A core set of risk factors in individuals at risk of rheumatoid arthritis: a systematic literature review informing the EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

Mankia, Kulveer; Siddle, Heidi J.; Matteo, Andrea Di; Alpizar-Rodriguez, D.; Kerry, Joel; Kerschbaumer, Andreas; Aletaha, Daniel; Emery, Paul

doi:10.1136/rmdopen-2021-001768

Cited by 20 publications

(16 citation statements)

References 61 publications

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“…CD can affect any of its segments whereas UC only affects the large intestine (3). RA is an autoimmune disease responsible for articular pain, swelling and stiffness; risk factors include family history and female gender (4). Both IBD and RA can be characterised by chronically raised levels of C-reactive protein (CRP) which is a widely used biomarker of inflammation.…”

Section: Introductionmentioning

confidence: 99%

A meta-analysis investigating the relationship between inflammation in autoimmune disease, elevated CRP, and the risk of dementia

2023

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Alzheimer’s Disease (AD) represents the most common type of dementia and is becoming a steadily increasing challenge for health systems globally. Inflammation is developing as the main focus of research into Alzheimer’s disease and has been demonstrated to be a major driver of the pathologies associated with AD. This evidence introduces an interesting research question, whether chronic inflammation due to pathologies such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) could lead to a higher risk of developing dementia. In both IBD and RA, increased levels of the inflammatory biomarker C-reactive protein (CRP) can be highlighted, the latter being directly implicated in neuroinflammation and AD. In this meta-analysis both the association between chronic inflammatory diseases and elevated levels of CRP during midlife were investigated to examine if they correlated with an augmented risk of dementia. Moreover, the association between increased CRP and modifications in the permeability of the Blood Brain Barrier (BBB) in the presence of CRP is explored. The results displayed that the odds ratio for IBD and dementia was 1.91 [1.15-3.15], for RA it was 1.90 [1.09-3.32] following sensitivity analysis and for CRP it was 1.62 [1.22-2.15]. These results demonstrate a higher risk of dementia in patients presenting chronic inflammation and that exists an independent association with high CRP in midlife. This paper builds on published research that suggest a critical role for CRP both in stroke and AD and provides an analysis on currently published research on multiple diseases (IBD and RA) in which CRP is raised as well as chronically elevated. CRP and the associated risk of dementia and further research indicated that the monomeric form of CRP can infiltrate the BBB/be released from damaged micro-vessels to access the brain. This meta-analysis provides first-time evidence that chronic elevation of CRP in autoimmune diseases is directly associated with an increased risk of later development of Alzheimer’s disease. Therefore, greater priority should be provided to the effective control of inflammation in patients with chronic inflammatory or autoimmune conditions and further long-term assessment of circulating CRP might inform of an individual’s relative risk of developing dementia.

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Section: Introductionmentioning

confidence: 99%

A meta-analysis investigating the relationship between inflammation in autoimmune disease, elevated CRP, and the risk of dementia

2023

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“…These are individuals without a diagnosis of RA who have either (i) genetic risk factors for RA, (ii) environmental risk factors for RA, (iii) systemic autoimmunity associated with RA, (iv) symptoms without clinical arthritis or (v) unclassified arthritis [ 7 ]. Core risk factors for RA have now been defined [ 8 ], and EULAR guidelines for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis have been published [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Given the increasing focus on prevention of RA [ 8 , 9 ], the present systematic review of studies to elicit preferences for RA treatments updates and extends the previous review [ 6 ] by including studies of the preferences of individuals who do not have RA, and those of ‘at risk’ populations for RA prevention [ 17 ]. This inquiry will explore differences between preference studies for RA treatment and prevention, and across different populations (patients, general public, at risk groups).…”

Section: Introductionmentioning

confidence: 99%

Systematic review of quantitative preference studies of treatments for rheumatoid arthritis among patients and at-risk populations

et al. 2022

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Treatments used for rheumatoid arthritis (RA) are under investigation for their efficacy to prevent RA in at risk groups. It is therefore important to understand treatment preferences of those at risk. We systematically reviewed quantitative preference studies of drugs to treat, or prevent RA, to inform the design of further studies and trials of RA prevention. Stated preference studies for RA treatment or prevention were identified through a search of five databases. Study characteristics and results were extracted, and the relative importance of different types of treatment attributes was compared across populations. Twenty three studies were included 20 of RA treatments (18 of patients; 2 of the general public) and 3 prevention studies with first-degree relatives (FDRs). Benefits, risks, administration method and cost (when included) were important determinants of treatment choice. A benefit was more important than a risk attribute in half of the studies of RA treatment that included a benefit attribute and 2/3 studies of RA prevention. There was variability in the relative importance of attributes across the few prevention studies. In studies with non-patient participants, attributes describing confidence in treatment effectiveness/safety were more important determinants of choice than in studies with patients. Most preference studies relating to RA are of treatments for established RA. Few studies examine preferences for treatments to prevent RA. Given intense research focus on RA prevention, additional preference studies in this context are needed. Variation in treatment preferences across different populations is not well understood and direct comparisons are needed.

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“…EULAR guidance for trials and observational studies in individuals at-risk of RA, based on expert consensus and evidence from systematic reviews (14,15), is now available and the scene is set for progress towards a new paradigm of prevention, rather than treatment of RA (16). Evaluation of candidate preventive therapies for RA is a nascent research area, though early findings are promising.…”

Section: Introductionmentioning

confidence: 99%

Perspectives of at-Risk Individuals on Preventive Intervention for Rheumatoid Arthritis: A Mini Review

Falahee

Raza

2022

Front. Immunol.

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There has been intense research focus on the biological mechanisms underlying the transition from health to disease for rheumatoid arthritis (RA) over recent years, and it is now well established that a state of autoimmunity precedes the development of symptoms for a large proportion of patients. This has led to an increased interest in the identification of at-risk groups and the potential for preventive intervention. The ability of several immunomodulatory agents to delay or prevent RA is under investigation and novel cellular therapies are in development. Preventive approaches are also being assessed in other chronic autoimmune diseases. For example, an anti-CD3 antibody has recently been shown to delay progression to type 1 diabetes in non-diabetic relatives of patients identified as being at high risk. The identification and treatment of individuals as being at risk of a disease where there is a degree of uncertainty around the potential for benefit is socially and ethically challenging. Recently reported difficulties in recruitment to RA prevention trials have underlined the importance of understanding the perspectives of at-risk individuals to identify barriers and facilitators that need to be addressed in order for preventive strategies to be acceptable. Understanding of their preferences for benefits and risks of preventive interventions can inform efficient intervention prioritization, prevention trial design and the development of informational resources for those at risk. In this review we summarize current knowledge of preferences for RA prevention and make recommendations for further research needed to ensure efficient development of preventive therapies and clinical implementation.

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A core set of risk factors in individuals at risk of rheumatoid arthritis: a systematic literature review informing the EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

Cited by 20 publications

References 61 publications

A meta-analysis investigating the relationship between inflammation in autoimmune disease, elevated CRP, and the risk of dementia

A meta-analysis investigating the relationship between inflammation in autoimmune disease, elevated CRP, and the risk of dementia

Systematic review of quantitative preference studies of treatments for rheumatoid arthritis among patients and at-risk populations

Perspectives of at-Risk Individuals on Preventive Intervention for Rheumatoid Arthritis: A Mini Review

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