British Society for Rheumatology

Childhood-onset Sjögren's disease is a rare and under-investigated rheumatic condition. The natural course of childhood-onset Sjögren's disease in adulthood in not known. This study aimed to evaluate long-term disease trajectories and complications of childhood-onset Sjögren's disease and explore management strategies. This combined retrospective and prospective analysis of a childhood-onset Sjögren's disease cohort with long-term follow-up into adulthood was done in individuals aged 13-36 years with childhood-onset Sjögren's disease recruited from a single tertiary adolescent and young adult rheumatology service at University College London Hospital, UK. Participants were either approached consecutively during routine clinical appointments, or their data were collected retrospectively from the time of diagnosis to the time of transition to the service, and prospectively thereafter. We mapped the cohort onto clinical phenotypes defined by the Florida Scoring System at disease onset and stratified them based on the Newcastle Sjögren's Stratification Tool at last assessment. Disease activity, symptom severity, and damage trajectories were assessed using European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), and Sjögren's Syndrome Disease Damage Index (SSDDI), respectively. People with related lived experience were involved in the study design and implementation. Between March 1, 2020, and June 30, 2024, we identified 30 children and young people diagnosed with childhood-onset Sjögren's disease based on expert opinion. Mean age at onset was 12·7 years (SD 3·3). 28 (93%) of 30 individuals were female and two (7%) were male. The most common disease manifestations at onset were fatigue (22 [73%] of 30 individuals), arthralgia (21 [70%]), dryness (17 [57%]), glandular swelling (15 [50%]), and skin rashes (ten [30%]). Diagnostic delay of more than 3 years from symptoms onset increased the prevalence of reported dryness (nine [100%] of nine vs eight [38%] of 21; p=0·0014). Children and young people with childhood-onset Sjögren's disease had two distinct disease activity and symptom trajectories (high ESSDAI: mean 3·9 [SD 2·2] vs low ESSDAI: mean 0·8 [1·1]; p<0·0001 and high ESSPRI: mean 5·6 [2·7] vs low ESSPRI: mean 3·1 [1·0]; p=0·036), which could not be predicted by sex or age at onset, symptom duration, or duration of follow-up. Damage accrual did not differ based on activity and symptom trajectory (p=0·080 and p=1·0, respectively). At last review, the median ESSDAI score was 2·0 (IQR 2·0-8·0) and the ESSPRI score was 5·3 (3·0-7·0). Four (13%) of 30 patients developed lymphoma and 17 (57%) accumulated damage (SSDDI score ≥1). This preliminary evaluation of long-term outcomes of childhood-onset Sjögren's disease in adulthood showed distinct patterns of disease and symptom trajectories and that a high proportion of children and young people develop damage in early adulthood. These findings highlight the need for improved research quality and evidence-based management strategies for better outcomes in this population. None.

Interstitial lung disease (ILD) is an important complication of systemic sclerosis (SSc), with high mortality and morbidity. Recent clinical studies in SSc‐ILD have led to US Food and Drug Administration–approved therapies in SSc‐ILD. Importantly, evidence from these studies has been extrapolated to guide management of ILDs of other systemic autoimmune rheumatic diseases. Pathogenesis of SSc‐ILD involves interplay between fibroblasts and the innate and adaptive immune system. A central role for the B cell compartment is supported by clinical and translational studies. We use a case from our center as a basis to discuss the pathogenesis of SSc‐ILD, autoantibodies in SSc‐ILD, and the role of B cells in the disease. We go on to consider treatment options for the case, the decision‐making algorithm for treatment, and risks associated with treatment.

