Pub Date : 2023-12-29DOI: 10.1007/s11926-023-01129-2
Anna Helena Jonsson
Purpose of Review
Rheumatoid arthritis is one of the most common rheumatic and autoimmune diseases. While it can affect many different organ systems, RA primarily involves inflammation in the synovium, the tissue that lines joints. Patients with RA exhibit significant clinical heterogeneity in terms of presence or absence of autoantibodies, degree of permanent deformities, and most importantly, treatment response. These clinical characteristics point to heterogeneity in the cellular and molecular pathogenesis of RA, an area that several recent studies have begun to address.
Recent Findings
Single-cell RNA-sequencing initiatives and deeper focused studies have revealed several RA-associated cell populations in synovial tissues, including peripheral helper T cells, autoimmunity-associated B cells (ABCs), and NOTCH3+ sublining fibroblasts. Recent large transcriptional studies and translational clinical trials present frameworks to capture cellular and molecular heterogeneity in RA synovium. Technological developments, such as spatial transcriptomics and machine learning, promise to further elucidate the different types of RA synovitis and the biological mechanisms that characterize them, key elements of precision medicine to optimize patient care and outcomes in RA.
Summary
This review recaps the findings of those recent studies and puts our current knowledge and future challenges into scientific and clinical perspective.
综述目的类风湿性关节炎是最常见的风湿病和自身免疫性疾病之一。虽然它可以影响许多不同的器官系统,但 RA 主要涉及关节滑膜组织的炎症。在是否存在自身抗体、永久性畸形的程度以及最重要的治疗反应方面,RA 患者表现出明显的临床异质性。这些临床特征表明,RA 的细胞和分子发病机制存在异质性,最近的一些研究已开始涉及这一领域。最近的发现单细胞 RNA 测序计划和更深入的重点研究揭示了滑膜组织中与 RA 相关的几种细胞群,包括外周辅助性 T 细胞、自身免疫相关 B 细胞 (ABC) 和 NOTCH3+ 下层成纤维细胞。最近的大型转录研究和转化临床试验提出了捕捉 RA 滑膜中细胞和分子异质性的框架。空间转录组学和机器学习等技术的发展有望进一步阐明不同类型的RA滑膜炎及其生物学机制,这些都是精准医疗的关键要素,可优化RA患者的护理和预后。
{"title":"Synovial Tissue Insights into Heterogeneity of Rheumatoid Arthritis","authors":"Anna Helena Jonsson","doi":"10.1007/s11926-023-01129-2","DOIUrl":"https://doi.org/10.1007/s11926-023-01129-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose of Review</h3><p>Rheumatoid arthritis is one of the most common rheumatic and autoimmune diseases. While it can affect many different organ systems, RA primarily involves inflammation in the synovium, the tissue that lines joints. Patients with RA exhibit significant clinical heterogeneity in terms of presence or absence of autoantibodies, degree of permanent deformities, and most importantly, treatment response. These clinical characteristics point to heterogeneity in the cellular and molecular pathogenesis of RA, an area that several recent studies have begun to address.</p><h3 data-test=\"abstract-sub-heading\">Recent Findings</h3><p>Single-cell RNA-sequencing initiatives and deeper focused studies have revealed several RA-associated cell populations in synovial tissues, including peripheral helper T cells, autoimmunity-associated B cells (ABCs), and NOTCH3<sup>+</sup> sublining fibroblasts. Recent large transcriptional studies and translational clinical trials present frameworks to capture cellular and molecular heterogeneity in RA synovium. Technological developments, such as spatial transcriptomics and machine learning, promise to further elucidate the different types of RA synovitis and the biological mechanisms that characterize them, key elements of precision medicine to optimize patient care and outcomes in RA.</p><h3 data-test=\"abstract-sub-heading\">Summary</h3><p>This review recaps the findings of those recent studies and puts our current knowledge and future challenges into scientific and clinical perspective.</p>","PeriodicalId":10761,"journal":{"name":"Current Rheumatology Reports","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139064234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-16DOI: 10.1007/s11926-023-01122-9
Fatima K. Alduraibi, Jasvinder A. Singh
Purpose of Review
To provide an updated understanding of risks and benefits of Janus kinase inhibitors (JAKi) versus biologic disease-modifying antirheumatic drugs (bDMARDs) in the management of rheumatoid arthritis (RA).
