Pub Date : 2024-05-01Epub Date: 2024-03-05DOI: 10.1097/BOR.0000000000001013
Kevin D Deane
Purpose of review: This review discusses updates in the prediction and prevention of future rheumatoid arthritis (RA).
Recent findings: In individuals with musculoskeletal symptoms and elevated antibodies to citrullinated proteins (ACPA) without clinical inflammatory arthritis (IA), a 'simple' score has a positive predictive value (PPV) of ∼28% for clinical IA/RA within 1 year, and a comprehensive score (including ultrasound) has a PPV of ∼71% for clinical RA within 5 years. Controlled clinical trials in individuals at-risk for future RA have been performed using corticosteroids, rituximab, atorvastatin, methotrexate, hydroxychloroquine and abatacept. Abatacept modestly reduced rates of incident clinical RA and imaging inflammation within the trials, rituximab delayed clinical IA, and methotrexate improved function, symptoms and imaging inflammation. Vitamin D with or without omega 3 fatty acids reduced incidence of autoimmune diseases, including RA. While not proven in controlled clinical trials, observational studies suggest exercise, weight loss and smoking cessation may reduce progression to clinical RA.
Summary: Prediction and prevention of RA is advancing although there are no currently approved interventions for prevention. Future studies should include deeper evaluation of the pathophysiology of RA development to improve prediction and identify key pathways to target in future clinical trials, as well as develop infrastructure to support prevention-related research.
综述的目的:本综述讨论了预测和预防未来类风湿性关节炎(RA)的最新进展:在有肌肉骨骼症状和瓜氨酸蛋白抗体(ACPA)升高但无临床炎症性关节炎(IA)的个体中,"简单 "评分对1年内临床IA/RA的阳性预测值(PPV)为28%,综合评分(包括超声波)对5年内临床RA的阳性预测值(PPV)为71%。对未来可能患上 RA 的高危人群进行了对照临床试验,使用了皮质类固醇、利妥昔单抗、阿托伐他汀、甲氨蝶呤、羟氯喹和阿帕他赛。在试验中,阿巴他赛普适度降低了临床 RA 病发率和影像学炎症,利妥昔单抗推迟了临床 IA,而甲氨蝶呤改善了功能、症状和影像学炎症。含有或不含有欧米伽 3 脂肪酸的维生素 D 可降低包括 RA 在内的自身免疫性疾病的发病率。小结:尽管目前还没有获得批准的预防干预措施,但 RA 的预测和预防工作正在取得进展。未来的研究应包括对RA发展的病理生理学进行更深入的评估,以提高预测能力,确定未来临床试验的目标关键途径,以及开发支持预防相关研究的基础设施。
{"title":"Rheumatoid arthritis: prediction of future clinically-apparent disease, and prevention.","authors":"Kevin D Deane","doi":"10.1097/BOR.0000000000001013","DOIUrl":"10.1097/BOR.0000000000001013","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review discusses updates in the prediction and prevention of future rheumatoid arthritis (RA).</p><p><strong>Recent findings: </strong>In individuals with musculoskeletal symptoms and elevated antibodies to citrullinated proteins (ACPA) without clinical inflammatory arthritis (IA), a 'simple' score has a positive predictive value (PPV) of ∼28% for clinical IA/RA within 1 year, and a comprehensive score (including ultrasound) has a PPV of ∼71% for clinical RA within 5 years. Controlled clinical trials in individuals at-risk for future RA have been performed using corticosteroids, rituximab, atorvastatin, methotrexate, hydroxychloroquine and abatacept. Abatacept modestly reduced rates of incident clinical RA and imaging inflammation within the trials, rituximab delayed clinical IA, and methotrexate improved function, symptoms and imaging inflammation. Vitamin D with or without omega 3 fatty acids reduced incidence of autoimmune diseases, including RA. While not proven in controlled clinical trials, observational studies suggest exercise, weight loss and smoking cessation may reduce progression to clinical RA.</p><p><strong>Summary: </strong>Prediction and prevention of RA is advancing although there are no currently approved interventions for prevention. Future studies should include deeper evaluation of the pathophysiology of RA development to improve prediction and identify key pathways to target in future clinical trials, as well as develop infrastructure to support prevention-related research.</p>","PeriodicalId":11145,"journal":{"name":"Current opinion in rheumatology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10959682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027629","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 : 2024-05-01Epub Date: 2024-02-21DOI: 10.1097/BOR.0000000000001009
Hailey Baker, J Kennedy Amaral, Robert T Schoen
Purpose of review: Postinfectious inflammatory arthritis can result from various pathogens, including bacteria, viruses, fungi, and parasites. Prompt identification and treatment of acute infection is vital, but some cases progress to chronic arthritis despite successful treatment of infection. Postinfectious inflammatory arthritis varies from mild, self-limited arthralgia to severe, refractory arthritis, necessitating ongoing disease-modifying treatment. This review explores the spectrum of postinfectious inflammatory arthritis to provide insights into effective management.
