bluuebunny/crossref_metadata_2025 huggingface dataset:
P060 A survey of COVID-19 infections in rheumatology patients in Shropshire, UK
Authors: Rashid Ali El , Patil Raghvendra Prasad , Burgress Lisa , Ball Patrick , Morrissey Hannah , Askari Ayman
Published: April 2023

Background/Aims

To assess the incidence and vulnerability of rheumatology patients to COVID-19 infection in early stages of pandemic.

Methods

Self completed questionnaire was posted to patients.

Results

Patients diagnosed with rheumatic diseases were categorised as people at high risk of infection with COVID-19 (pharmacologically immunosuppressed) and with possible worsening outcomes than the general population. This study was a self-completed questionnaire which was sent to all patients registered under a National Health Services specialist rheumatology department in the UK, between May 2020 and May 2021. A total of 610 responses were received and data was analysed statistically. The aim from this survey was to assess COVID19 infection prevalence amongst rheumatology patients under the care of this department, and to examine the profiles of patients with reported COVID-19 infection, their comorbidities, rheumatoid-related medications and infection severity and outcome. Of 610 responders diagnosed with rheumatoid diseases, 12 patients (1.96%) received a diagnosis of COVID-19 based on their clinical presentation.

However, when patients undertaken a Polymerase Chain Reaction

test, only 2 patients (16.6%) returned positive results. In both the COVID-19 and non-COVID groups 60% were shielding (n = 361). In our sample infection rate was around 30 times (1 in 50 rheumatoid patients, 2% in the sample population) the prevailing rate for the general population in the region (75 in 100,000, 0.075% in the general population). Negative testing did not preclude the presence of disease, but this may reflect poor efficacy and reliability of testing in the early days of the pandemic. The sample means and SD+/- were 63.96/13.23 for age and 27.76/5.79 for BMI. Sample population characteristics presented in Table 1.

Conclusion

This patient group were more vulnerable to COVID-19 infection compared to the general population but appear not to be at greater risk of severe disease.

Disclosure

A. El Rashid: None. R. Patil: None. L. Burgress: None. P. Ball: None. H. Morrissey: None. A. Askari: None.
P062 Immune responses to mRNA vaccines against SARS-CoV2 in patients with immune-mediated inflammatory rheumatic diseases
Authors: Santos Cristiana Sieiro , Calleja Antolín Sara , Morales Clara Moriano , Castro Carolina Álvarez , Díez Álvarez Elvira , Ruiz de Morales Jose Maria Garcia
Published: April 2023

Background/Aims

Patients with immune-mediated rheumatic diseases (IMRD) are commonly treated with immunosuppressors and are prone to infections. Recently introduced mRNA SARS-Cov2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-We aim to fully characterize B and T cell immune responses elicited by mRNA SARS-Cov2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccinés immunogenicity.

Methods

Humoral, CD4 and CD8 immune responses were investigated in 147 SARS-Cov2-naïve patients with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-Cov2 mRNA vaccine. Responses were compared with age, gender, and disease-matched IMRD patients not receiving immunosuppressors and with healthy controls

Results

IMRD patients showed decreased seroconversion rates (63% vs 100%, p = 0.04) and cellular immune responses (59% vs 100%, p = 0.007). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept deeply affected humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed severely impaired humoral responses but cellular responses were often preserved. Antibody titers were reduced with mycophenolate and azathioprine but preserved with leflunomide.

Conclusion

IMRD patients exhibit impaired SARS-CoV-2 vaccine-immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show the most deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine’s immunogenicity.

Disclosure

C. Sieiro Santos: None. S. Calleja Antolín: None. C. Moriano Morales: None. C. Álvarez Castro: None. E. Díez Álvarez: None. J. Garcia Ruiz de Morales: None.
P069 Stress matters: inflammatory arthritis patients' perspective of impact of stress
Authors: Jacklin Clare , Caton Emma , Matthews Sally
Published: April 2023

Background/Aims

The objective of this survey was to gather patients’ perspectives on how stress triggered their inflammatory arthritis as well as exacerbates flares in their disease.

Methods

NRAS wanted to reach people living with RA and other forms of inflammatory arthritis via a national survey to gauge how they recognise and manage stress, and whether health professionals considered stress as a factor in their active disease. The survey was designed to capture demographics, impact of stress on patients’ disease as well as work status and restrictions on lifestyle. The national online survey was distributed via all NRAS social media platforms as well as email.

Results

1265 responses from across the UK were gathered. The majority of respondents were female (87.0%) and over the age of 55 years old (70.5%). Approximately 45% had a disease duration of more than 10 years, 30% between 4 and 10 years, and 23% less than 3 years. When asked on a scale of 1 (not at all) to 5 (completely) how much stress had impacted the onset of their arthritis symptoms, 56% responded either ‘completely’ or ‘greatly’. Only 9% reported that stress did not have an impact on the onset of their symptoms. When asked if they felt a stressful event in the 12 months prior to their diagnosis had triggered their inflammatory arthritis 28% said yes and 48% responded maybe. Some of the top reported causes of stress prior to diagnosis were: death of a close family member, menopause, work difficulties and family commitments. The majority of respondents (67%) said that health professionals did not ask them about stress during the diagnosis process, with only 11% saying this was discussed. Participants were asked how much they agreed with the statement that they are often asked about their mental health in routine appointments - 75% disagreed or strongly disagreed.

