bluuebunny/crossref_metadata_2025_split huggingface dataset:
OA08 GWAS meta-analysis of ankylosing spondylitis and Behçet's disease identifies novel MHC-I-opathy genes
Authors: Saeed Mohammad 
Published: April 2024

Abstract

Background/Aims
Spondyloarthropathies (SpA) and Behçet's disease (BD) have clinical and HLA locus overlap and have been grouped under MHC-I-opathy [1]. Genetic overlap can help elucidate MHC-I-opathy pathogenesis. Ankylosing spondylitis (AS) is a primary SpA. Here, a cluster-based approach helps to identify overlapping loci between AS and BD of even modest significance.

Methods
Association clustering methods such as OASIS [2] reduce the multiple-testing burden and are therefore more powerful than single variant analysis for identifying modest genetic effects. Here, two large genome-wide association studies (GWAS) of AS (921 cases, 907 controls) and BD (1215 cases and 1278 healthy controls) from Turkiye, were subjected to OASIS meta-analyses to identify common non-HLA loci [3, 4]. Statistics used to identify significant loci included the novel OASIS locus index (OLI), defined as the product of maximum -logP at a locus with the ratio of actual to predicted number of significant SNPs.

Results
GWAS for both diseases had the highest significance at the HLA-locus. OASIS avoids the proportional signals problem, inherent in GWAS, by separately analysing highly significant loci (P &lt; 10-8). Hence, of the 234 independent modestly significant non-HLA loci, there were 16 loci common to both AS and BD (Figure 1). These included known MHC-I-opathy loci, 1p31.3 for IL23R (P = 5.37 E-06, OLI = 52.7) and 13q14.11 for LACC1 (P = 7.41 E-06, OLI= 65.3) [1, 5]. Novel loci included 3p21.31 containing CCR9 (P = 2.46 E-05, OLI=25.8), 3q22.3 containing CLDN18 (P = 5.37 E-05, OLI=31.4) and 4q27-4q28.1 containing FGF2 (P = 1.1 E-04, OLI=29.5).

Conclusion
Five loci containing pathologically relevant genes for MHC-I-opathy were identified using a cluster-based approach in AS and BD GWAS datasets. These large meta-analyses will help identify pathogenic pathways for MHC-I-opathy, an entity that has so far largely remained elusive [6].

Disclosure
M. Saeed: None.
OA36 Systemic juvenile idiopathic arthritis: the Great Ormond Street Hospital experience (2005-2021)
Authors: Foley Charlene Majella , McKenna Dearbhla , Gallagher Kathy , McLellan Kirsty , Alkhdher Hanof , Lacassagne Sandrine , Moraitis Elena , Papadopoulou Charalampia , Pilkington Clarissa , Al Obaidi Muthana , Eleftheriou Despina , Brogan Paul 
Published: April 2024

Abstract

Background/Aims
sJIA is a complex, systemic-inflammatory disorder. The proposed biphasic model of disease suggests that unchecked early auto-inflammation driven by increased innate immune activation, including dysregulation of IL-1 and IL-6, may lead to a state of chronic T-lymphocyte activation. This leads to an unfavourable balance of T-effector and regulatory cells that can drive chronic arthritis over time. It is therefore unsurprising that there is growing evidence to support instigation of IL-1 or IL-6 blockade as first-line treatment in sJIA. Early cytokine antagonist therapy could abrogate development of a population of these arthritis-causing T-cells to avert chronic systemic inflammation and arthritis. Aims: 1) describe clinical presentations, therapeutic interventions, complications, and remission rates at different time-points over disease course in sJIA; 2) identify potential therapeutic signals in patients with sJIA who received biologic treatment early in disease course compared to those who did not.

Methods
Retrospective review of all patients with sJIA at GOSH (02/10/05-21/10/21, inclusive). Data collected: patient demographics; clinical and laboratory data; treatment history; adverse events. Time-points for data collection: at diagnosis; 3-months; 1-year; last follow-up. Descriptive statistics reported as median and range or IQR for continuous variables, and as absolute frequencies and percentages for categorical variables. Comparisons of quantitative variables were made by Mann-Whitney U-test. Categorical data were compared using Fisher’s exact test (p-values&lt;0.05 were considered significant).