Recent findings: Research continues regarding the benefit of antimicrobial therapy, beyond treatment of the acute infection, to diminish the severity of postinfectious inflammatory arthritis. Following treatment of acute infection, most cases are self-limited so treatment is symptomatic. However, a difficult-to-predict fraction of cases develop chronic postinfectious inflammatory arthritis that can be challenging to manage. Recently, as more biologic, and targeted synthetic DMARDs have become available, treatment options have expanded.
Summary: In this article, we use the term 'postinfectious inflammatory arthritis' rather than 'reactive arthritis' because it describes a broader spectrum of diseases and emphasizes the common pathogenesis of a postinfectious inflammatory process. We summarize the conventional therapies and recent management developments for the most frequently encountered postinfectious inflammatory arthritides.
{"title":"Management of postinfectious inflammatory arthritis.","authors":"Hailey Baker, J Kennedy Amaral, Robert T Schoen","doi":"10.1097/BOR.0000000000001009","DOIUrl":"10.1097/BOR.0000000000001009","url":null,"abstract":"<p><strong>Purpose of review: </strong>Postinfectious inflammatory arthritis can result from various pathogens, including bacteria, viruses, fungi, and parasites. Prompt identification and treatment of acute infection is vital, but some cases progress to chronic arthritis despite successful treatment of infection. Postinfectious inflammatory arthritis varies from mild, self-limited arthralgia to severe, refractory arthritis, necessitating ongoing disease-modifying treatment. This review explores the spectrum of postinfectious inflammatory arthritis to provide insights into effective management.</p><p><strong>Recent findings: </strong>Research continues regarding the benefit of antimicrobial therapy, beyond treatment of the acute infection, to diminish the severity of postinfectious inflammatory arthritis. Following treatment of acute infection, most cases are self-limited so treatment is symptomatic. However, a difficult-to-predict fraction of cases develop chronic postinfectious inflammatory arthritis that can be challenging to manage. Recently, as more biologic, and targeted synthetic DMARDs have become available, treatment options have expanded.</p><p><strong>Summary: </strong>In this article, we use the term 'postinfectious inflammatory arthritis' rather than 'reactive arthritis' because it describes a broader spectrum of diseases and emphasizes the common pathogenesis of a postinfectious inflammatory process. We summarize the conventional therapies and recent management developments for the most frequently encountered postinfectious inflammatory arthritides.</p>","PeriodicalId":11145,"journal":{"name":"Current opinion in rheumatology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971267","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 : 2024-05-01Epub Date: 2024-02-23DOI: 10.1097/BOR.0000000000001007
Elena Myasoedova, Eric L Matteson
Purpose of review: To discuss changes in epidemiology, recent advances in understanding of the pathogenesis and management of selected extraarticular manifestations of rheumatoid arthritis (ExRA).