ObjectivesPatients with early inflammatory arthritis (EIA) need to be seen urgently to initiate treatment. Our community rheumatology clinic in Ontario, Canada was concerned that EIA cases may be delayed unnecessarily if referrals lacked sufficient detail to triage accurately. In a prior quality improvement project, we redesigned our triage process to include a patient survey (the “EIA Tool”), which was validated to identify referrals with EIA. In this study, we aimed to evaluate the sensitivity and specificity of the new triage process for referrals with unclear urgency after 12 months of use.MethodsAll referrals accepted by 1 rheumatologist were included from April 2020-July 2022. During the intervention period, we implemented the new triage process. The rheumatologist triaged all referrals as urgent, non-urgent, or unclear. Patients with unclear urgency were asked to complete the online EIA Tool prior to scheduling (Figure). Their survey result determined a triage score of urgent or non-urgent, and consultations were scheduled accordingly. Post-consultation, the rheumatologist determined the ‘true’ urgency score, while blinded to the pre-consultation score. Data were collected prospectively on all incoming referrals. We analyzed the data using descriptive statistics and calculated the sensitivity and specificity of the baseline and new triage processes.ResultsThe 16-month baseline period (April 2020 to July 2021) included 1296 referrals; 647 (50%) were triaged as urgent. The 12-month intervention period (August 2021-July 2022), included 888 referrals; 508 (57%) were triaged as urgent, and 97 (11%) were triaged as unclear. The EIA Tool was completed in all unclear cases; 93 patients submitted the survey online, and 4 patients without email completed the survey by phone. Most patients (86%) completed the survey within 1 day of receiving it. Unclear cases had a cycle time from referral to scheduling of 5 days, compared to 3 days for those who were not sent the EIA Tool. The sensitivity to identify urgent cases was 97% during the intervention versus 85% at baseline. The specificity during the intervention was 59% versus 70% at baseline.ConclusionThe EIA Tool helped us detect 97% of truly urgent cases, thereby reducing the risk of delayed treatment caused by triage error. We have since spread this process to 4 rheumatologists in our clinic. Our next step is to analyze urgent referral volume using statistical process control charts, in order to modify our scheduling algorithm.Supported by a CIORA grant

Abstract Background/Aims Podcasts have been around for over 20 years with recent expansion into the medical education. They form a popular way to access education in a portable format and enable learning. Methods The British Society for Rheumatology (BSR) launched its own Talking Rheumatology (TR) podcast channel in 2022. This includes clinical (TR spotlight), research (TR research) and general (guidelines, careers) podcasts. Podcasts are available via the BSR eLearning site and via all podcast platforms. We collected feedback on our pods via an online survey and download and ratings data from podcast providers. Results Our podcasts continue to grow and have become our most popular digital output. Since launching in 2022 we have had &amp;gt;56,000 downloads. Listeners can be found across the globe and represent the whole multi-disciplinary team. Our most popular episodes to date are: TR spotlight Sjögren’s syndrome (&amp;gt;2000 downloads) and TR research long term use of tocilizumab in GCA (&amp;gt;360 downloads). Topical podcasts like ‘CAR T cell therapy in SLE’ (334 downloads in the first 8 days) showed high download numbers on release indicating topics are current and in line with listeners interests. Feedback from our online survey (79 responses) has been extremely positive with 86% of survey respondents rating it good or very good. Listeners liked the fact that podcasts are easy to access and relevant. Free text comments include as follows: ‘succinct and informative’, ‘easy to digest’, ‘easy to access, different format’, ‘relevant to clinical practice’, ‘I like listening to people discussing topics in an informal way’, ‘professional and engaging’, ‘relevant to my role’, ‘good way to get CPD’, ‘really interesting topics’ and ‘expert guests help me improve my knowledge’. As well as being popular our podcasts are having an impact. For example listeners reported following listening to a relevant episode making a diagnosis of VEXAS syndrome and introducing a new telephone clinic to manage gout. One listener reported improved detection of treatment response and efficiency in clinic after listening. Conclusion Podcast downloads indicate topic choices are in line with key topics of interest to the rheumatology community. Feedback demonstrates learning through podcasts have led to changes in clinical practice. Current work is focusing on raising awareness, international reach (both listeners and guests) and evaluation of this relatively new modality. We’d love to hear any suggestions or feedback from the BSR community. Disclosure S. Gall: None. P.A. Watson: None. R. Benson: None. D. Southam: None. L. Coulson: None. C. Groves: None.