Conclusion

With the majority of respondents identifying that stress and stressful events exacerbate their symptoms of inflammatory arthritis, more should be done to measure and offer support for managing stress. While many had found their own ways of coping with stress more needs to be done to make support more easily accessible. Further research would be beneficial in identifying if managing stress within this patient population could significantly reduce inflammatory arthritis symptoms, reducing the distress and pain caused by flares and also reduce the impact on the health service of clinical intervention.

Disclosure

C. Jacklin: Grants/research support; InMedix funded with hands off grant this survey work. E. Caton: None. S. Matthews: None.
P088 New2JIA Right Start Service from JIA-at-NRAS
Authors: Wilson Debbie
Published: April 2023

Background/Aims

Building on the success of NRAS’s New2RA Right Start service, and after speaking to families and healthcare professionals it was clear that there is a need for a New2JIA Right Start service. “Parents are given an overwhelming amount of information about a new disease, along with countless hospital appointments, blood tests, physio appointments and medication to administer. Add to the mix, trying to explain to your child (if they're old enough) what is going on with their joints and why they are in so much pain and discomfort when you don't really understand yourself! Parents have to deal with all of this, often trying to hold down their job and having other children to look after. Then there's the worry of how your child's future will look. New2JIA Right Start would have been my saviour and my husband’s too.” JIA Ambassador

Methods

Healthcare professionals will refer families to JIA-at-NRAS through a simple (GDPR compliant) form on our website. This is received by JIA-at-NRAS and a zoom call is arranged with up to 6 other families, also referred with children of similar ages. During the call, all aspects of JIA will be discussed, and parents will have the opportunity to ask questions. Families will have a follow up zoom call 10 weeks later to see how they are getting on. The service is being launched in phases throughout the UK, with phase 1 in November 2022, phase 2 in February 2023 and phase 3 in May 2023. Impact measurements will be imbedded to make sure that we are not only meeting the needs of the service user, but also having a positive impact to their lives, their children’s and ensuring they feel better equipped to manage their child’s condition.

Results

This new service not only benefits families but also healthcare professionals. The benefits to families are to: better understand what JIA is, know how it can affect their child and family, not feel alone during a daunting and overwhelming time, get the right support, feel more in control of managing their child’s condition, talk to another parent who has a child with JIA and access useful information resources. The benefits to healthcare professionals are: knowing families have support straight away (including peer-to-peer support), knowing that families are being given trusted information, reduced burden on their team and regular contact with JIA-at-NRAS.

Conclusion

Results from the Mental Health Survey, in collaboration with all other JIA charities in 2022, showed that 82% of families said having a child diagnosed with JIA has impacted negatively on their mental health. This service is there to help reduce these anxieties and give them the understanding and tools needed to help manage their child’s condition.

Disclosure

D. Wilson: None.
P091 Outcomes following switching from originator to biosimilar product in children and young people with JIA
Authors: Kearsley-Fleet Lianne , Baildam Eileen , Beresford Michael W , Douglas Sharon , Foster Helen E , Southwood Taunton R , Hyrich Kimme L ,   UK JIA Biologics Register
Published: April 2023

Background/Aims

There are many biosimilar products available to use in children and young people with JIA. Due to competitive pricing, patients are being switched from biologic originator to biosimilar (non-medical switch). This analysis aims to describe characteristics of, and outcomes, following TNF-inhibitor originator to biosimilar switch in JIA.

Methods

All patients in the UK JIA Biologics Register switching from an originator to a biosimilar of the same product were identified. Patient characteristics are presented, including time on originator prior to switch. Patients were followed until their final follow-up form was returned. For those with >1 year of follow-up post-switch, treatment persistence and reasons for stopping are described.

Results

As of 28-Sept-2022, 202 children and young people had switched from originator to biosimilar; 125 adalimumab, 55 etanercept, and 22 infliximab (table). Switching was seen in all ILAR categories. Patients were predominantly female (63%), median age at JIA diagnosis six years, 11 years at originator start, 14 years at biosimilar start, median time on originator 2.2 years. Most patients had started originator as their first biologic (74%) and most started biosimilar with no significant treatment gaps. Five patients reported >1 year gap between originator stop and biosimilar start, suggesting a planned period off biologic therapy (two stopped for remission, one for adverse event, two unknown). Of the 134 patients with >1 year of follow-up available after switching (median 1.9 years per patient), 77 remained on biosimilar at their final follow-up, whilst 57 had stopped therapy. Of those who stopped, 10 had stopped for remission, 12 stopped for ineffectiveness, 18 for adverse event, and 17 other/missing reason. Thirty-nine patients then re-started biologic therapy (including four of the remission patients); 16 switched back to the originator mostly due to an adverse event on the biosimilar, and 23 started a different biologic therapy mostly due to inefficacy of the biosimilar.

Conclusion

Many children with JIA have now been switched from TNF-inhibitor originator to biosimilar product, with the majority still receiving their biosimilar after one year. Switching back to originator was uncommon, 12% overall after one year, suggesting good tolerance of non-medical switching in this patient population.

