Young women with chronic disease: A female perspective on the impact and management of rheumatoid arthritis

There is a bidirectional interaction between most immune cells and osteoblasts, osteoclasts and their precursor cells. The receptor activator of nuclear factor-kB ligand (RANKL)/RANK/osteoprotegerin (OPG) system plays an essential role in the formation of osteoblasts, but it also has implications in osteoclast biology and implicitly on the diseases characterized by bone loss. Proinflammatory cytokines existing at synovial level function as direct or indirect stimulators of osteoclast differentiation, but also of its survival or activity, although some cytokines may also play an antiosteocastogenic role. The fate of bone destruction is determined by the balance between osteoclastogenic and antiosteoclastogenic mediators. Our study has shown that the early initiation of the therapy with anti-TNF and anti-IL6 biological agents, in patients with rheumatoid arthritis, inhibits bone destruction, regardless of the anti-inflammatory activity in patients with rheumatoid arthritis.

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Psychosomatic Features, Compliance and Complementary Therapies in Rheumatoid Arthritis

Current Rheumatology Reviews ◽

10.2174/1573397115666191212114758 ◽

2020 ◽

Vol 16 (3) ◽

pp. 215-223

Author(s):

Rostislav A. Grekhov ◽

Galina P. Suleimanova ◽

Andrei S. Trofimenko ◽

Liudmila N. Shilova

Keyword(s):

Quality Of Life ◽

Rheumatoid Arthritis ◽

Interpersonal Relationships ◽

Behavioral Therapy ◽

Current Data ◽

Psychotherapeutic Interventions ◽

And Coping ◽

Regulation Of Emotion ◽

The Impact

This review highlights the issue of psychosomatic conditions in rheumatoid arthritis, paying special attention to new researches and trends in this field. Emerging concepts in all the major parts of the problem are covered consecutively, from the impact of chronic musculoskeletal pain on the emotional state to disease influence over quality of life, socio-psychological, and interpersonal relationships. Chronic pain is closely related to emotional responses and coping ability, with a pronounced positive effect of psychotherapeutic interventions, family and social support on it. Psychosexual disorders, anxiety, depression also commonly coexist with rheumatoid arthritis, leading to further decrease in quality of life, low compliance, and high suicide risk. Influence of psychosomatic conditions on the overall treatment effect is usually underestimated by rheumatologists and general practitioners. Psychosomatic considerations are of great importance for up-to-date management of rheumatoid arthritis, as they strongly influence the quality of life, compliance, and thereby disease outcomes. Two major approaches of psychological rehabilitation exist, both coping with pain through the regulation of emotion and psychotherapeutic intervention, which not only helps patients in coping with the disease, but also aimed at improving the overall adaptation of the patient. It includes techniques of relaxation, cognitive-behavioral therapy, and biofeedback therapy. Current data about the efficacy of the additional correcting therapies for patients with rheumatoid arthritis, both emerging and common ones, are discussed in the review.

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Aberrant expression of USF2 in refractory rheumatoid arthritis and its regulation of proinflammatory cytokines in Th17 cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2007935117 ◽

2020 ◽

Vol 117 (48) ◽

pp. 30639-30648

Author(s):

