Background: The lack of biomarkers to diagnose and monitor disease activity is one of the most significant unmet needs in psoriatic arthritis (PsA). Objectives: To investigate the diagnostic potential of serum biomarkers in distinguishing PsA from healthy controls (HC) and their association with clinical and sonographic disease activity and bone remodelling in erosive and axial PsA. Methods: Ninety-four PsA patients and fourteen HC were recruited for this study. All serum biomarkers were analysed using ELISA or MSD multiplex assays. The following inflammation-related biomarkers were selected: calprotectin, sVCAM-1, sICAM-1, NGAL, complementC9 and complement factor D (CFD). Selected biomarkers for their implication in structural joint changes included osteoprotegerin (OPG), RANKL, M-CSF and MMP-1,-3,-9. All patients underwent musculoskeletal ultrasound (MSUS) assessments of 44 joints and 6 entheses. The power Doppler (PD) and grey scale (GS) were scored using a validated semi-quantitative grading system 0-3, as previously described [1]. The total sum score was calculated for GS-synovitis (GSS; range 0-132) and PD-synovitis (PDS; range 0-132). An active joint on MSUS was defined as a GS score of ≥2 and/or PD score ≥1. All patients had radiographs of the hands and feet reported by a musculoskeletal radiologist to assess for structural damage due to PsA. Radiographs of the hands and feet were available on all patients from their participation in another study at our institution (recruitment in 2011-2012); these were compared to the most recent radiographs to assess for progressive structural damage. Radiographs of the sacroiliac joints were available on all patients. Hierarchical clustering and string analysis were performed to identify protein-protein interactions. Results: Serum concentrations of 11 inflammatory/bone-remodelling mediators (calprotectin, MMP-1, MMP-9, NGAL, CFD, complement C9, sICAM-1, sVCAM-1, RANK-L, M-CSF and OPG) were significantly elevated in PsA compared to HC (all p<0.01), with a shift in the RANKL/OPG ratio in favour of bone resorption also observed in PsA vs HC. ROC analysis demonstrated that sVCAM-1, MCSF, calprotectin, CFD, OPG, RANK-L, and NGAL had good sensitivity and specificity, all with an AUC>0.8; however, sVCAM-1 had the highest discriminatory capacity to distinguish PsA from HC with an AUC=0.941, p<0.0001. Furthermore, elevated levels of sVCAM-1 (p=0.02) were demonstrated in PsA patients with progressive structural damage. Significantly higher serum MMP-9 and NGAL levels (p=0.03) were associated with erosive disease (Figure 1). Serum MMP-9 and calprotectin correlated with SJC (p<0.0001), PDS (p<0.0001) and active joint count on ultrasound (p<0.01 and p<0.0001 respectively), while there was no correlation with CRP. Calprotectin was also associated with GSS (p<0.01). Additionally, MMP-9 correlated with DAPSA (p<0.001), DAS28 (p<0.05) and DAS28-CRP (p<0.001). Serum concentrations of RANKL (p<0.04) and CFD (p<0.03) were significantly higher and OPG lower (p<0.02) (figure 2) in PsA patients with radiographic sacroiliitis compared to patients without. Hierarchical clustering and string analysis highlighted 4 clusters, demonstrating that MMP-9, MMP-3, calprotectin, and RANK-L clustered and sVCAM-1, M-CSF, CFD and sICAM-1 clustered. String analysis demonstrated that MMP9 and NGAL are the focal points of interactions between all biomarkers, suggesting they are predictive of the erosive PsA disease phenotype. Conclusion: These data suggest serum levels of MMP-9, NGAL and sVCAM-1 may infer important prognostic information regarding the potential for an aggressive and destructive disease phenotype with MMP-9 also associated with MSUS synovitis and disease activity. Serum OPG, RANK-L and CFD were also associated with axial PsA. REFERENCES: [1] Brown AK, Quinn MA, Karim Z, Conaghan PG, Peterfy CG, Hensor E, et al. Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission: evidence from an imaging study may explain structural progression. Arthritis Rheum. 2006;54(12):3761-73. Acknowledgements: NIL. Disclosure of Interests: None declared.