Disclosure

L. Kearsley-Fleet: None. E. Baildam: None. M.W. Beresford: None. S. Douglas: None. H.E. Foster: None. T.R. Southwood: None. K.L. Hyrich: Member of speakers’ bureau; non-personal speakers fees from Abbvie. Grants/research support; BMS, UCB, Pfizer.
P094 Prevalence of fibromyalgia syndrome among patients with type 2 diabetes mellitus
Authors: Salman Sami , Abdali Huda
Published: April 2023

Background/Aims

Fibromyalgia syndrome (FMS) is a non-autoimmune rheumatological disorder characterized by chronic widespread pain, and often tenderness, with additional symptoms such as fatigue, lack of sleep, anxiety, and cognitive problems which are considered significant features in this syndrome. Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia that develops as a consequence of insulin deficiency [type1 DM T1DM)] and/or insulin resistance [type2 DM (T2DM)].

Methods

A descriptive cross-sectional study was conducted at Endocrine and Rheumatology unit at Baghdad Teaching Hospital during the period from November 2021 till April 2022. A total random sample of 200 Iraqi patients with Diabetes mellitus type 2 diagnosed according to the WHO criteria for diagnosis of diabetes mellitus (females 128 and males 72) and a total random sample of 200 healthy persons (126 females and 74 males) were involved in this study as controls. A special questionnaire designed for the purpose of the study was used for recording information from the patients and controls, which include demographical data for both group in addition information about current treatment for DM and duration of disease. The 2016 revision of American College of Rheumatology (ACR) criteria was used for the diagnosis of FMS.

Results

There was increase in the risk of developing FMS among diabetes mellitus patients compared to normal individuals (31% vs. 14.5%). Moreover, widespread pain, symptom severity score, and depression were significantly higher [P. Value (0.012, 0.007, 0.019)] respectively among diabetes mellitus patients compared to healthy individuals. It was found that there was a significant increase of having HbA1c increased by 1.38 among fibromyalgia patients compared to healthy individuals.

Conclusion

The prevalence of fibromyalgia among the studied sample with type 2 diabetes mellitus was high and there was correlation between the prevalence rate of FMS and poor DM control.

Disclosure

S. Salman: None. H. Abdali: None.
P106 Feasibility Study of Methotrexate use Improvement in Rheumatoid Arthritis using Biomarker Feedback: The MIRA Trial
Authors: Bluett James , Hyrich Kimme L , Keevil Brian , Doran Patty , Barton Anne
Published: April 2023

Background/Aims

MTX non-adherence is associated with reduced response, increased healthcare costs to the NHS and reduced quality of life for the patient. Often the prescriber is unable to determine if a patient is taking their medication as prescribed. There is a need to measure adherence directly to facilitate more precise and objective measurements of adherence to add to the clinicians tools and help to open up honest discussions and supportive interventions with patients. Our group has previously developed a sensitive biochemical assay for the detection of MTX adherence, MIRA is a feasibility trial designed to assess the feasibility of a randomised controlled trial of MTX biochemical adherence biofeedback.

Methods

MIRA is a prospective multi-centre randomised controlled trial to examine the feasibility of a fully powered randomised controlled trial to examine if a biochemical adherence guided intervention is superior to standard clinical care in RA patients prescribed MTX. RA patients prescribed oral MTX for ≥ two years were randomised 1:1 to receive biochemical adherence biofeedback or control. Clinico-demographics, biochemical MTX adherence and DAS-28 and were measured at baseline and three months. Participants in the intervention cohort were telephoned with their biochemical adherence results and adherence was explored. Ethical approval for MIRA was given by the North West - Haydock Research Ethics Committee (19/NW/0047) and all participants provided written informed consent.

Results

57 participants were recruited, withdrawal rate was 14% and reasons given were intercurrent illness, lost contact, withdrawn consent and one patient died during follow-up leaving full outcome data available for 49 participants. Baseline clinico-demographics were similar in control and intervention cohorts (Table 1). Biochemical adherence worsened in the control cohort and improved in the intervention cohort (17 to 30%, 15 to 8% respectively). Change in DAS(CDP)-28 during the trial worsened in the control cohort but improved in the intervention cohort (-0.04 STD 1.26 and 0.38 STD 0.78 respectively).

Conclusion

The results of the MIRA trial have demonstrated that the use of a biochemical adherence blood test with biofeedback is feasible as part of a clinical trial. The intervention demonstrated early evidence for efficacy justifying the need for a full definitive trial.

Disclosure

J. Bluett: None. K.L. Hyrich: None. B. Keevil: None. P. Doran: None. A. Barton: None.
P123 Biologic dose tapering: a patient perspective
Authors: Rahman Rayan , Beynon Celia
Published: April 2023

Background/Aims

Biological therapies target specific pathways within the inflammatory process involved in the pathogenesis of rheumatoid arthritis. They are costly and can be associated with side-effect burden for patients. Evidence on whether medications can be stopped or tapered in stable patients in remission or very low disease activity is limited. This approach may benefit by limiting side-effects and costs. Alongside understanding the efficacy of dose tapering it is also necessary to gain insight into how patients perceive this approach. Our aim was to identify key themes that arise when patients discuss their perspective on biologic dose tapering.