Recent Findings
Shared decision-making is needed in choosing between JAKi and bDMARDs. Cardiovascular disease, malignancy, and thromboembolic events guide this choice. In patients with active RA despite methotrexate use, tumor necrosis factor inhibitor is conditionally favored over JAKi for low-cardiovascular-risk patients and strongly favored in those with pre-existing cardiovascular disease or multiple cardiovascular risk factors. Suboptimal treatment of treatment-refractory RA patients may pose a greater absolute cardiovascular risk than with JAKi use. Use of aspirin and statin may be considered to reduce cardiovascular risk.
Summary
New safety data on JAKi has redefined the treatment approach in RA. JAKi remains an important oral medication option in active RA despite treatment with bDMARDs, especially in those with low cardiovascular risk.
最新研究结果在选择 JAKi 和 bDMARDs 时需要共同决策。心血管疾病、恶性肿瘤和血栓栓塞事件是选择的指导因素。在使用甲氨蝶呤的活动性RA患者中,对于心血管风险较低的患者,肿瘤坏死因子抑制剂有条件地优于JAKi,而对于已有心血管疾病或存在多种心血管风险因素的患者,肿瘤坏死因子抑制剂则更受青睐。与使用JAKi相比,对难治性RA患者进行次优治疗可能会带来更大的绝对心血管风险。可考虑使用阿司匹林和他汀类药物来降低心血管风险。总结 JAKi 的新安全性数据重新定义了 RA 的治疗方法。尽管使用了bDMARDs治疗,JAKi仍然是活动性RA患者的重要口服药物选择,尤其是对于心血管风险较低的患者。
{"title":"How to Use Janus Kinase Inhibitors in the Treatment of Rheumatoid Arthritis? A Clinical Assessment of Risks and Benefits","authors":"Fatima K. Alduraibi, Jasvinder A. Singh","doi":"10.1007/s11926-023-01122-9","DOIUrl":"https://doi.org/10.1007/s11926-023-01122-9","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose of Review</h3><p>To provide an updated understanding of risks and benefits of Janus kinase inhibitors (JAKi) versus biologic disease-modifying antirheumatic drugs (bDMARDs) in the management of rheumatoid arthritis (RA).</p><h3 data-test=\"abstract-sub-heading\">Recent Findings</h3><p>Shared decision-making is needed in choosing between JAKi and bDMARDs. Cardiovascular disease, malignancy, and thromboembolic events guide this choice. In patients with active RA despite methotrexate use, tumor necrosis factor inhibitor is conditionally favored over JAKi for low-cardiovascular-risk patients and strongly favored in those with pre-existing cardiovascular disease or multiple cardiovascular risk factors. Suboptimal treatment of treatment-refractory RA patients may pose a greater absolute cardiovascular risk than with JAKi use. Use of aspirin and statin may be considered to reduce cardiovascular risk.</p><h3 data-test=\"abstract-sub-heading\">Summary</h3><p>New safety data on JAKi has redefined the treatment approach in RA. JAKi remains an important oral medication option in active RA despite treatment with bDMARDs, especially in those with low cardiovascular risk.</p>","PeriodicalId":10761,"journal":{"name":"Current Rheumatology Reports","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138689424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-09-22DOI: 10.1007/s11926-023-01115-8
F Naz Cemre Kalayci, Seza Ozen
Purpose of review: The resident gut microbiota serves as a double-edged sword that aids the host in multiple ways to preserve a healthy equilibrium and serve as early companions and boosters for the gradual evolution of our immune defensive layers; nevertheless, the perturbation of the symbiotic resident intestinal communities has a profound impact on autoimmunity induction, particularly in systemic lupus erythematosus (SLE). Herein, we seek to critically evaluate the microbiome research in SLE with a focus on intestinal dysbiosis.
Recent findings: SLE is a complex and heterogeneous disorder with self-attack due to loss of tolerance, and there is aberrant excessive immune system activation. There is mounting evidence suggesting that intestinal flora disturbances may accelerate the formation and progression of SLE, presumably through a variety of mechanisms, including intestinal barrier dysfunction and leaky gut, molecular mimicry, bystander activation, epitope spreading, gender bias, and biofilms. Gut microbiome plays a critical role in SLE pathogenesis, and additional studies are warranted to properly define the impact of gut microbiome in SLE, which can eventually lead to new and potentially safer management approaches for this debilitating disease.
