Pub Date : 2020-09-01DOI: 10.1093/med/9780198831433.003.0032
N. Hassan, E. Choy
Interleukin 6 (IL-6) is a pleiotropic cytokine which has diverse biological activity, with wide-ranging effects on the immune system, homeostasis, and metabolism. It is the most abundant pro-inflammatory cytokine in the synovial joints and sera of patients with active rheumatoid arthritis (RA) and has been found to play a central role in the pathogenesis of the disease, causing joint inflammation and destruction, as well as systemic manifestations. Inhibition of IL-6 signalling has been investigated and developed as a potential treatment strategy for RA. Clinical trials have demonstrated the efficacy and safety of tocilizumab, a humanized monoclonal antibody directed against the IL-6 receptor, showing therapeutic benefit both in early RA and those considered to have refractory disease. The success of tocilizumab has spurred the development of an array of new biologic agents targeting the IL-6 pathway in RA.
{"title":"Interleukin-6 inhibitors","authors":"N. Hassan, E. Choy","doi":"10.1093/med/9780198831433.003.0032","DOIUrl":"https://doi.org/10.1093/med/9780198831433.003.0032","url":null,"abstract":"Interleukin 6 (IL-6) is a pleiotropic cytokine which has diverse biological activity, with wide-ranging effects on the immune system, homeostasis, and metabolism. It is the most abundant pro-inflammatory cytokine in the synovial joints and sera of patients with active rheumatoid arthritis (RA) and has been found to play a central role in the pathogenesis of the disease, causing joint inflammation and destruction, as well as systemic manifestations. Inhibition of IL-6 signalling has been investigated and developed as a potential treatment strategy for RA. Clinical trials have demonstrated the efficacy and safety of tocilizumab, a humanized monoclonal antibody directed against the IL-6 receptor, showing therapeutic benefit both in early RA and those considered to have refractory disease. The success of tocilizumab has spurred the development of an array of new biologic agents targeting the IL-6 pathway in RA.","PeriodicalId":135409,"journal":{"name":"Oxford Textbook of Rheumatoid Arthritis","volume":"57 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116110406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-01DOI: 10.1093/med/9780198831433.003.0042
D. Scott
The clinical outcomes measured in rheumatoid arthritis span three broad areas. Firstly, disease measures reflecting the presence and severity of joint inflammation. Secondly, end-organ damage particularly the extent and severity of joint damage. Thirdly, quality of life measures made by patients indicating the impact of their disease on their lives. Some are disease specific such as the Health Assessment Questionnaire (HAQ). Others are generic and applicable across all disease, such as the Short Form 36 (SF-36) and EuroQol. Several new patient-assessed outcome measures have been developed, such as the Patient-Reported Outcome Measurement Information System (PROMIS) and the Rheumatoid Arthritis Impact of Disease (RAID) score. Whether one of these new measures becomes dominant is currently uncertain. Clinical outcomes need to measure what is intended and have face, content, construct, and criterion validity. They also need to discriminate between states of interest reliably, exhibit sensitivity to change, and be easily measured and applied, given constraints of time, money, and interpretability. Different clinical outcomes are closely interrelated. Finally, clinical outcomes such as the EuroQol can be used to generate quality-adjusted life years (QALY), which are used in health economic studies. Measuring disease outcomes is essential for good medical care, which can only improve when clinicians know the results of their treatments and incorporate patients’ views.