Background Gout is the most common chronic inflammatory arthritis worldwide and the only curable. Yet, gout care remains suboptimal despite evidence of the benefits of a treat-to-target approach to normalise urate levels. The efficacy and cost effectiveness of nurse led care in this treat-to-target strategy has been well recognised (Fuller, 2020) Objectives: •To implement a patient centred treat-to-target urate lowering strategy within a holistic health promotion, secondary prevention model of advanced practice nursing.•To engage, raise awareness and educate patients about:i)the short and long-term health implications of hyperuricaemia andii)the merits of self-management strategies to improve their health outcome Methods With stakeholder agreement a gout clinic was established. The Making Every Contact Count (MECC) framework was used to implement the treat-to-target approach per the EULAR (European Alliance of Associations for Rheumatology) recommendations for the management of gout. Making every contact count, grounded in a behavioural change approach, promotes brief intervention therapy to support lifestyle behaviour change to make each routine contact with patients count in terms of chronic disease healtcare (Meade, 2022: Gwinnutt, 2023). The 12-question Gout Self-Management Knowledge Questionnaire was completed at baseline, followed by a nursing educational intervention through a planned gout programme and repeated at final visit (Fields, 2017). Results To date 102 patients have attended the clinic. Baseline and final clinic assessments are available for 42 patients. The number of clinic reviews per patient was 6. Thirty-five (83%) were male; mean age was 61 years (range 29-91); mean disease duration was 9 years (range 1-40). The mean time to diagnosis from symptom onset was 4 years (range 0-29). At baseline, 17 (40%) reported a family history and past experience of a urate-lowering therapy. The reported mean number of flares per-annum was 1-2 (n=20); 3-5 (n=17); >6 (n=5); 20 patients (48%) had podagra; 14 patients (33%) had tophi. Urate levels improved by 76%, falling from a baseline of 397 µmol/L to 301 µmol/L at final visit; an 83% improvement was seen in the Gout Self-Management Knowledge Questionnaire. The subjective numeric global health score (0-10, where 10 represents worst health status) showed a median score of 1.5 at baseline and 1 at final visit. Conclusion Findings demonstrated 1) normalisation of urate to target levels, 2) an improvement in patients' insight and 3) a parallel upgrading in patients reported global health score. References [1] Fuller, A., Jenkins, W., Doherty, M. and Abhishek, A., 2020. Nurse-led care is preferred over GP-led care of gout and improves gout outcomes: results of Nottingham Gout Treatment Trial follow-up study. Rheumatology, 59(3), pp.575-579.[2] Meade, O., O'Brien, M., Mc Sharry, J., Lawless, A., Coughlan, S., Hart, J., Hayes, C., Keyworth, C., Lavoie, K.L., Murphy, A.W. and Murphy, P., 2022. Enhancing the implementation of the Making Every Contact Count brief behavioural intervention programme in Ireland: protocol for the Making MECC Work research programme. HRB Open Research, 5.[3] Gwinnutt, J.M., Wieczorek, M., Balanescu, A., Bischoff-Ferrari, H.A., Boonen, A., Cavalli, G., De Souza, S., De Thurah, A., Dorner, T.E., Moe, R.H. and Putrik, P., 2023. 2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases. Annals of the rheumatic diseases, 82(1), pp.48-56.[4] Fields, T.R., Rifaat, A., Yee, A.M., Ashany, D., Kim, K., Tobin, M., Oliva, N., Fields, K., Richey, M., Kasturi, S. and Batterman, A., 2017, April. Pilot study of a multidisciplinary gout patient education and monitoring program. In Seminars in arthritis and rheumatism (Vol. 46, No. 5, pp. 601-608). WB Saunders. Acknowledgements: NIL. Disclosure of Interests Madeline O'Neill: None declared, Douglas Veale Shareholder of: Health Beacon, Speakers bureau: AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, MSD, Pfizer, UCB, Paid instructor for: Consultant/Advisor: AbbVie, Actelion, BMS, Galapagos, Gilead, Janssen, MSD, Pfizer, UCB, Regeneron/Sanofi, Novartis, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, BMS, Eli Lilly, Novartis Janssen, Pfizer, UCB, MSD, Eamonn Molloy: None declared, Carl Orr Speakers bureau: AbbVie, Patricia Minnock: None declared.