Recent findings: The incidence of ExRA overall and subcutaneous rheumatoid nodules in particular is declining after 2000. These trends reflect improved RA disease activity with early effective immunosuppressive treatments; changing environmental risk factors can be contributing. ExRA continues to carry a two-fold increased mortality risk. RA-associated interstitial lung disease (RA-ILD) is a major contributor to mortality, with no decline in incidence and scant therapeutic options. Individualized risk stratification for RA-ILD based on patient-level risk factors and biomarker profile is evolving with MUC5B as a major genetic risk factor. Clinical trials are underway to evaluate the benefits of novel antifibrotic therapies and targeted therapies for RA-ILD. The risk of cardiovascular disease in RA is generally amendable to treatment with disease-modifying antirheumatic drugs, although cardiovascular risk associated with JAK inhibition is not fully understood.
Summary: Despite reduction in incidence of ExRA overall, the incidence of RA-ILD shows no significant decline and remains a major therapeutic challenge. The use of novel antifibrotics and immunosuppressive drugs shows promise in slowing the progression of RA-ILD.
{"title":"Updates on interstitial lung disease and other selected extra-articular manifestations of rheumatoid arthritis.","authors":"Elena Myasoedova, Eric L Matteson","doi":"10.1097/BOR.0000000000001007","DOIUrl":"10.1097/BOR.0000000000001007","url":null,"abstract":"<p><strong>Purpose of review: </strong>To discuss changes in epidemiology, recent advances in understanding of the pathogenesis and management of selected extraarticular manifestations of rheumatoid arthritis (ExRA).</p><p><strong>Recent findings: </strong>The incidence of ExRA overall and subcutaneous rheumatoid nodules in particular is declining after 2000. These trends reflect improved RA disease activity with early effective immunosuppressive treatments; changing environmental risk factors can be contributing. ExRA continues to carry a two-fold increased mortality risk. RA-associated interstitial lung disease (RA-ILD) is a major contributor to mortality, with no decline in incidence and scant therapeutic options. Individualized risk stratification for RA-ILD based on patient-level risk factors and biomarker profile is evolving with MUC5B as a major genetic risk factor. Clinical trials are underway to evaluate the benefits of novel antifibrotic therapies and targeted therapies for RA-ILD. The risk of cardiovascular disease in RA is generally amendable to treatment with disease-modifying antirheumatic drugs, although cardiovascular risk associated with JAK inhibition is not fully understood.</p><p><strong>Summary: </strong>Despite reduction in incidence of ExRA overall, the incidence of RA-ILD shows no significant decline and remains a major therapeutic challenge. The use of novel antifibrotics and immunosuppressive drugs shows promise in slowing the progression of RA-ILD.</p>","PeriodicalId":11145,"journal":{"name":"Current opinion in rheumatology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971268","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 : 2024-05-01Epub Date: 2024-01-31DOI: 10.1097/BOR.0000000000001001
Silvia Sirotti, Robert Terkeltaub, Georgios Filippou
Purpose of review: In 1977, McCarty astutely observed, 'The variety of names suggested for the condition associated with deposits of calcium pyrophosphate dihydrate crystals is exceeded only by the variations of its clinical presentation'. Fast forward to 2024, a standardized nomenclature for calcium pyrophosphate deposition (CPPD) is still lacking. This review aims to delineate the challenges in characterizing CPPD through nomenclature and imaging.
Recent findings: Despite the effort of nomenclature standardization in 2011 by the EULAR, confusion persists in the literature and clinical practice, with pseudo-forms and obscure abbreviations. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) has launched a project to redefine CPPD nomenclature and formulate a user-friendly language for effective communication with patients and other stakeholders. Additionally, recent advancements in imaging, have shed light on various aspects of the disorder.
Summary: Almost 60 years from the first description of a clinical manifestation related to calcium pyrophosphate crystals, a common language describing the disorder is still lacking. A redefined CPPD nomenclature, together with lay-friendly terminology, would significantly contribute to the uniformity of CPPD research, enhance public understanding and awareness and improve doctor-patient communication and therefore disease outcomes. Imaging can provide deep insights into CPPD elements, promoting comprehension of this disorder.
