bluuebunny/crossref_metadata_2025_split huggingface dataset:
P062 Trust performance in managing inflammatory arthritis over time in England and Wales: a latent class analysis approach
Authors: Yang Zijing , Arumalla Nikita , Russell Mark D , Bechman Katie , Alveyn Edward , Gallagher Sarah , Price Elizabeth , Norton Sam , Galloway James 
Published: April 2024

Abstract

Background/Aims
To evaluate trust-level performance in time to initiation of disease-modifying antirheumatic drug (DMARD) therapy in patients with early inflammatory arthritis (EIA), with identification of change in performance trajectories over time and investigation of trust characteristics associated with this change.

Methods
We included 130 trusts from the UK contributing to the National Early Inflammatory Arthritis Audit (NEIAA) from 2018 to 2020. The primary outcome was days from referral to initiation of DMARD therapy in patients with EIA. Latent class growth mixture models were applied to identify distinct groups of trusts with similar trajectories of performance change over time. We used mixed-effects linear and multinomial logistic regression models to evaluate the association between delay in treatment and trust-level characteristics.

Results
The mean (SD) time to DMARD initiation was 53 (18) days, with an average 0.3-day decrease with each month over time. Four latent trajectories were identified in our cohort, with over 77% of individual trusts showing ongoing improvements in decreasing treatment waiting times. Prior to separating by latent class, time to DMARD initiation was shorter in trusts with higher rheumatology staffing, a local EIA treatment pathway and those with access to musculoskeletal ultrasound. Trusts with more nurses in the rheumatology department were less likely to be in the worse performance group (OR = 0.69 [95%CI 0.49, 0.93]).

Conclusion
In this cohort study, we observed a reduction in treatment waiting time over time. Trusts with better staffed and improved EIA clinical structure are likely to initiate definitive treatment earlier in patients with EIA.

Disclosure
Z. Yang: None. N. Arumalla: None. M.D. Russell: Honoraria; Lilly, Menarini, Galapagos. Grants/research support; NIHR. Other; Pfizer, Janssen, Biogen, and UCB. K. Bechman: Honoraria; Menarini, Galapagos. Grants/research support; NIHR,Versus Arthritis and Pfizer Global Medical Grants for Quality Improvement in Rheumatology Practice. Other; UCB. E. Alveyn: Other; UCB. S. Gallagher: None. E. Price: None. S. Norton: None. J. Galloway: Honoraria; AbbVie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB.
P079 Denosumab treatment for bone marrow oedema - a case series
Authors: Galloway Megan , Jacobs Alana , Ismajli Mediola 
Published: April 2024

Abstract

Background/Aims
This is a case series of patients treated with a single dose of denosumab to improve bone marrow oedema. Bone marrow oedema can cause significant pain and functional limitations. On MRI imaging, bone marrow oedema is identified as T1 hypointensities and T2 hyperintensities. Denosumab is a human monoclonal antibody that inhibits osteoclast bone absorption via binding to the cytokine RANKL [receptor activator of nuclear factor kappa-B ligand]. The exact aetiology of bone marrow oedema is unknown. It typically occurs in those aged between 40 to 60 years old. Studies have described therapeutic improvement with antiresorptive medications. Bone marrow oedema will generally resolve if left untreated. However, pharmacological treatments can curtail the clinical course.

Methods
This case series has emerged from Chelsea and Westminster hospital. Data was collected over a five year period for seven patients with bone marrow oedema [demonstrated on MRI] that were treated with denosumab. Six of the seven patients had a spontaneous insufficiency fracture associated with the bone marrow oedema on imaging. In our case series, two of the patients had bone marrow oedema in their hips and five in their knees. Denosumab was administered as a single 60mg subcutaneous injection. Response to treatment was ascertained by repeat MRI scan 2-4 months after denosumab treatment as well as patient reported outcomes.

Results
The average age of the patients was 56.4 years [age range 48-68 years]. Five of the patients [71%] reported improved symptoms at the affected site. Four patients [57%] had complete resolution of their bone marrow oedema on imaging with a further patient [14%] having an improved radiological appearance. Visual analogue scale [VAS] scores improved by 50%, although this data was only collected for some of the patients. No side-effects or complications were noted from the treatment. One of the patients who did not improve with denosumab treatment went on to have a total hip replacement due to complete loss of joint space. It is noteworthy that following further investigations, five of the seven patients were diagnosed with osteopenia on dual-energy x-ray absorptiometry [DEXA] scan, one had osteoporosis [and was subsequently commenced on alendronic acid] and one did not attend for their DEXA scan.