Abstract Background/Aims For people who have active rheumatoid arthritis (RA) despite treatment with conventional synthetic DMARDs, timely escalation to biologic and targeted synthetic DMARDs (b/tsDMARDs) improves outcomes and prevents morbidity. In recent years, there has been a concerted effort to lower the threshold at which patients qualify for funded access to b/tsDMARDs, including the publication of the NICE TA715 guideline for moderate severity RA. Our goal was to evaluate whether the initiation of b/tsDMARDs for RA has changed over time, and describe how this varies throughout England and Wales. Methods An observational cohort study was conducted for people with RA enrolled in the National Early Inflammatory Arthritis Audit (NEIAA) between May 2018 and April 2022, who had 12-month follow-up data available. Temporal changes in the proportion of individuals escalated to b/tsDMARDs within 12 months of initial rheumatology assessment were described. Interrupted time-series analysis was used to compare trends before and after the publication of the NICE TA715 guideline in July 2021. Logistic mixed-effects regression with case-mix adjustment was used to compare regional and hospital-level variation in b/tsDMARD initiation throughout England and Wales. Results Of 6,098 patients with RA who had available follow-up, 508 (8.3%) initiated b/tsDMARDs within 12 months of initial assessment. Rates of b/tsDMARD escalation increased modestly towards the end of the study period, with 9.2% of patients assessed between May 2021/22 being escalated to b/tsDMARDs within one year. There was no observed detrimental impact of the COVID-19 pandemic on rates of b/tsDMARD escalation. No significant changes in b/tsDMARD initiation were seen following the publication of the NICE TA715 guideline, which lowered the threshold for b/tsDMARD initiation to include people with moderate severity RA. Of individuals not escalated to b/tsDMARDs, 36.6% had a DAS28 greater than 3.2 at 12 months. The proportion of individuals escalated to b/tsDMARDs varied considerably by region. Individuals in Wales were half as likely to be escalated to b/tsDMARDs as those in London or North-West England (5.1% vs. 10.1% and 10.7%, respectively). Following case-mix adjustment, the intraclass correlation (ICC) for hospitals within each region was 0.17, compared with a between-region ICC of 0.0. This suggests that geographical variation in b/tsDMARD initiation reflects hospital-level differences, rather than systematic differences between the regions themselves. Conclusion Nationally, rates of escalation to b/tsDMARDs have remained relatively stable since 2018, despite the pandemic and the publication of the NICE TA715 guideline. Regionally, however, there is marked variation in b/tsDMARD escalation for people with RA. These disparities must be explored further and addressed if we are to ensure equitable access to b/tsDMARDs regardless of geography. Disclosure M.D. Russell: Honoraria; AbbVie, Lilly, Galapagos, Menarini, UCB, Viforpharma. Grants/research support; Sandoz UK. Other; Support for attending educational meetings from Lilly, Pfizer, Janssen, UCB. Z. Yang: None. N. Dooley: None. M. Gibson: None. B. Zuckerman: None. M.A. Adas: None. E. Alveyn: Other; Support for attending meetings from UCB. S. Patel: None. K. Bechman: Honoraria; Galapagos, UCB, Viforpharma. Grants/research support; NIHR. Other; Educational support from UCB. E. Price: None. S. Gallagher: None. C. Coalwood: None. A.P. Cope: Consultancies; GSK/Galvini, BMS, UCB, Janssen. Honoraria; Galapagos, AbbVie, BMS. Grants/research support; BMS. Other; Support for attending meetings from AbbVie, and has participated in a data/advisory board for GSK/Galvini. S. Norton: None. J.B. Galloway: Honoraria; Abbvie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, UCB. Grants/research support; Sandoz UK.

Interstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc), although disease behaviour is highly heterogeneous. While a usual interstitial pneumonia (UIP) pattern is associated with worse survival in other ILDs, its significance in SSc-ILD is unclear. We sought to assess the prognostic utility of a deep-learning high resolution CT (HRCT) algorithm of UIP probability in SSc-ILD. Patients with SSc-ILD were included if HRCT images, concomitant lung function tests and follow-up data were available. We used the Systematic Objective Fibrotic Imaging analysis Algorithm (SOFIA), a convolution neural network algorithm that provides probabilities of a UIP pattern on HRCT images. These were converted into the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED)-based UIP probability categories. Decline in lung function was assessed by mixed-effect model analysis and relationship with survival by Cox proportional hazards analysis. Five hundred and twenty-two patients were included in the study; 19.5% were classified as UIP not in the differential, 53.5% as low probability of UIP, 25.7% as intermediate probability of UIP, and 1.3% as high probability of UIP. A higher likelihood of UIP probability expressed as PIOPED categories was associated with worse baseline forced vital capacity (FVC), as well as with decline in FVC (P = 0.008), and worse 15-year survival (P = 0.001), both independently of age, gender, ethnicity, smoking history and baseline FVC or Goh et al. staging system. A higher probability of a SOFIA-determined UIP pattern is associated with more advanced ILD, disease progression and worse survival, suggesting that it may be a useful prognostic marker in SSc-ILD.

