Early Inflammatory Arthritis Patients Research Articles

E017 An early inflammatory arthritis questionnaire to enable enhanced triage and a scoping exercise to assess clinical utility

Abstract Background/Aims The quality of early inflammatory arthritis (EIA) referrals from primary care can vary even with a standardised referral form leading to large numbers of non-EIA patients being seen. Poor utilisation of EIA slots places pressure on an EIA service’s ability to see suspected EIA patients within 3 weeks of referral. To overcome this challenge, a questionnaire was devised to enable enhanced EIA triage and a scoping exercise was carried out to assess clinical utility. Methods 50 patients attending the EIA clinic completed the questionnaire (Table 1) either self-administered or via telephone prior to their appointment. Early Inflammatory Arthritis Screening Questionnaire (Table 1) Positive answers were scored 1 with a maximum score of 11. Following their appointment, the patient diagnosis was collected from patient records. Results Of the 50 patients, 14 (28%) had a confirmed EIA diagnosis and the other 36 (72%) patients had a range of alternative diagnoses. In the confirmed EIA group, the scores ranged from 5-8/11 with an average mean score of 7.0 and median of 7. Further analysis showed patients with a score over 5/11 including symptom duration of 12 months and under (Q1) identified all the confirmed EIA patients. Applying the above criteria to our 50 study patients resulted in 27/50 patients qualifying for an EIA appointment slot and 14/27 (52%) would have been confirmed with EIA. After applying these cut off criteria the sensitivity of the questionnaire was 100% and the specificity was 64%. The non-EIA group scores ranged from 0 - 8/11 with an average mean score of 4.9 and median score of 5. Conclusion In our service triage of EIA referrals on a standardised form resulted in poor utilisation of EIA slots. Triage using the questionnaire improved the EIA slot allocation and increased EIA conversion rate from 28% to 50%. This questionnaire appears to be a promising tool to improve utilisation of EIA appointments. Telephone assessment could be delivered by any member of the multidisciplinary team. Disclosure J. Burton: None. R. Sathananthan: None. S. Levy: None. N. Horwood: None. T. Ahmed: None. R. Suresh: None.

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.

Utility of Baseline Transcriptomic Analysis of Rheumatoid Arthritis Synovium as an Indicator for Long-Term Clinical Outcomes.

Objective:Rheumatoid arthritis is a chronic inflammatory autoimmune disease that can lead to synovial damage, persistent joint pain, and functional disability. Our objective was to evaluate baseline synovial transcriptome from early inflammatory arthritis patients (EIA) and identify pretreatment biomarkers that could potentially provide insights into long-term functional outcomes of rheumatoid arthritis (RA).MethodsSynovial biopsies from clinically inflamed knee joints were procured from either 17 EIA patients before initiation of disease modifying anti-rheumatic drug (DMARD) therapy (DMARD-naïve EIA) using the minimally invasive closed needle biopsy technique or advanced RA patients undergoing arthroplasty. Affymetrix Human Genome U133 Plus 2 microarray platform was used to profile the synovial transcriptome. The cohort was followed clinically for a median of 12.3 years, and patient data was collected at each visit. Short-term and long-term clinical outcomes were determined by assessing RA-associated clinical parameters Statistical adjustments were made to account for asynchronous clinical visits and duration of follow up.ResultsBased on the transcriptomic analysis, we identified 5 differentially expressed genes (DEGs), including matrix metalloproteinase (MMP)-1 (fibroblast collagenase) and MMP-3 (stromelysin-1) in DMARD-naïve EIA patients, relative to advanced RA patients (q < 0.05). Dichotomous expression of MMP-1 and MMP-3 mRNA and protein was confirmed by qPCR and immunohistochemistry respectively, based on which DMARD-naïve EIA subjects were classified as MMP-high or MMP-low. Hierarchical clustering of transcriptomic data identified 947 DEGs between MMP-high and MMP-low cohorts. Co-expression and IPA analysis of DEGs in the MMP-high cohort showed an enrichment of genes that participated in metabolic or biochemical functions and intracellular immune signaling were regulated through NF-κB and β-catenin complexes and correlated with markers of systemic inflammation. Analysis of short-term clinical outcomes in MMP-high cohort showed a significant reduction in the DAS-CRP scores relative to baseline (P <0.001), whereas area under the curve analyses of modified HAQ (mHAQ) scores correlated negatively with baseline MMP-1 (R = −0.59, P = 0.03). Further, longitudinal mHAQ scores, number of swollen joints, number of DMARDs and median follow-up duration appeared to be higher in MMP-low cohort.ConclusionOverall, our results indicate that the gene expression profiling of synovial biopsies obtained at the DMARD-naive stage in patients with EIA categorizes them into subsets with varying degrees of inflammation and can predict the future of long-term clinical outcome.

