Early Arthritis Research Articles

Disentangling heterogeneity in contemporary undifferentiated arthritis – A large cohort study using latent class analysis

ObjectivesUndifferentiated arthritis(UA) is clinically heterogeneous and differs in outcomes ranging from spontaneous resolution to RA-development. Therefore, we hypothesized that subgroups exist within UA and we aimed to identify homogeneous groups based on clinical features, and thereafter to relate these groups to the outcomes spontaneous resolution and RA-development. These outcomes can only be studied in UA-patients in which DMARD-treatment does not influence the natural disease course; these cohorts are scarce. MethodsWe studied autoantibody-negative UA-patients (not fulfilling 1987/2010 RA-criteria, no alternate diagnosis), included in the Leiden Early Arthritis Clinic between 1993 and 2006, when early DMARD-treatment in UA was infrequent. Latent class analysis was used to identify subgroups based on combinations of clinical features. Within these subgroups, test-characteristics were assessed for spontaneous resolution of arthritis and RA-development within 1 year. Results310 consecutive UA-patients were studied. Five classes were identified: location and number of swollen joints were most distinguishing. Classes were characterized by: 1) polyarthritis, often symmetric; 2) oligoarthritis, frequently with subacute onset; 3) wrist-monoarthritis, often with subacute onset, increased BMI and without morning stiffness; 4) small-joint monoarthritis, often without increased acute phase reactants, and 5) large-joint monoarthritis, often with subacute onset. Studying the classes in relation to the outcomes revealed that patients without spontaneous resolution (thus having persistent disease) were nearly absent in the classes characterized by monoarthritis (specificity >90%). Additionally, patients who developed RA were infrequent in monoarthritis classes (sensitivity <7%). ConclusionUsing a data-driven unsupervised approach, five subgroups within contemporary UA were identified. These have differences in the natural course of disease.

Humoral responses against HDL are linked to lipoprotein traits, atherosclerosis, inflammation and pathogenic pathways during early arthritis stages

Humoral responses against HDL are linked to lipoprotein traits, atherosclerosis, inflammation and pathogenic pathways during early arthritis stages

Isolated, displaced, talar body fracture: a case report and literature review.

Talar body fractures are uncommon fractures of the foot and its management results to be very hard due to retrograde vascularization and wide articular cartilage coverage of talar surface, which could easily lead to poor functional outcomes, avascular osteonecrosis and early post traumatic arthritis. We describe a case of displaced, vertical, talar body fracture in a 41-year-old patient treated with reduction and fixation by talar anteromedial approach coupled to medial malleolar osteotomy to better expose the fracture. Our literature review has found few studies, in addition with a low level of statistical evidence. We advocate for more studies with a bigger sample and with a design of randomized control trials.

A new serum biochemical marker of synovium turnover predicts radiographic progression in patients with early arthritis.

To investigate whether serum Col 3-4, a new biochemical marker of synovial tissue turnover, was associated with progression of joint damage in patients with early arthritis. A total of 788 early arthritis patients (<6 months of symptoms, 82% diagnosis of RA, 18% undifferentiated arthritis) from the prospective ESPOIR study were investigated. Progression was defined as an increase of 1 or 5 unit(s) in radiographic van der Heijde modified Sharp score between baseline and 1 or 5 years, respectively. Associations between baseline Col 3-4 and progression were assessed by logistic regression. Each standard deviation increase of baseline Col 3-4 levels was associated with an increased 5-yr total damage progression with an odds ratio (OR, 95% CI) of 1.51 (1.21, 1.88), which remained significant when DAS28, C-reactive protein and anti-citrullinated protein antibodies positivity were included in the model [OR (95% CI): 1.34 (1.01, 1.76)]. Further adjustment for bone erosion did not modify the association. Patients with both Col 3-4 in the highest quintile and bone erosion had a >2-fold higher risk of progression [OR (95% CI): 7.16 (2.31, 22)] than patients with either high Col 3-4 [2.91 (1.79, 4.73)] or bone erosion [2.36 (2.38, 3.70)] alone. Similar associations were observed for prediction of 12 months progression. Increased serum Col 3-4 is associated with a higher risk of structural progression, independently of major risk factors. Col 3-4 may be useful in association with bone erosion to identify patients with early arthritis at higher risk.

Improving our understanding of the paradoxical protective effect of obesity on radiographic damage: a large magnetic resonance imaging-study in early arthritis.