Conclusion
This series demonstrates that denosumab is an effective treatment for bone marrow oedema. Denosumab given as a single dose can be considered a safe treatment; there is not the risk of rebound worsening of bone density on treatment cessation that can be seen with prolonged treatment. Denosumab should be offered to patients who are symptomatic from bone marrow oedema to allow for quicker symptom relief and radiological improvement. Our findings are similar to that of a slightly larger case series of fourteen patients by Rolvien et al. published in 2017.

Disclosure
M. Galloway: None. A. Jacobs: None. M. Ismajli: None.
P090 Real-world data on immuno-modulation therapies and body mass index in children and young people with juvenile idiopathic arthritis
Authors: Hartley Karen , Jandial Sharmila , McErlane Flora , Sen Ethan , Sampath Sunil 
Published: April 2024

Abstract

Background/Aims
There is some evidence that children and young people (CYP) with Juvenile Idiopathic Arthritis (JIA) who are overweight/obese have less favourable disease control and treatment outcomes. The aim of this study was to investigate any association between BMI and total number of immune modulation therapies used in CYP with JIA.

Methods
This was a retrospective observational study at a tertiary paediatric rheumatology centre. Cross-sectional data was captured in April 2022 from CYP receiving immunomodulation therapies for JIA. Data on diagnosis, treatments and weight/height at last routine follow-up was included. BMI was calculated for each patient and centile assigned using Royal College of Paediatrics and Child Health electronic BMI charts as follows: BMI ≥85th to 94th centile - overweight, ≥95th centile - obese, as per population monitoring British 1990 growth reference (UK90).

Results
187 CYP were identified and 180 included (seven were excluded due to missing BMI data). Baseline demographic, disease and treatment data are summarised in Table A. 67% were female. Median (interquartile range (IQR)) age in years at diagnosis and follow-up was 4.3 (2.7, 8) and 11.9 (8.5, 14.4) respectively. At follow-up, 41.1% of CYP were either obese or overweight. The median (IQR) number of total immunomodulation therapies per patient according to BMI categories were: under/normal weight 2 (1, 3); overweight 3 (2, 3) and obese 3 (2, 5). The median (IQR) years of follow-up in under/normal weight, overweight and obese groups were 4.77 (2, 8.74); 5.27 (1.86, 7) and 5.5 (3, 9.1) respectively.

Conclusion
CYP that were overweight/obese received more therapies compared to under/normal weight. The high proportion (41%) of CYP in this study who were either overweight or obese is similar to prevalence (44.2%) for children in year six at school in this region. Corticosteroid use and limited physical activity is associated with inadequate control of joint inflammation and increased BMI but this data was not collected and is an important limitation, in addition to cross-sectional and retrospective study design. The overweight/obese group had longer follow-up and may have accumulated more therapies. Future research to evaluate optimal dosing of immunomodulation in CYP with high BMI is warranted.

Disclosure
K. Hartley: Grants/research support; NIHR BRC Internship. S. Jandial: None. F. McErlane: None. E. Sen: None. S. Sampath: None.
P110 Characteristics of Difficult to treat Rheumatoid Arthritis patients in a large District Hospital in the UK
Authors: Oo Kyaw Naing , Memon Murk , Sharma Poonam , Dahiya Sandeep 
Published: April 2024

Abstract

Background/Aims
Difficult-to-treat rheumatoid arthritis (D2T RA) has a notably higher impact on a patient’s quality of life and is a significant cost and service pressure to the health care provision in comparison to non-D2T RA. The primary aim of this study is to delineate the major contributing factors and characteristics of patients leading to a diagnosis of D2T RA, using the criteria established by the European League Against Rheumatism (EULAR).

Methods
A retrospective study was conducted within the Rheumatology department in a large district general hospital, with a catchment population of over 700,000 people. A cohort of 722 patients, all of which were on biologic Disease Modifying Anti-Rheumatic Medications (DMARDs) was selected. In this study, we present our findings for the first 95 consecutive patients.