{"title":"Possible Role of Dysbiosis of the Gut Microbiome in SLE.","authors":"F Naz Cemre Kalayci, Seza Ozen","doi":"10.1007/s11926-023-01115-8","DOIUrl":"10.1007/s11926-023-01115-8","url":null,"abstract":"<p><strong>Purpose of review: </strong>The resident gut microbiota serves as a double-edged sword that aids the host in multiple ways to preserve a healthy equilibrium and serve as early companions and boosters for the gradual evolution of our immune defensive layers; nevertheless, the perturbation of the symbiotic resident intestinal communities has a profound impact on autoimmunity induction, particularly in systemic lupus erythematosus (SLE). Herein, we seek to critically evaluate the microbiome research in SLE with a focus on intestinal dysbiosis.</p><p><strong>Recent findings: </strong>SLE is a complex and heterogeneous disorder with self-attack due to loss of tolerance, and there is aberrant excessive immune system activation. There is mounting evidence suggesting that intestinal flora disturbances may accelerate the formation and progression of SLE, presumably through a variety of mechanisms, including intestinal barrier dysfunction and leaky gut, molecular mimicry, bystander activation, epitope spreading, gender bias, and biofilms. Gut microbiome plays a critical role in SLE pathogenesis, and additional studies are warranted to properly define the impact of gut microbiome in SLE, which can eventually lead to new and potentially safer management approaches for this debilitating disease.</p>","PeriodicalId":10761,"journal":{"name":"Current Rheumatology Reports","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41108228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose of review: This review aims to evaluate recent findings on the role of environmental factors in the development and clinical presentation of idiopathic inflammatory myopathies (IIMs).
Recent findings: A targeted literature review was conducted to identify reports relevant to the association between environmental factors and IIMs published over the past three years. There has been an increasing number of publications dealing with the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination with the development of IIMs, highlighting the significant role of the antiviral immune response in the pathogenesis of the disease. Traditional environmental factors associated with the pathogenic process of IIM subclassifications included drugs such as statins and immune checkpoint inhibitors, ultraviolet radiation, smoking, air pollutants, and vitamin D deficiency. Correlations of seasonality and residence with the onset of certain IIM subtypes suggest a potential role of environmental triggers in the pathogenic process. An interplay between genetic predisposition and various environmental factors might contribute to the development of IIMs as well as the heterogeneous clinical and serological presentation of IIMs. The growing evidence on the role of environmental factors in the development of IIMs provides important clues to elucidate the pathophysiology of these disease entities. The mechanisms underlying the interactions between genetic predisposition and environmental factors should be investigated in the future.
{"title":"The Role of Environmental Factors in the Development of Idiopathic Inflammatory Myopathies: a Narrative Review.","authors":"Shintaro Yamamoto, Akira Yoshida, Takahisa Gono, Masataka Kuwana","doi":"10.1007/s11926-023-01120-x","DOIUrl":"10.1007/s11926-023-01120-x","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review aims to evaluate recent findings on the role of environmental factors in the development and clinical presentation of idiopathic inflammatory myopathies (IIMs).</p><p><strong>Recent findings: </strong>A targeted literature review was conducted to identify reports relevant to the association between environmental factors and IIMs published over the past three years. There has been an increasing number of publications dealing with the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination with the development of IIMs, highlighting the significant role of the antiviral immune response in the pathogenesis of the disease. Traditional environmental factors associated with the pathogenic process of IIM subclassifications included drugs such as statins and immune checkpoint inhibitors, ultraviolet radiation, smoking, air pollutants, and vitamin D deficiency. Correlations of seasonality and residence with the onset of certain IIM subtypes suggest a potential role of environmental triggers in the pathogenic process. An interplay between genetic predisposition and various environmental factors might contribute to the development of IIMs as well as the heterogeneous clinical and serological presentation of IIMs. The growing evidence on the role of environmental factors in the development of IIMs provides important clues to elucidate the pathophysiology of these disease entities. The mechanisms underlying the interactions between genetic predisposition and environmental factors should be investigated in the future.</p>","PeriodicalId":10761,"journal":{"name":"Current Rheumatology Reports","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1007/s11926-023-01117-6
Carly Conran, Jason Kolfenbach, Kristine Kuhn, Christopher Striebich, Larry Moreland
Purpose of review: A subset of patients with rheumatoid arthritis (RA) who fail multiple biologic therapies are deemed to have "difficult-to-treat" (D2T) RA. In 2021, a European Alliance of Associations for Rheumatology (EULAR) task force proposed a clinical definition of D2T RA. Here we review RA phenotypes and clinical assessment of RA, propose a different definition of D2T RA, discuss possible D2T RA risk factors, and summarize existing literature on the management of D2T RA.
