway activation; changes in urine biomarkers). Lastly, within SSc and vasculitis, there is a lack of biomarkers that predict response or disease progression, and that allow patients to be stratified for therapies. There remains a strong need to innovate clinical trial design, to identify systemic and tissue-level biomarkers that predict progression or response to therapy, endotype disease, and to continue developing therapies and therapeutic strategies for those with treatment-refractory disease. This document, based on expert consensus, should provide a roadmap for prioritising scientific endeavour in the field of rheumatology.
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Artritis Psoriásica , Artritis Reumatoide , Espondiloartritis Axial , Lupus Eritematoso Sistémico , Osteoartritis , Reumatología , Vasculitis , Humanos , Artritis Psoriásica/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Lupus Eritematoso Sistémico/terapia , Biomarcadores , Interleucina-23RESUMEN
Dr Charles L Christian arrived in New York City in 1953, having grown up in Wichita, Kansas, and graduating from medical school at Case Western Reserve in Cleveland, Ohio. In New York, Dr Christian embarked on training in internal medicine at Columbia's Presbyterian Hospital where he met an individual who would shape the course of his career, Dr Charles Ragan, a founder of the Arthritis Foundation. Dr Christian, or Chuck as he was usually called, went on to shape the developing field of rheumatology, advancing understanding of our most complex diseases as an investigator, master clinician, mentor, and academic leader. During an era when the cellular and humoral features of the immune system were just coming into focus, Chuck performed laboratory experiments with precision and creativity to achieve new understanding of 3 significant diseases: rheumatoid arthritis, systemic lupus erythematosus, and vasculitis. Review of his publications from the 1950s and 1960s provides a window into a time when figures were hand drawn and papers often had a single author. While the tools of technology that we rely on today were not available to Chuck, his insights have had a sustained impact on how we understand and treat autoimmune rheumatic diseases. His talents and his dedication to patients, colleagues, science, and medicine supported a lifetime of remarkable contributions.