Obesity conveys a risk for RA development, while paradoxically, associating with less radiographic progression after RA diagnosis. Using MRI we can study this surprising association in detail from MRI-detected synovitis and osteitis to MRI-detected erosive progression, which precedes radiographic progression. Previous research suggested obesity associates with less osteitis and synovitis. We therefore aimed to (i) validate the previously suggested association between BMI and MRI-detected osteitis/synovitis; (ii) study whether this is specific for ACPA-positive or ACPA-negative RA or also present in other arthritides; (iii) study whether MRI-detected osteitis associates with MRI-detected erosive progression; and (iv) study whether obesity associates with MRI-detected erosive progression. We studied 1029 early arthritis patients (454 RA, 575 other arthritides), consecutively included in Leiden Early Arthritis Clinic. At baseline patients underwent hand-and-foot MRI that were RAMRIS-scored, and 149 RA patients underwent follow-up MRIs. We studied associations between baseline BMI and MRI-detected osteitis/synovitis (using linear regression), and erosive progression (using Poisson mixed models). In RA, higher BMI associated with less osteitis at disease onset (β = 0.94; 95% CI: 0.93, 0.96) but not with synovitis. Higher BMI associated with less osteitis in ACPA-positive RA (β = 0.95; 95% CI: 0.93, 0.97), ACPA-negative RA (β = 0.97; 95% CI: 0.95, 0.99) and other arthritides (β = 0.98; 95% CI: 0.96, 0.99). Over 2 years, overweight and obesity associated with less MRI-detected erosive progression (P = 0.02 and 0.03, respectively). Osteitis also associated with erosive progression over 2 years (P < 0.001). High BMI relates to less osteitis at disease onset, which is not confined to RA. Within RA, high BMI and less osteitis associated with less MRI-detected erosive progression. This suggests that the protective effect of obesity on radiographic progression is exerted via a path of less osteitis and subsequently fewer MRI-detected erosions.

Safety outcomes in patients with rheumatoid arthritis treated with abatacept: results from a multinational surveillance study across seven European registries

BackgroundPatients with rheumatoid arthritis (RA) have an increased risk of infection and malignancy compared with the general population. Infection risk is increased further with the use of disease-modifying antirheumatic drugs (DMARDs), whereas evidence on whether the use of biologic DMARDs increases cancer risk remains equivocal. This single-arm, post-marketing study estimated the incidence of prespecified infection and malignancy outcomes in patients with RA treated with intravenous or subcutaneous abatacept.MethodsData were included from seven European RA quality registries: ATTRA (Anti-TNF Therapy in Rheumatoid Arthritis [Czech Republic]), DANBIO (Danish Rheumatologic Database), ROB-FIN (National Registry of Antirheumatic and Biological Treatment in Finland), ORA (Orencia and Rheumatoid Arthritis [France]), GISEA (Italian Group for the Study of Early Arthritis), BIOBADASER (Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases), and the SCQM (Swiss Clinical Quality Management) system. Each registry is unique with respect to design, data collection, definition of the study cohort, reporting, and validation of outcomes. In general, registries defined the index date as the first day of abatacept treatment and reported data for infections requiring hospitalization and overall malignancies; data for other infection and malignancy outcomes were not available for every cohort. Abatacept exposure was measured in patient-years (p-y). Incidence rates (IRs) were calculated as the number of events per 1000 p-y of follow-up with 95% confidence intervals.ResultsOver 5000 patients with RA treated with abatacept were included. Most patients (78–85%) were female, and the mean age range was 52–58 years. Baseline characteristics were largely consistent across registries. Among patients treated with abatacept, IRs for infections requiring hospitalization across the registries ranged from 4 to 100 events per 1000 p-y, while IRs for overall malignancy ranged from 3 to 19 per 1000 p-y.ConclusionsDespite heterogeneity between registries in terms of design, data collection, and ascertainment of safety outcomes, as well as the possibility of under-reporting of adverse events in observational studies, the safety profile of abatacept reported here was largely consistent with previous findings in patients with RA treated with abatacept, with no new or increased risks of infection or malignancy.