Abstract Background/Aims Inflammatory arthritis including rheumatoid arthritis (RA) causes significant work disability. Rapid diagnosis and early intervention can reduce the impact of disease. We have previously shown significant regional variation in care delivery. In this study we aim to study regional variation in work outcomes in early RA in England and Wales. Methods We used data from the UK National Early Inflammatory Arthritis Audit between April 2018 and March 2023 to identify patients with early-onset RA in England and Wales. At diagnosis, clinicians collected information on demographics and disease activity. Participants were invited to complete work outcome questionnaires at baseline and 3 months. Our analysis was restricted to patients with work data available at 3 months. The primary outcome was discontinuation of work due to arthritis. Patient characteristics were tabulated by region. Regression models (adjusted for age and gender) examined the associations between work discontinuation and region. Clustered standard errors were estimated to account for within-Trust correlations. Sensitivity models further explored the effects of deprivation and treatment delay. Results A total of 3,730 patients with confirmed RA provided work data. Mean age was 67, 62.3% were female and 7.8% from minority ethnic backgrounds. 14% were current smokers and 55.6% had one or more comorbidities. Median baseline DAS28 was 5.2 (IQR: 4.2-6.1). 363/3730 (10%) had stopped work due to RA by 3 months. 534/3,730 (14%) stopped work for any reason. In regression analysis, significant regional differences were seen in the odds of stopping work due to RA. The Midlands was the largest regional contributor of data and was used as the reference group. Patients from Northwest England were most likely to stop work by 3 months (age- and gender-adjusted OR 1.59, [95% CI 1.13-2.25]) with Midlands patients least likely. Sensitivity analysis showed that deprivation and treatment delay only partially attenuate the association between region and work outcome (OR for Northwest 1.57 [1.06-2.33]). Conclusion There is evidence of regional variation in the impact of new onset RA on work participation. Our analyses suggest that the associations are only partly explained by regional differences in care delivery or deprivation. Other factors such as job type and access to occupational health support warrant further investigation. Disclosure E. Alveyn: Other; Educational support from UCB. M. Adas: None. I. Sahbudin: None. A. Boonen: None. K. Bechman: Honoraria; UCB, Vifor Pharma. M.D. Russell: Honoraria; Abbvie, BioGen, Lilly, Galapagos, Menarini. Other; Educational grants from Lilly, Janssen, Pfizer, UCB. D. Nagra: Honoraria; Abbvie, Galapagos, Lilly. Other; Educational support from UCB. S. Gallagher: None. E. Price: None. K. Walker-Bone: None. S. Norton: None. J. Galloway: Honoraria; AbbVie, Celgene, Chugai, Gilead, Janssen, Eli Lilly, Pfizer, Roche and UCB.

Methotrexate (MTX) is the bed rock of inflammatory arthritis management. However, intolerance is a limiting factor for drug optimisation and retention. There is data to suggest subcutaneous (SC) MTX is better tolerated. It is less clear whether this strategy is effective in those where the oral preparation is inefficacious and its potential to avoid escalation to biologic therapy. To analyse the reasons for switching to SC MTX in a real-world setting, clinical outcomes achieved and proportion requiring biologic prescription. A retrospective survey of patients prescribed SC MTX in a university teaching hospital identified 352 patients. 298 switched from oral to SC MTX- 164 stopped oral MTX due to side effects, 134 stopped due to inefficacy, and 54 started SC MTX as first line therapy. 103 patients progressed to biologic therapy. Rheumatoid arthritis (RA): DAS-28 improved from a mean of 4.06 (0.63-8.06) to 2.83 (0.14-7.32) following the switch (p<0.0001). Psoriatic arthritis (PsA): total joint count improved from a mean of 7 (0-42) to 2 (0-25) (p<0.0001). Swollen joint count improved from a mean of 2 (0-26) to 1 (0-6) (p=0.09). SC MTX is an effective solution for RA and PsA, irrespective of whether oral MTX is inefficacious or intolerable. Where oral MTX was ineffective, a switch to SC achieved low disease activity despite multi-morbidity, long disease course and protracted oral MTX exposure. This intervention prevented over two-thirds of patients requiring biologics. SC MTX is a durable strategy with excellent disease outcomes and substantial economic benefits.

SummaryArchaeological remains can preserve some proteins into deep time, offering remarkable opportunities for probing past events in human history. Recovering functional proteins from skeletal tissues could uncover a molecular memory related to the life-history of the associated remains. We demonstrate affinity purification of whole antibody molecules from medieval human teeth, dating to the 13th–15th centuries, from skeletons with different putative pathologies. Purified antibodies are intact retaining disulphide-linkages, are amenable to primary sequences analysis, and demonstrate apparent immunoreactivity against contemporary EBV antigen on western blot. Our observations highlight the potential of ancient antibodies to provide insights into the long-term association between host immune factors and ancient microbes, and more broadly retain a molecular memory related to the natural history of human health and immunity.