{"title":"Describing calcium pyrophosphate deposition: undoing the tower of Babel!","authors":"Silvia Sirotti, Robert Terkeltaub, Georgios Filippou","doi":"10.1097/BOR.0000000000001001","DOIUrl":"10.1097/BOR.0000000000001001","url":null,"abstract":"<p><strong>Purpose of review: </strong>In 1977, McCarty astutely observed, 'The variety of names suggested for the condition associated with deposits of calcium pyrophosphate dihydrate crystals is exceeded only by the variations of its clinical presentation'. Fast forward to 2024, a standardized nomenclature for calcium pyrophosphate deposition (CPPD) is still lacking. This review aims to delineate the challenges in characterizing CPPD through nomenclature and imaging.</p><p><strong>Recent findings: </strong>Despite the effort of nomenclature standardization in 2011 by the EULAR, confusion persists in the literature and clinical practice, with pseudo-forms and obscure abbreviations. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) has launched a project to redefine CPPD nomenclature and formulate a user-friendly language for effective communication with patients and other stakeholders. Additionally, recent advancements in imaging, have shed light on various aspects of the disorder.</p><p><strong>Summary: </strong>Almost 60 years from the first description of a clinical manifestation related to calcium pyrophosphate crystals, a common language describing the disorder is still lacking. A redefined CPPD nomenclature, together with lay-friendly terminology, would significantly contribute to the uniformity of CPPD research, enhance public understanding and awareness and improve doctor-patient communication and therefore disease outcomes. Imaging can provide deep insights into CPPD elements, promoting comprehension of this disorder.</p>","PeriodicalId":11145,"journal":{"name":"Current opinion in rheumatology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184003","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 : 2024-05-01Epub Date: 2024-02-01DOI: 10.1097/BOR.0000000000001003
Hiroshi Kato, J Michelle Kahlenberg
Purpose of review: The approval of belimumab and anifrolumab has expanded the scope of treatment for systemic lupus erythematosus (SLE) patients. However, many patients remain refractory to currently available therapies and suffer from drug toxicities. This review will discuss approved and target-specific therapeutics in development that bring hope for better SLE treatments.
Recent findings: Since the last review on this subject in the journal, the FDA has approved anifrolumab and belimumab for SLE and lupus nephritis (LN), respectively. A fully humanized anti-CD20, obinutuzumab, met the primary end point in a phase II trial in LN. A Tyk2 inhibitor, deucravacitinib, and an antibody targeting plasmacytoid dendritic cells, litifilimab, met the primary end point in phase II trials in SLE and cutaneous lupus erythematosus (CLE). Ustekinumab and baricitinib met the primary end point in phase II but not in phase III trials.
Summary: While many drug candidates which met the end points in phase II trials have failed phase III trials, the number of target-specific therapies for SLE has continued to expand.
{"title":"Emerging biologic therapies for systemic lupus erythematosus.","authors":"Hiroshi Kato, J Michelle Kahlenberg","doi":"10.1097/BOR.0000000000001003","DOIUrl":"10.1097/BOR.0000000000001003","url":null,"abstract":"<p><strong>Purpose of review: </strong>The approval of belimumab and anifrolumab has expanded the scope of treatment for systemic lupus erythematosus (SLE) patients. However, many patients remain refractory to currently available therapies and suffer from drug toxicities. This review will discuss approved and target-specific therapeutics in development that bring hope for better SLE treatments.</p><p><strong>Recent findings: </strong>Since the last review on this subject in the journal, the FDA has approved anifrolumab and belimumab for SLE and lupus nephritis (LN), respectively. A fully humanized anti-CD20, obinutuzumab, met the primary end point in a phase II trial in LN. A Tyk2 inhibitor, deucravacitinib, and an antibody targeting plasmacytoid dendritic cells, litifilimab, met the primary end point in phase II trials in SLE and cutaneous lupus erythematosus (CLE). Ustekinumab and baricitinib met the primary end point in phase II but not in phase III trials.</p><p><strong>Summary: </strong>While many drug candidates which met the end points in phase II trials have failed phase III trials, the number of target-specific therapies for SLE has continued to expand.</p>","PeriodicalId":11145,"journal":{"name":"Current opinion in rheumatology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650447","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 : 2024-05-01Epub Date: 2024-01-31DOI: 10.1097/BOR.0000000000001002
Benjamin R Wagner, Panduranga S Rao
Purpose of review: Lupus nephritis is a common complication of systemic lupus erythematosus and is associated with significant morbidity and mortality. The utility of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of lupus nephritis is currently uncertain. Here, we summarize the rationale for their use among patient with lupus nephritis.