Methods

213 rheumatoid arthritis patients in the Cardiff & Vale Health Board on sub-cutaneous anti-TNF agents (certolizumab, etanercept, adalimumab, golimumab) were identified. An inclusion/exclusion criterion was then formulated after consultant review to determine which patients were in remission/low disease activity and may be suitable for dose tapering. 80/213 patients qualified, and a digital questionnaire was sent to 52/80 patients where 23/52 (44% response rate) of the patients responded. The questionnaire included single and multiple response questions. Open text answers were also available if patients wanted to include any other comments. The questionnaire focused on 4 main insights: Knowledge, Experience, Perspective and Practicalities. Questionnaire data was then thematically analysed.

Results

3 themes became prominent: [1] Hesitancy, [2] Fear, and [3] Information. [1] 83% of patients had never heard of dose tapering before the questionnaire, 61% were ‘unsure’ in their initial thoughts of dose tapering and 30% were ‘unsure’ in being considered for dose tapering. This indicates how limited understanding may contribute to patient hesitancy. [2] 18% of patients were initially ‘fearful’ and 61% of patients were afraid of ‘flaring’ again. Patients were fearful of the ‘length of time they need to wait for an appointment’ if they flared, with 57% of patients wanting ‘access to help if there was flare’. The concept of fear was multi-faceted occurring in both patients’ concerns surrounding their disease activity and practicalities related to care. [3] 35% of patients believed they did not have enough ‘information’ and 45% believed receiving more ‘information’ about tapering would make them more comfortable with the idea.

Conclusion

The hesitancy and fear patients had may be associated with the limited exposure and information they had of dose tapering - demonstrating this initial information barrier. Patients preferred mode of contact would be virtual and face-to-face support, or just solely face-to-face. 83% of patients preferred Rheumatologists as their main source of information for dose tapering, and discussed how leaflets, case histories and websites may help in future discussions surrounding dose tapering. These patient perspectives will help us to develop and implement a dose tapering strategy for our department.

Disclosure

R. Rahman: None. C. Beynon: None.
P129 DNA methylation of the tumour necrosis factor gene as a biomarker of diagnosis in early rheumatoid arthritis patients
Authors: Liu Melanie C , Ng Helen , Anioke Innocent , Ponchel Frederique
Published: April 2023

Background/Aims

Rheumatoid arthritis (RA) is an autoimmune inflammatory condition that affects the synovial joints. RA exists on a disease continuum where immunological changes occur before the onset of clinical symptoms. Changes in DNA methylation status of genes are thought to be early triggers of the progression from health to disease. Tumour necrosis factor (TNF) is a pro-inflammatory cytokine that contributes to RA. Recently it has been shown that the loss of DNA methylation in the promoter region of the TNF gene is related to early RA. This study aims to establish the predictive value of the levels of DNA methylation of the TNF gene as a biomarker for diagnosis of RA.

Methods

Blood samples from a retrospective cohort of patients with symptoms of inflammatory arthritis between 2010 and 2019 at the Leeds Early Arthritis Clinic were selected. Data obtained include clinical symptoms of disease progression over 2 years to establish a diagnosis. DNA methylation levels of the TNF gene were measured by quantitative polymerase chain reaction (qPCR) and analysed using binary logistic regression with forward (LR) variable selection for added value as a diagnostic biomarker.

Results

For the 284 patients with a mean age of 53.8, 202 (71.7%) were female and 82 (28.9%) were male. From N = 284, 190 (66.9%) were diagnosed with RA and 94 (33.1%) with another conditions. The predictive accuracy of the regression model was increased by 3.5% from 85.8% to 89.3% when TNF DNA-methylation levels was added to demographic and clinical variables. The AUC of the model with TNF was 0.940 compared to 0.911 without TNF DNA-methylation levels. The sensitivity and specificity of the prediction with DNA methylation data were 94.6% and 77.9% respectively. This TNF model has a positive predictive value of 90.2% and a negative predictive value of 87.0%.

Conclusion

DNA methylation of the TNF gene is an important biomarker for RA diagnosis. This study showed that including levels of TNF DNA-methylation improves the accuracy of diagnosing RA.

Disclosure

M.C. Liu: None. H. Ng: None. F. Ponchel: None.
P133 Attitudes to Technology supported Rheumatoid Arthritis care: Opportunities & Barriers for technology in RA - Key themes from Qualitative arm of Mixed-Methods Study
Authors: MacBrayne Amy , Curzon Paul , Soyel Hamit , Marsh William , Fenton Norman , Pitzalis Costantino , Humby Frances
Published: April 2023

Background/Aims

Rheumatoid arthritis (RA) outcomes have significantly improved with the treat-to-target paradigm, however this necessitates intensive monitoring. Demand outstrips capacity in rheumatology services, making mobile health (mHealth) an attractive prospect. However, software developers often design without understanding the needs of ultimate users, solving non-existent problems. EULAR’s ‘Points to Consider’ for remote care specifies that interventions “should be developed in collaboration with all stakeholders including the healthcare team … and people with RMDs” as an overarching principle. This study sought to understand existing challenges for end-users, how technology might support care, and the perceived barriers.