Results
A total of 76 children (female n = 40, 53%) were diagnosed with sJIA; median age was 4.5 years (range 0.6-14.1). A biologic disease modifying anti-rheumatic drug (bDMARD) alone was commenced as first-line treatment in 28% (n = 21/76) of the cohort; however, at last review, 84% (n = 64/76) had received treatment with a bDMARD. Clinically inactive disease (CID) was achieved by 88% (n = 67/76) of the cohort at last review; however, only 32% (24/76) achieved treatment-free CID. At 1-year follow-up, CID was achieved in a significantly greater proportion of children who received treatment with a bDMARD within 3-months of diagnosis compared to those who did not (90% versus 53%, p = 0.002).

Conclusion
We propose a UK treatment-algorithm for children diagnosed with sJIA (see figure). We recommend reappraisal of the current NHS England commissioning policy.

Disclosure
C. Foley: None. D. McKenna: None. K. Gallagher: None. K. McLellan: None. H. Alkhdher: None. S. Lacassagne: None. E. Moraitis: None. C. Papadopoulou: None. C. Pilkington: None. M. Al Obaidi: None. D. Eleftheriou: None. P. Brogan: None.
P016 Cardiovascular disease and rheumatoid arthritis among people with a history of cancer
Authors: Khubchandani Jagdish , Banerjee Sri , Onukogu Claret , Gonzales-Lagos Rafael 
Published: April 2024

Abstract

Background/Aims
Cardiovascular disease (CVD) is connected to many comorbidities and vascular diseases. Cancer also has certain inflammatory impact on the physiological mechanisms. However, the precise connection between these variables are unknown. In this research, we determined if there was an association between cardiovascular disease and overall mortality and how this connection may be modified by rheumatoid arthritis.

Methods
The National Health and Nutrition Examination Survey (NHANES) survey was conducted by the National Center for Health Statistics (NCHS) for the six cycles or years of 1999 to 2010 with mortality follow-up through December 31, 2019. This data is published biennially. Our study was conducted on participants with a history of cancer that were aged 40 years or older living in the United States with cardiovascular disease. CVD was determined by a history of stroke, congestive heart failure, coronary heart disease, and myocardial infarction. History of cancer was considered positive if the respondent answered “yes” to the question “Ever told you had cancer or malignancy”. We assessed RA status by using the arthritis question. We determined diabetes by healthcare worker diagnosed recall of the diagnosis of the disease. In this prospective analysis that we performed Complex Samples Cox regression with adjustment for known confounders to determine the relationship of chronic kidney disease and mortality, and if rheumatoid arthritis has an overall relationship in those living with diabetes.

Results
Among individuals living with cancer and rheumatoid arthritis, percent mortality for males was 58.2% and for females was 61.9%. For overall mortality, crude hazard ratio (HR) for diabetes was 2.13 (95% confidence interval [CI], 1.39-3.25 p &lt; 0.001). The adjusted HR was elevated, 1.86 (CI 1.17-2.96, p = 0.01), among people with cardiovascular disease who also had rheumatoid arthritis but close to 1.0 (1.36 CI 1.09-1.70, p = 0.01) among individuals with cardiovascular disease who had no rheumatoid arthritis, after adjusting for medical (cardiovascular disease, asthma, chronic kidney disease, chronic obstructive pulmonary disease, and obesity) and demographic risk factors (gender and age). Similar patterns do not exist in the general population.

Conclusion
Among individuals has had a history of cancer, not only does cardiovascular disease lead to two times higher overall mortality but also rheumatoid arthritis occurrence impacts the relationship between cardiovascular disease and overall mortality even after controlling for potential medical and demographic confounders. Cardiovascular is the primary cause of death in many high- and middle-income countries in the world. More prevention efforts need to be made in order to prevent CVD and treat rheumatoid arthritis.

Disclosure
J. Khubchandani: None. S. Banerjee: None. C. Onukogu: None. R. Gonzales-Lagos: None.
P055 Prevalence, incidence, and mortality of Raynaud’s phenomenon, scleroderma, Sjogren’s syndrome and systemic lupus erythematosus: an overview of systematic reviews and meta-analyses
Authors: Chen Anthony , Lax Stephanie , Grainge Matthew , Lanyon Peter , Pearce Fiona 
Published: April 2024

Abstract

Background/Aims
To comprehensively review any existing systematic reviews and/or meta-analysis on the prevalence, incidence, and mortality rates of Raynaud’s Phenomenon (RP), Sjögren’s Syndrome (SS), Scleroderma and Systematic Lupus Erythematosus (SLE).