Recent findings: SGLT2 inhibitors were initially developed as antihyperglycemic agents. They have since been shown to have additional, profound effects to slow the progression of chronic kidney disease and lessen the long-term risks of cardiovascular disease in large clinic trials of patients with chronic kidney disease, with and without diabetes, as well as in patients with and without proteinuria. Patients with recent exposure to immunosuppression were excluded from these trials due to concern for risk of infection. In the few, small trials of patients with lupus nephritis, SGLT2 inhibitors were found to be well tolerated. They have been shown to reduce proteinuria and to have modest beneficial effects on blood pressure and BMI among patients with lupus nephritis. They have not been shown to influence disease activity.
Summary: SGLT2 inhibitors may have a role in mitigating the chronic renal and cardiovascular effects of lupus nephritis. They should be introduced after kidney function has been stabilized with appropriate immunosuppression, in conjunction with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. They currently have no role in active disease.
{"title":"Sodium-glucose cotransporter 2 inhibitors: are they ready for prime time in the management of lupus nephritis?","authors":"Benjamin R Wagner, Panduranga S Rao","doi":"10.1097/BOR.0000000000001002","DOIUrl":"10.1097/BOR.0000000000001002","url":null,"abstract":"<p><strong>Purpose of review: </strong>Lupus nephritis is a common complication of systemic lupus erythematosus and is associated with significant morbidity and mortality. The utility of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of lupus nephritis is currently uncertain. Here, we summarize the rationale for their use among patient with lupus nephritis.</p><p><strong>Recent findings: </strong>SGLT2 inhibitors were initially developed as antihyperglycemic agents. They have since been shown to have additional, profound effects to slow the progression of chronic kidney disease and lessen the long-term risks of cardiovascular disease in large clinic trials of patients with chronic kidney disease, with and without diabetes, as well as in patients with and without proteinuria. Patients with recent exposure to immunosuppression were excluded from these trials due to concern for risk of infection. In the few, small trials of patients with lupus nephritis, SGLT2 inhibitors were found to be well tolerated. They have been shown to reduce proteinuria and to have modest beneficial effects on blood pressure and BMI among patients with lupus nephritis. They have not been shown to influence disease activity.</p><p><strong>Summary: </strong>SGLT2 inhibitors may have a role in mitigating the chronic renal and cardiovascular effects of lupus nephritis. They should be introduced after kidney function has been stabilized with appropriate immunosuppression, in conjunction with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. They currently have no role in active disease.</p>","PeriodicalId":11145,"journal":{"name":"Current opinion in rheumatology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184005","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 : 2024-05-01Epub Date: 2024-03-26DOI: 10.1097/BOR.0000000000001005
David A Fox
{"title":"Rheumatoid arthritis - the challenge of heterogeneity.","authors":"David A Fox","doi":"10.1097/BOR.0000000000001005","DOIUrl":"10.1097/BOR.0000000000001005","url":null,"abstract":"","PeriodicalId":11145,"journal":{"name":"Current opinion in rheumatology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184004","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 : 2024-05-01Epub Date: 2024-03-08DOI: 10.1097/BOR.0000000000001014
Jonathan D D'Gama, Bonnie L Bermas
Purpose of review: To discuss the current understanding regarding the use of biologic therapeutics in pregnancy.
