Abstract Background/Aims The MYOPROSP (NCT02468895) study is a prospective, multicentre observational cohort that recruited adult patients with idiopathic inflammatory myopathies (IIM) from 23 UK centres between 2016 and 2020. We previously have reported that, despite longer disease duration and more prior treatment failures, refractory adult IIM patients treated with rituximab in this cohort achieved a significantly higher Total Improvement Score (TIS) response rate than those on conventional immunosuppressants. However, 29.6% of refractory cases still responded poorly to rituximab, and clinically validated biomarkers that can predict response to rituximab remain lacking. We aim to investigate proteome and inflammatory transcriptional profile of refractory IIMs in response to rituximab treatment. Methods We conducted a translational extension of the above cohort study, leveraging prospectively collected PAXgene RNA (12) and serum samples (13) from the rituximab-treated cases to profile inflammatory gene expression and multiplex proteomic signatures in a paired pre- and post-treatment analysis. Male and female patients from diverse ethnic background and with diagnosis of anti-synthetase syndrome, dermatomyositis, immune-mediated necrotising myopathy and overlap myositis participated in the study. A 32-gene custom inflammation panel was assayed on the NanoString nCounter platform and the resulting transcript counts were analysed with nSolver 4.0. Inflammation-related proteins were quantified with the NULISAseq™ Inflammation Panel 250. Significantly differentially regulated proteins (p < 0.05) were selected for protein network analysis and gene ontology pathways. Results Differential gene transcription revealed that MX1, IFI6, IFI44L, ISG15, SOCS1, TNF, IL12-A and PD-L1 were significantly elevated in refractory myositis patients when pre- and post-rituximab-treated patient samples compared with healthy controls. Among inflammatory proteins, IL6, TNFRSF13 and IL36 were identified to be differentially regulated after rituximab treatment. Comparing rituximab responders to non-responders, a distinct set of proteins including IL6ST, IFNW1, IL17A, TNFRSF1, IL36B, and TNSF8, showed significant differential regulation. Gene ontology analysis demonstrated association of these markers with immune response, adaptive immune response, T cell activation, cytokine stimulus and cytokine mediated signalling pathways. Conclusion Refractory myositis patients exhibit up-regulation of the type I interferon pathway, and proteome analysis identified differentially expressed markers, which show promise for predicting rituximab treatment outcome. Further investigations are warranted with larger sample size. Disclosure S.S. Rane: None. X. Lyu: None. P. Gordon: Grants/research support; Alexion (PI at King’s College Hospital for ALXN1210-DM-310), Argenx (PI at King’s College Hospital for ARGX-113-2007 and ARGX-113-2011), Bristol-Myers Squibb (Chief investigator for UK for POETYK SLE), Celltrion Healthcare (Funded to attend EULAR convergence in 2023), Eli Lilly (PI at King’s College Hospital for MOJAK), Galapagos (Advisor or Review Panel Member, Consultant, Chief investigator in UK. H. Gunawardena: None. N. McHugh: None. A. Prabu: None. P. Lanyon: Other; AstraZeneca (Advisor or Review Panel Member), CSL Vifor (Grant/Research Support, Speaker/Honoraria), CSL Vifor (Grant/Research Support, Speaker/Honoraria). J. Miller: None. V. Ong: None. A. Isaacs: None. P. New: None. C. Yee: None. C. Cotton: None. P. Kiely: None. E. Stathopoulou: None. J. Taylor: None. R. Jeffery: None. A. Bharadwaj: None. J.B. Lilleker: None. J.A. Lamb: Grants/research support; Eli Lilly (Grant/Research Support). H. Chinoy: Grants/research support; Eli Lilly (Grant/Research Support). Other; AstraZeneca, Janssen, Pfizer (Advisor or Review Panel Member).