Results
Of the selected 95 patients, 13% met the EULAR criteria for D2T RA. The key characteristics within this subset include 75% being sero-positive (both Rheumatoid factor and anti-cyclic citrullinated peptide), 66% being categorized as obese, and 42% having concurrent fibromyalgia and osteoarthritis. Among these 13% D2T RA patients, 25% demonstrated a high disease activity index and 75% showed moderate severity. All these patients had been started on at least two conventional DMARDs including methotrexate before escalating to more advanced treatments in line with NICE guidelines. From the subgroup of high disease activity D2T RA patients, 67% had tried at least three types of biologic or targeted synthetic DMARDs (b/ts DMARDs), and 33% had been trialled on four different types of b/ts DMARDs. Similarly, out of the medium severity D2T RA subgroup, 45% had tried three and four DMARDs respectively and 10% had been given five biologic or synthetic DMARDs.

Conclusion
The major contributing factors leading to D2T RA within this study population appear to be seropositivity for both RF and anti-CCP, obesity, and the presence of comorbidities like fibromyalgia and osteoarthritis. The intertwined relationship between these factors emphasizes the need for a comprehensive and individualized approach to managing patients with D2T RA. Although this cohort is larger than the previous studies, the sample size is relatively small. We aim to look at the remaining 627 patients to identify trends and modifiable risk factors that could help prevent the future development of D2T RA.

Disclosure
K. Oo: None. M. Memon: None. P. Sharma: None. S. Dahiya: None.
P140 IgG Autoantibodies with Increased Affinity for Epithelial Cells in Severe Systemic Sclerosis
Authors: Moezinia Carine , Wong Valerie , Watson James , Nagib Lydia , Garces Sandra Lopez , Lopez Henry , Martin George , Zhang Siyu , Abdi Bahja Ahmed , Denton Christopher , Abraham David , Stratton Richard J 
Published: April 2024

Abstract

Background/Aims
In health IgG immunoglobulins form a network through interaction with cell surface proteins and controlled by regulatory cells, whereas in autoimmune diseases IgG responses become skewed towards higher affinity and potentially damaging responses against self-antigens. Moreover, recent studies have demonstrated activation of the epithelial layer of skin in systemic sclerosis (SSc), implicating keratinocytes as a target of the autoimmune process. We investigated the presence of plasma IgG autoantibodies directed against keratinocytes and sought correlation with clinical parameters in well-characterized patients.

Methods
Diffuse SSc (dcSSc), limited SSc (lcSSc) and healthy control (HC) plasma samples (each n = 30), were assayed in an anti-epithelial cell antibody assay (AEpCA), using fixed keratinocytes to evaluate binding of IgG . Clinical characteristics of patients with positive versus negative AEpCA were compared. The capacity for SSc IgG to activate epithelial cells was assessed using keratinocytes in vitro.

Results
Preliminary serial dilution assay of SSc and HC plasma (n = 10) showed enhanced affinity of SSc IgG for keratinocytes (ANOVA p &lt; 0.001 for overall effect SSc vs HC IgG p &lt; 0.0048 for dose effect)(Figure 1A). Dilution of 1/80 gave optimal differential binding in the AEpCA assay (corrected p &lt; 0.027 for SSc vs HC at 1/80). Further HC, dcSSc, and lcSSc plasma samples (each n = 30) were screened, demonstrating increased AEpCA titre in SSc (Figure 1B) (Kruskall-Wallace test p &lt; 0.014 for lcSSc vs HC, p &lt; 0.041 for dcSSc vs HC). SSc patients with positive AEpCA had higher skin scores (mRSS) (AEPCA neg 5(0-24); AEpCA pos 9(0-40) p &lt; 0.0032), higher frequency of ATA antibody (AEpCA neg ATA pos 6/30; AEpCA pos ATA pos 13/30, chi squared p = 0.052) more interstitial lung disease (AEPCA neg 7/30, AEpCA pos 13/30, p NS)(Figure 1C) and trend towards higher use of immunosuppression. SSc but not HC IgG activated keratinocytes in vitro, triggering IL-1α release.

Conclusion
In this study, we have shown evidence of IgG autoantibodies with increased affinity for keratinocytes in the plasma of SSc patients. Positive testing for the AEpCA was associated with more severe skin disease and lung involvement. The perturbed IgG network in such patients could be activating through common epithelial cells antigens in the skin and lung.

