Research (Articles)
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Perceptions and experiences of individuals at-risk of rheumatoid arthritis (RA) knowing about their risk of developing RA and being offered preventive treatment: systematic review and thematic synthesis of qualitative studies.Objectives: There is increasing interest in identifying individuals at-risk of rheumatoid arthritis (RA) and initiating early treatment to prevent or delay the onset of arthritis. We aimed to describe the perceptions and experiences of at-risk individuals and to inform the conduct of clinical trials and studies, and clinical practice. Methods: A systematic review and thematic synthesis of qualitative studies was conducted. Two review authors independently screened studies for inclusion, appraised their methodological quality using the Critical Appraisal Skills Programme checklist and assessed confidence in the findings using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in Evidence from Reviews of Qualitative Research approach. Results: Seven studies involving 115 individuals at-risk of developing RA were included. Three major themes (seven subthemes) were identified: understanding the risk of developing RA (knowledge of RA and identification of potential risk factors); preventive interventions to reduce the risk of developing RA (understanding the value and role of preventive interventions, and engagement with preventive interventions); and perceptions of predictive testing for RA (benefits of predictive testing, decision to undertake predictive testing and concerns about predictive testing). Moderate confidence in most review findings was evident. Conclusion: While there are clear benefits in informing individuals at-risk of RA about their risk following predictive testing and offering preventive treatment, there are potential barriers to engagement, intensified by the burden of uncertainty. Identification of the optimum approaches for presenting risk information, including the risks and benefits of engaging with preventive interventions, is urgently needed to support individuals at-risk of RA in their decision making.
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Prescribing anti-rheumatic drugs in pregnancy and breastfeeding-the British Society for Rheumatology guideline scope.Prescribing anti-rheumatic drugs in pregnancy and breastfeeding-the British Society for Rheumatology guideline scope
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Relationship Between Inflammation and Metabolism in Patients With Newly Presenting Rheumatoid Arthritis.Background: Systemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy-based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA. Methods: Serum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional 1H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation. Results: Using PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (p<0.001) metabolome was detectable. Likewise, following categorisation of CRP into tertiles, patients in the lowest CRP tertile and the highest CRP tertile were statistically discriminated using OPLS-DA analysis of both serum (p=0.033) and urinary (p<0.001) metabolome. The most highly weighted metabolites for these models included glucose, amino acids, lactate, and citrate. These findings suggest increased glycolysis, perturbation in the citrate cycle, oxidative stress, protein catabolism and increased urea cycle activity are key characteristics of newly presenting RA patients with elevated CRP. Conclusions: This study consolidates our understanding of a previously identified relationship between serum metabolite profile and inflammation and provides novel evidence that there is a relationship between urinary metabolite profile and inflammation as measured by CRP. Identification of these metabolic perturbations provides insights into the pathogenesis of RA and may help in the identification of therapeutic targets.
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Rheumatoid arthritis prevention: any takers?Rheumatoid arthritis prevention: any takers?
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Rituximab 500 mg 6-monthly infusions is an option in maintenance therapy of ANCA-associated vasculitis.Rituximab 500 mg 6-monthly infusions is an option in maintenance therapy of ANCA-associated
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Spontaneously Resolving Joint Inflammation Is Characterised by Metabolic Agility of Fibroblast-Like Synoviocytes.Fibroblast-like synoviocytes (FLS) play an important role in maintaining joint homeostasis and orchestrating local inflammatory processes. When activated during injury or inflammation, FLS undergo transiently increased bioenergetic and biosynthetic demand. We aimed to identify metabolic changes which occur early in inflammatory disease pathogenesis which might support sustained cellular activation in persistent inflammation. We took primary human FLS from synovial biopsies of patients with very early rheumatoid arthritis (veRA) or resolving synovitis, and compared them with uninflamed control samples from the synovium of people without arthritis. Metabotypes were compared using NMR spectroscopy-based metabolomics and correlated with serum C-reactive protein levels. We measured glycolysis and oxidative phosphorylation by Seahorse analysis and assessed mitochondrial morphology by immunofluorescence. We demonstrate differences in FLS metabolism measurable after ex vivo culture, suggesting that disease-associated metabolic changes are long-lasting. We term this phenomenon 'metabolic memory'. We identify changes in cell metabolism after acute TNFα stimulation across disease groups. When compared to FLS from patients with early rheumatoid arthritis, FLS from patients with resolving synovitis have significantly elevated mitochondrial respiratory capacity in the resting state, and less fragmented mitochondrial morphology after TNFα treatment. Our findings indicate the potential to restore cell metabotypes by modulating mitochondrial function at sites of inflammation, with implications for treatment of RA and related inflammatory conditions in which fibroblasts play a role.