Comparison of phenotypic properties of innate lymphoid cells at various stages of rheumatoid arthritis

Autoimmune diseases currently take a leading place in terms of frequency of occurrence in the population, among which 1 percent is occupied by rheumatoid arthritis (RA). Remission in this type of disease is extremely rare and requires constant use of pharmacotherapy. Studying the pathogenesis of RA is necessary to study to search for new drug targets. It is known that T helpers 1 (Th) and Th17 are involved in the development of RA. However, some researchers suggest that ILCs play a role in the development of RA. ILCs are “innate analogues” of Th, due to the fact that this subpopulation synthesizes the same cytokines. ILC1 is innate analogs of Th1, ILC2-Th2, ILC3-Th17. ILCs are tissue-resident innate lymphoid cells that have functional diversity and regulate the direction of the immune response through the production of cytokines.We used peripheral blood mononuclear cells (PBMCs) from patients (n = 19) and conditionally healthy donors (n = 10) as material. The group of patients was divided biologic disease-modifying anti-rheumatic drugs (bDMARDs) and Metotrexate (MTX) and of stage of RA (early and very early arthritis, advanced and late). PBMCs were stained with monoclonal antibodies. ILCs were identified as Lin-CD127+, CD294+ILCs (ILC2) were measured in the general population, CD117-CD294-ILCs were identified as ILC1, and CD117+CD294-ILCs were identified as ILC3.We obtained the following results: ILC1 was significantly reduced in patients treated with MTX comparison with patients on bDMARDs and healthy donors. However, patients on MTX with advanced RA had low levels of ILC2 and ILC3 compared to patients on bDMARDs. ILC2 significantly increased in patients with early stages of RA comparison with patients with advanced RA. However, ILC1 was significantly reduced in patients treated with MTX, and ILC3 increased significantly in patients treated with MTX comparison with bDMARDs. Expression of PD1 on ILC1 was increased compared to patients treated with bDMARDs. However, ILC3 patients with advanced stages on MTX had increased expression of PD1 comparison with patients taking bDMARDs. The ILC3 of donors was significantly increased comparison with patients on bDMARDs.

Characterisation of prodromal and very early psoriatic arthritis: a systematic literature review informing a EULAR taskforce

BackgroundIdentifying subjects at risk of imminent psoriatic arthritis (PsA) would allow these subjects to participate in therapeutic interventions to delay or prevent PsA development.MethodsA systematic literature review (SLR) was conducted...

Online Patient-Reported Outcome Measure Engagement is Dependent on Demographics and Locality: Findings From an Observational Cohort.

Online patient-reported outcome measures (PROMs) enable remote collection of perceptions of health status, function, and well-being. We aimed to explore patterns of PROM completion in patients with early inflammatory arthritis (EIA) recruited to the National Early Inflammatory Arthritis Audit (NEIAA). NEIAA is an observational cohort study design; we included adults from this cohort with a new diagnosis of EIA from May 2018 to March 2020. The primary outcome was PROM completion at baseline, 3 months, and 12 months. Mixed effects logistic regression and spatial regression models were used to identify associations between demographics (age, gender, ethnicity, deprivation, smoking, and comorbidity), clinical commissioning groups, and PROM completion. Eleven thousand nine hundred eighty-six patients with EIA were included, of whom 5331 (44.5%) completed at least 1 PROM. Patients from ethnic minority backgrounds were less likely to return a PROM (adjusted odds ratio [aOR] 0.57, 95% CI 0.48-0.66). Greater deprivation (aOR 0.73, 95% CI 0.64-0.83), male gender (aOR 0.86, 95% CI 0.78-0.94), higher comorbidity burden (aOR 0.95, 95% CI 0.91-0.99), and current smoker status (aOR 0.73, 95% CI 0.64-0.82) also reduced odds of PROM completion. Spatial analysis identified 2 regions with high (North of England) and low (Southeast of England) PROM completion. We define key patient characteristics (including ethnicity) that influence PROM engagement using a national clinical audit. We observed an association between locality and PROM completion, with varying response rates across regions of England. Completion rates could benefit from targeted education for these groups.

ANKLE ARTHRODESIS USING TTC (TIBIOTALOCALCANEAL) NAIL IN THE TREATMENT OF NEGLECTED TRIMALLEOLAR FRACTURES OF ANKLE WITH EARLY ARTHRITIS; CASE REPORT

Introduction: Patients rst consult traditional healers and it is when the signs persist that they consult the surgeon for a swollen and painful ankle. Initially we always performed anatomical repairs with osteosynthesis, but the majority of patients still complained of pain and disability. We therefore performed an arthrodesis on neglected post-traumatic ankles. The objective of our study was to describe the result of arthrodesis ankle using TTC (tibiotalocalcaneal) nail on a neglected post-traumatic ankle and to propose a therapeutic indication in the face of any neglected ankle fracture. This was a case of 38/m with 3 months old neglected trimalleolar ankle fr Material and Method: acture with early arthritis treated with ankle arthrodesis using ttc nail. Follow up taken over 3 months by serial x-rays and clinical evaluation. The average follow-up was 3 months and our results were satisfactory radiologically and Results: clinically. Discussion: Arthrodesis with ttc nail appears here as an important alternative in the treatment of neglected ankle fractures with early changes of arthritis

Comment: Humoral responses against HDL are linked to lipoprotein traits, atherosclerosis, and pathogenic pathways during early arthritis stages: Reply.