Recent findings: High disease activity at the time of diagnosis or prior to treatment with a biologic is associated with the development of D2T RA. Prolonged time from diagnosis to beginning treatment has been consistently associated with the development of D2T RA. Other clinical factors such as burden of disease, extraarticular disease, obesity, smoking, pain, fatigue, and psychological conditions have inconsistent associations with D2T RA according to current literature. D2T RA is a relatively new concept that represents an area of great need for research regarding the characterization of those with the disease as well as how best to treat the disease. With this gained knowledge, rheumatologists will be able to better identify patients at the time of diagnosis that are likely to develop D2T RA to help guide management.
{"title":"A Review of Difficult-to-Treat Rheumatoid Arthritis: Definition, Clinical Presentation, and Management.","authors":"Carly Conran, Jason Kolfenbach, Kristine Kuhn, Christopher Striebich, Larry Moreland","doi":"10.1007/s11926-023-01117-6","DOIUrl":"10.1007/s11926-023-01117-6","url":null,"abstract":"<p><strong>Purpose of review: </strong>A subset of patients with rheumatoid arthritis (RA) who fail multiple biologic therapies are deemed to have \"difficult-to-treat\" (D2T) RA. In 2021, a European Alliance of Associations for Rheumatology (EULAR) task force proposed a clinical definition of D2T RA. Here we review RA phenotypes and clinical assessment of RA, propose a different definition of D2T RA, discuss possible D2T RA risk factors, and summarize existing literature on the management of D2T RA.</p><p><strong>Recent findings: </strong>High disease activity at the time of diagnosis or prior to treatment with a biologic is associated with the development of D2T RA. Prolonged time from diagnosis to beginning treatment has been consistently associated with the development of D2T RA. Other clinical factors such as burden of disease, extraarticular disease, obesity, smoking, pain, fatigue, and psychological conditions have inconsistent associations with D2T RA according to current literature. D2T RA is a relatively new concept that represents an area of great need for research regarding the characterization of those with the disease as well as how best to treat the disease. With this gained knowledge, rheumatologists will be able to better identify patients at the time of diagnosis that are likely to develop D2T RA to help guide management.</p>","PeriodicalId":10761,"journal":{"name":"Current Rheumatology Reports","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41113427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-09-01DOI: 10.1007/s11926-023-01108-7
Syed Obaidur Rahman, Frédérique Bariguian, Ali Mobasheri
Purpose of review: This narrative review article comprehensively explains the pathophysiology of osteoarthritis (OA) pain perception, how the gut microbiota is correlated with it, possible molecular pathways involved in probiotics-mediated OA pain reduction, limitations in the current research approaches, and future perspectives.
Recent findings: The initiation and progression of OA, including the development of chronic pain, is intricately associated with activation of the innate immune system and subsequent inflammatory responses. Trauma, lifestyle (e.g., obesity and metabolic disease), and chronic antibiotic treatment can disrupt commensal homeostasis of the human microbiome, thereby affecting intestinal integrity and promoting leakage of bacterial endotoxins and metabolites such as lipopolysaccharides (LPS) into circulation. Increased level of LPS is associated with knee osteophyte severity and joint pain. Both preclinical and clinical studies strongly suggest that probiotics may benefit patients with OA pain through positive gut microbiota modulation and attenuating low-grade inflammation via multiple pathways. Patent data also suggests increased interest in the development of new innovations that involve probiotic use for reducing OA and joint pain. Recent data suggest that probiotics are attracting more and more attention for OA pain management. The advancement of knowledge in this area may pave the way for developing different probiotic strains that can be used to support joint health, improve treatment outcomes in OA, and reduce the huge impact of the disease on healthcare systems worldwide.