Background Since the advent of numerous biologic therapies and small molecular drugs targeting specific cytokines and signalling pathways; the management of patients with psoriatic arthritis (PsA) has significantly improved. However, at least 40% of PsA patients exhibit an incomplete or failure to respond to these treatments. While the outcomes of patients with psoriasis (Pso) has dramatically improved with monoclonal antibody therapies targeting IL-23 and IL-17A; achieving a measurable low disease activity state such as minimal disease activity (MDA) for musculoskeletal manifestations of psoriatic disease is infrequent. Given the complex and heterogeneity of signalling pathways, cytokines and cell types resulting in synovio-entheseal disease in PsA; new treatment strategies must be evaluated to induce deep and sustainable clinical responses in all the phenotypic domains of psoriatic disease (cutaneous, synovium, entheseal and axial). (1) In patients who do not achieve remission in all clinical domains on a biologic monotherapy or combination of a biologic therapy with an oral synthetic agent; dual targeted anti-cytokines strategies or combined biologic with a targeted oral small molecule are a possible treatment option. Objectives To describe a series of four patients with recalcitrant psoriatic disease and failure to respond to previous treatment regimens who were successfully treated with dual immunomodulatory therapies. Methods Patients on dual immunomodulatory therapies attending our department were prospectively followed and clinical response monitored. Results: Table 1. Age/gender Diagnosis prior therapies combination therapy dose adverse events Case 1 49/ Male PsA + PsO Methotrexate, adalimumab, etanercept, infliximab, golimumab, certolizumab, ustekinumab, secukinumab, ixekizumab Baracitinib + infliximab 4mg OD + 5mg/kg Q8W None Case 2 51/ Male PsA + PsO Methotrexate, etanercept, adalimumab, ustekinumab, infliximab, secukinumab, apremilast, ixekizumab, brodalumab, guselkumab Adalimumab + guselkumab 40mg QoW +100mg Q8W None Case 3 51/ Female PsA + PsO Methotrexate, sulphasalazine, etarnercept, certolizumab, leflunomide, infliximab, adalimumab, secukinumab, ustekinumab, tofacitinib, abatacept, baracitinib Adalimumab + tofacinitib 40mg QoW + 5mg BD None Case 4 39/ Male PsA +PsO Methotrexate, etanercept, ustekinumab, adalimumab, secukinumab, ixekizumab, sulphasalazine Ixekizumab + baracitinib 80mg Q4W+ 4mg OD None Figure 1. Mini-Arthroscopy of left knee for Case 3 prior to starting dual immunomodulator therapy. (A ) Macroscopic aspects of synovitis (B ) Synovium vascularization Conclusion Multiple pathways and mediators are responsible for the initiation of and sustained joint inflammation and damage seen in PsA. A phase II trial of ABT-122, a biologic engineered to target both TNF and IL-17A showed statistically significant superior efficacy outcomes at multiple time points based on ACR50, ACR70 and psoriasis outcome measures (PASI75/PASI90) when compared to adalimumab, with similar safety profile.(2) Safety concerns such as infectious risks are important considerations with such strategies; however, the targeted second-generation anti-cytokine biologics and targeted JAK-I have exhibited improved safety profiles.(3) In our small case series, patients have not, to date, experienced adverse events of combination therapy. References [1]Haberman RH, Castillo R, Scher JU. Induction of remission in biologic-naive, severe psoriasis and PsA with dual anti-cytokine combination. Rheumatology. 2021;60(7):e225-e6. [2]Mease PJ, Genovese MC, Weinblatt ME, Peloso PM, Chen K, Othman AA, et al. Phase II Study of ABT-122, a Tumor Necrosis Factor– and Interleukin-17A–Targeted Dual Variable Domain Immunoglobulin, in Patients With Psoriatic Arthritis With an Inadequate Response to Methotrexate. Arthritis & Rheumatology. 2018;70(11):1778-89. [3]Scher JU, Ogdie A, Merola JF, Ritchlin C. Moving the Goalpost Toward Remission: The Case for Combination Immunomodulatory Therapies in Psoriatic Arthritis. Arthritis & Rheumatology. 2021;73(9):1574-8. Disclosure of Interests None declared

Background The diagnosis of psoriatic arthritis (PsA) is largely based on clinical phenotype due to the heterogeneity of the presenting features, which can include synovio-entheseal disease, dactylitis, skin and nail disease, uveitis and axial involvement. (1) In contrast to rheumatoid arthritis (RA), PsA is a seronegative inflammatory arthropathy. Rheumatoid factor (RF) and Anti-CCP antibodies are usually absent in PsA, and if patients do have positive serological findings for RF or CCP, the titres tend to be low. (2) Seronegativity for RF has a significantly high discriminant value in the Classification Criteria for Psoriatic arthritis (CASPAR), such that a negative RF forms one of the five possible criteria; thus serological testing is often done once at the initial diagnostic appointment. (3) A previous study in the context of RA has shown that there is a tendency for repeated serological testing with as much as 70% of patients having RF tested more than once.(4) Repeated testing amounts to additional expense and is rarely needed in PsA. The literature on the frequency of repeated serology testing in PsA patients is absent. Objectives To determine how often was serology for RF and anti-CCP antibodies repeated in a PsA cohort. Methods A cohort of consecutive patients attending the rheumatology clinic at our centre with a diagnosis of PsA were included. We reviewed the laboratory results of individual patients to determine how many times each patient had been tested for RF and anti-CCP antibodies. Results 118 patients with a diagnosis of PsA were included. 