Baseline IgG-Fc N-glycosylation profile is associated with long-term outcome in a cohort of early inflammatory arthritis patients

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease for which prediction of long-term prognosis from disease’s outset is not clinically feasible. The importance of immunoglobulin G (IgG) and its Fc N-glycosylation in inflammation is well-known and studies described its relevance for several autoimmune diseases, including RA. Herein we assessed the association between IgG N-glycoforms and disease prognosis at 2 years in an early inflammatory arthritis cohort.MethodsSera from 118 patients with early inflammatory arthritis naïve to treatment sampled at baseline were used to obtain IgG Fc glycopeptides, which were then analyzed in a subclass-specific manner by liquid chromatography coupled to mass spectrometry (LC-MS). Patients were prospectively followed and a favorable prognosis at 2 years was assessed by a combined index as remission or low disease activity (DAS28 < 3.2) and normal functionality (HAQ ≤ 0.25) while on treatment with conventional synthetic DMARDs and never used biologic DMARDs.ResultsWe observed a significant association between high levels of IgG2/3 Fc galactosylation (effect 0.627 and adjusted p value 0.036 for the fully galactosylated glycoform H5N4F1; effect −0.551 and adjusted p value 0.04963 for the agalactosylated H3N4F1) and favorable outcome after 2 years of treatment. The inclusion of IgG glycoprofiling in a multivariate analysis to predict the outcome (with HAQ, DAS28, RF, and ACPA included in the model) did not improve the prognostic performance of the model.ConclusionPending confirmation of these findings in larger cohorts, IgG glycosylation levels could be used as a prognostic marker in early arthritis, to overcome the limitations of the current prognostic tools.

A Bayesian network approach incorporating imputation of missing data enables exploratory analysis of complex causal biological relationships.

Bayesian networks can be used to identify possible causal relationships between variables based on their conditional dependencies and independencies, which can be particularly useful in complex biological scenarios with many measured variables. Here we propose two improvements to an existing method for Bayesian network analysis, designed to increase the power to detect potential causal relationships between variables (including potentially a mixture of both discrete and continuous variables). Our first improvement relates to the treatment of missing data. When there is missing data, the standard approach is to remove every individual with any missing data before performing analysis. This can be wasteful and undesirable when there are many individuals with missing data, perhaps with only one or a few variables missing. This motivates the use of imputation. We present a new imputation method that uses a version of nearest neighbour imputation, whereby missing data from one individual is replaced with data from another individual, their nearest neighbour. For each individual with missing data, the subsets of variables to be used to select the nearest neighbour are chosen by sampling without replacement the complete data and estimating a best fit Bayesian network. We show that this approach leads to marked improvements in the recall and precision of directed edges in the final network identified, and we illustrate the approach through application to data from a recent study investigating the causal relationship between methylation and gene expression in early inflammatory arthritis patients. We also describe a second improvement in the form of a pseudo-Bayesian approach for upweighting certain network edges, which can be useful when there is prior evidence concerning their directions.

Bone changes in early inflammatory arthritis assessed with High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT): A 12-month cohort study.