{"title":"Clinical outcomes","authors":"D. Scott","doi":"10.1093/med/9780198831433.003.0042","DOIUrl":"https://doi.org/10.1093/med/9780198831433.003.0042","url":null,"abstract":"The clinical outcomes measured in rheumatoid arthritis span three broad areas. Firstly, disease measures reflecting the presence and severity of joint inflammation. Secondly, end-organ damage particularly the extent and severity of joint damage. Thirdly, quality of life measures made by patients indicating the impact of their disease on their lives. Some are disease specific such as the Health Assessment Questionnaire (HAQ). Others are generic and applicable across all disease, such as the Short Form 36 (SF-36) and EuroQol. Several new patient-assessed outcome measures have been developed, such as the Patient-Reported Outcome Measurement Information System (PROMIS) and the Rheumatoid Arthritis Impact of Disease (RAID) score. Whether one of these new measures becomes dominant is currently uncertain. Clinical outcomes need to measure what is intended and have face, content, construct, and criterion validity. They also need to discriminate between states of interest reliably, exhibit sensitivity to change, and be easily measured and applied, given constraints of time, money, and interpretability. Different clinical outcomes are closely interrelated. Finally, clinical outcomes such as the EuroQol can be used to generate quality-adjusted life years (QALY), which are used in health economic studies. Measuring disease outcomes is essential for good medical care, which can only improve when clinicians know the results of their treatments and incorporate patients’ views.","PeriodicalId":135409,"journal":{"name":"Oxford Textbook of Rheumatoid Arthritis","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122283664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-01DOI: 10.1093/med/9780198831433.003.0001
D. Scott
The name for rheumatoid arthritis was provided by Alfred Baring Garrod in the late 1850s. Before this period there are descriptions of patients who seem to have had the disease which appeared from the late 1700s onwards, with more descriptions appearing after 1800. Analysis of portraits from the Flemish school of painters have suggested some of these showed features indicative of rheumatoid arthritis. However, the interpretation of the findings in these paintings is highly subjective. There is also some evidence from palaeopathological studies that skeletal remains from several thousand years ago in North America showed features suggestive of rheumatoid arthritis. As with the interpretation of art, this is a relatively subjective field and the findings remain controversial. The key points made in this chapter are that rheumatoid arthritis was definitely present in the nineteenth century and may have been present before them. Whether it is a modern disease or has a long history remains speculative.
{"title":"The history of rheumatoid arthritis","authors":"D. Scott","doi":"10.1093/med/9780198831433.003.0001","DOIUrl":"https://doi.org/10.1093/med/9780198831433.003.0001","url":null,"abstract":"The name for rheumatoid arthritis was provided by Alfred Baring Garrod in the late 1850s. Before this period there are descriptions of patients who seem to have had the disease which appeared from the late 1700s onwards, with more descriptions appearing after 1800. Analysis of portraits from the Flemish school of painters have suggested some of these showed features indicative of rheumatoid arthritis. However, the interpretation of the findings in these paintings is highly subjective. There is also some evidence from palaeopathological studies that skeletal remains from several thousand years ago in North America showed features suggestive of rheumatoid arthritis. As with the interpretation of art, this is a relatively subjective field and the findings remain controversial. The key points made in this chapter are that rheumatoid arthritis was definitely present in the nineteenth century and may have been present before them. Whether it is a modern disease or has a long history remains speculative.","PeriodicalId":135409,"journal":{"name":"Oxford Textbook of Rheumatoid Arthritis","volume":"121 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125185138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-01DOI: 10.1007/978-1-907673-91-7_6
M. Østergaard, M. Axelsen, M. Boesen
{"title":"Magnetic resonance imaging in rheumatoid arthritis","authors":"M. Østergaard, M. Axelsen, M. Boesen","doi":"10.1007/978-1-907673-91-7_6","DOIUrl":"https://doi.org/10.1007/978-1-907673-91-7_6","url":null,"abstract":"","PeriodicalId":135409,"journal":{"name":"Oxford Textbook of Rheumatoid Arthritis","volume":"111 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133924600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-01DOI: 10.1093/med/9780198831433.003.0012
K. Raza, Catherine M. McGrath, L. Boheemen, D. Schaardenburg
The typical evolution of rheumatoid arthritis (RA) is that a person, with genetic risk factors, develops autoantibodies and subclinical inflammation under relevant environmental influences. There are indications that the primary site of the pathology is at mucosal surfaces (e.g. in the gums, lungs, and/or the gut), after which the disease translocates to the joints. Preclinical RA can be defined at the phase during which no clinically apparent features are present (i.e. no symptoms of inflammatory arthritis or clinically apparent joint swelling) but during which RA related biologic derangements such as the presence of autoantibodies are present. This chapter presents an overview of the risk factors, stages, and events occurring during the pre-RA phase. A better understanding of the factors involved will enable more accurate prediction of RA at the individual level and selection of high-risk individuals for inclusion in preventive studies. Several pharmacologic and non-pharmacologic studies aiming to prevent or delay the onset of RA in at-risk individuals are currently underway. It is hoped that such interventions in the pre-RA and indeed in the preclinical-RA phases will allow us to reduce the risk of RA and prevent RA developing in at least a proportion of at-risk patients.