Dan Hu ◽

Emily C. Tjon ◽

Karin M. Andersson ◽

Gabriela M. Molica ◽

Minh C. Pham ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

T Cells ◽

Transcription Factor ◽

Proinflammatory Cytokines ◽

Th17 Cells ◽

Gene Set Enrichment Analysis ◽

Aberrant Expression ◽

Signature Genes ◽

The Impact

IL-17–producing Th17 cells are implicated in the pathogenesis of rheumatoid arthritis (RA) and TNF-α, a proinflammatory cytokine in the rheumatoid joint, facilitates Th17 differentiation. Anti-TNF therapy ameliorates disease in many patients with rheumatoid arthritis (RA). However, a significant proportion of patients do not respond to this therapy. The impact of anti-TNF therapy on Th17 responses in RA is not well understood. We conducted high-throughput gene expression analysis of Th17-enriched CCR6+CXCR3−CD45RA−CD4+T (CCR6+T) cells isolated from anti-TNF–treated RA patients classified as responders or nonresponders to therapy. CCR6+T cells from responders and nonresponders had distinct gene expression profiles. Proinflammatory signaling was elevated in the CCR6+T cells of nonresponders, and pathogenic Th17 signature genes were up-regulated in these cells. Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in nonresponders. Importantly, short hairpin RNA targetingUSF2in pathogenic Th17 cells led to reduced expression of proinflammatory cytokines IL-17A, IFN-γ, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as transcription factor T-bet. Together, our results revealed inadequate suppression of Th17 responses by anti-TNF in nonresponders, and direct targeting of the USF2-signaling pathway may be a potential therapeutic approach in the anti-TNF refractory RA.

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POS1234 IMPACT OF THE CHANGE IN ADMINISTRATION ROUTE OF TOCILIZUMAB AND ABATACEPT, DUE TO THE COVID-19 LOCKDOWN ON DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3126 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 900.1-900

Author(s):

L. Diebold ◽

T. Wirth ◽

V. Pradel ◽

N. Balandraud ◽

E. Fockens ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Physical Activity ◽

Disease Activity ◽

Univariate Analysis ◽

Route Of Administration ◽

Anxiety And Depression ◽

Administration Route ◽

Factors Associated ◽

The Impact

Background:Among therapeutics used to treat rheumatoid arthritis (RA), Tocilizumab (TCZ) and Abatacept (ABA) are both biologic agents that can be delivered subcutaneously (SC) or intravenously (IV). During the first COVID-19 lockdown in France, all patients treated with IV TCZ or IV ABA were offered the option to switch to SC administration.Objectives:The primary aim was to assess the impact of changing the route of administration on the disease activity. The second aim was to assess whether the return to IV route at the patient’s request was associated with disease activity variation, flares, anxiety, depression and low physical activity during the lockdown.Methods:We conducted a prospective monocentric observational study. Eligibility criteria: Adult ≥ 18 years old, RA treated with IV TCZ or IV ABA with a stable dose ≥3 months, change in administration route (from IV to SC) between March 16, 2020, and April 17, 2020. The following data were collected at baseline and 6 months later (M6): demographics, RA characteristics, treatment, history of previous SC treatment, disease activity (DAS28), self-administered questionnaires on flares, RA life repercussions, physical activity, anxiety and depression (FLARE, RAID, Ricci &Gagnon, HAD).The primary outcome was the proportion of patients with a DAS28 variation>1.2 at M6. Analyses: Chi2-test for quantitative variables and Mann-Whitney test for qualitative variables. Factors associated with return to IV route identification was performed with univariate and multivariate analysis.Results:Among the 84 patients who were offered to switch their treatment route of administration, 13 refused to change their treatment. Among the 71 who switched (48 TCZ, 23 ABA), 58 had a M6 follow-up visit (13 lost of follow-up) and DAS28 was available for 49 patients at M6. Main baseline characteristics: female 81%, mean age 62.7, mean disease duration: 16.0, ACPA positive: 72.4%, mean DAS28: 2.01, previously treated with SC TCZ or ABA: 17%.At M6, the mean DAS28 variation was 0.18 ± 0.15. Ten (12.2%) patients had a DAS28 worsening>1.2 (ABA: 5/17 [29.4%] and TCZ: 5/32 [15.6%], p= 0.152) and 19 patients (32.8%) had a DAS28 worsening>0.6 (ABA: 11/17 [64.7%] and TCZ: 8/32 [25.0%], p= 0.007).At M6, 41 patients (77.4%) were back to IV route (26 TCZ, 15 ABA) at their request. The proportion of patients with a DAS28 worsening>1.2 and>0.6 in the groups return to IV versus SC maintenance were 22.5%, 42.5% versus 11.1% and 22.2% (p=0.4), respectively. The univariate analysis identified the following factors associated with the return to IV route: HAD depression score (12 vs 41, p=0.009), HAS anxiety score (12 vs 41, p=0.047) and corticosteroid use (70% vs 100%, p=0.021), in the SC maintenance vs return to IV, respectively.Conclusion:The change of administration route of TCZ and ABA during the first COVID-19 lockdown was infrequently associated with a worsening of RA disease. However, the great majority of the patients (77.4%) request to return to IV route, even without disease activity worsening. This nocebo effect was associated with higher anxiety and depression scores.Disclosure of Interests:None declared