Abstract Background/Aims Organ damage remains an important predictor of morbidity and mortality in systemic lupus erythematosus (SLE). The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) is the only validated clinician completed tool for measuring this. Routinely collected electronic health records (EHR) provide a data source about unselected patients. Optimising the SDI for use in this setting provides the chance for studying SLE damage in a larger, more representative context than traditional hospital cohorts. This study aimed to (1) develop an electronic adaptation of the SDI (eSDI) suitable for use within an EHR dataset, the UK Clinical Practice Research Datalink (CPRD), and (2) examine preliminary associations between damage and mortality. Methods A retrospective cohort study was conducted using CPRD GOLD (study period 1990-2020). Adults (≥18 years) with SLE were selected using our previously published algorithm. Damage items were operationalised from SDI definitions using diagnostic, procedural, and medication codes. Associations between individual and overall damage (eSDI > 0) and mortality were tested using univariate and multivariable logistic regression adjusting for age, sex, smoking, ethnicity, and baseline comorbidities. Odds ratios (OR) with 95% confidence intervals (CI) were reported. Results 8,363 SLE patients were included (87.5% female, mean age 46.7 ± 16 years); 1,004 deaths occurred during follow-up. Overall, 42.3% developed damage (eSDI > 0). The most frequent items were osteoporosis (10.4%), malignancy (8.4%), and cataract (7.4%), with musculoskeletal, ocular, and cardiovascular the most affected domains. Most damage items were associated with increased mortality on univariate analysis. The highest odds were seen for malignancy (OR 6.26, 95% CI 5.27-7.42), pulmonary fibrosis (OR 4.89, 95% CI 3.15-7.48), and significant tissue loss (OR 6.82, 95% CI 2.95-15.60). The presence of any damage (eSDI > 0) was strongly associated with mortality (adjusted OR 4.46, 95% CI 3.57-5.57, p < 0.001) in the multivariable model. Age at diagnosis (OR 1.06, 95% CI 1.05-1.07), male sex (OR 1.40, 95% CI 1.08-1.80), and smoking (OR 1.62, 95% CI 1.29-2.03) were independent predictors of death. Conclusion Assessment of SLE-related organ damage using EHR data is feasible. Damage was common and independently associated with a fourfold increase in the odds of mortality, even after adjustment for demographic and comorbidities. EHR datasets therefore provides a viable and important opportunity for further study of SLE damage in the ‘real world’ setting; further work interrogating the associations between damage and survival as well as patterns of damage will be valuable. Disclosure J. Ellis: None. N. McHugh: None. J.D. Pauling: Honoraria; JDP has undertaken consultancy work and/or received speaker honoraria from Janssen, Astra Zeneca, Boehringer Ingelheim, IsoMab, Sojournix Pharma and Permeatus Inc. I. Bruce: Consultancies; INB has received consulting fees from AstraZeneca, Eli Lilly, GSK, Takeda, UCB and Dragonfly Therapeutics. Honoraria; INB was a speaker for AstraZeneca, Janssen, GSK and UCB. Grants/research support; INB has received grant support from GSK, Janssen and Astra Zeneca. S. Gor: None. J.H. Humphreys: None. H. Vaughan-Williams: None. E. Korendowych: None. S. Skeoch: None. A. McGrogan: None.

OBJECTIVES:Evidence evaluating effectiveness of biologic and targeted synthetic DMARDs (b/tsDMARDs) in adults with PsA after exposure to three or more b/tsDMARDs is lacking. We aimed to evaluate response to sequential lines of b/tsDMARDs. METHODS:In this multicentre retrospective observational study, 22 hospitals submitted data from routine clinic appointments of patients with PsA treated with b/tsDMARDs. Purposive sampling obtained a study population exposed to advanced lines of therapy. Effectiveness outcome measures (Psoriatic Arthritis Response Criteria [PsARC]/tender joint count [TJC]/swollen joint count [SJC]) at baseline and first follow-up (12-16 weeks) for each line were recorded. Odds of achieving PsARC in 2nd/3rd line were compared with 4th+ line. RESULTS:Four hundred and thirty-seven participants (163 male, 274 female) and 1459 treatment courses were included: 430 1st line, 633 2nd/3rd line and 396 4th+ line. The adjusted odds ratio (95% CI) for achieving PsARC in 1st line vs 2nd/3rd line was 1.91 (1.40, 2.60) and 4th+ line vs 2nd/3rd line was 1.13 (0.84, 1.55). There was no significant difference in change from baseline TJC/SJC between 2nd/3rd and 4th+ lines. CONCLUSION:In this cohort the highest chance of a positive PsARC response was to 1st line b/tsDMARD: twice the chance of response vs 2nd/3rd line. The chance of a positive PsARC response to 4th+ lines of b/tsDMARD was not significantly different from 2nd/3rd lines after adjustment. This indicates that patients in a UK cohort can continue to have a meaningful response to later lines of treatment. This is the first available evidence of response to later lines of b/tsDMARD treatment in PsA.