Methods
An umbrella review of systematic reviews and/or meta-analysis was undertaken using two electronic databases - PubMed and Embase (OVID). The searches were limited to English language and a publication period of 2000-2023. Any systematic reviews and/or meta-analysis reporting the prevalence, incidence, or all-cause/cause-specific mortality of the studied diseases were collected. The number of included and excluded studies were reported through the PRISMA checklist. The pooled estimate and its corresponding 95% confidence intervals and P-values were reported from each included study. If there were no pooled estimates reported in the study, a narrative synthesis of their results was reported.

Results
In this umbrella review, a total of 43 systematic reviews and/or meta-analysis were reported, of which 1 was RP, 5 SS, 11 scleroderma and 26 SLE. The pooled prevalence and incidence rates for RP was 4.85% (95% CI: 2.08-8.71%) and 0.25% (95% CI: 0.19-0.32%), respectively. There was a lack of mortality findings for RP. The global prevalence rate for SS was reported to be 60.82 per 100,000 (95% CI: 43.79-77.94). The pooled incidence rate and cardiovascular mortality risk ratio were reported to be 6.92 (95% CI: 4.98-8.86) per 100,000 person-years and 1.48 (0.77-2.85), respectively. The pooled prevalence and incidence rates for scleroderma were found to be 17.6 (95% CI 15.1, 20.5) and 1.4 (1.1-1.9) per 100,000 person-years-at-risk. The pooled standardised mortality ratio (SMR) for Scleroderma ranged from 2.82 to 3.4. The global prevalence rate for SLE was found to be 43.7 (15.87-108.92) per 100,000. Incidence rates for SLE were found to be 5.14 (95% CI: 1.4-15.13) per 100,000. SMR of SLE ranged from 1.35-4.60.

Conclusion
Included studies reported varying values for the prevalence, incidence, all-cause/cause-specific findings of SS, scleroderma, and SLE. This could be due to differences in study populations, diagnostic criteria, case definitions, and included studies’ design. Although there were number of systematic reviews and/or meta-analysis investigating the epidemiology of scleroderma and SLE, there were few in RP and SS.

Disclosure
A. Chen: None. S. Lax: None. M. Grainge: None. P. Lanyon: None. F. Pearce: None.
P177 The prevalence and incidence of psoriasis and psoriatic arthritis in England from 2009-2019: an observational study using primary care data
Authors: Vivekanantham Arani , Burn Edward , Moncusi Marta Pineda , Khalid Sara , Alhambra Daniel Prieto , Coates Laura C 
Published: April 2024

Abstract

Background/Aims
Psoriasis (PsO) and psoriatic arthritis (PsA) greatly impact quality of life and result in substantial personal and societal costs. Complete and up-to-date data on the prevalence and incidence of these conditions and whether these change over time and vary by age is important for healthcare service planning so that specialist care and funding can be appropriately allocated.

Objective
to determine the prevalence and incidence of PsO and PsA in males and females from 2009-2019 across all age groups in England.

Methods
We used Clinical Practice Research Datalink AURUM, a primary care electronic health record database, including 20% of the English population. The codes used to identify patients with PsO and PsA were selected by rheumatologists and dermatologists and cross-checked with published code lists from other studies. All included patients must have data for at least 1 year before their diagnosis. The annual incidence and point prevalence were calculated from 2009-2019 and stratified by age/sex. The study period ended in 2019 to avoid COVID-19 pandemic affecting results.

Results
The prevalence of PsO and PsA in males and females has increased annually, peaking in 2019 (PsO males 2.41% [95% confidence interval (CI) 2.40, 2.42];
PsO females 2.60% [95% CI 2.59-2.61]; PsA males 0.20% [95% CI 0.20-0.20]; PsA females 0.21% [95% CI 0.21- 0.22]), as illustrated in Table 1. In 2019, the prevalence of PsO and PsA was highest in the over 65 years age group; PsO 4.25% [95% CI 4.22-4.28] and PsA 0.38% [95% CI 0.37-0.38]. The annual incidence (per 100,000 person years) of PsO has gradually decreased in males (from 168 [164-171] in 2009 to 148 [145-151] in 2019) but in females it has been stable with a slight annual decrease (from 180 [177-184] in 2009 to 173 [170-176]) in 2019. The annual incidence for PsA has increased in both males and females; 13 (12-14) in 2009 and 15 (14-16) in 2019 for males and 12 (11-13) in 2009 and 18 (17-19) in 2019 for females.