Recent findings: Our understanding of the mechanisms underlying the potential fetal and infant exposure to biologics as well as a growing body of empirical evidence from real world use of biologics in pregnancy have demonstrated that biologics are generally compatible preconception and during pregnancy. Long-term effects of exposure to biologic agents in utero are not known, but will be uncovered in time. Biosimilars, which are becoming more popular, may not always share the same safety profiles as their originators.
Summary: Biologics have revolutionized the management of rheumatologic disease and ushered in a new era of clinical remission among patients. These agents, developed and introduced into clinical use at the beginning of the new millennium, are very potent, yet their efficacy in treating disease often in reproductive aged women, raises questions regarding their safety during pregnancy. These therapeutics can cause immunosuppression and can inhibit immunologic circuits that are not only involved in disease pathophysiology but hypothetically could impact the development of the fetal immune system. Reassuringly, biologics, typically antibodies or antibody-based proteins, are introduced to the fetus via the typical route of transplacental antibody transfer, and thus only begin to be transferred in appreciable amounts in the second trimester (after organogenesis). From theoretic and empirical standpoints, biologic use during pregnancy appears well tolerated for fetal development and to not substantially affect infant immune development.
{"title":"Safety of biologic agents for the management of rheumatic diseases during pregnancy.","authors":"Jonathan D D'Gama, Bonnie L Bermas","doi":"10.1097/BOR.0000000000001014","DOIUrl":"10.1097/BOR.0000000000001014","url":null,"abstract":"<p><strong>Purpose of review: </strong>To discuss the current understanding regarding the use of biologic therapeutics in pregnancy.</p><p><strong>Recent findings: </strong>Our understanding of the mechanisms underlying the potential fetal and infant exposure to biologics as well as a growing body of empirical evidence from real world use of biologics in pregnancy have demonstrated that biologics are generally compatible preconception and during pregnancy. Long-term effects of exposure to biologic agents in utero are not known, but will be uncovered in time. Biosimilars, which are becoming more popular, may not always share the same safety profiles as their originators.</p><p><strong>Summary: </strong>Biologics have revolutionized the management of rheumatologic disease and ushered in a new era of clinical remission among patients. These agents, developed and introduced into clinical use at the beginning of the new millennium, are very potent, yet their efficacy in treating disease often in reproductive aged women, raises questions regarding their safety during pregnancy. These therapeutics can cause immunosuppression and can inhibit immunologic circuits that are not only involved in disease pathophysiology but hypothetically could impact the development of the fetal immune system. Reassuringly, biologics, typically antibodies or antibody-based proteins, are introduced to the fetus via the typical route of transplacental antibody transfer, and thus only begin to be transferred in appreciable amounts in the second trimester (after organogenesis). From theoretic and empirical standpoints, biologic use during pregnancy appears well tolerated for fetal development and to not substantially affect infant immune development.</p>","PeriodicalId":11145,"journal":{"name":"Current opinion in rheumatology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058909","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 : 2024-05-01Epub Date: 2024-02-09DOI: 10.1097/BOR.0000000000001004
Elizabeth Park, Joan Bathon
Purpose of review: Rheumatoid arthritis (RA) patients remain at higher cardiovascular (CV) risk compared to non-RA patients, driven by accelerated atherosclerosis, leading to plaque rupture and acute CV events (CVE), including heart failure (HF). It has been hypothesized that chronic inflammation is the main driving force behind such outcomes. We summarize the current evidence supporting this hypothesis, focusing on arterial disease and myocardial disease.