Journal Article Accepted manuscript Comment: Humoral responses against HDL are linked to lipoprotein traits, atherosclerosis, and pathogenic pathways during early arthritis stages: Reply Get access Javier Rodríguez-Carrio, Javier Rodríguez-Carrio Area of Immunology, Department of Functional Biology, Faculty of Medicine, University of Oviedo, Oviedo, SpainInstituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain Corresponding author: Javier Rodríguez-Carrio, MSc, PhD, Area of Immunology, Department of Functional Biology, Faculty of Medicine, University of Oviedo, Campus El Cristo, C/Julián Clavería s/n, L-19, 33006—Oviedo, Spain, E-mail: rodriguezcjavier@uniovi.es Phone number: +34 98510 2789 Search for other works by this author on: Oxford Academic PubMed Google Scholar Ana Suárez Ana Suárez Area of Immunology, Department of Functional Biology, Faculty of Medicine, University of Oviedo, Oviedo, SpainInstituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, kead205, https://doi.org/10.1093/rheumatology/kead205 Published: 09 May 2023 Article history Received: 25 April 2023 Accepted: 03 May 2023 Published: 09 May 2023

Methotrexate treatment in early psoriatic arthritis in comparison to rheumatoid arthritis: an observational nationwide study

IntroductionWe aimed to compare the proportions of patients with newly diagnosed psoriatic arthritis (PsA) and rheumatoid arthritis (RA) remaining on methotrexate (regardless of other disease-modifying antirheumatic drug (DMARD)-changes), and proportions...

A PROSPECTIVE STUDY TO EVALUATE EFFECTIVENESS OF KINESIO TAPING IN NON-TRAUMATIC CHRONIC KNEE PAIN

Background: Kinesio tape has multiple benefits including decreasing pain, increasing proprioception, increasing quadriceps muscle strength, and improving lymphaticcirculation at the knee joint. To evaluate the effectiveness of kinesiotape innon traumatic chronic knee pain. Material and Methods: Aprospective study was done from august 2020 to January 2022 in nscb medical college jabalpur on 80 patients with patello femoral arthritis of knee joint and early grade medial joint line arthritis of knee joint(kellgenlawrencegrading) in which kinesio tape was applied over knee for 6 days by an orthopaedicsurgeonand followed up at end of 1st , 2nd , 3rd , 4th week and outcomes were measured using WOMAC(western Ontario and mcmaster university arthritis index) and Vas(visual analogue scale) scores. Results: VAS score(pre application:7.12, after 4 weeks:4.68)and WOMAC score( pre application:46.18, after 4 weeks:35.65)showed a statistically decrease in scores in cases of patellofemoral arthritis and early grade medial joint line arthritis of knee joint.(p value &lt;0.001) Conclusion: Kinesio tape appears to beaneffective,easy and cheap method in early symptomaticpatello femoralosteoarthritis and early grade medial joint line arthritis of knee joint.

