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Healthcare
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Rheumatoid Arthritis Prevention and Control
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Rheumatoid Arthritis Prevention and Control

A special issue of Healthcare (ISSN 2227-9032).

Deadline for manuscript submissions: closed (11 June 2021) | Viewed by 14760

Special Issue Editors

Dr. Kulveer Mankia

E-Mail Website
Guest Editor
Faculty of Medicine and Health, School of Medicine, University of Leeds, Leeds, UK
Interests: preclinical and early rheumatoid arthritis (RA); RA prevention; ultrasound and MRI; palindromic rheumatism; mucosal autoimmunity and RA; clinical trials in RA
Prof. Dr. Paul Emery

E-Mail Website
Guest Editor
Faculty of Medicine and Health, School of Medicine, University of Leeds, Leeds, UK
Interests: Inflammatory Arthritis including RA; psoriatic arthritis; AS; SLE; Scleroderma; Sjogren Syndrome; immunotherapy; disease prevention; ultrasound; MRI

Special Issue Information

The management of rheumatoid arthritis (RA) has been revolutionised by the early arthritis paradigm, with prompt identification and treatment now the central focus of RA clinical care around the world. Despite this approach and despite the array of treatments available, only a minority of patients achieve sustained disease remission. An even smaller proportion realise the ultimate goal of drug-free remission.

In addition to the long held ambition of controlling clinically established arthritis, the recognition of a preclinical phase of RA has now raised the exciting prospect of arthritis prevention. Biomarkers such as autoantibodies, clinical symptoms and high-resolution imaging can be used to accurately identify individuals who are "at-risk" of developing RA. Studying cohorts of at-risk individuals also provides unique insights into the pathobiology of RA, which will inform preventative strategies.

Prevention and cure are arguably the major unmet needs in RA. For the prevention of RA, there are many important questions to address. How do specific risk factors influence the pathobiology of RA, and which should we target to prevent arthritis? What drives RA-related autoimmunity, and how significant is the development of subclinical joint inflammation on imaging? Do at-risk individuals want to undertake preventative interventions? In those individuals in whom arthritis cannot be prevented, optimal control and drug free remission becomes the ambition. How can this be achieved using the therapies currently available to us?

In this Special Issue, we aim to address these intriguing areas, which are major contemporary challenges in rheumatology research and practice.

Dr. Kulveer Mankia
Prof. Dr. Paul Emery
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Healthcare is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Rheumatoid arthritis
  • Preclinical disease
  • Prevention
  • Risk-factors
  • Remission
  • Cure

Published Papers (5 papers)

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Research

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14 pages, 589 KiB  
Communication
Can Studying Genetically Predisposed Individuals Inform Prevention Strategies for RA?
by Amanda Fowler-Woods, Irene Smolik, Vidyanand Anaparti, Liam O’Neil and Hani El-Gabalawy
Healthcare 2021, 9(10), 1301; https://0-doi-org.brum.beds.ac.uk/10.3390/healthcare9101301 - 29 Sep 2021
Cited by 3 | Viewed by 2226
Abstract
Rheumatoid arthritis (RA) is a prevalent autoimmune disorder in which complex genetic predisposition interacts with multiple environmental factors to precipitate chronic and progressive immune-mediated joint inflammation. Currently, in most affected individuals, ongoing suppression of the inflammation is required to prevent irreversible damage and [...] Read more.
Rheumatoid arthritis (RA) is a prevalent autoimmune disorder in which complex genetic predisposition interacts with multiple environmental factors to precipitate chronic and progressive immune-mediated joint inflammation. Currently, in most affected individuals, ongoing suppression of the inflammation is required to prevent irreversible damage and functional loss. The delineation of a protracted preclinical period in which autoimmunity is initially established and then evolves to become pathogenic provides unprecedented opportunities for interventions that have the potential to prevent the onset of this lifelong disease. Clinical trials aimed at assessing the impact of specific prevention strategies require the identification of individuals who are at high risk of future RA development. Currently, these risk factors include a strong family history of RA, and the detection of circulating RA-associated autoantibodies, particularly anti-citrullinated protein antibodies (ACPA). Yet, even in such individuals, there remains considerable uncertainty about the likelihood and the timeframe for future disease development. Thus, individuals who are approached to participate in such clinical trials are left weighing the risks and benefits of the prevention measures, while having large gaps in our current understanding. To address this challenge, we have undertaken longitudinal studies of the family members of Indigenous North American RA patients, this population being known to have a high prevalence of RA, early age of onset, and familial clustering of cases. Our studies have indicated that the concepts of “risk” and “prevention” need to be communicated in a culturally relevant manner, and proposed prevention interventions need to have an appropriate balance of effectiveness, safety, convenience, and cultural acceptability. We have focused our proposed prevention studies on immunomodulatory/anti-inflammatory nutritional supplements that appear to strike such a complex balance. Full article
(This article belongs to the Special Issue Rheumatoid Arthritis Prevention and Control)
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Review