Erosion development is of crucial significance as it impacts prognosis and therapy decisions in patients with inflammatory joint diseases. Our study aimed to determine the sensitivity of high-resolution peripheral quantitative computed tomography (HR-pQCT) to detect change of bone surface over time and to identify erosion development in early inflammatory arthritis (EIA) patients. Moreover, the contribution of prognostic factors on periarticular bone damage in the first year of diagnosis assessed by HR-pQCT was explored. 46 patients with arthritic symptoms for less than one year, and a clinical diagnosis of inflammatory arthritis were prospectively imaged at baseline and 12-months. HR-pQCT scans of the 2nd and 3rd MCP joints and CR of the hands and feet were performed. Joint space width (JSW), total bone mineral density (Tt.BMD), erosion presence and volume were assessed with HR-pQCT. Scan-rescan precision was assessed to define an individual-level least significant change (LSC) criterion. Regression analyses explored prognostic factors for bone damage progression. We observed no significant group-level changes in JSW, Tt.BMD or erosion volume. 20% or fewer joints demonstrated individual-level changes greater than the LSC criterion for mean JSW, Tt.BMD and erosion volume. HR-pQCT detected more erosions than CR in the 2nd and 3rd MCP. Increased symptom duration at diagnosis was weakly associated (P<0.10) with lower JSW minimum and higher JSW standard deviation. Gradual degradation of JSW, proportional to symptom duration, was detected by HR-pQCT. EIA patients need to be closely monitored for exacerbation of arthritis and progression of periarticular bone damage.

P81 The impact of musculoskeletal ultrasound on the referral of patients with suspected inflammatory arthritis from primary care

Abstract Background Musculoskeletal ultrasound (MSUS) is a helpful adjunct to clinical history and examination in the assessment of patients with suspected early inflammatory arthritis (EIA). Whereas MSUS is used widely by rheumatologists, data regarding the extent to which general practitioners (GPs) utilise MSUS in the assessment of patients with suspected EIA remain lacking. In this service evaluation, we aimed to quantify the MSUS workload originating from primary care, and its impact on the referral pathway of patients with suspected EIA. Methods We studied all patients ≥16 years of age who had an MSUS of the hands and wrists performed by the radiology department at the Queen Elizabeth Hospital (Gateshead, UK) between 1st January and 31st December 2018, and where the scan request originated from a GP within primary care. Electronic records were retrospectively reviewed to ascertain the scan request clinical details, radiology report, and subsequent referral of the patient for rheumatology review. The study was registered with the Trust Clinical Improvement Office. Results 189 patients were scanned: 137 (72%) female, median (IQR, range) age 56 (43-65, 16-91) years. Ultrasonographic abnormalities (synovial hypertrophy, synovitis and/or tenosynovitis) were observed in 31/87 (36%) of suspected EIA patients, and 22/102 (22%) patients without suspicion of EIA, with subsequent referral to rheumatology in 24 and 4 cases from each group respectively. Of the 24 patients with suspected EIA who were referred for rheumatological assessment, 7 were subsequently diagnosed with EIA (one seropositive rheumatoid arthritis [RA], three seronegative RA, two unspecified IA, one reactive arthritis) with a median (range) time from MSUS request to rheumatology referral of 36 (-5 - 58) days. None of the 4 patients referred from the non-EIA group were diagnosed with an inflammatory arthritis. Conclusion MSUS is widely used by GPs within our region for the assessment of suspected EIA, despite local and national guidelines supporting referral without imaging within 3 days of presentation. Furthermore, we show evidence that GPs interpret scan reports within the individual patient clinical context, with rheumatology referral less likely where the clinical suspicion of EIA is low. Normal MSUS findings contributed to avoidance of referral in 56/87 (64%) of suspected EIA cases, substantially reducing EIA referrals to secondary care. However, MSUS requests within primary care also contributed towards a delay in referral for a small number of patients with confirmed EIA, which we plan to address by signposting to local EIA referral guidelines within the radiology request system. A prospective study of MSUS in the triaging of EIA referrals to secondary care, combined with a qualitative study of the impact of MSUS on GP decision making, are warranted to better understand the potential impact of MSUS in the primary care setting for improved patient care and resource allocation. Disclosures K.F. Baker None. E. Fatone None. J. Hamilton None.