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Symptoms in first-degree relatives of patients with rheumatoid arthritis: evaluation of cross-sectional data from the symptoms in persons at risk of rheumatoid arthritis (SPARRA) questionnaire in the PRe-clinical EValuation of Novel Targets in RA (PREVeNT-RA) CohortBackground: First-degree relatives (FDRs) of people with rheumatoid arthritis (RA) have a fourfold increased risk of developing RA. The Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire was developed to document symptoms in persons at risk of RA. The aims of this study were (1) to describe symptoms in a cohort of FDRs of patients with RA overall and stratified by seropositivity and elevated CRP and (2) to determine if patient characteristics were associated with symptoms suggestive of RA. Methods: A cross-sectional study of FDRs of patients with RA, in the PREVeNT-RA study, who completed a study questionnaire, provided a blood sample measured for rheumatoid factor, anti-CCP and CRP and completed the SPARRA questionnaire. Moderate/severe symptoms and symmetrical, small and large joint pain were identified and described. Symptoms associated with both seropositivity and elevated CRP were considered suggestive of RA. Logistic regression was used to determine if symptoms suggestive of RA were associated with patient characteristics. Results: Eight hundred seventy participants provided all data, 43 (5%) were seropositive and 122 (14%) had elevated CRP. The most frequently reported symptoms were sleep disturbances (20.3%) and joint pain (17.9%). Symmetrical and small joint pain were 11.3% and 12.8% higher, respectively, in those who were seropositive and 11.5% and 10.7% higher in those with elevated CRP. In the logistic regression model, seropositivity, older age and feeling depressed were associated with increased odds of small and symmetrical joint pain. Conclusions: This is the first time the SPARRA questionnaire has been applied in FDRs of patients with RA and has demonstrated that the presence of symmetrical and small joint pain in this group may be useful in identifying people at higher risk of developing RA.
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'It's just a great muddle when it comes to food': a qualitative exploration of patient decision-making around diet and gout.Objective: Our aim was to understand whether, why and how patients choose to modify their diets after developing gout. Methods: We conducted an inductive thematic secondary analysis of qualitative data from 43 interviews and four focus groups with UK participants with gout (n = 61). Results: Participants commonly initiated dietary changes as part of a self-management strategy for gout. Reasons for making such dietary changes included: desperation; a desire for control; and belief that it would be possible to achieve successful management through diet alone; but not weight loss. Participants who did not make changes or who reverted to previous dietary patterns did so because: they believed urate-lowering therapy was successfully managing their gout; medication allowed normal eating; they did not find 'proof' that diet would be an effective treatment; or the dietary advice they found was unrealistic, unmanageable or irrelevant. Dietary modification was patient led, but patients would have preferred the support of a health-care professional. Beliefs that diet could potentially explain and modify the timing of flares gave patients a sense of control over the condition. However, the belief that gout could be controlled through dietary modification appeared to be a barrier to acceptance of management with urate-lowering therapy. Conclusions: Perceptions about gout and diet play a large role in the way patients make decisions about how to manage gout in their everyday lives. Addressing the reasons why patients explore dietary solutions, promoting the value of urate-lowering therapy and weight loss and drawing on strong evidence to communicate clearly will be crucial in improving long-term clinical management and patient experience.
