Ultrasound is not associated with the presence of systemic autoimmunity or symptoms in individuals at risk for rheumatoid arthritis

Brulhart, Laure; Alpizar-Rodriguez, D.; Nissen, Mary Jo; Zufferey, Pascal; Ciubotariu, Ileana; Fleury, Grégory; Lazarou, Ilias; Gabay, Cem; Finckh, Axel

doi:10.1136/rmdopen-2019-000922

Cited by 17 publications

(13 citation statements)

References 25 publications

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“…However, if imaging is used to define IA that is not identifiable on examination (i.e., subclinical IA), that may change the approach to prevention where "treatable" IA is identified by imaging earlier than is possible by physical examination. While potentially beneficial, that approach could also lead to overtreatment, in particular because of the known high variability in interpreting images, and also because "synovitis" on imaging can be detected in symptom-free individuals from the general population (49,50). As such, it may be some time before the appropriate role of imaging is understood for use in defining the presence of current "actionable" disease in the absence of findings of IA on examination, as well as prediction and prevention in IA/RA.…”

Section: Paradigm Shift To Ra Prevention: Challenges and Opportunitiesmentioning

confidence: 99%

Rheumatoid Arthritis Pathogenesis, Prediction, and Prevention: An Emerging Paradigm Shift

Deane

Holers

2020

Arthritis & Rheumatology

163

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Rheumatoid arthritis (RA) is currently diagnosed and treated when an individual presents with signs and symptoms of inflammatory arthritis (IA) as well as other features, such as autoantibodies and/or imaging findings, that provide sufficient confidence that the individual has RA‐like IA (e.g., meeting established classification criteria) that warrants therapeutic intervention. However, it is now known that there is a stage of seropositive RA during which circulating biomarkers and other factors (e.g., joint symptoms) can be used to predict if and when an individual who does not currently have IA may develop future clinically apparent IA and classifiable RA. Indeed, the discovery of the “pre‐RA” stage of seropositive disease has led to the development of several clinical trials in which individuals are studied to identify ways to delay or prevent the onset of clinically apparent IA/RA. This review focuses on several issues pertinent to understanding the prevention of RA. These include discussion of the pathogenesis of pre‐RA development, prediction of the likelihood and timing of future classifiable RA, and a review of completed and ongoing clinical trials in RA prevention. Furthermore, this review discusses challenges and opportunities to be addressed to effect a paradigm shift in RA, where in the near future, proactive risk assessment focused on prevention of RA will become a public health strategy in much the same manner as cardiovascular disease is managed today.

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Section: Paradigm Shift To Ra Prevention: Challenges and Opportunitiesmentioning

confidence: 99%

Rheumatoid Arthritis Pathogenesis, Prediction, and Prevention: An Emerging Paradigm Shift

Deane

Holers

2020

Arthritis & Rheumatology

163

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“…Power Doppler on ultrasound was associated with the presence of unclassified arthritis (ie, at least one swollen join at physical examination), but not with any of the other preclinical phases of RA, thus not supporting the indiscriminate use of musculoskeletal ultrasound in a screening strategy for RA in a population with a limited risk of developing RA. 67…”

Section: Findings To Date Musculoskeletal Ultrasoundmentioning

confidence: 99%

Cohort profile: SCREEN-RA: design, methods and perspectives of a Swiss cohort study of first-degree relatives of patients with rheumatoid arthritis

et al. 2021

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PurposeRheumatoid arthritis (RA) is an insidious autoimmune disease, with an immunological onset years before diagnosis. Early interventions in preclinical stages could prevent or minimise the progression towards irreversible joint damage. The SCREEN-RA cohort (Evaluation of a SCREENing strategy for Rheumatoid Arthritis) aims to characterise the preclinical stages of the disease, to identify environmental risk factors, and to discover or validate novel biomarkers predictive for RA development.ParticipantsSCREEN-RA includes an at-risk population for RA, namely first-degree relatives of patients with established RA.Findings to dateThe cohort started in 2009 is composed of mostly asymptomatic healthy individuals (total n=1458, 7262 person-years), with a mean age of 44 years at enrolment, 74% female and 91% Caucasian ethnicity. During the study period, 16 participants have developed RA. All participants provide baseline serum, DNA and RNA samples, and in a subset, stool samples and oral examination are performed for microbiota assessment. At enrolment, 10% of participants had asymptomatic autoimmunity associated with RA (n=147), 10% presented ‘clinically suspect arthralgias’ (n=143) and 3% reported arthralgias in conjunction with autoimmunity or high genetic risk (n=51). Studies with this cohort have uncovered risk factors for RA development, such as female hormonal factors, poor oral health or intestinal dysbiosis.Future plansFuture directions include immunological and ‘multiomics’ approaches to discover new biological markers of progression towards RA, as well as testing preventive interventions in ‘high-risk’ population.

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“…The corollary is that US may not be as informative in lower-risk individuals who do not yet have imminent clinical arthritis. In line with this, a recent US study of 273 first-degree relatives of RA patients (FDRs), of whom only 8% were anti-cyclic citrullinated peptide antibodies (ACPA)-positive, found no overall increase in US synovitis in this population [20]. Likewise, in the Amsterdam seropositive arthralgia cohort, whilst grey-scale synovitis was associated with progression to IA, intraarticular PD signal was infrequently identified and was not predictive of progression to IA [17].…”

Section: The Utility Of Ultrasound In Managing Individuals At-risk Ofmentioning

confidence: 85%

The Role of Musculoskeletal Ultrasound in the Rheumatoid Arthritis Continuum

et al. 2020

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Purpose of Review Rheumatoid arthritis (RA) is no longer considered a fixed phenotype but rather a disease continuum. This review outlines the current and potential value of applying ultrasound (US) along this continuum: from the prediction of progression to RA in at-risk individuals, to confirmation of the early diagnosis of RA, as well as the consideration of differential diagnoses, and the use in disease monitoring and defining remission. Recent Findings In individuals at-risk of RA (i.e., positive autoantibodies with symptoms but without synovitis), US has shown a promising predictive value for the development of clinical arthritis, providing the opportunity to improve risk stratification (and disease prevention) of these individuals. The detection of inflammation on US in patients with early undifferentiated arthritis, in which a definite diagnosis cannot be reached, could predict evolution to persistent arthritis, mostly RA. This, in addition to the US potential ability to identify disease specific patterns for different rheumatic conditions, might facilitate early diagnosis and, therefore, improve the management of patients with RA, or other types of inflammatory arthritides. US has also demonstrated the capability to predict radiographic progression, and relapse risk after treatment discontinuation, in RA patients in remission according to the clinical instruments, raising implications in the management, including therapy discontinuation, of these patients. Summary US has an undeniable value in the management of patients at different stages along the RA continuum. Further research is needed to identify which groups of patients benefit the most from US imaging.

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Ultrasound is not associated with the presence of systemic autoimmunity or symptoms in individuals at risk for rheumatoid arthritis

Cited by 17 publications

References 25 publications

Rheumatoid Arthritis Pathogenesis, Prediction, and Prevention: An Emerging Paradigm Shift

Rheumatoid Arthritis Pathogenesis, Prediction, and Prevention: An Emerging Paradigm Shift

Cohort profile: SCREEN-RA: design, methods and perspectives of a Swiss cohort study of first-degree relatives of patients with rheumatoid arthritis

The Role of Musculoskeletal Ultrasound in the Rheumatoid Arthritis Continuum

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