Methods

Semi-structured interviews were devised collaboratively between rheumatologists and computer scientists, informed by discussions with an RA patient group. Key focus topics included daily life, flares, pain management, medications, clinic appointments, and perceived opportunities and barriers. People >18 years old with a diagnosis of RA were recruited whilst awaiting appointments, & in the day unit at Mile End Hospital (Barts Health NHS Trust). Clinicians were recruited from multiple centres across London & South-East England. The study was registered (CMPS ID [43816]). Ethical approval was obtained through the Bloomsbury Research and Ethics Committee (19/LO/1345). Patient interviews were conducted by PC, Clinician interviews were conducted by AMB between October 2019-March 2020. Interviews were transcribed, and coded for themes using grounded theory techniques, identifying central themes. Coders (AMB & PC) utilised consensual coding, ensuring consistency.

Results

21 people with RA and 14 clinicians were interviewed. People with RA’s primary goal is to improve independence and quality and life, whereas clinicians primarily focus on remission. However, both groups identified consensual opportunities and barriers. Key themes with supporting quotes are detailed in table 1:

Conclusion

Opportunities for technology to improve care include: utilising remote monitoring to provide a broader picture of disease behaviour, improving access to care & co-ordinating care plans across primary and secondary care, improving the quality of disease education & empower people with RA to self-manage, the need for individualised care, and preservation of the therapeutic relationship when care is delivered remotely. Barriers can be sub-divided into patient, clinician, healthcare system, and technological.

Disclosure

A. MacBrayne: None. P. Curzon: None. H. Soyel: None. W. Marsh: None. N. Fenton: None. C. Pitzalis: None. F. Humby: None.
P150 The Triptryium wilfordii derivative celastrol has anti-fibrotic effects in systemic sclerosis
Authors: Leask Andrew , Stratton Richard J , Xu Shiwen , Chitturi Pratyusha
Published: April 2023

Background/Aims

Scleroderma (systemic sclerosis, SSc) is an autoimmune inflammatory-fibrosis syndrome that damages the skin and internal organs and is considered a prototypic complex fibrotic disease. In SSc, persistently activated myofibroblasts are maintained by an excessive, autocrine mechanotranductive/pro-adhesive signaling loop. Drugs targeting this pathway are therefore of likely therapeutic benefit in SSc. The mechanosensitive transcriptional co-activator, yes activated protein-1 (YAP1), is activated in SSc fibroblasts. The terpenoid plant-derivative celastrol has recently been identified as a YAP inhibitor; however, if celastrol can alleviate SSc fibrosis, and its underlying mechanism of action, is as yet unclear.

Methods

We cultured age-, sex-, and site-matched human dermal fibroblasts sampled from healthy individuals and patients with early onset (<18 month after first diagnosis) diffuse cutaneous scleroderma (systemic sclerosis, dcSSc) and treated with or without transforming growth factor β1 (TGFβ1, 4ng/ml) in the presence or absence of celastrol (500nM). We also subjected C57BL6J mice to the inflammatory-driven bleomycin-induced model of skin SSc, in the presence or absence of celastrol (28days, every day, 0.1U bleomycin, 1mg/kg celastrol). RNA expression was assessed using RNAseq and real-time polymerase chain reaction analysis. Protein expression was determined using Western blot and enzyme-linked immunosorbent assay. Fibrosis was monitored by hematoxylin and eosin and trichrome staining of tissue sections, and by using indirect immunofluorescence analysis with anti-alpha-smooth muscle actin (SMA) antibodies to detect myofibroblasts.

Results

In dermal fibroblasts, celastrol impaired the ability of TGFβ1 to induce an SSc-like pattern of gene expression, including the induction of cellular communication network factor 2 (CCN2), collagen I and TGFβ1 protein (N = 6, all p < 0.01). Celastrol also alleviated the persistent fibrotic phenotype of dermal fibroblasts cultured from lesions of SSc patients, including the overproduction of CCN2 and collagen (N = 3, p < 0.05). Finally, in the bleomycin-induced model of SSc dermatopathology, celastrol inhibited skin thickness/collagen deposition in vivo and blocked nuclear localization of YAP in SMA-positive myofibroblasts (all N = 6, p < 0.01).

Conclusion

Our data are consistent with the hypothesis that compounds, such as celastrol, that antagonize the YAP pathway warrant further consideration as potential treatments for SSc skin fibrosis.

Disclosure

A. Leask: Grants/research support; CIHR, NSERC, Arthritis Society of Canada. R.J. Stratton: None. S. Xu: None. P. Chitturi: None.
P151 Prevalence and risk factors of osteoporosis in Indian systemic sclerosis patients
Authors: Tanna Dhaval , Ghosh Shounak , Telang Kaustubh , Ekbote Gayatri , Singal Vinay , Gupta Rajiva
Published: April 2023

Background/Aims

Systemic sclerosis (SSc) is a systemic autoimmune disease in which osteoporosis has been reported to be more prevalent than in healthy individuals. Bone loss is hypothesised to be related to vasculopathy in SSc, but the causative pathways are not very clear. This study was conducted to investigate the prevalence of osteoporosis in Indian patients with SSc and to assess its association with various disease-related characteristics.