Stromal cell markers are differentially expressed in the synovial tissue of patients with early arthritis.

IntroductionPrevious studies have shown increased expression of stromal markers in synovial tissue (ST) of patients with established rheumatoid arthritis (RA). Here, ST expression of stromal markers in early arthritis in relationship to diagnosis and prognostic outcome was studied.MethodsST from 56 patients included in two different early arthritis cohorts and 7 non-inflammatory controls was analysed using immunofluorescence to detect stromal markers CD55, CD248, fibroblast activation protein (FAP) and podoplanin. Diagnostic classification (gout, psoriatic arthritis, unclassified arthritis (UA), parvovirus associated arthritis, reactive arthritis and RA), disease outcome (resolving vs persistent) and clinical variables were determined at baseline and after follow-up, and related to the expression of stromal markers.ResultsWe observed expression of all stromal markers in ST of early arthritis patients, independent of diagnosis or prognostic outcome. Synovial expression of FAP was significantly higher in patients developing early RA compared to other diagnostic groups and non-inflammatory controls. In RA FAP protein was expressed in both lining and sublining layers. Podoplanin expression was higher in all early inflammatory arthritis patients than controls, but did not differentiate diagnostic outcomes. Stromal marker expression was not associated with prognostic outcomes of disease persistence or resolution. There was no association with clinical or sonographic variables.ConclusionsStromal cell markers CD55, CD248, FAP and podoplanin are expressed in ST in the earliest stage of arthritis. Baseline expression of FAP is higher in early synovitis patients who fulfil classification criteria for RA over time. These results suggest that significant fibroblast activation occurs in RA in the early window of disease.

Use of complementary and alternative medicines is associated with delay to initiation of disease-modifying anti-rheumatic drug therapy in early inflammatory arthritis.

To study the predictors of complementary and alternative medicine (CAM) use in patients with early inflammatory arthritis (EIA), and its impact on delay to initiation of disease-modifying anti-rheumatic drugs (DMARD). Data were collected prospectively from EIA patients aged ≥ 21 years. Current or prior CAM use was ascertained by face-to-face interview. Predictors of CAM use and its effect on time to DMARD initiation were determined by multivariate logistic regression and Cox proportional hazards, respectively. One hundred and eighty patients (70.6% female, 58.3% Chinese), of median (interquartile range [IQR]) age 51.1 (40.9-59.8) years and symptom duration 16.6 (9.2-26.6) weeks were included: 83.9% had rheumatoid arthritis, 57% were seropositive. Median (IQR) Disease Activity Score in 28-joints (DAS28) was 4.3 (2.8-5.7), modified Health Assessment Questionnaire (mHAQ) was 0.38 (0.0-0.88) and 41.3% were CAM users. Chinese race (odds ratio [OR] 5.76 [95%CI 2.53-13.1]), being non-English speaking (OR 2.68 [95% CI 1.18-6.09]), smoking (OR 3.35 [95% CI 1.23-9.15] and high DAS28 (OR 2.73 [95% CI 1.05-7.09] were independent predictors of CAM use. CAM users initiated DMARD later (median [IQR] 21.5 [13.1-30.4] vs. 15.6 [9.4-22.7] weeks in non-users, P = 0.005). CAM use and higher DAS28 were associated with a longer delay to DMARD initiation (hazard ratio [HR] 0.69, 95% CI 0.50-0.95 and 0.63, 95% CI 0.43-0.91, respectively) while higher mHAQ was associated with a shorter delay (HR 1.59, 95% CI 1.08-2.34) and race, education level, being non-English speaking, smoking and seropositivity were not associated. Healthcare professionals should be aware of the unique challenges in treating patients with EIA in Asia. Healthcare beliefs regarding CAM may need to be addressed to reduce treatment delay.

Components of treatment delay in rheumatoid arthritis differ according to autoantibody status: validation of a single-centre observation using national audit data.