Objectives:SLE, the exemplar autoimmune multisystem disease, is still burdened by excess morbidity and mortality. Damage is a key mediator of this. Studies of damage in outside-of-hospital cohorts are lacking, limiting understanding of real-world patient outcomes. The objectives were thus to design an instrument for measurement of SLE organ damage (eSDI) usable within a UK electronic primary care healthcare database [Clinical Practice Research Datalink (CPRD)] and describe the accrual of damage and mortality associations in an SLE cohort. Methods:A cohort of SLE individuals, including incident and prevalent cases, was identified in the CPRD. Organ damage item definitions were made usable for the electronic registry setting. Prevalence of damage in the overall cohort was described using descriptive statistics. Associations with mortality and damage (expressed in two ways, SDI > 0 ever, or modelled as a continuous cumulative variable) were examined using multivariable logistic regression, Kaplan-Meier analysis and extended Cox proportional hazards analysis in the incident SLE population. Results:We identified 8363 SLE patients in total, of whom the eSDI measured damage in 3537 (42.3%). The most common items were osteoporosis (10.39%), malignancy (8.4%) and cataract (7.4%). Damage across all organ systems was associated with an increased odds of death (e.g. malignancy [odds ratio 6.33 (95% CI 5.34, 7.49)]. Development of damage (eSDI >0 or as a numerical damage score) was significantly associated with an increased hazard of mortality. Conclusion:The use of an adapted eSDI for community electronic health records is feasible and enables widening of the study of damage and its morbidity and mortality consequences to primary care populations. This is more likely to reflect the real-world accumulation and outcomes of damage over time in SLE.

Introduction Psoriatic arthritis (PsA) is a form of inflammatory arthritis linked to psoriasis. Previous research from the UK has found that many people feel unsupported when diagnosed with PsA and lack confidence in managing their condition. This realist review aims to understand what works and does not work for whom and in what circumstances, in relation to healthcare professionals engaging with people to support them in developing self-management skills.Methods and analysis This protocol was developed by defining the scope of the review, using a brief directed literature review to support discussion by an expert group of researchers, healthcare professionals and a patient partner. A theoretical domains framework was generated, consisting of nine initial programme theories. These were further refined with input from Patient and Public Involvement and Engagement groups and used to develop a database search strategy.A systematic search of MEDLINE, CINAHL, Embase, Emcare and APA PsycINFO will be carried out, supplemented by citation tracking, exploration of grey literature and a mixed methods survey of rheumatology health professionals. Data selection will be performed by a minimum of two reviewers and data from included sources will be extracted using a template. Data will be synthesised narratively with respect to the identified initial programme theories, using these data to refine or refute these theories. This will generate refined programme theories to explain what works for whom and in what circumstances.Ethics and dissemination Ethical approval for the health professionals survey was granted through the Research Ethics Committee, University of the West of England (Project ID: 10991848). Outputs will be disseminated to the research community through conference presentations and a peer-reviewed journal article. The strategy for sharing outputs with patients and health professionals will be discussed and agreed with knowledge user groups.