综述的目的:这篇叙事性综述文章全面阐述了骨关节炎(OA)痛觉的病理生理学、肠道微生物群与之的相关性、益生菌介导的OA疼痛减轻可能涉及的分子途径、当前研究方法的局限性以及未来展望:OA 的发生和发展,包括慢性疼痛的发展,与先天性免疫系统的激活和随后的炎症反应密切相关。创伤、生活方式(如肥胖和代谢性疾病)和慢性抗生素治疗会破坏人体微生物群的共生平衡,从而影响肠道完整性,促进细菌内毒素和代谢产物(如脂多糖)渗入血液循环。LPS 水平的升高与膝关节骨质增生的严重程度和关节疼痛有关。临床前研究和临床研究都有力地表明,益生菌可通过积极的肠道微生物群调节,并通过多种途径减轻低度炎症,从而使有 OA 疼痛的患者受益。专利数据还表明,人们对使用益生菌减轻 OA 和关节疼痛的创新开发越来越感兴趣。最近的数据表明,益生菌在治疗 OA 疼痛方面吸引了越来越多的关注。该领域知识的进步可能会为开发不同的益生菌株铺平道路,这些益生菌株可用于支持关节健康、改善 OA 的治疗效果以及减少该疾病对全球医疗保健系统的巨大影响。
{"title":"The Potential Role of Probiotics in the Management of Osteoarthritis Pain: Current Status and Future Prospects.","authors":"Syed Obaidur Rahman, Frédérique Bariguian, Ali Mobasheri","doi":"10.1007/s11926-023-01108-7","DOIUrl":"10.1007/s11926-023-01108-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>This narrative review article comprehensively explains the pathophysiology of osteoarthritis (OA) pain perception, how the gut microbiota is correlated with it, possible molecular pathways involved in probiotics-mediated OA pain reduction, limitations in the current research approaches, and future perspectives.</p><p><strong>Recent findings: </strong>The initiation and progression of OA, including the development of chronic pain, is intricately associated with activation of the innate immune system and subsequent inflammatory responses. Trauma, lifestyle (e.g., obesity and metabolic disease), and chronic antibiotic treatment can disrupt commensal homeostasis of the human microbiome, thereby affecting intestinal integrity and promoting leakage of bacterial endotoxins and metabolites such as lipopolysaccharides (LPS) into circulation. Increased level of LPS is associated with knee osteophyte severity and joint pain. Both preclinical and clinical studies strongly suggest that probiotics may benefit patients with OA pain through positive gut microbiota modulation and attenuating low-grade inflammation via multiple pathways. Patent data also suggests increased interest in the development of new innovations that involve probiotic use for reducing OA and joint pain. Recent data suggest that probiotics are attracting more and more attention for OA pain management. The advancement of knowledge in this area may pave the way for developing different probiotic strains that can be used to support joint health, improve treatment outcomes in OA, and reduce the huge impact of the disease on healthcare systems worldwide.</p>","PeriodicalId":10761,"journal":{"name":"Current Rheumatology Reports","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10186329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-09-28DOI: 10.1007/s11926-023-01116-7
Eva Vermeer, Renske C F Hebing, Maartje M van de Meeberg, Marry Lin, Tim G J de Meij, Eduard A Struys, Gerrit Jansen, Michael T Nurmohamed, Maja Bulatović Ćalasan, Robert de Jonge
Purpose: This review aims to critically evaluate the potential benefit of either oral or subcutaneous administration of methotrexate (MTX) in various immune-mediated inflammatory disorders (IMIDs) through analysis of efficacy, toxicity, pharmacokinetics and pharmacodynamics of both administration routes.