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AB0008 THE IMPACT OF STAT4 RS7574865, IL6 RS1800795, IL6R RS2228145 AND RS4845618 ON RHEUMATOID ARTHRITIS SUSCEPTIBILITY IN BELARUSIAN POPULATION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1990 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1307.1-1308

Author(s):

E. Siniauskaya ◽

T. Kuzhir ◽

V. Yagur ◽

R. Goncharova

Keyword(s):

Rheumatoid Arthritis ◽

Blood Donors ◽

Genetic Model ◽

Online Tool ◽

Genotype Frequencies ◽

Systemic Disorder ◽

Autoimmune Pathogenesis ◽

The Impact ◽

Arthritis Susceptibility

Background:Rheumatoid arthritis (RA) is a chronic systemic disorder of the connective tissue of still unknown aetiology and complex autoimmune pathogenesis that primarily affects small joints. HLA alleles provide for 11-37% of the RA heritability, suggesting the substantial role of the non-HLA loci in genetic predisposition to RA. Among non-HLA loci,IL6, IL6RandSTAT4genes attract attention, however, the data concerning their influence on RA risk are somewhat contradictory.Objectives:The aim of the study was to analyze the involvement of four SNPs (STAT4rs7574865,IL6rs1800795,IL6Rrs2228145 and rs4845618) in RA susceptibility.Methods:187 patients diagnosed with RA (mean age 58.2 ± 11.9), and 380 healthy blood donors (mean age 37.18 ± 10.69 years) were included into the study. DNA extraction from peripheral blood samples was performed using the phenol-chloroform method. SNPs were genotyped using the real-time PCR with fluorescent probes. The allele and genotype frequencies were compared using the χ2 test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using the VassarStats online tool.Results:Utilizing recessive genetic model we found an association between TT genotype ofSTAT4rs7574865 (OR = 2.362; 95%CI [1.0378 – 5.376], p = 0.038) and RA. ForIL6rs1800795, it was found that CC genotype had significantly higher frequency among patients with rheumatoid arthritis as compared to that in controls (OR = 1.52; 95%CI [1.02 – 2.27], p = 0.0456). No associations ofIL6Rrs2228145 and rs4845618 SNPs with risk of RA were found in the total group of patients vs. controls. It was also shown thatIL6rs1800795 CC genotype frequency was significantly higher among the patients with RF-negative status (p = 0.0019).Conclusion:Thus, we provide evidence for association of theSTAT4rs7574865 andIL6rs1800795 variants with risk of RA in the Belarusian population, some features of interplay being revealed between gene polymorphisms analyzed and RA antibody status. Abovementioned SNPs may contribute to RA genetic susceptibility in the Belarusian population.Disclosure of Interests:None declared

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POS1180 TREATMENT COMPLIANCE OF PATIENTS WITH RHEUMATOID ARTHRITIS DURING THE FIRST WAVE OF THE SARS-CoV-2/COVID-19 PANDEMIC IN PORTUGAL: RESULTS FROM THE COVID IN RA (COVIDRA) SURVEY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1152 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 871.2-871

Author(s):

F. Araujo ◽

N. Gonçalves ◽

A. F. Mourão

Keyword(s):