Disclosure
C. Moezinia: None. V. Wong: None. J. Watson: None. L. Nagib: None. S. Lopez Garces: None. H. Lopez: None. G. Martin: None. S. Zhang: None. B. Ahmed Abdi: None. C. Denton: None. D. Abraham: None. R.J. Stratton: None.
P150 Diagnostic utility of anti-cN1A autoantibody testing in sporadic inclusion body myositis
Authors: Al-Attar Mariam , Khoo Thomas , Lilleker James B , Chinoy Hector 
Published: April 2024

Abstract

Background/Aims
Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients aged over 50 years. Diagnostic criteria encompass clinical, biochemical, and myopathological features. Certain myopathological features possess high specificity but low sensitivity; reliance on such findings may lead to delayed or misdiagnoses. The discovery of autoantibodies against cytosolic 5'-Nucleotidase 1A (cN1A) in sIBM patients suggests an autoimmune component in pathogenesis, but the inclusion of this autoantibody in diagnostic criteria remains uncertain. Additionally, optimal testing methodology has not been established, with varying techniques (e.g., ELISA/line-blot) in use. We assessed antibody profiles in an sIBM cohort and reviewed diagnoses in anti-cN1A positive patients.

Methods
This study was based at the Northern Care Alliance NHS Foundation Trust which hosts a tertiary neuromuscular referral service for the North-West of England. Data sources included myositis clinic and immunology results databases. All patients tested using a validated myositis line-blot immunoassay (EUROLINE 16 Antigen et cN1A [EUROIMMUN]) November 2021-April 2023 were included. Diagnoses of all tested patients were identified through case-note review. Sensitivity and specificity metrics were calculated based on diagnosis and anti-cN1A antibody status.

Results
The total number of patients tested for anti-cN1A was 495. Of these, 10 patients had a diagnosis of sIBM. The true-positive and false-negative rates were both 50% (n = 5 each). Of the 485 patients who did not have sIBM, true-negativity was 97.52% (n = 473) and false-positivity 2.47% (n = 12). Overall, anti-cN1A had a sensitivity of 50%, specificity of 97.52%, positive predictive value of 29.41% and negative predictive value of 98.95% for sIBM (Table 1). Patients with a false-positive anti-cN1A antibody had diagnoses of: primary Raynaud’s (n = 5); undifferentiated CTD (n = 3); systemic sclerosis (n = 2); non-sIBM myositis (n = 2).

Conclusion
Anti-cN1A detected using the EUROLINE 16 Antigen assay has high specificity but lacks sensitivity for sIBM, consistent with previous literature. These findings suggest that this assay performs similarly to other cN1A detection methodologies and has utility in confirming the diagnosis of sIBM where there is clinical suspicion. Further real-world analysis of antibody data in larger cohorts is required to clarify the role of serological testing in sIBM diagnostic criteria, to improve diagnostic delays and misclassifications.

Disclosure
M. Al-Attar: None. T. Khoo: None. J.B. Lilleker: None. H. Chinoy: None.
P156 Type I interferon is raised across connective tissue diseases and is associated with haematological abnormalities and specific autoantibody profiles
Authors: Madenidou Anastasia-Vasiliki , Rice Gillian I , Dyball Sarah , Parker Benjamin , Briggs Tracy A , Bruce Ian N 
Published: April 2024

Abstract

Background/Aims
The overlapping clinical and serological features among connective tissue diseases (CTDs) suggest a shared molecular aetiology. A molecular taxonomy of CTDs offers new opportunities in clinical trial design, which can potentially be translated into targeted treatment. In a previous study of 164 patients, we identified a type I interferon (IFN) positive subgroup within an unselected CTD cohort associated with specific clinical and serological features. Here, we aim to investigate the relationship between type I IFN and the clinical and immunological phenotype in a larger CTD cohort and determine whether a distinct subpopulation of patients can be identified.

Methods
Adult patients with at least 1 CTD clinical feature and CTD-related autoantibody were recruited from five rheumatology centres in North West England into the Lupus Extended Autoimmune Phenotype (LEAP) cohort. A 24-gene interferon-stimulated gene (ISG) score was calculated using NanoString as described by Neasens et al. 2022.