Recent findings: Recent studies comparing the efficacy of oral versus subcutaneous MTX administration in IMIDs have revealed contradicting results. Some reported higher efficacy with subcutaneous administration, while others found no significant difference. Regarding toxicity, some studies have challenged the notion that subcutaneous administration is better tolerated than oral administration, while others have supported this. Pharmacokinetic studies suggest higher plasma bioavailability and increased accumulation of MTX-polyglutamates (MTX-PGs) in red blood cells (RBCs) with subcutaneous administration during the initial treatment phase. However, after several months, similar intracellular drug levels are observed with both administration routes. There is no conclusive evidence supporting the superiority of either oral or subcutaneous MTX administration in terms of efficacy and adverse events in IMIDs. Subcutaneous administration leads to higher plasma bioavailability and initial accumulation of MTX-PGs in RBCs, but the difference seems to disappear over time. Given the variable findings, the choice of administration route may be based on shared decision-making, offering patients the option of either oral or subcutaneous administration of MTX based on individual preferences and tolerability. Further research is needed to better understand the impact of MTX-PGs in various blood cells and TDM on treatment response and adherence to MTX therapy.
{"title":"Oral Versus Subcutaneous Methotrexate in Immune-Mediated Inflammatory Disorders: an Update of the Current Literature.","authors":"Eva Vermeer, Renske C F Hebing, Maartje M van de Meeberg, Marry Lin, Tim G J de Meij, Eduard A Struys, Gerrit Jansen, Michael T Nurmohamed, Maja Bulatović Ćalasan, Robert de Jonge","doi":"10.1007/s11926-023-01116-7","DOIUrl":"10.1007/s11926-023-01116-7","url":null,"abstract":"<p><strong>Purpose: </strong>This review aims to critically evaluate the potential benefit of either oral or subcutaneous administration of methotrexate (MTX) in various immune-mediated inflammatory disorders (IMIDs) through analysis of efficacy, toxicity, pharmacokinetics and pharmacodynamics of both administration routes.</p><p><strong>Recent findings: </strong>Recent studies comparing the efficacy of oral versus subcutaneous MTX administration in IMIDs have revealed contradicting results. Some reported higher efficacy with subcutaneous administration, while others found no significant difference. Regarding toxicity, some studies have challenged the notion that subcutaneous administration is better tolerated than oral administration, while others have supported this. Pharmacokinetic studies suggest higher plasma bioavailability and increased accumulation of MTX-polyglutamates (MTX-PGs) in red blood cells (RBCs) with subcutaneous administration during the initial treatment phase. However, after several months, similar intracellular drug levels are observed with both administration routes. There is no conclusive evidence supporting the superiority of either oral or subcutaneous MTX administration in terms of efficacy and adverse events in IMIDs. Subcutaneous administration leads to higher plasma bioavailability and initial accumulation of MTX-PGs in RBCs, but the difference seems to disappear over time. Given the variable findings, the choice of administration route may be based on shared decision-making, offering patients the option of either oral or subcutaneous administration of MTX based on individual preferences and tolerability. Further research is needed to better understand the impact of MTX-PGs in various blood cells and TDM on treatment response and adherence to MTX therapy.</p>","PeriodicalId":10761,"journal":{"name":"Current Rheumatology Reports","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41093793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-11-14DOI: 10.1007/s11926-023-01119-4
Johannes Knitza, Sebastian Kuhn, Latika Gupta
Purpose of review: This article serves as a comprehensive review, focusing on digital approaches utilized in the diagnosis, monitoring, and treatment of patients with idiopathic inflammatory myopathies (IIM). The authors critically assess the literature published in the last three years, evaluating the advancements and progress achieved in this specific domain.
Recent findings: Remarkable strides have been made in the realm of digital diagnostic support, particularly in image analysis and clinical prediction models, showing promise in aiding the diagnosis of IIM. The field of remote patient monitoring has also witnessed significant advancements, revolutionizing the care process by offering more convenient, data-driven, and continuous monitoring for IIM patients. Various digital tools, such as wearables, video- and voice consultations, and electronic patient-reported outcomes, have been extensively explored and implemented to enhance patient care. Survey studies consistently reveal a high acceptance of telehealth services among patients. Additionally, internet-based studies have facilitated the efficient and rapid recruitment of IIM patients for research purposes. Moreover, the integration of sensors and exoskeletons has shown great potential in significantly improving the functionality and quality of life for individuals with muscle weakness caused by IIM. The integration of digital health solutions in the care of IIM patients is steadily gaining attention and exploration. Although the existing evidence is limited, it does indicate that patients can be adequately and safely supported through digital means throughout their entire healthcare journey. The growing interest in digital health technologies holds the promise of improving the overall management and outcomes for individuals with idiopathic inflammatory myopathies.