OBJECTIVES:Immune mediated inflammatory diseases (IMID) affect women of childbearing age, yet there is a lack of evidence about the risk of adverse pregnancy outcomes and the interaction with medication. This study aims to characterize prescribing patterns and pregnancy outcomes in women with an IMID diagnosis. METHODS:Pregnancies to women with rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PsO), spondyloarthritis (SpA) and inflammatory bowel disease (IBD) were identified within the Clinical Practice Research Datalink, between 1 January 2000 and 31 June 2020, and matched to pregnancies in women with no such diagnosis. Drug prescribing patterns were described during and surrounding pregnancy. The risk of spontaneous pregnancy loss and major congenital malformations (MCMs) were evaluated compared with women without an IMID. Exposure to commonly prescribed disease-modifying anti-rheumatic drugs was evaluated. RESULTS:The risk of a spontaneous pregnancy loss ranged from adjusted hazard ratio (HRadj) 1.01 (95% CI: 0.79, 1.28) for PsA to HRadj 1.18 (95% CI: 1.07, 1.30) for IBD when compared with women without these conditions. No significant increases in the overall risk of MCMs were observed, with the exception of IBD where it reached borderline significance based on sensitivity analyses [adjusted odds ratio 1.31 (95% CI: 1.00, 1.71)]. No evidence of an increased risk of spontaneous loss was observed in women taking azathioprine, mesalazine and sulfasalazine. CONCLUSION:We found no increased risk of spontaneous loss in women with RA, PsA or SpA but a small increase in women with psoriasis or IBD. There was a borderline increased risk of all MCMs in offspring of women with IBD, which should be interpreted cautiously because of potential residual confounding.

Objectives: To identify clinical features distinguishing anti-synthetase syndrome (ASyS)-related ILD (ASyS-ILD) from non-ASyS ILD and to compare outcomes across ILD subgroups.Methods: We utilized an international, real-world physician-reported database to compare ASyS-ILD and ILD related to other causes. Comparative analysis was performed against the overall control group, and the five main control ILD disease subgroups. Logistic regression assessed associations with supplemental oxygen use and ILD-hospitalization, and Cox proportional hazards models evaluated associations with all-cause mortality. Results: Among 1,557 ASyS-ILD and 828 controls, ASyS-ILD patients were younger, had more acute onset, and had worse restrictive physiology. Nonspecific interstitial pneumonia (NSIP) was the most common radiological pattern across all groups. In ASyS-ILD, NSIP (55%) was followed by organizing pneumonia (OP, 19%), similar to ILD in dermatomyositis (DM) with and without MDA5 antibodies (NSIP 53% and 64%, OP 32% and 11%, respectively). NSIP remained common in rheumatoid arthritis (RA) and systemic sclerosis (SSc) ILD (39% and 59%) but was followed by usual interstitial pneumonia (36% and 14%). Compared with controls, ASyS-ILD had higher odds of hospitalization (OR 1.81, 95%CI 1.38-2.37). Mortality in ASyS-ILD was primarily pulmonary then cardiovascular, Five-year survival in ASyS-ILD was 94.7% which was comparable or higher than most control subgroups, except anti-MDA5-associated ILD (90.3%). ASyS-ILD had higher all-cause mortality (HR 1.66, 95%CI 1.03–2.66) than controls. Conclusions: ASyS-ILD is characterized by a younger, more acute, and symptomatic onset compared with other ILDs, and is associated with higher hospitalization rates and worse mortality, underscoring its overall more severe clinical course.