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20 pages, 537 KiB  
Review
Defining the Optimal Strategies for Achieving Drug-Free Remission in Rheumatoid Arthritis: A Narrative Review
by Hanna Gul, Kate Harnden and Benazir Saleem
Healthcare 2021, 9(12), 1726; https://0-doi-org.brum.beds.ac.uk/10.3390/healthcare9121726 - 13 Dec 2021
Cited by 3 | Viewed by 2952
Abstract
Background: It is now accepted that the optimum treatment goal for rheumatoid arthritis (RA) is sustained remission, as this has been shown to be associated with the best patient outcomes. There is little guidance on how to manage patients once remission is achieved; [...] Read more.
Background: It is now accepted that the optimum treatment goal for rheumatoid arthritis (RA) is sustained remission, as this has been shown to be associated with the best patient outcomes. There is little guidance on how to manage patients once remission is achieved; however, it is recommended that patients can taper therapy, with a view to discontinuing and achieving drug-free remission if treatment goals are maintained. This narrative review aims to present the current literature on drug-free remission in rheumatoid arthritis, with a view to identifying which strategies are best for disease-modifying anti-rheumatic drug (DMARD) tapering and to highlight areas of unmet clinical need. Methods: We performed a narrative review of the literature, which included research articles, meta-analyses and review papers. The key search terms included were rheumatoid arthritis, remission, drug-free remission, b-DMARDS/biologics, cs-DMARDS and tapering. The databases that were searched included PubMed and Google Scholar. For each article, the reference section of the paper was reviewed to find additional relevant articles. Results: It has been demonstrated that DFR is possible in a proportion of RA patients achieving clinically defined remission (both on cs and b-DMARDS). Immunological, imaging and clinical associations with/predictors of DFR have all been identified, including the presence of autoantibodies, absence of Power Doppler (PD) signal on ultrasound (US), lower disease activity according to composite scores of disease activity and lower patient-reported outcome scores (PROs) at treatment cessation. Conclusions: DFR in RA may be an achievable goal in certain patients. This carries importance in reducing medication-induced side-effects and potential toxicity, the burden of taking treatment if not required and cost effectiveness, specifically for biologic therapy. Prospective studies of objective biomarkers will help facilitate the prediction of successful treatment discontinuation. Full article
(This article belongs to the Special Issue Rheumatoid Arthritis Prevention and Control)
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11 pages, 779 KiB  
Review
Should We Be Screening for and Treating Periodontal Disease in Individuals Who Are at Risk of Rheumatoid Arthritis?
by Zhain Mustufvi, Stefan Serban, James Chesterman and Kulveer Mankia
Healthcare 2021, 9(10), 1326; https://0-doi-org.brum.beds.ac.uk/10.3390/healthcare9101326 - 05 Oct 2021
Cited by 1 | Viewed by 2037
Abstract
There is increasing evidence supporting an association between periodontal disease (PD) and rheumatoid arthritis (RA), both mechanistically and clinically. Trials have shown that treating PD in people with RA may improve RA disease activity. Patients with musculoskeletal symptoms without arthritis, who test positive [...] Read more.
There is increasing evidence supporting an association between periodontal disease (PD) and rheumatoid arthritis (RA), both mechanistically and clinically. Trials have shown that treating PD in people with RA may improve RA disease activity. Patients with musculoskeletal symptoms without arthritis, who test positive for cyclic-citrullinated protein antibodies, are at risk of RA (CCP+ at-risk), with seropositivity preceding arthritis onset by months or years. Importantly, there is evidence to suggest that periodontal inflammation may precede joint inflammation in CCP+ at-risk and, therefore, this could be a trigger for RA. There has been increased research interest in RA prevention and the phenotyping of the pre-RA disease phase. This review will examine the merits of identifying individuals who are CCP+ at-risk and performing screening for PD. In addition, we discuss how PD should be treated once identified. Finally, the review will consider future research needed to advance our understanding of this disease association. Full article
(This article belongs to the Special Issue Rheumatoid Arthritis Prevention and Control)
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12 pages, 821 KiB  