{"title":"Digital Approaches for Myositis.","authors":"Johannes Knitza, Sebastian Kuhn, Latika Gupta","doi":"10.1007/s11926-023-01119-4","DOIUrl":"10.1007/s11926-023-01119-4","url":null,"abstract":"<p><strong>Purpose of review: </strong>This article serves as a comprehensive review, focusing on digital approaches utilized in the diagnosis, monitoring, and treatment of patients with idiopathic inflammatory myopathies (IIM). The authors critically assess the literature published in the last three years, evaluating the advancements and progress achieved in this specific domain.</p><p><strong>Recent findings: </strong>Remarkable strides have been made in the realm of digital diagnostic support, particularly in image analysis and clinical prediction models, showing promise in aiding the diagnosis of IIM. The field of remote patient monitoring has also witnessed significant advancements, revolutionizing the care process by offering more convenient, data-driven, and continuous monitoring for IIM patients. Various digital tools, such as wearables, video- and voice consultations, and electronic patient-reported outcomes, have been extensively explored and implemented to enhance patient care. Survey studies consistently reveal a high acceptance of telehealth services among patients. Additionally, internet-based studies have facilitated the efficient and rapid recruitment of IIM patients for research purposes. Moreover, the integration of sensors and exoskeletons has shown great potential in significantly improving the functionality and quality of life for individuals with muscle weakness caused by IIM. The integration of digital health solutions in the care of IIM patients is steadily gaining attention and exploration. Although the existing evidence is limited, it does indicate that patients can be adequately and safely supported through digital means throughout their entire healthcare journey. The growing interest in digital health technologies holds the promise of improving the overall management and outcomes for individuals with idiopathic inflammatory myopathies.</p>","PeriodicalId":10761,"journal":{"name":"Current Rheumatology Reports","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92153076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1007/s11926-023-01118-5
Muhammad A Khan
Purpose of review: To commemorate the 50th anniversary of the groundbreaking discovery of a remarkably strong association between HLA-B*27 and ankylosing spondylitis (AS).
Recent findings: In addition to HLA-B*27, more than 116 other recognized genetic risk variants have been identified, while epigenetic factors largely remain unexplored in this context. Among patients with AS who carry the HLA-B*27 gene, clonally expanded CD8 + T cells can be found in their bloodstream and within inflamed tissues. Moreover, the α and β chain motifs of these T-cell receptors demonstrate a distinct affinity for certain self- and microbial-derived peptides, leading to an autoimmune response that ultimately results in the onset of the disease. These distinctive peptide-binding and presentation characteristics are a hallmark of the disease-associated HLA-B*27:05 subtype but are absent in HLA-B*27:09, a subtype not associated with the disease, differing by only a single amino acid. This discovery represents a significant advancement in unraveling the 50-year-old puzzle of how HLA-B*27 contributes to the development of AS. These findings will significantly accelerate the process of identifying peptides, both self- and microbial-derived, that instigate autoimmunity. This, in return, will pave the way for the development of more accurate and effective targeted treatments. Moreover, the discovery of improved biomarkers, in conjunction with the emerging technology of electric field molecular fingerprinting, has the potential to greatly bolster early diagnosis capabilities. A very recently published groundbreak paper underscores the remarkable effectiveness of targeting and eliminating disease-causing T cells in a HLA-B*27 patients with AS. This pivotal advancement not only signifies a paradigm shift but also bolsters the potential for preventing the disease in individuals carrying high-risk genetic variants.