Rheumatoid Arthritis ◽

Inflammatory Diseases ◽

Immunosuppressive Treatment ◽

Treatment Compliance ◽

Web Based ◽

Symptoms Of Depression ◽

Immune Mediated ◽

Attending Physician ◽

The Impact ◽

E Mail

Background:The outcomes of the infection by the SARS-CoV-2 in patients with immune-mediated inflammatory diseases were largely unknown during the early days of the COVID-19 pandemic. It was hypothesized that these patients were at higher risk of morbidity and mortality due to their inherent immune dysfunction and immunosuppressive therapy. Several rheumatology societies issued recommendations urging patients not to stop their anti-rheumatic treatments.Objectives:To assess treatment compliance of patients with rheumatoid arthritis (RA) during the first wave of the SARS-CoV-2/COVID-19 pandemic in Portugal.Methods:The web-based survey COVIDRA (COVID in RA) was developed to assess the impact of the first wave mandatory confinement in patients with RA focusing on 5 domains: RA symptoms, attitudes towards medication, employment status, physical exercise and mental health. The questionnaire was sent to RA patients through e-mail and social media of the Portuguese Society of Rheumatology and two patient associations; and it was filled locally at two rheumatology centers in Lisbon. Recruitment took place during June and July 2020. Descriptive statistics were generated by the survey software and were afterwards transported and evaluated using appropriate biostatistics software.Results:We obtained 441 valid questionnaires. Most respondents were female (88.4%), caucasian (93.6%), with a mean age of 58 (+/-13) years. The majority (57.6%) had longstanding disease (>10 years) and were treated with csDMARDs (63.2%) and/or bDMARDs/tsDMARDS (23,7%). Only 14% (N=61) discontinued or reduced the dosage or frequency of their RA treatment. Most of these changes were previously planned by the attending physician (27.9%). Only 11 patients (18%) discontinued their immunosuppressive medication out of fear of becoming infected with SARS-CoV-2 (corresponding to 2.5% of total responders). Another 11 patients did so because they had no prescription, couldn’t go to the community/hospital pharmacy or couldn’t afford the medication. Although these numbers preclude any statistical analysis, when compared to patients who persisted on their treatment, those discontinuing due to fear of contagion were younger (56.4 vs 58.5 years), all female (100 vs 86.8%), with long-lasting disease (≥ 11 years) (90.9% vs 57.5%), more frequently treated with bDMARDs (36.4 vs 23.1%) and presenting more symptoms of depression (54.5 vs 49.7%).Conclusion:Most RA patients complied with their treatment during the first wave of the SARS-CoV-2 pandemic in Portugal. Only a minority changed their immunosuppressive treatment due to fear of SARS-CoV-2 infection. Very similar rates of immunosuppressive discontinuation due to fear of contagion were reported by other authors (such as Schmeiser et al, Pineda-sic et al and Fragoulis et al).Disclosure of Interests:Filipe Araujo Speakers bureau: Pfizer, Biogen, Novartis, Menarini, Consultant of: MSD, Nuno Gonçalves: None declared, Ana Filipa Mourão: None declared.

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Physical activity in patients with rheumatoid arthritis - an agile lifelong behaviour: a qualitative meta-synthesis

RMD Open ◽

10.1136/rmdopen-2021-001635 ◽

2021 ◽

Vol 7 (2) ◽

pp. e001635

Author(s):

Emma Swärdh ◽

Christina Opava ◽

Nina Brodin

Keyword(s):

Rheumatoid Arthritis ◽

Physical Activity ◽

Web Of Science ◽

Body Awareness ◽

Main Theme ◽

Inclusion Criteria ◽

Online Databases ◽

Taking Action ◽

The Impact

BackgroundPhysical activity (PA) in rheumatoid arthritis (RA) is considered a cornerstone in the treatment. To highlight aspects involved in supporting a positive PA behaviour, it is important to understand the patients’ perceptions of the phenomenon.ObjectiveThe aim of this qualitative meta-synthesis was to explore and synthesise patient perceptions of PA in RA.MethodsA purposeful search was conducted across three online databases (PubMed, CINAHL and Web of Science). The methodological quality of the included studies was appraised, and data were extracted and analysed using an interpretive inductive thematic synthesis.ResultsFifteen studies met the inclusion criteria and were included. PA was identified as an agile lifelong behaviour, with one main theme: The disease as a persistent catalyst for or against PA illustrating how the constant presence of the disease itself underlies the entire process of a life with or without regular PA. Seven subthemes: ‘considering aggravated symptoms’, ‘acknowledging the impact on health’, ‘becoming empowered and taking action’, ‘keeping informed to increase awareness’, ‘creating body awareness’, ‘dealing with social support’ and ‘feeling satisfied with circumstances and achievements’ were interpreted as facilitators and/or challenges.ConclusionThis synthesis has identified PA as an agile lifelong behaviour in which the disease pervades all aspects of an individuals’ perception of PA. Placed in a theoretical context, our findings outline a model for tailoring PA support to the drivers and determinants of a certain individual, which will improve clinical practice for the benefit of both health professionals and patients with RA.

