Current opinion in rheumatology最新文献

Purpose of review: Cellular therapies such as CD19-targeting CAR T cells are a rapidly evolving field in an area of unmet clinical needs: autoimmune diseases including systemic sclerosis (SSc). The aim of this review is to summarize the available data on safety and efficacy of CAR T-cell therapy in SSc and to discuss upcoming developments and challenges for the near future.

Recent findings: Several case reports and series recently described the treatment of SSc patients with CD19-targeting CAR T cells, which resulted in profound B-cell depletion and downregulation of autoimmunity. Encouraging results on efficacy in several disease manifestations were reported including skin and organ fibrosis. Also, vascular phenomena including digital ulcerations improved. The safety profile showed mostly mild-to-moderate cytokine release syndrome (CRS) and low rates of neurotoxicity. Infectious complications ranged from mild upper airway infections to pneumonia. However, a case of herpes simplex reactivation with secondary lethal haemophagocytosis was also described.

Summary: Current evidence suggests very promising effects of CD19-CAR T-cell therapy on several SSc manifestations. Additional larger trials are needed. Current frontiers are patient selection, refining lymphodepletion protocols, and expanding target antigens beyond CD19.

Purpose of review: This review will attempt to summarize the most potentially impactful new data on the treatment of systemic vasculitic conditions, including ANCA-associated vasculitis (AAV), giant cell arteritis, polymyalgia rheumatica and Takayasu arteritis.

Recent findings: Rituximab, cyclophosphamide, upadacitinib, baricitinib, mepolizumab, benralizumab and tocilizumab have all had new clinical trials and observational data from real world registries showing their treatment benefit in various vasculitic conditions. The recently developed classification criteria for five different vasculitic conditions (AAV, giant cell arteritis, and Takayasu arteritis), very important for clinical trial recruitment, have serious methodological issues that continue to be present in the new criteria sets and these need to be addressed before they can be widely adopted.

Summary: Important new data over the last several years for the treatment of systemic vasculitis have the potential to change how these conditions are managed. The remaining issues outlined in this review still need to be addressed to best serve vasculitis patients.

Purpose of review: The systemic vasculitidies are a group of diseases characterized by vascular inflammation, with varying features and frequencies across the globe. Our review aims to highlight recent epidemiologic data and key findings on these disorders that have been published over the past 18 months.

Recent findings: Advances in imaging techniques, increased disease awareness, and improved diagnostic and therapeutic management has altered the demographic and prognostic landscape of the systemic vasculitidies. Updated data driven classification criteria have allowed for better characterization and epidemiologic research in these disease states. The ethno-geographic variability and influence of genetic and environmental factors in the pathogenesis of systemic vasculitis is further highlighted by recent epidemiologic studies, with new trends in certain populations postulated to be secondary to increases in genetic diversity.

Summary: Recent data highlights the geographic, ethnic, and seasonal variability of the systemic vasculitidies. The use of advanced imaging techniques and updated classification systems, coupled with new epidemiologic studies from underrepresented populations, shed further light on the burden and characteristics of these diseases globally.

Purpose of review: Significant progress has been made in improving the outcomes of patients with systemic lupus erythematosus (SLE) largely through advances in drug discovery as well as enhancements in overall clinical management. This review provides insights into the basis for observed improvements in long-term outcomes through analyses of organ damage, mortality, healthcare utilization, and quality of life.

Recent findings: Patients with SLE in the first half of the twentieth century faced a 50% chance of surviving beyond 7 years. However, in modern times, age standardized mortality has greatly improved, and comorbidities that adversely affect outcomes are receiving far more attention than in prior eras.

Summary: It is a remarkable era for patients with SLE, with multiple targeted therapies transforming management. Yet, damage prevention still begins with early diagnosis and rapid attainment of remission. Treat to target strategies should be coupled with adjunctive measures, such as strict blood pressure control as well as cardiovascular and metabolic risk management.

Purpose of review: Idiopathic inflammatory myopathies (IIMs) carry substantial extra-muscular comorbidities. The purpose of this review is to provide a focused synthesis of recent population-based data on the epidemiology of key comorbidities in IIMs: atherosclerotic cardiovascular disease (ASCVD), venous thromboembolism (VTE), psychiatric and neurocognitive disorders, and bone health.

Recent findings: IIM patients have approximately two-fold increased risk of ASCVD and of other cardiovascular events, like VTE. These risks likely result from several factors, including chronic systemic inflammation, physical inactivity, treatment side effects. Anti-HMGCR immune necrotizing inflammatory myopathy (IMNM), is a subtype of IIM that requires special consideration regarding dyslipidemia management, where statin alternatives are necessary. Furthermore, psychiatric and neurocognitive comorbidities are common, and likely under-recognized among IIM patients, and perhaps especially so in inclusion body myositis (IBM) patients. Finally, IIM patients have an increased risk of accelerated bone loss likely due to systemic inflammation, muscle damage and physical inactivity, and glucocorticoid exposure.

Summary: Cardiovascular care, psychiatric/neurocognitive disorders, and osteopenia/osteoporosis are highly prevalent and often underrecognized in IIMs. Effective management of these IIM-associated comorbidities requires a multidisciplinary, comprehensive care approach, and further work is needed to adapt existing risk-stratification and screening tools for the unique needs of IIMs patients.