Objectives To determine the prevalence of anti-drug antibodies (ADAs) in patients with psoriatic arthritis (PsA) treated with biological disease-modifying antirheumatic drugs (bDMARDs) and to evaluate associations with serum drug levels, clinical efficacy and safety.Methods A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided systematic review was conducted. MEDLINE, Embase and Cochrane CENTRAL were searched from inception to September 2025. Randomised controlled trials and observational studies reporting ADA measurement in adults with PsA receiving bDMARDs were included. The risk of bias was assessed using the Cochrane Risk of Bias Tool 2 and the Risk of Bias in Non-randomised Studies of Interventions.Results 28 studies (19 randomised controlled trials and 9 observational studies) were included. ADA prevalence varied widely between bDMARDs and across studies of the same drug and was not directly comparable due to immunoassay heterogeneity. The highest ADA prevalence was observed with adalimumab, infliximab and golimumab followed by ustekinumab, ixekizumab, certolizumab pegol and guselkumab, while secukinumab and etanercept demonstrated very low or absent immunogenicity. Across tumour necrosis factor (TNF) inhibitor studies, ADAs were consistently associated with lower serum drug levels and reduced clinical response, while concomitant methotrexate was associated with lower ADA prevalence. In contrast, serum drug level and clinical outcome data for interleukin (IL)-17, IL-12/23 and IL-23 inhibitors were limited or lacking. Immunogenicity-related adverse events were uncommon, and evidence was insufficient to establish an association with ADAs across bDMARDs.Conclusion ADA prevalence in PsA varies widely between bDMARDs and across studies of the same bDMARD. ADAs appear most clinically relevant for TNF inhibitors, whereas evidence for other biological classes remains limited. Immunoassay heterogeneity limits comparability, highlighting the need for standardised prospective studies.PROSPERO registration number CRD420251121662.

OBJECTIVES:Our objective was to determine whether early detection of undiagnosed PsA in a primary care psoriasis population improves outcome in physical function at 24 months post-registration. METHODS:A multicentre, prospective, parallel group cluster randomized controlled trial in patients with psoriasis was conducted. Participants with suspected inflammatory arthritis on screening were referred for an assessment of PsA [enhanced surveillance (ES) arm: at baseline, and 12 and 24 months; standard care (SC) arm: at 24 months]. The primary outcome measure was the HAQ Disability Index (HAQ-DI) at 24 months post-registration in participants diagnosed with PsA. RESULTS:A total of 2225 participants across 135 general practitioner practices registered: 1123 allocated to ES and 1102 to SC. The primary analysis population consisted of 87 participants with a positive diagnosis of PsA: 64 in ES, 23 in SC. The adjusted odds ratio (OR) for achieving a HAQ-DI score of 0 at 24 months post-registration in ES compared with SC was 0.64 [95% CI (0.17, 2.38)], and the adjusted OR of achieving a higher (non-zero) HAQ-DI score at 24 months post-registration in ES relative to SC arm was 1.12 (95% CI 0.67, 1.86), indicating no evidence of a difference between the two treatment groups (P = 0.66). CONCLUSION:The trial was underpowered for demonstrating the prespecified treatment effect; in patients with psoriasis there was no evidence that early diagnosis of PsA by ES in primary care changes physical function at 24 months compared with SC. CLINICAL TRIAL REGISTRATION:The TUDOR trial is registered as ISRCTN38877516.

OBJECTIVE:Idiopathic inflammatory myopathies (IIMs, myositis) are rare systemic autoimmune disorders that lead to muscle inflammation, weakness, and extramuscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis data set to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes. METHODS:We performed association analyses on 14,903 individuals (3,206 patients and 11,697 controls) with genotypes and imputed data from the Trans-Omics for Precision Medicine reference panel. Fine-mapping and expression quantitative trait locus colocalization analyses in myositis-relevant tissues indicated potential causal variants. Functional annotation and network analyses using the random walk with restart (RWR) algorithm explored underlying genetic networks and drug repurposing opportunities. RESULTS:Our analyses identified novel risk loci and susceptibility genes, such as FCRLA, NFKB1, IRF4, DCAKD, and ATXN2 in overall IIMs; NEMP2 in polymyositis; ACBC11 in dermatomyositis; and PSD3 in myositis with anti-histidyl-transfer RNA synthetase autoantibodies (anti-Jo-1). We also characterized effects of HLA region variants and the role of C4. Colocalization analyses suggested putative causal variants in DCAKD in skin and muscle, HCP5 in lung, and IRF4 in Epstein-Barr virus (EBV)-transformed lymphocytes, lung, and whole blood. RWR further prioritized additional candidate genes, including APP, CD74, CIITA, NR1H4, and TXNIP, for future investigation. CONCLUSION:Our study uncovers novel genetic regions contributing to IIMs, advancing our understanding of myositis pathogenesis and offering new insights for future research.