Objective. To determine whether time to treatment following symptom onset differs between RA patients according to autoantibody status.Methods. A single-centre retrospective analysis of a UK early RA inception cohort was first undertaken to identify those components of the patient journey that differed by serological subtype. Data from a UK national audit of early inflammatory arthritis patients was accessed to replicate the key finding.Results. A total of 173 RA patients were diagnosed over a 31-month period, of whom 80 (46%) were ACPA/RF double-seropositive (ACPA+/RF+), 53 (31%) ACPA−/RF−, 17 (10%) ACPA+/RF− and 23 (13%) RF+/ACPA−. Overall, ACPA+/RF+ patients experienced significantly longer symptom duration before DMARD initiation. This was accounted for by delays in their presentation to primary care following symptom onset—a finding that was robustly confirmed in an independent dataset of 2192 UK early RA patients. In contrast, ACPA−/RF− patients were significantly more likely to experience delays in DMARD initiation after presenting to secondary care.Conclusion. Causes of treatment delays in early RA differ according to patients’ autoantibody status. More insidious symptom onset and/or distinct health-seeking behaviours among ACPA+/RF+ patients may contribute to late presentations in primary care, whereas ACPA−/RF− patients experience delayed diagnosis and treatment in secondary care. These observations inform the research agenda, potentially influencing the design of service delivery for early arthritis patients.

Cost-Effectiveness Model for Evaluating New Diagnostic Tests in the Evaluation of Patients With Inflammatory Arthritis at Risk of Having Rheumatoid Arthritis.

New opportunities have emerged for early diagnosis with the arrival of new technologies that assess the impact of genomics, proteomics, metabolomics, and cytomics on rheumatoid arthritis (RA) risk. This early health technology assessment study assesses the short-term cost effectiveness of 4 add-on diagnostic tests in early inflammatory arthritis patients at risk of RA. We modeled 4 diagnostic add-on tests to the American College of Rheumatology/European League Against Rheumatism 2010 RA classification criteria, covering the first year after diagnosis, using Rotterdam Early Arthritis Cohort data. Sensitivity, specificity, and costs were assigned to the magnetic resonance imaging of hands and feet (sensitivity 0.90, specificity 0.60, cost €756), interleukin-6 (IL-6) serum level test (sensitivity 0.70, specificity 0.53, cost €50), B cell-related gene expression (sensitivity 0.60, specificity 0.90, cost €150), and gene assay for RA (sensitivity 0.40, specificity 0.85, cost €750), based on literature and expert opinion. Outcomes were evaluated using the unweighted diagnostic net benefit (UDNB) and the incremental cost-effectiveness ratio (ICER) in all patients (n = 552), intermediate-risk patients (n = 263), and seronegative patients (n = 329). The highest UDNB was found when using the B cell assay in intermediate-risk patients (43%, ICER €5,314), while the IL-6 test in seronegative patients resulted in the lowest UDNB (-11.4%, ICER €7,650). If a threshold of €20,000 is applied, the B cell assay would be preferred over the other alternatives, with a 78% probability of being cost effective for intermediate-risk patients, 57% for all patients, and 73% for seronegative patients. Diagnostic add-on tests favoring specificity over sensitivity with a headroom less than €370 per test are cost effective, with the largest diagnostic benefit occurring in intermediate-risk patients.

OP0270-HPR Should A Successful Early Inflammatory Arthritis Clinic Also Address Cardiac Risk?

BackgroundRA patients have higher cardiovascular disease (CVD) risk. There is a 60% increase in the risk of death from cardiovascular causes compared with the general population and, survival rates for...

AB0251 The Impact of Missing Anti-Citrullinated Protein Antibody (ACPA) Serology on Outcomes in Early Rheumatoid Arthritis: Results from Catch (Canadian Early Arthritis Cohort)

BackgroundAnti-citrullinated protein antibody (ACPA) is a serum biomarker that is as sensitive as, but more specific than the rheumatoid factor (RF) and detected earlier in RA [1,2]. Although ACPAs are...