OA41 Online MDT patient education for early inflammatory arthritis

Abstract Background/Aims Patient education in early inflammatory arthritis (EIA) promotes understanding and engagement with treatment, empowering patients to use self-management in their long-term health condition. It is embedded in national guidance and audit. Individual appointments are time consuming, and groups sessions became impossible during the COVID-19 pandemic. Our education sessions have evolved to a monthly online meeting which aims to be engaging, effective and time efficient. Methods Face-to-face group education afternoons were previously embedded into our early arthritis pathway. Presentations and opportunities for questions were given by a rheumatology consultant, nurse, physiotherapist, podiatrist and occupational therapist. Sessions lasted 2 hours and local charity representatives attended. Group education sessions completely stopped with the COVID-19 pandemic restrictions. This successful MDT model was moved to a monthly Microsoft Teams meeting and condensed to 1 hour. Sessions continue to consist of five short presentations, introduction to charity representatives and opportunity for questions. Following the session, all patients received links to videos of the talks for future reference, contact details for the MDT and local charities, and a link to download our local rheumatology self management app. Patients who are unable to attend also receive this content by email. Patient feedback was gathered through an online questionnaire. Results Attendance has increased over time with 75% of our new EIA patients now attending each month. Feedback from 16 patients rated 75% of all talks as extremely useful or useful. 89% are interested in attending future meetings. 93% had already used or plan to use our rheumatology self management app. Positive patient feedback included: “the whole team were brilliant giving advice and answering questions”, “nice to see the specialists' faces, and to get the feeling they really cared”, and “a perfectly sensible and productive way to introduce all the options for help and support”. Some patients did not feel confident to ask questions in the meeting. Email and telephone advice lines were signposted. Attendance was increased by 40% by a short telephone reminder of the appointment. Conclusion An online meeting has proven to be a time efficient and effective way of providing multidisciplinary education and introducing self management. A short time investment from each MDT member gives breadth to the education. Inviting all newly diagnosed early arthritis patients and encouraging attendance by a short telephone call has maximised reach. Ensuring all patients are sent presentation videos to re-watch and the self referral details further facilitates self management. The format could easily be adapted to other patient education events. Disclosure C. Gwynne: None. S. Gilbard: None. Z. Weller: None. M. Clemence: None. C. Parsons: None. R. Penford: None.

P093 Clinical outcomes and care quality standards in young adult patients with early inflammatory arthritis: Results from a national cohort

Abstract Background/Aims Emerging adulthood is a unique developmental period between late adolescence and establishment of personal and social identity associated with adulthood. Emerging adult populations may have distinctive experiences of adult healthcare and their needs may differ from those of older healthcare users. Little is known about the patterns of presentation, experiences of care or disease outcomes of emerging adults in adult rheumatology settings. We used the National Early Inflammatory Arthritis Audit (NEIAA) to describe differences between emerging and older adult patients diagnosed with early inflammatory arthritis (EIA). Methods NEIAA is an observational cohort design study assessing care against National Institute for Health and Clinical Excellence quality metrics. Adults in England and Wales with a confirmed new diagnosis of inflammatory arthritis between May 2018 and April 2022 were grouped into two categories: emerging adults (16-24 years) and older patients (≥25 years). Patient characteristics, disease phenotype (including oligo- or polyarticular presentation) and initial treatment strategy were described. Results A total of 20,472 patients were included. 571 (2.8%) diagnosed with EIA were emerging adults (EA); this group had higher proportions of females (71.8%). Compared to older patients, EA patients were less likely to ever smoke (44.1% vs 69.5%) and had fewer comorbidities. EA patients were more likely to have oligoarticular symptoms (&amp;lt;5 tender and swollen joints; 53% vs 37%). Symptom duration prior to diagnosis was longer for EA patients (46% describing symptom duration &amp;gt;6 months vs 37%). Median Disease Activity Score/DAS28 at presentation was lower (4.2 vs 4.7). There were no differences in symptom burden as measured by the mean musculoskeletal health questionnaire (25 vs 24). EA patients completed fewer patient reported outcomes (33% vs 39%), but were more likely to complete all forms (20% vs 17%). Disease modifying anti-rheumatic drugs treatment strategies appeared similar, although more EA patients did not start medications by three months (26% vs 19%). Fewer EA patients received steroids (56% vs 71%).There were no significant differences between groups in patient numbers referred within three days of symptom onset from primary care or reviewed within three weeks with treatment initiation within six weeks in rheumatology care. More of the EA group were in employment at diagnosis. The EA population reported higher impairment at work (Work Productivity and Activity Index overall score 38% vs 30%, driven by difference in presenteeism). Conclusion Low proportion of EA patients in this EIA population raises concern that the study is not capturing a representative sample of this younger and developmentally distinct population. Available data suggest important differences in time to presentation, disease pattern and pathways of care between EA and older patients. EA population deserves further detailed investigation, exploring frequency and patterns of EIA and identifying particular issues faced when using adult rheumatology services. Disclosure M. Adas: None. N. Arumalla: None. D. Mclaughlin: None. J. Galloway: Honoraria; from AbbVie, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Pfizer, Roche and UCB. J. Ledingham: Other; is a BSR trustee. F. Mcerlane: None.