OBJECTIVES:This study aimed to compare time to diagnosis among patients with psoriatic arthritis (PsA) with that of patients with rheumatoid arthritis (RA) and compare initial treatment and outcomes. METHODS:Patients with PsA were identified from the National Early Inflammatory Arthritis Audit between May 2018 and October 31, 2019, and matched to patients with RA (1:1) on age and sex. Patient characteristics and time to diagnosis were compared between PsA and RA groups. Further comparisons were made, restricted to matched pairs of patients with polyarticular PsA, including disease activity, disease impact, and treatment initiation. RESULTS:In total, 2120 patients with PsA were matched to patients with RA, of which 1250 had polyarticular disease. Symptom duration before referral was longer in patients with PsA than that in patients with RA. Patients with PsA had a longer time from general practitioner (GP) presentation to diagnosis (mean, 112 v 89 days; hazard ratio [HR], 0.87; 95% CI, 0.79-0.96; P = .007), including a delay in diagnosis once referrals were received in secondary care (HR, 0.86; 95% CI, 0.80-0.95; P = .002). In patients with polyarticular disease, less disease-modifying antirheumatic drugs (DMARDs) were prescribed at baseline to patients with PsA compared with those to patients with RA (54.0% and 69.0%, respectively; P < .001). Patients with RA had a higher Disease Activity Score in 28 joints at baseline, but by 3 months, the average score was 0.27 (95% CI, 0.13-0.4) higher in patients with PsA. CONCLUSIONS:Compared with patients with RA, patients with PsA have a longer duration of symptoms before referral and a longer interval between presentation to the GP and receiving a diagnosis. Most people agreed a treat-to-target strategy but fewer DMARDs were commenced for patients with PsA than those for patients with RA and a lower improvement in disease activity was achieved at 3 months, suggesting undertreatment.

OBJECTIVES:Develop an interpretable machine learning model to detect patients with newly diagnosed psoriatic arthritis (PsA) in a cohort of psoriasis patients and identify important clinical indicators of PsA in primary care. METHODS:We developed models using UK primary care electronic health records from the Clinical Practice Research Datalink (CPRD). The study population consisted of a cohort of (PsA free) patients with incident psoriasis who were followed prospectively. We used Bayesian networks (BNs) to identify patients who developed PsA using primary care variables measured prior to diagnosis and compared the results to a random forest (RF). Variables included patient demographics, musculoskeletal symptoms, blood tests, and prescriptions. The importance of each variable used in the models was evaluated using permutation variable importance. Model discrimination was measured using the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (PRAUC). RESULTS:We identified a cohort of 122,330 patients with an incident psoriasis diagnosis between 1998 and 2019 in the CPRD, of whom 2460 patients went on to develop PsA. Our best BN achieved an AUC of 0.823, and PRAUC of 0.221, compared to the AUC of 0.851 and PRAUC of 0.261 of the RF. Psoriasis duration, nonsteroidal anti-inflammatory drug prescriptions, nonspecific arthritis, nonspecific arthralgia, and C-reactive protein blood tests were all important variables in our models. CONCLUSIONS:We were able to identify psoriasis patients at higher risk, and important indicators, of PsA in UK primary care. Further work is required to evaluate our model's usefulness in assisting PsA screening.