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Intimate Partner Violence and the Risk of Developing Fibromyalgia and Chronic Fatigue Syndrome.Intimate partner violence (IPV) is a global public health issue with a variety of ill health consequences associated with exposure. Due to the stimulation of chronic stress and inflammatory pathways, childhood abuse has been associated with the subsequent development of functional syndromes such as fibromyalgia and chronic fatigue syndrome (CFS). Although IPV in women appears to elicit similar biochemical responses, this association has not been tested thoroughly in IPV survivors. These functional syndromes are complex in etiology and any indication of their risk factors would benefit health care professionals managing this population. Therefore, we aimed to investigate the association between exposure to IPV with functional syndromes: fibromyalgia and CFS. We conducted a retrospective open cohort study using "The Heath Improvement Network" database between January 1, 1995 and December 1, 2017. A total of 18,547 women who were exposed to IPV were each matched by age to four controls who were not exposed (n = 74,188). The main outcome measures were the risk of developing fibromyalgia and CFS. These were presented as adjusted incidence rate ratios (aIRR) with 95% confidence intervals (CIs). We found that 97 women in the exposed group developed fibromyalgia (incidence rate [IR] = 1.63 per 1,000 person-years) compared to 239 women in the unexposed group (IR = 0.83 per 1,000 person-years). Following adjustment, this translated to an IRR of 1.73 (95% CI = [1.36, 2.22]). Similarly, 19 women developed CFS in the exposed group (IR = 0.32 per 1,000 person-years), compared to 53 in the unexposed group (0.18 per 1,000 person-years), which translates to an aIRR of 1.92 (95% CI = [1.11, 3.33]). Therefore, we have identified an association between a history of IPV in women and the development of these functional syndromes, which may provide more information to inform the biopsychosocial pathway precipitating the development of fibromyalgia and CFS.
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Management of bone health in idiopathic inflammatory myopathies : a two-center audit in the United Kingdom and Hong KongBackground: Patients with inflammatory idiopathic myopathies (IIM) face elevated risks of osteoporosis and fragility fracture. Aim: To evaluate current practice relating to bone health in adult patients with IIM in the United Kingdom and Hong Kong (HK). Methods: Patients were identified from IIM patient lists. Demographics, osteoporosis risk factors, DXA scans, and bone protection treatment were recorded. Adherence to regional standards was evaluated for each center. Following this, in the United Kingdom, up-to-date DXA scans were performed. Results: Of 136 patients identified, 51 met selection criteria (UK, n = 20, HK, n = 31). Mean age in the United Kingdom was 59 (IQR 54-66); in Hong Kong, 65 (IQR 52.5-70). Most were female (UK 70%; HK 77%), current or previous steroid treatment was common (UK 90%; HK 100%) and some had experienced fragility fracture (UK 15%; HK 9%). The mean daily dose of prednisolone that patients were prescribed during the study was 12.5 mg (UK) and 14.3 mg (HK). Some patients had had a DXA scan (UK 50%; HK 35%) though several were outdated. Among those with BMD measured (UK, n = 20; HK, n = 11), osteopenia prevalence was 35% (UK) and 36% (HK) while osteoporosis was 5% (UK) and 36% (HK). Notably, 25% (UK) and 64% (HK) exceeded treatment thresholds. Treatments included anti-osteoporotic agents (UK 55%; HK 15%), Vitamin D/calcium supplements (UK 95%; HK 52%), or no treatment (UK 5%, HK 15%). Conclusion: Poor compliance with guidelines exists in both centers, particularly around investigation and monitoring of bone health for IIM patients. Integrated care models and increased resource allocation to bone health are imperative to improve management of this aspect of IIM.
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Understanding the impact of systemic lupus erythematosus on work amongst South Asian people in the UK: An explorative qualitative studySLE has a range of fluctuating symptoms affecting individuals and their ability to work. Although South Asian (SA) patients are at increased risk of developing SLE there is limited knowledge of the impact on employment for these patients in the UK. Understanding ethnicity and disease-specific issues are important to ensure patients are adequately supported at work. Semi-structured interviews were conducted with patients of SA origin to explore how SLE impacted on their employment. Thematic analysis was used to analyse the data which are reported following COREQ guidelines. Ten patients (8 female; 2 male) were recruited from three rheumatology centres in the UK and interviewed between November 2019 and March 2020. Patients were from Indian (n = 8) or Pakistani (n = 2) origin and worked in a range of employment sectors. Four themes emerged from the data: (1) Disease related factors; (2) Employment related factors; (3) Cultural and interpersonal factors impacting on work ability; (4) Recommendations for improvement. Patients' ability to work was affected by variable work-related support from their hospital clinicians, low awareness of SLE and variable support from their employers, and cultural barriers in their communities that could affect levels of family support received. These findings highlight the need for additional support for SA patients with SLE in the workplace.