Review
What Is the Value of Ultrasound in Individuals ‘At-Risk’ of Rheumatoid Arthritis Who Do Not Have Clinical Synovitis?
by Andrea Di Matteo, Davide Corradini and Kulveer Mankia
Healthcare 2021, 9(6), 752; https://0-doi-org.brum.beds.ac.uk/10.3390/healthcare9060752 - 18 Jun 2021
Cited by 8 | Viewed by 3068
Abstract
The identification of biomarkers that help identify individuals at imminent risk of progression to rheumatoid arthritis (RA) is of crucial importance for disease prevention. In recent years, several studies have highlighted the value of musculoskeletal (MSK) ultrasound (US) in predicting progression to inflammatory [...] Read more.
The identification of biomarkers that help identify individuals at imminent risk of progression to rheumatoid arthritis (RA) is of crucial importance for disease prevention. In recent years, several studies have highlighted the value of musculoskeletal (MSK) ultrasound (US) in predicting progression to inflammatory arthritis (IA) in individuals ‘at-risk’ of RA. These studies have highlighted the following main aspects: first, in RA-related autoantibody-positive individuals, MSK symptoms seem to develop before ‘sub-clinical’ joint inflammation occurs on US. Second, the detection of ‘sub-clinical’ synovitis (and/or bone erosions) greatly increases the risk of IA development in these ‘at-risk’ individuals. US has a potential key role for better understanding the ‘pre-clinical’ stages in individuals ‘at-risk’ of RA, and for the early identification of those individuals at high risk of developing IA. Further research is needed to address questions on image analysis and standardization. In this review, we provide an overview of the most relevant studies which have investigated the value of US in the prediction of RA development in individuals ‘at-risk’ of RA who have MSK symptoms, but no clinical evidence of IA. We highlight recent insights, limitations, and future perspectives of US use in this important population. Full article
(This article belongs to the Special Issue Rheumatoid Arthritis Prevention and Control)
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15 pages, 687 KiB  
Review
Challenges and Opportunities of Targeted Behavioral Interventions for Groups at Risk for Developing Rheumatoid Arthritis
by Alessandra Zaccardelli and Jeffrey A. Sparks
Healthcare 2021, 9(6), 641; https://0-doi-org.brum.beds.ac.uk/10.3390/healthcare9060641 - 28 May 2021
Cited by 3 | Viewed by 3464
Abstract
Background: Rheumatoid arthritis (RA) is a serious autoimmune disease which causes painful, swollen joints and can impact quality of life and increase morbidity and mortality. There are several preclinical stages of RA that correspond to at-risk groups that include: genetic risk, risk [...] Read more.
Background: Rheumatoid arthritis (RA) is a serious autoimmune disease which causes painful, swollen joints and can impact quality of life and increase morbidity and mortality. There are several preclinical stages of RA that correspond to at-risk groups that include: genetic risk, risk from behaviors, elevation of RA-related autoantibodies, and early clinical disease manifestations such as undifferentiated arthritis. Early interventions are crucial to slowing progression to and potentially preventing RA onset. Modification of behaviors among at-risk individuals may decrease RA risk. There are several challenges and opportunities in implementing preventative behavioral interventions, which may vary within different at-risk groups. Methods: We performed a narrative review of the literature, including meta-analyses focused on RA risk-related behaviors as well as publications investigating the potential efficacy of behavioral modifications on RA risk. Results: There are multiple behavioral risk factors associated with RA, including smoking, obesity, low physical activity, low quality diet, and poor dental hygiene, which may contribute to progression to clinical RA. Meta-analyses have been performed for smoking, excess body weight, and physical activity. Likelihood of adopting behavioral modifications may increase as RA risk increases. Conclusions: Clinicians may be able to tailor preventative approaches to various RA at-risk groups to help reduce RA risk, but further research is needed. A better understanding of the relationship of behaviors with RA risk and optimized approaches to implementing behavioral changes may allow for clinicians to tailor their preventative approaches for at-risk individuals. Full article
(This article belongs to the Special Issue Rheumatoid Arthritis Prevention and Control)
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