Methods

This was a cross-sectional, case-control study performed in a 1,250 bedded tertiary care hospital. Between August 2017 and June 2019, all consecutive patients attending the outpatient and in-patient departments of the Department of Rheumatology & Clinical Immunology at our institute, classified as SSc as per the ACR/EULAR 2013 criteria, were included after taking their informed consent. Age and gender-matched healthy controls were included and all enrolled subjects were subjected to a dual energy X-ray absorptiometry (DEXA) scan. Demographic and clinical details of all patients were recorded. Osteoporosis was defined as per the WHO definition of a T score ≤ -2.5. The study was approved by the Institutional Review Board and the Institutional Ethics Committee.

Results

90 patients with SSc and 45 age and gender-matched healthy controls were included in the study. Confounding factors for bone health, like smoking or alcohol intake, the proportion of post-menopausal women, and past or family history of fragility fractures, were matched between the two groups. The prevalence of osteoporosis among SSc cases was significantly higher than in the healthy controls (34.4% vs. 6.6%, p < 0.001). In univariate analysis, age, low body mass index (BMI), post-menopausal status, diffuse cutaneous phenotype, gastrointestinal involvement, digital ulcers, and pulmonary arterial hypertension were found to be significantly associated with osteoporosis. Multivariate analysis revealed that the presence of osteoporosis was significantly associated with lower BMI, post-menopausal status, and the presence of digital ulcers in patients. Interestingly, glucocorticoid use did not appear to increase the risk of osteoporosis in our cohort.

Conclusion

Patients with systemic sclerosis and digital ulcers, low BMI, or post-menopausal status are at high risk of developing osteoporosis and therefore should be screened for osteoporosis by DEXA scan to prevent unforeseen fracture-related morbidity and mortality. Glucocorticoids may not be the major culprit as evidenced by this study, while control of disease activity may lead to better bone health status.

Disclosure

D. Tanna: None. S. Ghosh: None. K. Telang: None. G. Ekbote: None. V. Singal: None. R. Gupta: None.
P154 Real-world audit of patients with idiopathic inflammatory myositis-related interstitial lung disease in a European population
Authors: Loganathan Aravinthan , Sturney Sharon , Foley Noeleen , Hartley Tom , Tansley Sarah
Published: April 2023

Background/Aims

The British Society for Rheumatology (BSR) has released guidelines for managing idiopathic inflammatory myositis (IIM). Our centre operates specialist clinics for scleroderma and lupus, but to date, IIM patients are seen in a general CTD clinic. As part of work to establish a dedicated myositis clinic, we collated data on 71 patients under active follow-up with myositis spectrum disease deemed appropriate for follow-up within a specialist clinic. We aimed to review patients diagnosed with IIM-ILD and review serological immune profile, screening practices for pulmonary involvement, findings on CT/pulmonary function tests (PFTs) and pharmacological management.

Methods

We performed a detailed retrospective review of the notes of suitable patients, identified using diagnostic codes attached to clinic letters.

Results

71 patients were identified: 14 with anti-synthetase syndrome (ARS), 21 with dermatomyositis (DM), 13 with polymyositis (PM), 3 with immune-mediated necrotising myopathy (IMNM) and 17 with overlap syndrome. 65% (46/70) of adult IIM patients were screened for pulmonary involvement. Screening practices of patients based on antibody profile and myositis subtype are further described in the table. 31% of patients (22/70) had IIM-ILD, of which 12 had ARS, 4 had PM, 1 had DM and 5 had overlap disease (2 PM/scleroderma, 1 DM/ARS, 1 DM/scleroderma and 1 scleroderma/ARS). 21/22 underwent PFTs; 53% of patients had active ILD over an average of 51.8 months. On imaging, 76.2% (16/22) had changes consistent with ILD. Ground glass change and reticulation were demonstrated in 50% of scans. In comparison, honeycombing and traction bronchiectasis was found in 22% and 44% of scans, respectively. A non-specific interstitial pneumonia (NSIP) pattern was described in 44% of scans, organising pneumonia (OP) pattern in 22%, and 17% had a mixed OP and NSIP pattern. 20/22 patients were prescribed high-dose steroids, csDMARD therapy or aggressive immunosuppression (cyclophosphamide or rituximab).

Conclusion

Our review demonstrates that 65% of patients with adult IIM were screened for ILD. NSIP and OP were the most common radiological appearances. Half of our cohort required aggressive immunosuppression, cyclophosphamide being the most commonly prescribed agent and mycophenolate being preferred for maintenance therapy. No patients were prescribed tacrolimus or ciclosporin. Despite treatment, 52% of patients had evidence of progressive disease on serial PFTs.

Disclosure

A. Loganathan: Grants/research support; Arthritis Australia. S. Sturney: None. N. Foley: None. T. Hartley: None. S. Tansley: None.
P158 Defining distinct fibroblast populations in systemic sclerosis skin using functional characterization and single-cell RNA sequencing
Authors: Clark Kristina E , Xu Shiwen , Ong Voon H , Buckley Christopher D , Denton Christopher
Published: April 2023

Background/Aims

Fibroblasts isolated by traditional explant culture from skin biopsies in systemic sclerosis (SSc) have a profibrotic and “migratory” phenotype. Single cell RNAseq (scRNAseq) studies suggest other fibroblast subpopulations may be important in SSc pathogenesis. We have isolated a second fibroblast population termed “resident” from whole skin in SSc. We used bulk and scRNAseq to further characterise these populations.