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Impact of glucocorticoids on the incidence of lupus-related major organ damage: a systematic literature review and meta-regression analysis of longitudinal observational studies.Objective: In systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence. Methods: We conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966-October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with <5 years of follow-up, <50 patients, different outcomes and special populations were excluded. Results: We selected 49 articles including 16 224 patients, 14 755 (90.9%) female with a mean age and disease duration of 35.1 years and of 37.1 months. The mean follow-up time was 104.9 months. For individual damage items, the average daily GC dose was associated with the occurrence of overall cardiovascular events and with osteoporosis with fractures. A higher average cumulative dose adjusted (or not)/number of follow-up years and a higher proportion of patients on GC were associated with the occurrence of osteonecrosis. Conclusions: We confirm associations of GC use with three specific damage items. In treating patients with SLE, our aim should be to maximise the efficacy of GC and to minimise their harms.
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Global Deletion of 11β-HSD1 Prevents Muscle Wasting Associated with Glucocorticoid Therapy in Polyarthritis.Glucocorticoids provide indispensable anti-inflammatory therapies. However, metabolic adverse effects including muscle wasting restrict their use. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) modulates peripheral glucocorticoid responses through pre-receptor metabolism. This study investigates how 11β-HSD1 influences skeletal muscle responses to glucocorticoid therapy for chronic inflammation. We assessed human skeletal muscle biopsies from patients with rheumatoid arthritis and osteoarthritis for 11β-HSD1 activity ex vivo. Using the TNF-α-transgenic mouse model (TNF-tg) of chronic inflammation, we examined the effects of corticosterone treatment and 11β-HSD1 global knock-out (11βKO) on skeletal muscle, measuring anti-inflammatory gene expression, muscle weights, fiber size distribution, and catabolic pathways. Muscle 11β-HSD1 activity was elevated in patients with rheumatoid arthritis and correlated with inflammation markers. In murine skeletal muscle, glucocorticoid administration suppressed IL6 expression in TNF-tg mice but not in TNF-tg11βKO mice. TNF-tg mice exhibited reductions in muscle weight and fiber size with glucocorticoid therapy. In contrast, TNF-tg11βKO mice were protected against glucocorticoid-induced muscle atrophy. Glucocorticoid-mediated activation of catabolic mediators (FoxO1, Trim63) was also diminished in TNF-tg11βKO compared to TNF-tg mice. In summary, 11β-HSD1 knock-out prevents muscle atrophy associated with glucocorticoid therapy in a model of chronic inflammation. Targeting 11β-HSD1 may offer a strategy to refine the safety of glucocorticoids.
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Addressing the unmet need for self-management strategies in idiopathic inflammatory myositisNo abstract available.
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The social media Infodemic of health-related misinformation and technical solutionsThis paper discusses the role of social media algorithms in the spread of misinformation during the COVID-19 pandemic. It aims to propose solutions to combat misinformation and promote accurate, evidence-based public health information.
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Evaluating the Construct of Damage in Systemic Lupus Erythematosus.Objective: The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI. Methods: We conducted a 3-part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group. Results: Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life-course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment. Conclusion: We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development.