Vitamin D status of patients with early inflammatory arthritis

The present study aimed to investigate the vitamin D status in patients with early inflammatory arthritis (EIA). We conducted a retrospective study among patients who presented with EIA at the outpatient rheumatology clinic of a tertiary referral center between March 2012 and February 2013. In total, 101 subjects with EIA (≥1 swollen joint and symptom duration of ≤6 months, not explained by another disease) and 101 healthy controls matched for age, sex, and the month of serum vitamin D measurements were enrolled. Serum 25-hydroxy vitamin D (25-OHD) concentrations were assessed by radioimmunoassay. Vitamin D "deficiency" and "severe deficiency" were defined as serum 25-OHD levels <20 and <10 ng/mL, respectively. Among EIA patients, rheumatoid arthritis (RA) was classified according to the 2010 American College of Rheumatology/European League against Rheumatism criteria. Vitamin D deficiency was highly prevalent among EIA patients, but no significant differences in the frequency of vitamin D deficiency of EIA patients and controls were observed (75.2 vs 65.3%, p = 0.106). Additionally, in spring and summer, EIA patients had significantly lower serum 25-OHD concentrations than controls, but the opposite trend was observed in autumn. Among 101 EIA patients, 38 (37.1%) were classified as having RA. Severe vitamin D deficiency in EIA patients was significantly associated with the higher likelihood of being classified as having RA. In conclusion, the frequency of vitamin D deficiency in EIA patients was comparable to that in controls, but severe vitamin D deficiency was associated with the presence of RA among EIA patients.

Enhanced and persistent levels of interleukin (IL)-17+CD4+ T cells and serum IL-17 in patients with early inflammatory arthritis

Prognosis of patients with early inflammatory arthritis (EIA) is highly variable. The aim of this study was to compare, longitudinally and cross-sectionally, the levels of cytokine-expressing cells in peripheral blood (PB) from patients with EIA to those in established rheumatoid arthritis (RA) and healthy controls (HC). PB mononuclear cells from HC (n = 30), patients with EIA (n = 20) or RA (n = 38) were stimulated with phorbol myristate acetate (PMA)/ionomycin for 3 h, and stained for cell markers and cytokines. Serum cytokines and chemokines were measured by Luminex. Patients with EIA were reassessed at 6 and 12 months. The percentage of interleukin (IL)-17⁺ interferon (IFN)-γ⁻ CD4⁺ T cells [T helper type 17 (Th17)] was increased in RA and EIA versus HC. Serum IL-1β, IL-2, IL-4 IL-17 and macrophage inflammatory protein (MIP)-1α were increased in RA and EIA versus HC. IL-1Ra, IL-15 and IFN-α were increased in EIA versus HC. IL-6 and tumour necrosis factor (TNF)-α was increased in RA but not EIA versus HC. Disease activity scores in EIA patients improved over 12 months' treatment. Th17 percentage at baseline was correlated with both rheumatoid factor (RF) titre and functional deficit at 12 months. Baseline levels of serum granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6 and IL-8 were correlated with Larsen score at 12 months. There were no significant changes in cytokine-expressing CD4⁺ T cells over time, although the percentage of IL-6⁺monocytes increased. IL-17⁺ CD4⁺ T cells and serum IL-17 levels are increased in EIA. IL-6-expressing monocytes increase during the first year of disease, irrespective of disease-modifying anti-rheumatic drug (DMARD) therapy. We observed incomplete clinical responses, suggesting EIA patients need more intensive early therapy.