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Long-term effectiveness of elderly health care voucher scheme strategies: a system dynamics simulation analysis

BMC Public Health ◽

10.1186/s12889-021-11280-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ka Chun Chong ◽

Hong Fung ◽

Carrie Ho Kwan Yam ◽

Patsy Yuen Kwan Chau ◽

Tsz Yu Chow ◽

...

Keyword(s):

Primary Care ◽

Chronic Disease ◽

Public Sector ◽

System Dynamics ◽

The Elderly ◽

Healthcare Services ◽

Dynamics Simulation ◽

Public And Private ◽

The Public ◽

The Impact

Abstract Background The elderly healthcare voucher (EHCV) scheme is expected to lead to an increase in the number of elderly people selecting private primary healthcare services and reduce reliance on the public sector in Hong Kong. However, studies thus far have reported that this scheme has not received satisfactory responses. In this study, we examined changes in the ratio of visits between public and private doctors in primary care (to measure reliance on the public sector) for different strategic scenarios in the EHCV scheme. Methods Based on comments from an expert panel, a system dynamics model was formulated to simulate the impact of various enhanced strategies in the scheme: increasing voucher amounts, lowering the age eligibility, and designating vouchers for chronic conditions follow-up. Data and statistics for the model calibration were collected from various sources. Results The simulation results show that the current EHCV scheme is unable to reduce the utilization of public healthcare services, as well as the ratio of visits between public and private primary care among the local aging population. When comparing three different tested scenarios, even if the increase in the annual voucher amount could be maintained at the current pace or the age eligibility can be lowered to include those aged 60 years, the impact on shifts from public-to-private utilization were insignificant. The public-to-private ratio could only be marginally reduced from 0.74 to 0.64 in the first several years. Nevertheless, introducing a chronic disease-oriented voucher could result in a significant drop of 0.50 in the public-to-private ratio during the early implementation phase. However, the effect could not be maintained for an extended period. Conclusions Our findings will assist officials in improving the design of the EHCV scheme, within the wider context of promoting primary care among the elderly. We suggest that an additional chronic disease-oriented voucher can serve as an alternative strategy. The scheme must be redesigned to address more specific objectives or provide a separate voucher that promotes under-utilized healthcare services (e.g., preventive care), instead of services designed for unspecified reasons, which may lead to concerns regarding exploitation.

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A syndemics approach to exercise is medicine

Health An Interdisciplinary Journal for the Social Study of Health Illness and Medicine ◽

10.1177/13634593211021481 ◽

2021 ◽

pp. 136345932110214

Author(s):

Caitlin Vitosky Clarke ◽

Brynn C Adamson

Keyword(s):

Mental Illness ◽

Chronic Disease ◽

Social Factors ◽

Social Conditions ◽

Self Concept ◽

Exercise Interventions ◽

Narrow Scope ◽

The Social ◽

Exercise Promotion ◽

The Impact

This paper offers new insights into the promotion of the Exercise is Medicine (EIM) framework for mental illness and chronic disease. Utilising the Syndemics Framework, which posits mental health conditions as corollaries of social conditions, we argue that medicalized exercise promotion paradigms both ignore the social conditions that can contribute to mental illness and can contribute to mental illness via discrimination and worsening self-concept based on disability. We first address the ways in which the current EIM framework may be too narrow in scope in considering the impact of social factors as determinants of health. We then consider how this narrow scope in combination with the emphasis on independence and individual prescriptions may serve to reinforce stigma and shame associated with both chronic disease and mental illness. We draw on examples from two distinct research projects, one on exercise interventions for depression and one on exercise interventions for multiple sclerosis (MS), in order to consider ways to improve the approach to exercise promotion for these and other, related populations.

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