Idiopathic inflammatory myopathies (IIM) are a group of rare autoimmune diseases that cause muscle inflammation and can present as overlapping syndrome with other connective tissue diseases. Up to 70% of patients will have a myositis-specific and/or myositis-associated antibodies. Autoantibodies help clarify the diagnosis and provide important prognostic information in relation to the risk of associated interstitial lung disease and other complications. Anti DNA damage binding antibody (anti-DDB1) is an autoantibody previously linked to IIM, which has not been reported widely in literature. We present a case of 73-year-old female with autoimmune connective tissue disease, who was found to have anti-DDB1 antibody. A 73-year-old female presented to secondary care with dyspnoea and productive cough developing over 2-3 months. Her past medical history included hyperthyroidism and mild emphysema. CT chest showed fibrotic NSIP and a pericardial effusion in addition to oesophageal dilation. Additional symptoms included joint pain and Raynaud’s phenomenon. Initial laboratory investigations identified a positive ANA (speckled pattern), myositis and scleroderma immunoblot were positive for Anti Ro-52. Cardiac biomarkers were elevated with Troponin I of 74 and creatine kinase (CK) just above normal range at 217. A clinical diagnosis of systemic sclerosis/myositis spectrum autoimmune connective tissue disease was made. Given the rapid onset of interstitial lung disease (ILD) and suspicion of cardiac involvement (later supported on cardiac MRI) the patient completed 6 cycles of cyclophosphamide, followed by mycophenolate mofetil. She responded to treatment and remains clinically stable. Extended spectrum autoantibody testing was undertaken at the University of Bath using radio-immunoprecipitation. An unknown ∼120KDa band was identified which was sent for mass spectrometry analysis. This autoantigen was identified as Anti-DDB1. The detection of anti-DDB1 offers new insights into the broader spectrum of IIM-related autoantibodies. This is the second description of anti-DDB1 in the literature. Anti-DDB1 was previously described in six Japanese patients, who had mild IIM without organ involvement. Our case highlights that these autoantibodies can also be associated with more severe disease, with both pulmonary and cardiac involvement. Further information is needed on the prevalence of anti-DDB1 in different populations and the clinical spectrum associated with these autoantibodies. The wider detection of novel autoantibodies, such as anti-DDB1, may help refine diagnostic criteria and improve patient outcomes in connective tissue diseases. Anti-DDB1 is an autoantibody associated with IIM spectrum disease. Patients may have organ involvement including rapidly progressive interstitial lung disease and myocarditis. Given the limited information available regarding anti-DDB1, further research is needed to assess its utility in the diagnosis, management, and prognosis of IIM. Understanding the role of anti-DDB1 in IIM could lead to more tailored therapeutic approaches and better outcomes for patients, especially those with atypical or overlapping autoimmune syndromes. H. Toye: None. A. Aziz: None. F. McMorrow: None. H. Lu: None. N. McHugh: None. S. Tansley: Honoraria; Honorarium from Boehringer Ingelhiem.

OBJECTIVES:To develop and evaluate the performance of multicriteria decision analysis (MCDA)-driven candidate classification criteria for antisynthetase syndrome (ASSD). METHODS:A list of variables associated with ASSD was developed using a systematic literature review and then refined into an ASSD key domains and variables list by myositis and interstitial lung disease (ILD) experts. This list was used to create preferences surveys in which experts were presented with pairwise comparisons of clinical vignettes and asked to select the case that was more likely to represent ASSD. Experts' answers were analysed using the Potentially All Pairwise RanKings of all possible Alternatives method to determine the weights of the key variables to formulate the MCDA-based classification criteria. Clinical vignettes scored by the experts as consensus cases or controls and real-world data collected in participating centres were used to test the performance of candidate classification criteria using receiver operating characteristic curves and diagnostic accuracy metrics. RESULTS:Positivity for antisynthetase antibodies had the highest weight for ASSD classification. The highest-ranked clinical manifestation was ILD, followed by myositis, mechanic's hands, joint involvement, inflammatory rashes, Raynaud phenomenon, fever, and pulmonary hypertension. The candidate classification criteria achieved high areas under the curve when applied to the consensus cases and controls and real-world patient data. Sensitivities, specificities, and positive and negative predictive values were >80%. CONCLUSIONS:The MCDA-driven candidate classification criteria were consistent with published ASSD literature and yielded high accuracy and validity.