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EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis.Background: Despite growing interest, there is no guidance or consensus on how to conduct clinical trials and observational studies in populations at risk of rheumatoid arthritis (RA). Methods: An European League Against Rheumatism (EULAR) task force formulated four research questions to be addressed by systematic literature review (SLR). The SLR results informed consensus statements. One overarching principle, 10 points to consider (PTC) and a research agenda were proposed. Task force members rated their level of agreement (1-10) for each PTC. Results: Epidemiological and demographic characteristics should be measured in all clinical trials and studies in at-risk individuals. Different at-risk populations, identified according to clinical presentation, were defined: asymptomatic, musculoskeletal symptoms without arthritis and early clinical arthritis. Study end-points should include the development of subclinical inflammation on imaging, clinical arthritis, RA and subsequent achievement of arthritis remission. Risk factors should be assessed at baseline and re-evaluated where appropriate; they include genetic markers and autoantibody profiling and additionally clinical symptoms and subclinical inflammation on imaging in those with symptoms and/or clinical arthritis. Trials should address the effect of the intervention on risk factors, as well as progression to clinical arthritis or RA. In patients with early clinical arthritis, pharmacological intervention has the potential to prevent RA development. Participants' knowledge of their RA risk may inform their decision to participate; information should be provided using an individually tailored approach. Conclusion: These consensus statements provide data-driven guidance for rheumatologists, health professionals and investigators conducting clinical trials and observational studies in individuals at risk of RA.
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Epidemiology of disease-activity related ophthalmological manifestations in Systemic Lupus Erythematosus: A systematic review.Objective: Ophthalmic complications in Systemic Lupus Erythematosus (SLE) are broad and can occur in up to a third of patients. The British Isles Lupus Assessment Group (BILAG) 2004 Index identifies 13 ocular manifestations of active SLE, as opposed to those related to previous disease activity and/or the consequences of therapy. We conducted a systematic review of published literature to determine the frequency of ophthalmic manifestations of active SLE. Methods: A systematic literature search of Ovid MEDLINE and EMBASE from their respective inceptions to July 2020 was conducted to identify cohort, case-control and cross-sectional studies. Results: 22 studies meeting eligibility criteria were included. Most studies featured small sample sizes and were judged to have a high risk of methodological bias. The number and quality of studies did not allow us to confidently estimate the incidence of the conditions. No studies reported epidemiological data for orbital inflammation/myositis/proptosis. The prevalence of each of the other ocular manifestations, with the exception of retinal vaso-occlusive disease, was consistently less than 5%. Retinal vasculitis, uveitis and isolated cotton wool spots tended to be associated with more active SLE disease. Conclusion: The prevalence of eye disease due to SLE activity is uncommon, but clinicians should be aware that some conditions tend to be associated with more active systemic disease. Further studies to determine the incidence and risk factors for these ophthalmic manifestations are needed.
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COVID-19 severity, breakthrough infections and vaccine safety in young individuals with autoimmune diseases : insights from the COVAD studyNotwithstanding the wealth of literature on COVID-19, studies focusing on young adults with autoimmune diseases (AD) are lacking. To determine early (within 7 days) and late (after 7 days) anti-SARS-CoV-2 vaccine-related adverse events (AEs), post-vaccine disease flares, COVID-19 severity and breakthrough infections (B-INFs) in young people with rheumatic diseases (RMDs) and non-rheumatic autoimmune diseases (nr-ADs) compared to healthy controls (HC). Data were captured through the international COVID-19 vaccination in autoimmune diseases (COVAD) 1 and 2 questionnaires. Of 20,685 complete responses, we identified 6010 from patients aged 18-35 years (1692 RMD, 400 nrADs, 3918 HC) who received up to 4 vaccine doses. BNT162b2 was the most frequently administered vaccine and prior to vaccination, 7% of people with nrAD were taking immunosuppressants (IS) versus 80% in RMDs. Early mild AEs were more frequent in RMDs (93%) and nr-ADs (92%) compared to HC (85%). The frequency of late mild AEs was < 20% in all groups. Severe AEs were rare. SARS-CoV-2 infection rates were similar across all groups, however, RMD patients reported a single episode of infection more frequently than nrADs and HC, while nrADs reported multiple infections more frequently than RMD. Self-reported disease flares were reported by 10% or RMD and 7% of nrAD patients. Our study reinforces the safety of anti-SARS-CoV-2 vaccine also in young people with ADs, but it also highlights that among young individuals the number and clinical picture of SARS-CoV-2 infections is affected more by the type of AD rather than by coexisting IS therapy.