Methods

Forearm skin from dcSSc (n = 3) and HC (n = 3) was biopsied. “Migratory” fibroblasts were isolated by standard explant culture. The remaining biopsy fragments underwent collagenase digestion to yield a second “resident” fibroblast population. Functional characterization included 3-D collagen gel contraction, migratory scratch-wound assays and western blot comparing expression of pro-collagen I, CTGF and αSMA. Significant difference in gene expression was defined by fold change≥1.5, and adjusted p-value<0.05. scRNAseq was performed on 12 SSc whole skin biopsies, and 3 HC, using the 10X Genomics platform.

Results

Both SSc fibroblast populations showed a fibrotic phenotype with overexpression of COL1, CTGF and αSMA compared to HC, but with reduced expression αSMA in resident compared to migratory SSc fibroblasts (p < 0.05). RNAseq confirmed 1483 genes being significantly differentially expressed between the SSc fibroblast populations (Table 1). All four populations clustered separately on hierarchical clustering. 10 fibroblast clusters were identified using scRNAseq of whole skin. Of these, cluster 0 and 4 showed greater expression of COL10A1, and STC2 in keeping with migratory fibroblasts. Increased expression of CCL2, and EGR1 were seen in clusters 3 and 6, representing the resident fibroblast population. Gene set enrichment analysis (GSEA) confirmed concordance between KEGG pathway upregulation of the migratory and resident fibroblast clusters and bulk RNAseq analysis. Resident fibroblasts showed upregulation of complement and coagulation genes, and JAK/STAT signalling pathway. There was upregulation of glycolysis gluconeogenesis, and PPAR signalling in migratory fibroblasts. There was agreement in GSEA findings between relevant scRNAseq clusters and bulkRNAseq for resident and migratory subpopulations.

Conclusion

We have isolated for the first time two distinct profibrotic fibroblast populations from SSc skin with altered expression of key genes associated with SSc pathogenesis. Future work will define their role in SSc pathogenesis, potentially facilitating a more targeted treatment approach.

Disclosure

K.E. Clark: None. S. Xu: None. V.H. Ong: None. C.D. Buckley: None. C. Denton: None.
P171 Bimekizumab in bDMARD-naïve patients with active psoriatic arthritis: improvements in PsARC over 24 weeks in the Phase 3 BE OPTIMAL trial
Authors: McInnes Iain , Ink Barbara , Bajracharya Rajan , Taieb Vanessa , Tillett William R
Published: April 2023

Background/Aims

Bimekizumab (BKZ) is a humanised monoclonal IgG1 antibody that acts by selectively inhibiting IL-17F in addition to IL-17A and has demonstrated clinical efficacy vs placebo (PBO) in both joint and skin outcomes in patients with active psoriatic arthritis (PsA). We report interim 24-week (wk) PsARC response rates along with HRQoL estimates in bDMARD-naïve patients with active PsA from the phase 3, pivotal BE OPTIMAL trial (NCT03895203).

Methods

BE OPTIMAL is a randomised multicentre, double-blind, PBO-controlled to wk 16, followed by 36-wks maintenance phase, active reference, parallel-group, phase 3 study. Patients were randomised (2:3:1) to receive PBO, BKZ 160 mg every 4 weeks (Q4W), or active reference (adalimumab [ADA]) 40 mg every 2 weeks (Q2W). At wk 16, patients receiving PBO were switched to BKZ 160 mg Q4W; other patients remained on their original dose. We report PsARC to wk 16 and wk 24, and the association of PsARC response with HRQoL-related outcomes for the randomised set. Data are reported as non-responder imputation (NRI) and observed cases.

Results

852 patients were randomised at the baseline (PBO: 281; BKZ: 431; ADA: 140). Baseline characteristics were comparable between the three groups (mean age: 48.7 yrs; BMI: 29.20 kg/m2; disease duration: 5.9 yrs and 46.8% were males). At wk 16, PsARC response (NRI) was achieved by: PBO, 40.2%; BKZ, 80.3% and ADA, 82.1%. At wk 24, PsARC response increased in those PBO patients switched to BKZ: PBO/BKZ, 76.2%; BKZ, 77.3% and ADA, 80.0% (Table). Clinically meaningful improvement in HAQ-DI and SF-36 physical component summary (PCS), and improvements in FACIT-Fatigue were achieved from baseline among PsARC responders compared to non-responders (Table). Over the course of 24 weeks, safety was consistent with previous BKZ studies and no new safety signals were observed.

Conclusion

BKZ in bDMARD-naïve PsA patients demonstrated rapid and clinically relevant improvements in musculoskeletal outcomes compared to PBO at wk 16 and patients who switched to BKZ from PBO at wk 16 have a similar response rate at wk 24. Patients with PsARC response had numerically greater improvements in HRQoL-related outcomes. No new safety signals were observed.