Background: Prognostic prediction tools to identify people with psoriasis at risk of developing psoriatic arthritis (PsA) are an active area of research [1]. However, existing methods often rely on secondary care cohort studies which can lead to a small sample size and restrict model complexity. The Clinical Practice Research Datalink (CPRD) is a large, population based longitudinal cohort which presents the opportunity to develop Dynamic Prediction Models (DPMs). DPMs allow us to account for changes over time and update predictions using the most recent covariate information. One way to do this is by using landmark models, which have been used for similar purposes in other disease areas [2]. Objectives: To develop a DPM to identify predictors for the development of PsA in UK primary care. Methods: We conducted a cohort study using routinely collected UK primary care data from the CPRD. Patients with incident psoriasis aged between 16 and 89, and no prior evidence of PsA, were identified and followed between 1998 to 2019. Relevant clinical predictors were identified using Read codes, with code list developed in consultation with rheumatologists. These included musculoskeletal symptoms, blood tests and prescriptions, building on prior work by Green [3]. Patient demographics including age, gender, BMI, alcohol, and smoking status were also included in the model. A DPM was developed using a landmark analysis framework [4]. Landmarks are time points in the study period from which we wish to make predictions, with models fitted using the subset of the patients still at risk at that time and their most recent covariate information. We used annual landmarks post psoriasis diagnosis to predict the development of PsA within 3 years. We fitted a Cox proportional hazards model, allowing a different baseline hazard for each landmark to produce a single set of variable coefficients. We report the hazard ratio and 95% confidence intervals. Variable selection was conducted using a lasso method with 5-fold cross validation to balance model complexity and predictive accuracy. Results: We identified 122,330 incident cases of psoriasis of whom 2,460 developed PsA, with a median follow up time of 5.67 years. Hazard ratios and 95% confidence intervals are shown in Figure 1 for the demographic variables, and Figure 2 for the clinical variables. From Figure 1, we see the highest hazard ratios in age categories between 30 and 50, and the lowest in those over 60. We also see an increased risk in men, and those with BMI categories over 25. Of note, we found an increased risk of developing PsA in patients with a primary care C-reactive protein (CRP) blood test, regardless of the result of the test (Figure 2). We also found an association in those with a high plasma viscosity (PV). Psoriasis treatment, which included phototherapy or prescriptions for acitretin, ciclosporin, or dimethyl fumarate was also associated with an increased risk (HR 2.61, 95% CI 2.21 – 3.09), which could be a proxy for psoriasis severity. Patients with a non-steroidal anti-inflammatory drug (NSAID) prescription also showed an elevated risk (2.24, 2.09 – 2.39). From the musculoskeletal symptoms, we found the largest hazard ratios in patients with Read codes for unspecified arthritis (not associated with a particular joint) (2.67, 2.32 – 3.09), finger pain (2.28, 1.89 – 2.75) and knee swelling (2.22, 1.78 – 2.77). Conclusion: We used a landmarking approach that accounts for changes over time to identify factors for the development of PsA. Future work will focus on out-of-sample predictions using alternative models that are tailored towards prediction, under the same landmarking framework. REFERENCES: [1] Eder et al. Arthritis & Rheumatology (2023) doi: 10.1002/art.42661.[2] Keogh et al. Epidemiology (2019) doi: 10.1097/EDE.0000000000000920.[3] Green et al. Rheumatology (2022) doi: 10.1093/rheumatology/keab310.[4] van Houwelingen, & Putter (2012) CRC Press. doi: 10.1201/b11311. Acknowledgements: UCB Biopharma SRL provided funding support in the context of this Investigator Initiated Study. Disclosure of Interests: Alex Rudge UCB, Neil McHugh Janssen, UCB, William Tillett Abbvie, Amgen, BMS, Celgene, Eli-Lilly, GSK, Janssen, MSD, Novartis, Ono-Pharma, Pfizer, UCB, Abbvie, Amgen, Celgene, Eli-Lilly, Janssen, Pfizer, UCB, Theresa Smith: None declaredFigure 1HRs and 95% CIs for Demographic Variables. Figure 2HRs and 95% CIs for Clinical and Laboratory Variables.