Current Rheumatology Reports最新文献

Purpose of review: Axial spondyloarthritis (axSpA) is a chronic multi-organ rheumatic disease affecting various tissues, and recent key advancements have provided significant insight into understanding its immunopathology.

Recent findings: Expanded CD8⁺ T cell subsets bearing unique T cell receptor (TCR) motifs (TRAV21/TRBV9) in HLA-B27-positive axSpA patients or those with acute anterior uveitis were recently identified. These T cells can bind to self- and bacterial-derived peptides, supporting the "arthritogenic peptide" hypothesis. Monoclonal antibody-mediated elimination of these expanded T cells has shown potential as a novel treatment for axSpA in a phase II clinical trial, offering a groundbreaking therapeutic approach. In addition to T cells, neutrophils have emerged as important mediators of both inflammation and new bone formation in axSpA, potentially contributing to HLA-B27-independent immune pathomechanisms. Key neutrophil-derived molecules-such as macrophage migration inhibitory factor, hypoxia-inducible factor 1-alpha, caspase recruitment domain-containing protein 9, and neutrophil extracellular traps (NETs)-have been shown in preclinical models to promote Th17-mediated inflammation and reduce regulatory T cell numbers. These mechanisms may be relevant to axSpA pathogenesis and represent potential new therapeutic targets. In recent years, significant progress has been made in understanding the immunopathology of axSpA through both HLA-B27-dependent and -independent mechanisms. However, key questions remain. The pathogenic HLA-B27:05-bound peptides driving CD8⁺ T cell expansion remain unidentified. Moreover, due to the diversity of TCR motifs that recognize self- and microbial peptides, therapies targeting a single TCR (e.g., TRBV9) may have limited efficacy. Further research is needed to clarify axSpA pathogenesis across both pathways.

Purpose of review: Patients with rheumatoid arthritis (RA) need tailored guidance when it comes to family planning decisions, including contraception, pregnancy, and breastfeeding. To achieve the best reproductive health outcomes, a coordinated, multidisciplinary approach is essential. This article aims to support healthcare providers in addressing key reproductive health concerns for both male and female patients, such as timing conception, infertility, and the management of RA medications during pregnancy and lactation.

Recent findings: Some women with RA may experience subfertility, however assisted reproductive technology is a safe option. RA disease activity may change for some women during pregnancy, but this is influenced by disease activity going into pregnancy and medication use in pregnancy. Pregnancy complications are more common among women with RA compared to the general population, which may be explained, in part, by disease activity, extra-articular manifestations of RA, and/or use of certain medications. Neonates exposed to biologic medications in utero can receive all recommended vaccinations. Contraception, including emergency contraception, is safe for women with RA. Preliminary data suggests pregnancy termination is safe in women with RA and does not increase the risk for disease flare. RA is a chronic inflammatory disease that can impact both women and men during their reproductive years. Rheumatologists have an essential role in patient's reproductive health and family planning. This article highlights key considerations and offers strategies to assist providers in understanding and supporting their patients' reproductive goals.

Purpose of review: This update examines the current policy landscape for biosimilars, particularly those approved for treating rheumatoid arthritis. We review recent literature and recommend policies to align the biosimilars market with the goals of the Biologic Price Competition and Innovation Act (BPCIA). We examine updated evidence on biosimilar safety and effectiveness, recent FDA guidance on interchangeability, and challenges posed by anti-competitive behaviors and government regulations. Additionally, we analyze financial incentives and market dynamics affecting biosimilar adoption and competition.

Recent findings: Building on the extensive body of RCT data demonstrating the safety and effectiveness of biosimilars, real-world evidence from North America and Europe now confirms these findings, including in patients who switched therapies. Increased biosimilar prescribing will depend on disseminating safety data and strategies to enhance patient-physician communication. The FDA updated its interchangeability guidance to no longer require large clinical studies, citing updated understanding of safety data; this may facilitate more direct price-based competition. Congress and the Federal Trade Commission need to address anticompetitive behaviors including patent law loopholes, the role of PBMs in inflating drug prices, vertical integration of healthcare conglomerates, and changes to funding for government agencies charged with reviewing biosimilar drugs. Medicare reimbursement rates and the 340B program still unfairly incentivize use of bio-originator products. There are many barriers to achieving the goals of the BPCIA. With necessary changes, the U.S. can realize the goal of a competitive and sustainable biosimilar market that gradually reduces total drug expenditures and out-of-pocket costs over time without stifling innovation.