{"title":"Pre-rheumatoid arthritis","authors":"K. Raza, Catherine M. McGrath, L. Boheemen, D. Schaardenburg","doi":"10.1093/med/9780198831433.003.0012","DOIUrl":"https://doi.org/10.1093/med/9780198831433.003.0012","url":null,"abstract":"The typical evolution of rheumatoid arthritis (RA) is that a person, with genetic risk factors, develops autoantibodies and subclinical inflammation under relevant environmental influences. There are indications that the primary site of the pathology is at mucosal surfaces (e.g. in the gums, lungs, and/or the gut), after which the disease translocates to the joints. Preclinical RA can be defined at the phase during which no clinically apparent features are present (i.e. no symptoms of inflammatory arthritis or clinically apparent joint swelling) but during which RA related biologic derangements such as the presence of autoantibodies are present. This chapter presents an overview of the risk factors, stages, and events occurring during the pre-RA phase. A better understanding of the factors involved will enable more accurate prediction of RA at the individual level and selection of high-risk individuals for inclusion in preventive studies. Several pharmacologic and non-pharmacologic studies aiming to prevent or delay the onset of RA in at-risk individuals are currently underway. It is hoped that such interventions in the pre-RA and indeed in the preclinical-RA phases will allow us to reduce the risk of RA and prevent RA developing in at least a proportion of at-risk patients.","PeriodicalId":135409,"journal":{"name":"Oxford Textbook of Rheumatoid Arthritis","volume":"101 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129330607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-01DOI: 10.1093/med/9780198831433.003.0016
Douglas J. Veale, Ursula Fearon
Synovial tissue is the primary tissue inflamed in rheumatoid arthritis. Initial studies of synovial biopsies were obtained during arthroplasty or using a needle to biopsy the joint percutaneously. Recently, small needle arthroscopy or ultrasonography guided techniques have become more widely available to visualize and reliably obtain synovial biopsies. These techniques have allowed significant progress in the study of rheumatoid arthritis pathogenesis, even at the earliest stages of disease. Currently, research efforts are underway to use synovial biopsies to identify patients and to discover biomarkers that will enable clinicians to predict the course of the disease and perhaps to identify more appropriately the correct therapy for patients with rheumatoid arthritis. In this chapter, we describe the advances in synovial tissue biopsy research and how it has improved our knowledge of rheumatoid arthritis pathogenesis, informed our understanding of possible biomarkers for diagnosis and stratification, and potentially may aid in the prediction of disease outcome and response to treatment.
{"title":"Synovial biopsies","authors":"Douglas J. Veale, Ursula Fearon","doi":"10.1093/med/9780198831433.003.0016","DOIUrl":"https://doi.org/10.1093/med/9780198831433.003.0016","url":null,"abstract":"Synovial tissue is the primary tissue inflamed in rheumatoid arthritis. Initial studies of synovial biopsies were obtained during arthroplasty or using a needle to biopsy the joint percutaneously. Recently, small needle arthroscopy or ultrasonography guided techniques have become more widely available to visualize and reliably obtain synovial biopsies. These techniques have allowed significant progress in the study of rheumatoid arthritis pathogenesis, even at the earliest stages of disease. Currently, research efforts are underway to use synovial biopsies to identify patients and to discover biomarkers that will enable clinicians to predict the course of the disease and perhaps to identify more appropriately the correct therapy for patients with rheumatoid arthritis. In this chapter, we describe the advances in synovial tissue biopsy research and how it has improved our knowledge of rheumatoid arthritis pathogenesis, informed our understanding of possible biomarkers for diagnosis and stratification, and potentially may aid in the prediction of disease outcome and response to treatment.","PeriodicalId":135409,"journal":{"name":"Oxford Textbook of Rheumatoid Arthritis","volume":"310 6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127492267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-01DOI: 10.1093/med/9780198831433.003.0002
D. Aletaha, H. Radner
Rheumatoid arthritis (RA) affects approximately 1% of the adult population. It is currently considered a chronic disease for which there is no cure, but remission has become an achievable goal with optimal treatment. Both disability and enormous cost are functions of the disease over time. It is therefore crucial to treat RA early and persistently until remission is present. The challenge of treatment of early RA is not the lack of effective medicine, but rather the ethical and economic considerations related to risk-benefit and cost-benefit. Overtreating patients with disease-modifying antirheumatic drugs (DMARDs) is often feared, but the potential undertreatment of patients with RA can have accelerated structural consequences. This chapter covers diagnosis of RA, from the initial evaluation of patients with new-onset arthritis to important differential diagnoses. Critical diagnostic features are explained, and the 2010 European League Against Rheumatism (EULAR) classification criteria are described and rationalized. The importance of distinction between classification and diagnosis is highlighted.