134: Interleukin-27 as a novel antagonist of ectopic lymphoid-like structure development in early inflammatory arthritis

Evaluation of joint tissue from early inflammatory arthritis patients through ultrasound-guided synovial biopsy has enabled disease classification based on local pathology. For example, the disease can be classed as fibroblast-, myeloid- or lymphoid-driven. Lymphoid histopathology can be further divided into patients displaying either diffuse infiltrates, or ectopic lymphoid-like structures (ELS) reminiscent of the follicular compartments in secondary lymphoid organs. Approximately 25% of rheumatoid arthritis (RA) patients develop ELS and display severe symptoms associated with local immune cell priming and autoantibody production. However, cytokine control of ELS development in inflammatory arthritis is poorly defined. Interleukin (IL)-27 is a negative regulator of adaptive immune responses. To investigate the role of IL-27 in inflammatory arthritis, wild type (WT) and IL-27 receptor (IL-27R)-deficient mice were exposed to antigen-induced arthritis. IL-27R-deficient mice developed exacerbated inflammatory arthritis, displaying increased synovial infiltrate, hypertrophy and bone erosions. Heightened peripheral T H 17- and B-cell responses in IL-27R-deficiency were reflected in increased serum IL-17 levels and antigen-specific IgG titers. Strikingly, IL-27R-deficient mice developed synovial histopathology reminiscent of RA patients with ELS, comprising synovial lymphoid aggregates with distinct T-cell (CD3 + ), B-cell (B220 + ) and DC (F/480 + , CD21 + ) areas that were absent in WT mice. Development of lymphoid aggregates was associated with elevated synovial expression of homeostatic chemokines that promote ectopic lymphoneogenesis (e.g. Cxcl13, Ccl21 ) and the transcriptional regulator Bcl-6 , which is involved in germinal center organization and functional regulation. Ectopic lymphoneogenesis in IL-27R-deficient mice was not associated with an increase in synovial IL-6 or IL-21 expression. Studies in clinical RA patients reflect our experimental outcomes and reveal reduced synovial IL-27 expression in patients with joint histopathology comprising ELS compared to patients with diffuse lymphocytic infiltrates. Thus, IL-27 may negatively regulate the formation of ELS in human pathologies such as RA and represents a potential biomarker of synovial histopathology in early RA.

FRI0139 The correlation of self-reported behavioral co-morbidities and disease activity in early inflammatory arthritis patients: A prospective study

BackgroundInflammatory arthritis patients experience a host of behavioral alterations that include depression, fatigue, sleep disturbances, and cognitive dysfunction. These behavioral comorbidities are apparent throughout the process of diagnosis and treatment...

SAT0080 Ankle synovitis and its prognostic implications in a very early arthritis cohort

BackgroundAnkle synovitis occurs in over a third of early inflammatory arthritis patients and may be present in isolation. However, the clinical outcomes associated with ankle involvement in this population are...

Incidence and predictors of secondary fibromyalgia in an early arthritis cohort

ObjectivesSecondary fibromyalgia (FM) is common among patients with inflammatory arthritis, but little is known about its incidence and the factors leading to its development. The authors examined the incidence of...

Lack of seroconversion of rheumatoid factor and anti-cyclic citrullinated peptide in patients with early inflammatory arthritis: a systematic literature review

Serological markers are thought to be useful in predicting which patients with early inflammatory arthritis (EIA) will progress to RA. The objective of this study is to determine the per cent RF and anti-CCP seroconversion in EIA patients at 1-5 years of follow-up: 80% of established RA is RF or CCP positive. We conducted a systematic literature review of all English publications and recent abstracts from ACR and EULAR. Patients ≥16 years of age with at least one swollen joint and symptoms < 2 years were included. Twelve publications met the criteria: 10 studies included data on RF, while only 5 addressed anti-CCP. Sample sizes ranged from 15 to 395 and follow-up was 6-60 months. There was marked heterogeneity between studies; therefore, results could not be pooled for a meta-analysis. Baseline RF and anti-CCP positivity was also highly variable: 8-55 and 4-45%, respectively. Seroconversion rates for EIA were 1.9-5.0% at up to 30 months follow-up for RF and 1.3-8.9% at up to 60 months follow-up for anti-CCP. There is minimal change in RF or anti-CCP positivity up to 5 years of follow-up. Prevalence data for RF in established RA is significantly higher than the baseline values reported here. The low rates of seroconversion would suggest a lower prevalence in EIA and the reason for this difference remains unknown. It is unclear whether antibody-negative patients are more likely to remit and be lost to follow-up in established RA populations.