{"title":"HLA-B*27 and Ankylosing Spondylitis: 50 Years of Insights and Discoveries.","authors":"Muhammad A Khan","doi":"10.1007/s11926-023-01118-5","DOIUrl":"10.1007/s11926-023-01118-5","url":null,"abstract":"<p><strong>Purpose of review: </strong>To commemorate the 50th anniversary of the groundbreaking discovery of a remarkably strong association between HLA-B*27 and ankylosing spondylitis (AS).</p><p><strong>Recent findings: </strong>In addition to HLA-B*27, more than 116 other recognized genetic risk variants have been identified, while epigenetic factors largely remain unexplored in this context. Among patients with AS who carry the HLA-B*27 gene, clonally expanded CD8 + T cells can be found in their bloodstream and within inflamed tissues. Moreover, the α and β chain motifs of these T-cell receptors demonstrate a distinct affinity for certain self- and microbial-derived peptides, leading to an autoimmune response that ultimately results in the onset of the disease. These distinctive peptide-binding and presentation characteristics are a hallmark of the disease-associated HLA-B*27:05 subtype but are absent in HLA-B*27:09, a subtype not associated with the disease, differing by only a single amino acid. This discovery represents a significant advancement in unraveling the 50-year-old puzzle of how HLA-B*27 contributes to the development of AS. These findings will significantly accelerate the process of identifying peptides, both self- and microbial-derived, that instigate autoimmunity. This, in return, will pave the way for the development of more accurate and effective targeted treatments. Moreover, the discovery of improved biomarkers, in conjunction with the emerging technology of electric field molecular fingerprinting, has the potential to greatly bolster early diagnosis capabilities. A very recently published groundbreak paper underscores the remarkable effectiveness of targeting and eliminating disease-causing T cells in a HLA-B*27 patients with AS. This pivotal advancement not only signifies a paradigm shift but also bolsters the potential for preventing the disease in individuals carrying high-risk genetic variants.</p>","PeriodicalId":10761,"journal":{"name":"Current Rheumatology Reports","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89717247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01Epub Date: 2023-08-19DOI: 10.1007/s11926-023-01111-y
Rathnam Venkat, Zachary S Wallace, Jeffrey A Sparks
Purpose of review: To review the impact of disease-modifying antirheumatic drugs (DMARDs) on COVID-19 severity and vaccine immunogenicity and to discuss COVID-19 outcomes in patients with rheumatoid arthritis (RA).
Recent findings: Rituximab is associated with severe COVID-19 and impaired vaccine immunogenicity via its B cell-depleting mechanism. JAK inhibitors and glucocorticoids have been modestly associated with severe COVID-19 and impaired vaccine immunogenicity. TNF inhibitors may have a protective effect against severe COVID-19 and do not appear to affect vaccine immunogenicity. Clinical trials have shown improved seroconversion and antibody titers when methotrexate is held around vaccine doses, but this may yield increased risk of RA flare. Patients with RA are also impacted by DMARD disruption, RA flares, and post-acute sequelae of COVID-19 after COVID-19 infection. Given the risks of COVID-19, rituximab should be used with caution in RA. Holding methotrexate doses around COVID-19 vaccination improves immunogenicity but may increase RA flare risk.
{"title":"Considerations for Pharmacologic Management of Rheumatoid Arthritis in the COVID-19 Era: a Narrative Review.","authors":"Rathnam Venkat, Zachary S Wallace, Jeffrey A Sparks","doi":"10.1007/s11926-023-01111-y","DOIUrl":"10.1007/s11926-023-01111-y","url":null,"abstract":"<p><strong>Purpose of review: </strong>To review the impact of disease-modifying antirheumatic drugs (DMARDs) on COVID-19 severity and vaccine immunogenicity and to discuss COVID-19 outcomes in patients with rheumatoid arthritis (RA).</p><p><strong>Recent findings: </strong>Rituximab is associated with severe COVID-19 and impaired vaccine immunogenicity via its B cell-depleting mechanism. JAK inhibitors and glucocorticoids have been modestly associated with severe COVID-19 and impaired vaccine immunogenicity. TNF inhibitors may have a protective effect against severe COVID-19 and do not appear to affect vaccine immunogenicity. Clinical trials have shown improved seroconversion and antibody titers when methotrexate is held around vaccine doses, but this may yield increased risk of RA flare. Patients with RA are also impacted by DMARD disruption, RA flares, and post-acute sequelae of COVID-19 after COVID-19 infection. Given the risks of COVID-19, rituximab should be used with caution in RA. Holding methotrexate doses around COVID-19 vaccination improves immunogenicity but may increase RA flare risk.</p>","PeriodicalId":10761,"journal":{"name":"Current Rheumatology Reports","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10383251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}