Conclusion
The increasing prevalence of PsO and PsA highlights the importance of organising healthcare services to meet this need, particularly in the elderly population.

Disclosure
A. Vivekanantham: None. E. Burn: None. M. Pineda Moncusi: None. S. Khalid: None. D. Prieto Alhambra: Consultancies; DP-A’s research group has received consultancy or speaker fees from Astellas, Amgen, AstraZeneca, and UCB Biopharma. Grants/research support; DP-A’s research group has received research grants from the European Medicines Agency; the Innovative Medicines Initiative; and Amgen, Chiesi, and UCB Biopharma. L.C. Coates: Grants/research support; LCC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Novartis and Pfizer; worked as a paid consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene.
E001 Pre-screen chest X-ray before starting methotrexate in autoimmune disease
Authors: Khan Muhammad A , Khan Abdul , Vijayan Aswathy , Hajilou Ashcaan , Win Myat 
Published: April 2024

Abstract

Background/Aims
This audit seeks to assess adherence to BSR guidelines and NICE recommendations concerning chest X-ray screening before initiating methotrexate. We also aim to evaluate the time elapsed from X-ray to radiologist reporting and the frequency of methotrexate initiations for various diagnoses.

Methods
We identified 127 cases from the rheumatology department (2017-2021) involving patients aged 18 or older with diagnoses of rheumatoid arthritis, psoriatic arthritis, lupus, or autoimmune connective tissue disease. We checked patient records for evidence of pre-treatment chest X-rays

Results
Rheumatoid arthritis was the most common diagnosis for methotrexate initiation. Out of the 127 patients, 102 underwent chest X-rays (80%), while 23 did not. For 2 patients, the status of chest X-ray performance remained unknown. The breakdown of percentages by hospital was as follows: QEQM (87%), WHH (70%), KCH (77%). The distribution of report times across the three hospitals was as follows: 1-7 days (52%), 8-14 days (4%), 15-31 days (12%), 32-62 days (11%), 63-100 days (15%), 101+ days (6%).

Conclusion
Urgent reporting of chest X-rays is imperative. Proposed solutions include flagging X-rays as urgent by incorporating a 'Patient starting Methotrexate?’ query. If selected 'yes’ this would flag the report as urgent on the Soliton system. This allows for prompt reporting of these X-rays with timely starting of the DMARDs treatment in various autoimmune conditions. This was done as beforehand, X-rays were not reported in a prompt manner even if they were stated as urgent in the requests. A smaller post-audit analysis involving 15 patients achieved 100% compliance of reporting within one week by implementing these changes.

Disclosure
M.A. Khan: None. A. Khan: None. A. Vijayan: None. A. Hajilou: None. M. Win: None.
E006 Providing information on arthritis medication: a service evaluation
Authors: Ryan Sarah , Hider Samantha , Paskins Zoe 
Published: April 2024

Abstract

Background/Aims
Traditionally patients commencing disease modifying anti-rheumatic medications (DMARDs) attended a face to face consultation with a rheumatology nurse or pharmacist, to discuss benefits, concerns and safety monitoring. The pandemic has led to an increase in the use of remote methods of information sharing including telephone consultations. The aim of this service evaluation was to elicit patients preferences on receiving information on arthritis medications to help inform service development.

Methods
A service evaluation with contributions from patients and stakeholders was designed and registered with the trust. Patients who were commencing or taking DMARDs attending, one of two hospital sites, in North Staffordshire were asked to complete a short questionnaire from November 2022-April 2023. Some patients completed the questionnaire at the end of their telephone drug counselling appointment with the assistance of the nurse whilst others completed the questionnaire whilst attending in person for their appointment. The questionnaire focused on the preferred format for receiving information on arthritis medications including a face to face appointment with a health professional (even if this meant a wait), telephone consultation, attending a group counselling session, having a drug information leaflet with the option to contact a health professional to answer any questions or watching a video on a device with internet access (computer, smart phone or tablet). The importance of receiving information on the same day as commencing treatment was also explored.