Recent findings: RA patients demonstrate higher prevalence of subclinical atherosclerosis (high risk plaque and arterial inflammation) compared to non-RA patients, with RA disease activity correlating independently with CVE and death. Nonischemic HF with preserved ejection fraction (HFpEF) is more common in RA compared to non-RA, with subclinical myocardial structural and functional alterations also more prevalent in RA. HFpEF and myocardial remodeling and dysfunction bear a strong and independent association with inflammatory correlates.
Summary: All of this suggests that inflammation contributes to enhanced risk of CVE in RA. A more accurate and specific CV risk stratification tool for RA, incorporating biomarkers or imaging, is needed. Likewise, more prospective studies outlining the trajectory from preclinical to clinical HF, incorporating biomarkers and imaging, are also needed.
综述目的:与非类风湿性关节炎(RA)患者相比,类风湿性关节炎(RA)患者的心血管(CV)风险仍然较高,原因是动脉粥样硬化加速,导致斑块破裂和急性 CV 事件(CVE),包括心力衰竭(HF)。据推测,慢性炎症是造成这种结果的主要原因。我们总结了目前支持这一假设的证据,重点关注动脉疾病和心肌疾病:与非 RA 患者相比,RA 患者亚临床动脉粥样硬化(高危斑块和动脉炎症)的发病率更高,RA 疾病活动与 CVE 和死亡独立相关。与非RA患者相比,射血分数保留的非缺血性心房颤动(HFpEF)在RA患者中更为常见,亚临床心肌结构和功能改变在RA患者中也更为普遍。HFpEF和心肌重塑及功能障碍与炎症相关性有很强的独立关联。我们需要一种结合生物标志物或成像技术的更准确、更具体的 RA CV 风险分层工具。同样,还需要进行更多的前瞻性研究,结合生物标志物和成像技术,勾勒出从临床前高血压到临床高血压的发展轨迹。
{"title":"Cardiovascular complications of rheumatoid arthritis.","authors":"Elizabeth Park, Joan Bathon","doi":"10.1097/BOR.0000000000001004","DOIUrl":"10.1097/BOR.0000000000001004","url":null,"abstract":"<p><strong>Purpose of review: </strong>Rheumatoid arthritis (RA) patients remain at higher cardiovascular (CV) risk compared to non-RA patients, driven by accelerated atherosclerosis, leading to plaque rupture and acute CV events (CVE), including heart failure (HF). It has been hypothesized that chronic inflammation is the main driving force behind such outcomes. We summarize the current evidence supporting this hypothesis, focusing on arterial disease and myocardial disease.</p><p><strong>Recent findings: </strong>RA patients demonstrate higher prevalence of subclinical atherosclerosis (high risk plaque and arterial inflammation) compared to non-RA patients, with RA disease activity correlating independently with CVE and death. Nonischemic HF with preserved ejection fraction (HFpEF) is more common in RA compared to non-RA, with subclinical myocardial structural and functional alterations also more prevalent in RA. HFpEF and myocardial remodeling and dysfunction bear a strong and independent association with inflammatory correlates.</p><p><strong>Summary: </strong>All of this suggests that inflammation contributes to enhanced risk of CVE in RA. A more accurate and specific CV risk stratification tool for RA, incorporating biomarkers or imaging, is needed. Likewise, more prospective studies outlining the trajectory from preclinical to clinical HF, incorporating biomarkers and imaging, are also needed.</p>","PeriodicalId":11145,"journal":{"name":"Current opinion in rheumatology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706358","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 : 2024-05-01Epub Date: 2024-03-26DOI: 10.1097/BOR.0000000000001012
Nathan M Johnson, Fotios Koumpouras
Purpose of review: Recent advances in hematology-oncology have pioneered cell-mediated elimination of pathologic B-cell populations employing chimeric antigen receptor (CAR) T cells. In this review, we discuss recent adoption of CAR-T treatment for severe refractory autoimmune disease. We highlight unique aspects of the autoimmune model and review current clinical data regarding treatment of rheumatologic disease.