P047 Experiences of working with early inflammatory arthritis: a qualitative descriptive study

Abstract Background/Aims Work instability and work disability are common consequences of inflammatory arthritis with 40% of people with rheumatoid arthritis in Ireland leaving the workforce in the first five-years of diagnosis. Although medical and drug therapy advances have significantly decreased disease activity and work absenteeism, work loss among employees with inflammatory arthritis remains high and retaining work ability remains a challenge. EULAR self-management recommendations for those with inflammatory arthritis specifically highlight the need to address work issues as part of routine clinical care to successfully support work retention. Current Irish work-based services are suboptimal and could be augmented by an improved understanding of the challenges associated with working with arthritis and clients’ priorities for work interventions in early disease. The aim of this study was to describe the impact of early inflammatory arthritis on work participation. Methods The study design employed a Qualitative Descriptive (QD) framework and was guided by the COREQ criteria to for designing and reporting qualitative studies. Thirty individuals (24 women) of working age (age 18-69 years) with inflammatory arthritis (&amp;lt;2 years duration) who were in paid employment or fulltime education were interviewed using one-off semi-structured interviews. Data was analysed using thematic analysis. Results Half of participants (n = 15) reported work disability within the first two-years post diagnosis. Physical and psychosocial sequelae of early disease were reported as negatively impacting work capacity. Prioritisation of work above all other life roles was widely reported in early disease and was synonymous with internalised anxiety and worry reflecting the invisible burden of maintaining employment whilst concurrently adjusting to the diagnosis. Fear, and a forced reconstructed future negatively influenced work participation and perceived work capacity. Disclosure of diagnosis early in the disease trajectory was identified as a sensitive issue. Most participants reported preconceived ideas of negative results of disclosure further adding to internalised worry. However, disclosure was synonymous with positive outcomes and influenced capacity for sustained working. As such, support with disclosure is required to reduce premature work cessation early in the disease trajectory for people with inflammatory arthritis. Conclusion The scale of early work disability in Ireland appears to be higher than previously understood. Although early medical intervention has improved disease management, significant work-based restrictions in early disease remain. Exploring the subjective experience is fundamental when identifying work participation restrictions and should inform the type of work support required. While disclosure of diagnosis in the work environment is associated with anxiety and fear, disclosure is influential in supporting capacity to retain work participation. Internalised and invisible work-related anxieties present early in the disease need to be acknowledged and addressed by healthcare providers as part of routine early healthcare to avoid work disability. Disclosure Y. Codd: None. Á. Coe: None. D. Kane: None. R.H. Mullan: None. T. Stapleton: None.

P129 DNA methylation of the tumour necrosis factor gene as a biomarker of diagnosis in early rheumatoid arthritis patients

Abstract Background/Aims Rheumatoid arthritis (RA) is an autoimmune inflammatory condition that affects the synovial joints. RA exists on a disease continuum where immunological changes occur before the onset of clinical symptoms. Changes in DNA methylation status of genes are thought to be early triggers of the progression from health to disease. Tumour necrosis factor (TNF) is a pro-inflammatory cytokine that contributes to RA. Recently it has been shown that the loss of DNA methylation in the promoter region of the TNF gene is related to early RA. This study aims to establish the predictive value of the levels of DNA methylation of the TNF gene as a biomarker for diagnosis of RA. Methods Blood samples from a retrospective cohort of patients with symptoms of inflammatory arthritis between 2010 and 2019 at the Leeds Early Arthritis Clinic were selected. Data obtained include clinical symptoms of disease progression over 2 years to establish a diagnosis. DNA methylation levels of the TNF gene were measured by quantitative polymerase chain reaction (qPCR) and analysed using binary logistic regression with forward (LR) variable selection for added value as a diagnostic biomarker. Results For the 284 patients with a mean age of 53.8, 202 (71.7%) were female and 82 (28.9%) were male. From N = 284, 190 (66.9%) were diagnosed with RA and 94 (33.1%) with another conditions. The predictive accuracy of the regression model was increased by 3.5% from 85.8% to 89.3% when TNF DNA-methylation levels was added to demographic and clinical variables. The AUC of the model with TNF was 0.940 compared to 0.911 without TNF DNA-methylation levels. The sensitivity and specificity of the prediction with DNA methylation data were 94.6% and 77.9% respectively. This TNF model has a positive predictive value of 90.2% and a negative predictive value of 87.0%. Conclusion DNA methylation of the TNF gene is an important biomarker for RA diagnosis. This study showed that including levels of TNF DNA-methylation improves the accuracy of diagnosing RA. Disclosure M.C. Liu: None. H. Ng: None. F. Ponchel: None.