Purpose of this review: Rare diseases, although individually infrequent, collectively impact a substantial number of people. Collaborative translational research using biospecimens is essential for advancing our understanding of the diverse characteristics and pathophysiology of rare diseases. Biobanks play a pivotal role in this endeavor by collecting, processing, transporting, and storing biospecimens, thereby serving as invaluable resources for medical research. In this review, we explore currently available biobanks, with a specific focus on those dedicated to rare rheumatic diseases. We also examine accessible best practice guidelines for establishing and maintaining high-quality biobanks, discuss the limitations and propose future directions for enhancing biobanking efforts in rare disease research.

Recent findings: Advances in molecular and genomic technologies have expanded the role of biobanks, enhancing biomarker discovery and precision medicine. However, despite growth in biobanking capabilities, key challenges persist concerning ethics, interoperability, and biospecimen exchange, prompting active responses by various regulatory and governing bodies. Biobanking has transformed rare disease research. Strengthening national and international collaborations is essential for driving progress in this field and accelerating the development of novel therapeutic and precision medicine approaches.

Purpose of review: Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a rare systemic autoimmune disease characterized by a clinically amyopathic presentation and a high-risk association with rapidly progressive interstitial lung disease. Although frequently fatal, the underlying mechanisms remain incompletely understood. This review provides a comprehensive summary of recent advances in research on MDA5-DM, aiming to deepen our understanding of its pathogenic mechanisms and to accelerate future basic research that will contribute to the development of novel therapeutic strategies.

Recent findings: Recent advancements have shed light on various aspects of this disease, including genetic and environmental factors contributing to disease susceptibility and the immunopathological processes and cytokine networks. Furthermore, significant progress has been made in understanding the pathogenicity, epitope recognition, and production mechanisms of anti-MDA5 antibodies, which have long been subjects of debate. On the therapeutic front, in addition to the conventional triple-combination regimen, emerging efficacy of JAK inhibitors and rituximab has been recognized. The development of biologics targeting lymphocytes offers additional hope for advancing therapeutic options. Advancing our understanding of the latest pathophysiological mechanisms of MDA5-DM is expected to pave the way for the development of safer and more effective therapeutic strategies.

Purpose of review: The co-existence of gout and psoriatic disease (PD) is long standing but more recently frequently encountered in clinical settings due to increased awareness of their shared comorbidities and clinical phenotypes, often posing diagnostic and management challenges. Here we review the overlap in gout and PD focusing on shared clinical features, common inflammatory pathophysiology and comorbidities which may prompt a diagnosis of 'Psout' and lead to changes in management.

Recent findings: Several epidemiological studies have highlighted the increased incidence of hyperuricemia and gout in those with PD and vice versa. Although the role of monosodium urate (MSU) crystals is well recognized in activation of innate immunity via inflammasome and NETosis, it is likely that they have a role in triggering adaptive immunity via antigen presenting cells and their autocrine effect on keratinocytes in psoriasis (PSO), ultimately leading to T cell secretion of proinflammatory cytokines such as IL17. Hyperuricemia (HU) is common in PD (up to 30%) and underpins metabolic syndrome comorbidities that are common to both gout and PD. Shared clinical phenotypes and co-morbidities are routinely observed in clinical practice yet there is a paucity of evidence evaluating the effect of treating hyperuricemia/gout on PD activity, with small scale clinical trials showing a positive effect. There were no studies to our knowledge assessing gout disease activity with concurrent treatment of PD. The association between gout and PD is likely due to shared multimorbidity and perhaps to a smaller extent, the direct role of HU in triggering the release of proinflammatory cytokines in PD. There is often a significant overlap in clinical and radiological presentation of gout and Psoriatic arthritis (PsA). In those with atypical response to standard treatments of the primary condition (either gout or PsA), it would be plausible to investigate and treat for the other 'secondary' condition. This is particularly relevant and relatively feasible in those with PsA (and features of HU and multimorbidity) who respond poorly to standard immunomodulating treatments.

Purpose of review: Many individuals with rheumatoid arthritis (RA) continue to suffer from pain despite treatment with disease-modifying antirheumatic drugs. In this review, we aim to summarize the evidence for non-pharmacological approaches for managing pain in RA.