Recent findings: To date, several CAR-Ts are FDA approved for Multiple Myeloma and B-cell malignancies and have demonstrated extraordinary clinical responses in refractory disease. Realizing the central role of B-cells in certain autoimmune diseases, CAR-T is now being explored for achieving drug-free remission induction, and potentially cure, of several rheumatologic diseases. The largest experience to date in the field of autoimmunity, building off the University Hospital Erlangen groups' earlier success treating a single patient with CD19-CAR in severe refractory SLE, Mackensen et al. enrolled five patients in a compassionate use program. Following autologous CD19-CAR T infusion, they demonstrated drug-free clinical and laboratory remission for at least 12 months in all five patients, with reconstitution of B cells expressing a naïve phenotype.
Summary: CAR-T treatment has shown striking drug-free responses in severe lupus and other autoimmune diseases, creating a need for further exploration and development.
综述的目的:血液肿瘤学的最新进展开创了利用嵌合抗原受体(CAR)T 细胞通过细胞介导消除病理性 B 细胞群的方法。在这篇综述中,我们讨论了最近采用 CAR-T 治疗严重难治性自身免疫性疾病的情况。我们强调了自身免疫模型的独特之处,并回顾了目前治疗风湿病的临床数据:迄今为止,美国食品及药物管理局(FDA)已批准几种CAR-T用于治疗多发性骨髓瘤和B细胞恶性肿瘤,并已在难治性疾病中显示出非凡的临床反应。由于认识到 B 细胞在某些自身免疫性疾病中的核心作用,CAR-T 目前正被用于实现无药缓解诱导,并有可能治愈多种风湿性疾病。埃尔兰根大学医院的研究小组早先成功用 CD19-CAR 治疗了一名重症难治性系统性红斑狼疮患者,在此基础上,Mackensen 等人又在一项同情使用计划中招募了五名患者,这是迄今为止自身免疫领域最大规模的治疗。在自体 CD19-CAR T 细胞输注后,他们证明所有五名患者的临床和实验室治疗均在至少 12 个月内无药物缓解,并重建了表达天真表型的 B 细胞。摘要:CAR-T 治疗已在重症狼疮和其他自身免疫性疾病中显示出惊人的无药物反应,因此需要进一步探索和开发。
{"title":"Chimeric antigen receptors: \"CARs\" in the fast lane for rheumatology.","authors":"Nathan M Johnson, Fotios Koumpouras","doi":"10.1097/BOR.0000000000001012","DOIUrl":"10.1097/BOR.0000000000001012","url":null,"abstract":"<p><strong>Purpose of review: </strong>Recent advances in hematology-oncology have pioneered cell-mediated elimination of pathologic B-cell populations employing chimeric antigen receptor (CAR) T cells. In this review, we discuss recent adoption of CAR-T treatment for severe refractory autoimmune disease. We highlight unique aspects of the autoimmune model and review current clinical data regarding treatment of rheumatologic disease.</p><p><strong>Recent findings: </strong>To date, several CAR-Ts are FDA approved for Multiple Myeloma and B-cell malignancies and have demonstrated extraordinary clinical responses in refractory disease. Realizing the central role of B-cells in certain autoimmune diseases, CAR-T is now being explored for achieving drug-free remission induction, and potentially cure, of several rheumatologic diseases. The largest experience to date in the field of autoimmunity, building off the University Hospital Erlangen groups' earlier success treating a single patient with CD19-CAR in severe refractory SLE, Mackensen et al. enrolled five patients in a compassionate use program. Following autologous CD19-CAR T infusion, they demonstrated drug-free clinical and laboratory remission for at least 12 months in all five patients, with reconstitution of B cells expressing a naïve phenotype.</p><p><strong>Summary: </strong>CAR-T treatment has shown striking drug-free responses in severe lupus and other autoimmune diseases, creating a need for further exploration and development.</p>","PeriodicalId":11145,"journal":{"name":"Current opinion in rheumatology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184002","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}