Results
64 patients took part in the survey. No demographic data was collected. The most popular method for receiving information on arthritis medications was a face to face appointment, even if it meant a delay in starting medication (n = 32,50%). The second most popular method was an information leaflet with the option to discuss any concerns via the telephone (n = 12,19 %). The third preference to receive information were via a video, again with the option to discuss concerns remotely (n = 10, 16%) or a telephone appointment, even if it meant a delay in starting medication (n 10,16%) Surprisingly although no patients expressed a preference to attend a group counselling session, 36 (56%) would attend if offered. When presented with the option of having information on the same day as the decision was made to commence medication, or, having to wait to discuss the mediation with a health professional, there was a strong preference to see a health professional (n = 46, 72%)

Conclusion
Patients clearly value discussing commencing DMARDs with a health professional even if this means a delay in treatment. Having just one approach to information giving does not equate with individual needs and a range of options regarding information delivery that the patient can select from is required.

Disclosure
S. Ryan: None. S. Hider: None. Z. Paskins: None.
E015 Importance of smoking cessation in rheumatological outcomes
Authors: Osikoya-Yekini Modupe , Walshe William , Bharadwaj Anurag , Nandagudi Anupama 
Published: April 2024

Abstract

Background/Aims
Smoking is a major preventable risk factor for many rheumatological diseases and can influence the severity of symptoms in conditions such as psoriatic arthritis (PsA), ankylosing spondylitis, giant cell arteritis (GCA) and systemic lupus erythematosus (SLE). The increased risk due to smoking is dose dependent. The objective was to identify the proportion of patients with rheumatological conditions who smoke and to ensure that smoking cessation advice is given in line with NICE guidelines.

Methods
A retrospective qualitative study with data collected from electronic patient records (EPR) between September and November 2022 across multiple rheumatology clinics. Data included age, gender, smoking status, diagnosis, disease duration, comorbidities, treatment, and smoking advice status.

Results
459 patients were analysed (68% female), of which 11% were smokers, 6% were ex-smokers, 83% were non-smokers, and 1 vapes regularly. Among the smokers, 72% were female. The median age was 61 years, with a range of 18-91 years. The commonest age range for all patients is 71-80 years, while the commonest age range among smokers was 41-50 years at 28%. The commonest disease duration among smokers is 1-5 years.
The most common disease diagnosis among smokers were RA (30%), PsA (19%) and SLE (6%). Regarding disease activity among smokers, 36% had mild, 56% had moderate, and 8% had severe disease activity.
Among the 12 patients with respiratory comorbidities; 6 had asthma, and 4 had COPD. Among the 21 patients with cardiovascular comorbidities; 13 had hypertension, and 6 had hypercholesterolaemia.
For patients on cDMARDS, 26% were on methotrexate, 11% were on sulfasalazine, 9.4% were on hydroxychloroquine and 2% were on leflunomide. 13% were on prednisolone, while 7.5% had required methylprednisolone injections. 11% were on bDMARDs, most commonly adalimumab.
Smoking cessation advice was documented in 4%, whereas 96% had no evidence of any smoking cessation advice.

Conclusion
This study illustrates the most common age range of smokers in this cohort was 41-50 years (28%), which was almost twice the equivalent national level (14.3% in 45-54 years). Nationally, the most common age range is 25-34 years (15.8%). Patients with rheumatological disease who smoked were of younger age compared to non-smokers, and smoking rates were higher in females compared to males. Smoking cessation advice was only documented in 4% of this cohort. This indicates much scope for improvement, and enhanced disease control in a population with multiple challenges, primarily socioeconomically. VBA (Very Brief Advice) has been shown to be the single most effective and clinically proven preventive action a clinical can give to patients in relation to smoking cessation. The NCSCT (National Centre for Smoking Cessation Training) encourages the 3A’s (ASK, ADVICE, ACT).

Disclosure
M. Osikoya-Yekini: None. W. Walshe: None. A. Bharadwaj: None. A. Nandagudi: None.