Purpose of review: Lupus erythematosus (LE) encompasses a spectrum of autoimmune diseases with significant heterogeneity, ranging from cutaneous lupus erythematosus (CLE), confined to the skin, to systemic lupus erythematosus (SLE), which affects multiple internal organs. The underlying pathogenesis of lupus skin lesions and the heterogeneity among various subtypes remain elusive and require further investigation. This review synthesizes recent progress in elucidating the mechanisms of lupus skin injury, providing novel perspectives on diagnosis and therapeutic strategies, while also outlining promising avenues for future investigation.

Recent findings: Key insights include the active pathogenic role of keratinocytes, essential involvement of neutrophils, the central role of type I interferon (IFN-I) signaling, and a preactivated molecular state in nonlesional skin. Emerging distinctions between CLE and SLE lesions, as well as the role of photosensitivity, are also examined. These findings highlight modifiable environmental factors as critical parts for LE prevention and establish a new paradigm for future precision medicine in LE.

Summary: These novel findings enrich the complex pathogenic network underlying lupus skin injury, accelerating the transition toward precision medicine. Rational prevention, early diagnosis, and targeted treatment represent the core principles and a promising vision for the future evolution of lupus management.

Purpose of review: Systemic sclerosis (SSc) remains a therapeutic challenge, with conventional immunosuppressive strategies showing inconsistent effects and no disease modifying activity. The lack of head-head trials comparing immunosuppressives with emerging antifibrotic agents further complicates treatment decisions in SSc. This review aims to provide an update on the recent advances in targeted therapies for SSc, with a focus on novel biologics and small molecules that specifically modulate key mechanisms.

Recent findings: Advances in molecular profiling have revealed inflammatory and fibrotic endotypes within SSc while imaging studies support a fibroinflammatory subset, highlighting potential therapeutic targets.

Summary: A literature search for clinical trials between January 2020 and April 2025 from PubMed/MEDLINE, clinicaltrials.gov, euclinicaltrials.eu databases for targeted therapies in systemic sclerosis revealed a total of 117 clinical trials, of which we described the design, methods and endpoints from 14 studies (2 conference abstracts, 11 trials and 1 case series). These study results offer hope for patients with systemic sclerosis and pave way for future studies directing the development of patient-specific guidelines.

Purpose of review: Our objective is to propose an expert opinion focusing on most important and recent developments in calcium pyrophosphate deposition (CPPD) epidemiology. We highlight recent findings published in the past 18 months and their potential implications for research and patient care.

Recent findings: We discuss new understanding of CPPD prevalence through advances in imaging modalities, advances in synovial fluid analyses (SFA), updates on disease phenotypes, and potential sources of misdiagnosis of CPPD. We present recent data regarding extra-articular associations of CPPD, particularly cardiovascular events and osteoporotic fractures. We discuss new therapeutic options. We identify barriers to improving research in CPPD, and tools currently available to overcome certain pitfalls.

Summary: Improved knowledge in the epidemiology of asymptomatic CPPD and symptomatic CPPD disease is crucial to improving recognition of this still underdiagnosed disease, and to understanding patient phenotypes and their outcomes. Future research will require prospective designs to establish the prevalence of CPPD disease phenotypes and to provide more precise data according to each phenotype, both in terms of epidemiological findings and treatment responses, to develop personalized medicine.

Purpose of review: Patients with systemic sclerosis (SSc) often seek advice regarding diet including functional foods, and complementary and alternative medicine (CAM) as adjunctive therapies. This review summarizes existing literature regarding these approaches.

Recent findings: Study results of low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, And Polyols (FODMAP), Mediterranean and ketogenic diets suggest symptom reduction and beneficial microbiota modulation in SSc, though sample sizes are small. Nitrate-rich and antioxidant supplements such as omega-3 fatty acids show promise in lowering inflammation and oxidative stress in the circulation. Herbal remedies like curcumin have demonstrated antifibrotic properties in preclinical models. Topical agents (e.g., rosemary oil, vitamin E gel) and nutritional vitamins (e.g., C, D, E) are also frequently used, though robust clinical trials are lacking.

Summary: CAM, dietary interventions, and functional foods may aid in SSc management, but more rigorous research is needed to provide definitive evidence.

Purpose of review: This review provides updates on juvenile dermatomyositis pathogenesis and treatment.

Recent findings: JDM pathogenesis research updates in genetic risk factors include C4 copy number. Studies clarify myositis-specific autoantibodies' (MSA) role in disease pathogenesis and more myositis-associated antibody (MAA) clinical associations. Recent studies validate an interferon (IFN)-regulated gene score and an IFN-related monocyte surface protein marker, SIGLEC-1. Vasculopathy and mitochondrial dysfunction evidence increases, both with ties to IFN. Studies point to not only T and B cells, but monocytes, macrophages, and neutrophils as dysregulated in JDM. Regarding treatment, there are growing reports of success with therapies targeting IFN-signaling (Janus kinase inhibitors), dazukibart (anti-IFN-beta), and anifrolumab (anti-IFNAR1). Chimeric antigen receptor (CAR) T-cell therapy targeting B-cells in a growing number of adult myositis patients and one JDM patient have dramatic reports of achieving drug-free remission.

Summary: Growing evidence show genetic markers, MSA, IFN, vasculopathy, varied immune cells, and mitochondrial dysfunction having important roles in JDM pathogenesis. Some refractory patients show benefit with newer IFN pathway-targeted therapies and cellular CAR-T-cell therapy. Further collaborative research on disease pathogenesis, treatment targets, and innovate clinical trial design is needed to increase access to more efficacious treatments in JDM.