Recent findings: Few studies have examined the effect of non-pharmacological therapies on pain in patients with RA. Of these studies, many were not designed to specifically target pain and examined pain as a secondary outcome. While most studies reported within group improvements in pain, the magnitude of improvement varied, and differences between intervention and control groups often were not statistically significant. We recommend non-pharmacologic approaches for management of RA, based primarily on data for improving pain-related outcomes (e.g., physical function, overall health), as opposed to pain itself. The evidence base for non-pharmacologic interventions for pain remains poor, and there is a critical need for large RCTs designed to specifically target pain.

Purpose of review: This review highlights key ultrasound applications for evaluating extra-articular involvement in rheumatic diseases, including the lungs, vessels, salivary glands, muscles, nerves, skin, and nails. It explores recent advances, emerging areas of assessment, and future research directions. Additionally, the review examines current limitations in the routine use of ultrasound for these purposes and considers the potential of new technologies, such as shear-wave elastography, contrast-enhanced ultrasound, and artificial intelligence, to enhance the early detection and monitoring of extra-articular manifestations in rheumatic diseases.

Recent findings: Extra-articular manifestations in patients with rheumatic diseases are crucial for diagnosis, management (including treatment strategies), and prognosis, making accurate assessment essential. Growing evidence supports the role of ultrasound in assessing these manifestations for diagnosis, monitoring, and gaining insights into disease pathogenesis. Recent studies emphasize the significant utility of ultrasound in evaluating extra-articular involvement across various organ systems, including the lungs, vessels, salivary glands, muscles, nerves, skin, and nails. Technological advances, such as shear-wave elastography, contrast-enhanced ultrasound, and artificial intelligence, are expanding the scope and precision of ultrasound applications. Despite its potential, challenges such as operator dependency, lack of standardized protocols, and the need for specialized training hinder its widespread adoption. Ultrasound is a non-invasive, cost-effective, and radiation-free imaging modality with high diagnostic accuracy, making it a valuable tool for assessing extra-articular manifestations in rheumatic diseases. Emerging technologies may further enhance its clinical utility. However, efforts to standardize techniques and improve accessibility are necessary to optimize its integration into routine practice.

Purpose of review: To summarize the state of research and recent studies on non-pharmacological therapies for osteoarthritis (OA).

Recent findings: High intensity interval training is an exercise-based intervention with some new, promising findings for people with OA. Among mind-body therapies, Tai Chi has the strongest evidence base to date. Diet + exercise has the strongest evidence for weight management in OA, with recent research focusing on maintenance of weight loss and non-calorie restrictive dietary patterns. Among psychological interventions, Cognitive Behavioral Therapy has the strongest evidence base, with some support for Acceptance and Commitment Therapy and mindfulness-based interventions. There is a clear role for non-pharmacological therapies for OA. Future research should address the effectiveness of interventions for which evidence is still limited, strategies for maintenance, heterogeneity of patients' responses to these therapies, and implementation in clinical and community settings.

Purpose of review: This review aims to explore the emerging concept of difficult-to-treat axial spondyloarthritis (D2T-axSpA), including its definitions, clinical challenges, and management strategies. The objective, as presented at the SPARTAN 2024 Annual Meeting, is to delineate the evolving framework for identifying and addressing D2T-axSpA, with a focus on inflammatory and non-inflammatory mechanisms of treatment failure and the implications for clinical practice.

Recent findings: Studies have highlighted a prevalence of D2T-axSpA ranging from 19.5 to 28.3% in real-world cohorts, with associated risk factors including peripheral arthritis, comorbidities, and female gender. Recent advances include the Assessment of SpondyloArthritis International Society's (ASAS) preliminary definition of "difficult-to-manage axSpA" (D2M-axSpA), which encompasses treatment-refractory cases and broader management challenges and `treatment refractory axSpA´ where objective evidence of ongoing inflammation is mandatory.  D2T-axSpA presents significant challenges due to persistent disease activity and the interplay of inflammatory and non-inflammatory drivers. The emerging definitions and research into personalized treatment strategies promise to refine clinical management. Future directions emphasize biomarker-driven precision medicine, novel therapeutic combinations, and holistic care models to improve outcomes in this complex patient population.