{"title":"Diagnosis","authors":"D. Aletaha, H. Radner","doi":"10.1093/med/9780198831433.003.0002","DOIUrl":"https://doi.org/10.1093/med/9780198831433.003.0002","url":null,"abstract":"Rheumatoid arthritis (RA) affects approximately 1% of the adult population. It is currently considered a chronic disease for which there is no cure, but remission has become an achievable goal with optimal treatment. Both disability and enormous cost are functions of the disease over time. It is therefore crucial to treat RA early and persistently until remission is present. The challenge of treatment of early RA is not the lack of effective medicine, but rather the ethical and economic considerations related to risk-benefit and cost-benefit. Overtreating patients with disease-modifying antirheumatic drugs (DMARDs) is often feared, but the potential undertreatment of patients with RA can have accelerated structural consequences. This chapter covers diagnosis of RA, from the initial evaluation of patients with new-onset arthritis to important differential diagnoses. Critical diagnostic features are explained, and the 2010 European League Against Rheumatism (EULAR) classification criteria are described and rationalized. The importance of distinction between classification and diagnosis is highlighted.","PeriodicalId":135409,"journal":{"name":"Oxford Textbook of Rheumatoid Arthritis","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122722106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-01DOI: 10.1093/med/9780198831433.003.0011
A. Mil
The diagnosis of rheumatoid arthritis (RA) is based on a combination of symptoms, signs, and investigation results. As such, it is mainly based on pattern recognition. Classification criteria are not developed to make accurate diagnoses in individual patients, but for the primary purpose of defining homogeneous disease groups for scientific studies. The RA classification criteria have changed over time. This chapter discusses the process of diagnosing RA, the range of clinical characteristics that contribute to this process, its relationship with evolving classification criteria for the condition, and important differential diagnoses. Current recommendations encourage early recognition of arthritis and RA. Since clinical presentation may differ with disease stage, this chapter will also review how the RA phenotype changes as prearthritis progresses to early undifferentiated arthritis and established RA.
{"title":"Clinical features of rheumatoid arthritis","authors":"A. Mil","doi":"10.1093/med/9780198831433.003.0011","DOIUrl":"https://doi.org/10.1093/med/9780198831433.003.0011","url":null,"abstract":"The diagnosis of rheumatoid arthritis (RA) is based on a combination of symptoms, signs, and investigation results. As such, it is mainly based on pattern recognition. Classification criteria are not developed to make accurate diagnoses in individual patients, but for the primary purpose of defining homogeneous disease groups for scientific studies. The RA classification criteria have changed over time. This chapter discusses the process of diagnosing RA, the range of clinical characteristics that contribute to this process, its relationship with evolving classification criteria for the condition, and important differential diagnoses. Current recommendations encourage early recognition of arthritis and RA. Since clinical presentation may differ with disease stage, this chapter will also review how the RA phenotype changes as prearthritis progresses to early undifferentiated arthritis and established RA.","PeriodicalId":135409,"journal":{"name":"Oxford Textbook of Rheumatoid Arthritis","volume":"519 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116703923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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