E045 Clinical triage: Investing in the front door

Abstract Background/Aims The processes and IT systems that support the referral pathway are complex. The focus on referral optimisation and out-patient transformation has provided an opportunity to do things differently. Getting It Right First Time recommendations highlight the importance of ensuring rheumatologists focus on conditions which require specialist rheumatology input. As part of an integrated musculoskeletal (MSK) service we are able to redirect referrals regarding non-inflammatory conditions to our MSK and Community Pain teams. This project evaluates the impact of clinical triage. Methods Consultant-led triage introduced in July 2021. Directory of services updated and met with primary care networks leads to inform them of the changes. Letter co-designed with GPs to send out to patients when referral responded to with immediate specialist advice. Triage job planned with an allocation of 45 minutes per day. Referrals are reviewed on the electronic referral system and accepted, returned or redirected to another service. Standard responses developed to ensure consistency. All triage outcomes recorded in a spreadsheet. Review undertaken of returned referrals to identify any patients who were re-referred. To ascertain the proportion of patients triaged to early inflammatory arthritis (EIA) appointments who were diagnosed with an EIA, National Early Inflammatory Arthritis Audit data was analysed before and after changes to triage. Results Between January and June 2022 we received 1194 referrals; 761 (64%) were accepted, 289 (24%) returned, 43 (4%) redirected to another service and 73 (6%) returned with immediate specialist advice. Of the 289 referrals that were returned, 74 (25%) were returned for more information, 61 (21%) with a request to examine the patient, 118 (41%) were deemed inappropriate, 14 (4%) were patients already under our care and 22 (8%) were returned for other reasons. We received a further referral for 46/74 of those returned for more information, 45/61 following the request to examine the patient, 13/118 of those returned as not felt appropriate and 3/73 of those returned with immediate specialist advice. In total, we saved 278 new patient appointments over a 6-month period. Allowing for the time job planned, this was a net gain of 6 new patient appointments a week. In 2019, 37% of patients seen in an EIA appointment were diagnosed with an EIA compared to 51% in 2022. Conclusion Investment in clinical triage has saved a considerable number of appointments. For some patients it has provided an immediate specialist opinion or redirected them to a more appropriate service. It has helped to ensure that we are seeing patients who require specialist rheumatology input. Next steps are to share this work more widely and develop resources for patients and primary care to help promote a different way of working and delivering specialist advice. Disclosure E. MacPhie: None. S.M. Fish: None. A. Madan: None. C. Rao: None. S. Horton: None.

P042 Using a Genetic PROBability tool (G-PROB) to aid diagnosis of patients with inflammatory arthritis: results from the Norfolk Arthritis Register

Abstract Background/Aims Recent translational advances in genetics report the ability to accurately predict the diagnosis of patients presenting with synovitis, providing potential to accelerate treatment and improve patient outcomes. One tool is G-PROB, which uses genetic information to calculate conditional probabilities, known as G-probabilities ranging from 0 to 100%, for defined diseases. In the original study, G-PROB was configured to discriminate between patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), spondyloarthritis (SpA), gout and “other rheumatological diseases” using reported bias-adjusted odds ratios from 250 known single nucleotide polymorphisms and human leukocyte antigen variants of uncorrelated risk variants. The original study tested G-PROB on 243 patients with synovitis. Our aim was to assess whether G-PROB could aid diagnosis using data from the Norfolk Arthritis Register (NOAR), a large observational cohort of patients with early inflammatory arthritis. Methods Genotypes, and clinician diagnosis were obtained from NOAR. The same prevalence settings and risk variants as the original study were used. Six G-probabilities each corresponding to one disease were created for each patient and performance was assessed using linear regression without intercept, negative and positive predictive values (NPV, PPV), and receiver-operator-curve (ROC) analysis. Results From NOAR, 2031 genotyped patients were identified and underwent case note review to determine the clinician diagnosis. Clinician diagnoses included RA (n = 767), PsA (n = 106), SpA (n = 15), SLE (n = 14), gout (n = 5), and “other” (n = 65). For n = 1059, case notes were not available resulting in exclusion. The mean G-probability was 41% for those which corresponded to clinician-defined disease, which was significantly higher compared to 12% for those that did not (95%CI -0.30 to -0.28). As reported in the original study, G-probabilities were concordant with real disease status (β regression coefficient of 1.03 vs 0.99, where 1.00 is ideal). We found 42% of all G-probabilities were &amp;lt;5%, corresponding to a NPV of 99%, where it was possible to deprioritise &amp;gt;1 disease for 100% of patients, &amp;gt;2 diseases for 96% of patients, and &amp;gt;3 diseases for 69% of patients. We found 17.8% of patients had a single G-probability &amp;gt;50% corresponding to a PPV of 41%. This compared to 45% of patients, and PPV of 64% reported in the original study. Accuracy of G-probabilities to discriminate clinician-defined disease was similar in our cohort (AUC of 0.86 95% CI 0.84-0.87) compared to the original study (AUC 0.84 95% CI 0.81-0.86). In 57% of patients in our cohort, the disease with the highest G-probability corresponded to the clinician-defined disease compared to 53% in the original study. Conclusion We were able to replicate several findings of the original study in a large independent cohort including calibration, high NPV, but PPV was lower, suggesting that G-PROB is most valuable as a tool to rule out diagnoses. Disclosure R.M. Hum: None. S.D. Sharma: None. M. Stadler: None. N. Nair: None. S. Viatte: None. C. Yap: None. J.H. Humphreys: None. A. MacGregor: None. M. Yates: None. M. Soomro: None. S.M. Verstappen: None. P. Ho: None. A. Barton: None. J. Bowes: None.