Results
Most patients had lupus (36%). 160 of 344 (46.5%) patients had a positive ISG score across all CTDs with 64/125 (51%) of lupus patients (Fig.1). Patients with positive ISG score were younger and had longer disease duration (p &lt; 0.005 for both). There were no differences in mucocutaneous or internal organ involvement between the ISG subgroups. The ISG-positive group had significantly increased frequency of specific autoantibodies (anti-Smith, anti-Chromatin, anti-RNP, anti-Ro) and Rheumatoid Factor, and haematological abnormalities (lower haemoglobin, and lower total white cell and neutrophil counts) in an adjusted model including the CTD subtype.

Conclusion
In CTD patients, IFN type I positivity was identified across a subset of patients of all CTDs and is associated with specific autoantibodies and haematological parameters; these results support the findings of our previous smaller study. The identification of an IFN I-positive subgroup within an unselected CTD regardless of clinical diagnosis supports a molecular-based approach to treatment.

Disclosure
A. Madenidou: Grants/research support; Janssen and UCB. G.I. Rice: None. S. Dyball: Grants/research support; UCB, Novartis,Eli Lilly. B. Parker: Honoraria; Fresenius-Kabi and AbbVie. Member of speakers’ bureau; Eli Lilly and Roche. Grants/research support; Genzyme/Sanofi and GlaxoSmithKline. T.A. Briggs: Grants/research support; Janssen. I.N. Bruce: Consultancies; AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck Serono and UCB. Member of speakers’ bureau; AstraZeneca, GlaxoSmithKline and UCB. Grants/research support; Genzyme/Sanofi, GlaxoSmithKline, Roche, Novartis, Janssen and UCB.
P158 Cutaneous vasculitis in systemic lupus erythematosus: trends of incidence and risk factors
Authors: Saleh Ahmed , Gordon Caroline , Reynolds John 
Published: April 2024

Abstract

Background/Aims
Cutaneous vasculitis (CV) is the most common form of vasculitis observed in patients with SLE; however, the precise epidemiological trends and underlying risk factors remain uncertain. The aim of this study was to define the incidence, prevalence, and risk factors of CV in systemic lupus erythematosus (SLE) patients over a period of 20 years.

Methods
The Birmingham Lupus Cohort is a longitudinal observational cohort of patients with SLE. All patients fulfilled the 1997 ACR Updated Classification Criteria for SLE. Inception patients were recruited within three years of their fourth ACR criterion. Disease activity was assessed using the classic BILAG index and laboratory results recorded. The BILAG vascular domain was used to determine the incidence rate, which refers to the rate at which new cases of minor and major CV attributed to active SLE occur. Cox proportional hazards frailty models were developed to identify clinical and laboratory variables associated with development of CV.

Results
We analysed 392 patients, of whom 375 (92.5%) were females. There were 213 (55.0%) White, 72 (18.6%) African-Caribbean, 82 (21.1%) South Asian, 9 (2.3%) East Asian, and 11 (2.8%) other ethnicities. The median (IQR) age at enrolment was 33 (26 - 44) years and the median duration of follow up was 9.2 (5.1 - 14.7) years. The incidence rates of minor and major CV were reported in Table 1. In Cox proportional hazards models, there was a positive association between CV and discoid rash (hazard ratio [HR] 2.16 [95% CI: 1.01, 4.61]), Raynaud’s phenomenon (HR 5.67 [95% CI: 4.11, 7.81]), livedo reticularis (HR = 4.69 [95% CI: 1.83, 12.0]), arthritis (HR 3.02 [95% CI: 2.20, 4.15]), renal involvement (OR 2.40 [95% CI: 1.55, 3.71]), haematological involvement (HR = 2.46 [95% CI: 1.80, 3.36]), and Afro-Caribbean descent (HR 1.96 [95% CI: 1.03, 3.74]). In addition, CV was positively associated with anti-dsDNA (HR = 2.33 [95% CI: 1.67, 3.27]), low C3 or C4 (HR 2.29 [95% CI: 2.18, 4.10]), and history of anti-Ro or anti-La (HR = 1.92 [95% CI: 1.15, 3.21]).

Conclusion
The incidence rates of CV decrease over the duration of follow-up and are associated with defined clinical and serological features.

Disclosure
A. Saleh: Grants/research support; A.S. is a sponsored PhD student by the Egyptian ministry of higher education represented by The Egyptian Bureau for Cultural & Educational Affairs in London. C. Gordon: None. J. Reynolds: None.