Disclosure

I. McInnes: Grants/research support; IM has received grants/research support from Astra Zeneca, Abbvie, BMS, Compugen, Cabaletta, EveloBio, Eli Lilly, GSK, Janssen, Novartis, Moonlake, Novartis, Sanofi, UCB Pharma, XinThera. B. Ink: Shareholder/stock ownership; BI is a shareholder of AbbVie, GlaxoSmithKline and UCB Pharma. R. Bajracharya: Other; RB is an employee of UCB Pharma. V. Taieb: Other; VT is employee of UCB Pharma. W.R. Tillett: Other; WRT has received Research Grant, consulting or speaker fees from Abbvie, Amgen, Eli Lilly, Janssen, GSK, MSD, Novartis, OVA Pharma, Pfizer and UCB Pharma.
P173 Evaluating disease activity in established psoriatic arthritis with ultrasound
Authors: Sundanum Sonia , Darcy Hannah , Gallagher Philomena , Young Francis , O'Neill Lorraine , Veale Douglas J
Published: April 2023

Background/Aims

Early diagnosis, tight disease activity control and a treat-to-target approach are now recognised as critical factors that improve the outcome of patients with psoriatic arthritis (PsA). The traditional method used to assess disease activity is clinical examination (CE) by counting the number of tender and swollen joints. Ultrasound (US) has proven its superiority over CE for assessing the presence of synovitis in some studies. We aimed to identify the frequency and location of subclinical synovitis in a cohort of PsA patients with established disease.

Methods

Patients with established PsA were recruited. All gave informed, written consent and local ethical approval was obtained. All patients had a standard CE including 68/66 tender/swollen joint count. Grayscale (GS) and power doppler (PD) US of a standard set of 44 joints was performed using a GE logiq-P9 machine utilising 6-15-MHz and 8-18-MHz linear transducers. GS and PD were scored on a 0-3 semiquantitative scale for each joint. The presence of US active joints was defined as a GS-score ≥2 and/or PD-score ≥1.

Results

78 patients were enrolled; 46/78 were female with a median age = 61 years (range 41-80). Median duration of PsA disease = 31.5 years (range 41-80), 40/78 were on bDMARDs and 27/78 on csDMARDs. The median TJC = 2 (range of 0-6) and mean CRP = 3.2 (SD 3.5). The most common sites for subclinical synovitis were wrists, knees, and metatarsophalangeal joints (see Table 1). 36 patients (46.2%) achieved a clinical state of minimal disease activity (MDA). 11 patients in MDA (30.5%) had a PD-score of > 1, suggesting they did not achieve minimal ultrasound disease activity (MUDA).

Conclusion

These data demonstrate that a proportion of established PsA patients deemed to have MDA actually have sonographic evidence of active disease. A previous study showed that PD-synovitis in PsA patients in clinical remission was a strong predictor of disease flare. It is unclear if subclinical synovitis in PsA is linked to radiographic progression. Combining CE and sonographic evaluation is an attractive approach to identifying subclinical disease. However, a validated ultrasound composite index, which includes the key joint areas frequently affected in PsA, is needed.

Disclosure

S. Sundanum: None. H. Darcy: None. P. Gallagher: None. F. Young: None. L. O'Neill: None. D. Veale: None.
P175 Creating a social movement for change to transform care and drive down diagnostic delay in axial SpA
Authors: Eddison Joe , Webb Dale , Hamilton Jill , Marshall Liz , MacAuley Fiona
Published: April 2023

Background/Aims

It should be possible for every person experiencing symptoms of axial SpA to receive a diagnosis within one year of symptom onset. In June 2021, NASS published a route map to achieve a gold standard time of one year. Starting from a current baseline average of 8.5 years, the achievement of this goal will require transformational change. Above all, to attain such a dramatic change in time to diagnosis, we must win hearts and minds, build a movement of people who want to work with us to create change, and demonstrate proof of concept for our ideas.

Methods

Our campaign is designed around two key considerations. Firstly, a broad theory of change that describes how we can create system-wide change. Secondly, an understanding of the patient journey from symptom onset to diagnosis by a rheumatologist. Our theory of change first builds a ‘burning platform’, setting out why action and change is needed; we will use this to influence the thinking and behaviour of the public, policy makers and health care professionals. We will use a range of levers to create change in care processes; these will result in earlier diagnosis. Our first impact report described our work and impact to date in implementing this theory of change.

Results

We have been successful in building the burning platform for change, including commissioning the first economic model of the economic costs of delayed diagnosis. We have brought these, and other new data, to the attention of Ministers, other parliamentarians, policymakers, and HCPs. We have influenced the funders of the National Early Inflammatory Arthritis Audit to include new datapoints on time to diagnosis so that, for the first time, we will have comprehensive national audit data to track changes in performance. We have supported the Best MSK Health Collaborative to embed our approach in a new national axial SpA patient pathway. We are working with 19 rheumatology departments to implement the gold standard through our Aspiring to Excellence programme, and our new cadre of 12 Champions in Primary Care will be working together to drive improvement in identification and referral of suspected axial SpA patients. We have presented our burning platform to conferences and regional SpA academies. We have demonstrated proof of concept in our public awareness campaign which has reached 1.5 million people through social media, with 900,000 people watching our campaign videos, and already 5,000 people completing the online symptom checker.

Conclusion

We are building a social movement for change. We are influencing the thinking and behaviour across rheumatology. We are starting to see tangible changes in care processes. We have more work to do to translate this into the achievement of a one year time to diagnosis.

Disclosure

J. Eddison: None. D. Webb: None. J. Hamilton: None. L. Marshall: None. F. MacAuley: None.