OA04 Association of clinical and demographic factors with quality of life, functional status, depression, and fatigue in patients presenting with, and at risk of, rheumatoid arthritis

Abstract Background/Aims Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these “at-risk” stages is not well described. This study assessed health-related quality of life (HRQoL), functioning, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) and RA. Methods Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in 838 patients with CSA, UA or RA recruited to the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F, respectively. Descriptive statistics and multivariate linear regression were performed to assess associations between clinical/demographic variables and PROMs. Results Patients with RA at initial presentation had worse PROMs than those with CSA or UA. However, HRQoL was decreased in all groups. In patients with CSA/UA, HRQoL was comparable to data relating to chronic conditions such as heart failure, severe COPD or mild angina from the Health Survey for England (HSE). Associations between predictor variables and PROMs are summarised in Table 1. Increased functional disability was associated with female sex, older age, obesity, lower quintiles of social deprivation, increased disease activity and polypharmacy. HRQoL was associated with increased disease activity and polypharmacy. The severity of depression (PHQ-9) increased with older age, increasing BMI, living in areas with the lowest quintile of social deprivation, increased disease activity and polypharmacy. Fatigue (FACIT-F) was associated with female sex, increasing BMI, disease activity and polypharmacy. After adjusting for the demographic and clinical factors, the diagnosis assigned at baseline did not affect any of the studied PROMs, but disease activity and polypharmacy were strongly linked to poorer scores across all PROMs. Conclusion Patients with musculoskeletal symptoms who are at risk of RA present with a high health burden. Early intervention may be needed to improve quality of life from initial presentation. Disclosure B. Torlinska: Corporate appointments; BT is employed by Visible Analytics Ltd.. Grants/research support; BT receives funding from the NIHR. K. Raza: Consultancies; KR declares personal fees from Abbvie and Sanofi outside of the submitted work. Grants/research support; KR declares funding from Bristol Myers Squibb outside of the submitted work, KR is supported by the NIHR Birmingham Biomedical Research Centre, the MRC Versus Arthritis Centre for Musculoskeletal Ageing Research and the Research into Inflammatory Arthritis Centre Versus Arthritis, University of Birmingham, UK. A. Filer: Grants/research support; AF is supported by the NIHR Birmingham Biomedical Research Centre, the MRC Versus Arthritis Centre for Musculoskeletal Ageing Research and the Research into Inflammatory Arthritis Centre Versus Arthritis, University of Birmingham, UK, AF declares funding outside of the submitted work from Abbvie, Roche, Janssen, UCB, Nascient, Mestag, GSK. G. Jutley: None. I. Sahbudin: None. R. Singh: None. P. de Pablo: None. E. Rankin: None. B. Rhodes: None. N. Amft: None. E. Justice: None. C. McGrath: None. S. Baskar: None. J. Trickey: None. M. Calvert: Consultancies; MC has received personal fees outside of the submitted work from Astellas, Aparito Ltd., CIS Oncology, Takeda, Merck, Daiichi Sanko, Glaukos, GSK, and the Patient-Centered Outcomes Research Institute. Grants/research support; MC is Director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, Director of the Centre for Patient Reported Outcomes Research and is a NIHR Senior Investigator, MC receives funding from NIHR, UKRI, NIHR Birmingham Biomedical Research Centre, NIHR Surgical Reconstruction and Microbiology Research Centre, NIHR ARC West Midlands, UK Spine and Health Data Research at the University of Birmingham and University Hospitals Birmingham, UK, Innovate UK (part of UK Research and InnovatioRin), Macmillan Cancer Support, UCB Pharma, Janssen, GSK, and Gilead. M. Falahee: None.