117 patients had RF antibody testing at least once and all 118 patients had a minimum of one anti-CCP antibody test. 59/117 (50.4%) patients had RF checked more than once and 28/117 (23.9%) had testing at least 3 times. 3 patients had an initial positive RF which was negative on subsequent testing. Anti-CCP antibody was checked on all 118 patients. 41/118 (34.7%) patients had anti-CCP checked more than once and 13/118 (11.0%) patients had testing at least 2 times. One patient had an initial equivocal anti-CCP antibody titre which was subsequently negative on repeat testing. Conclusion As opposed to RA, PsA has not been associated with the presence of circulating antibodies. The presence or absence of RF in PsA patients has for long been a subject of debate. (3) In cases of peripheral polyarticular PsA, which may be difficult to distinguish from RA, serological testing can be useful to identify RA. However, studies have found that RF can be present in 5-13% of PsA patients. (5) In the context of RA, serological conversion from negative to positive is infrequent and repeat testing is not recommended. (6) Over half of the patients in our PsA cohort had repeated RF testing. Certainly this is unlikely to be helpful or cost effective and serial serology measurements in PsA patients should be avoided. References [1]Veale DJ, Fearon U. The pathogenesis of psoriatic arthritis. The Lancet. 2018;391(10136):2273-84. [2]Merola JF, Espinoza LR, Fleischmann R. Distinguishing rheumatoid arthritis from psoriatic arthritis. RMD Open. 2018;4(2):e000656. [3]Veale DJ, Fearon U. What makes psoriatic and rheumatoid arthritis so different? RMD Open. 2015;1(1):e000025-e. [4]Orr C, Young F, Veale DJ. AB0243 How Often Are Serology Tests Repeated in RA Patients, and What Are the Merits? Annals of the Rheumatic Diseases. 2015;74(Suppl 2):972. [5]Punzi L, Podswiadek M, Oliviero F, Lonigro A, Modesti V, Ramonda R, et al. Laboratory findings in psoriatic arthritis. Reumatismo. 2007;59 Suppl 1:52-5. [6]Reid AB, Wiese M, McWilliams L, Metcalf R, Hall C, Lee A, et al. Repeat serological testing for anti-citrullinated peptide antibody after commencement of therapy is not helpful in patients with seronegative rheumatoid arthritis. Internal Medicine Journal. 2020;50(7):818-22. Disclosure of Interests None declared

Background Synovial biopsies are increasingly performed in both clinical setting and translational research.1 An unmet need in the field is the standardisation of synovial biopsies handling and analysis procedures. Objectives The aim of this collaborative work was to create a consensual set of points to consider for handling and analysis of synovial biopsies in clinical practice and translational research through EULAR Synovitis Study Group (ESSG). Methods The items were identified and formulated based on a comprehensive literature review.1 A task force (TF) of EULAR Synovitis Study Group (ESSG) members were constituted and TF members were consulted through a 2-stage eDelphi process. the 2 sequential rounds occurred in 9 months. The first written round occurred in June 2016. Members were sent a written questionnaire containing items divided in 2 parts. The items were identified and formulated based on a comprehensive literature review. The first part of the questionnaire referred to clinical practice containing 5 subsections: biopsy sampling, biopsy handling, histological analysis, staining and immunohistochemistry (IHC), biopsy analysis and pathologist’s report. The second part referred to translational research and contained 6 subsections (same 5 plus RNA analysis). Every participant was asked to score each item with a 5 points Likert (0: strongly disagree, 5: strongly agree), comments were allowed for each item. Items with a median score above 3.5 on 5 and a percentage of agreement above 70% were for the next round. Items with lower score were either suppressed of modified according to participants’ comments. Anonymized detailed results were circulating through participants between each round. The face to face meeting occurred at ESSG meeting in June 2017. Results 27 ESSG members from 19 centres were contacted by email. 20 participants from 17 centres answered (response rate of 74%). Response rates for next rounds were 100%. First questionnaire contained 44 items for Part 1 Clinical practice. 52.3% (23items/44) were selected for the second round based on their score and agreement percentage. 83% (19items/23) were selected for the third round. First questionnaire contained 43 items for the second part about translational research. 44% (19 items/43) were selected for second round based on their score and agreement percentage. 95% (18 items/19) were selected for third round (figure 1). Third oral round allowed to obtain a final set of items unanimously (table 1). Conclusions We hereby propose a set of consensual points to consider on analysis of synovial biopsies in clinical practice and translational research. This standardisation initiative was conducted through ESSG members using a validated consensus method. Reference [1] Orr C, Sousa E, Boyle DL, Buch MH, Buckley CD, Cañete JD, et al. Synovial tissue research: a state-of-the-art review. Nat Rev Rheumatol2017;13(8):463–75. Disclosure of Interest None declared

Background Dendritic cell (DC) are a heterogeneous group of antigen presenting cells that can be subdivided into CD1c+ & CD141+ DC. CD141+ DC are a rare population of DC that were first discovered in 2010 in human peripheral blood. Due to their rarity very little is known about the function of these cells in other tissue in or indeed disease. These newly described DC subset have thus never been described in Inflammatory Arthritis (IA) or any of the rheumatic diseases. Objectives To identify CD141 DC in IA synovium and functionally assess if these cells play a pathogenic role in IA. Methods CD141+DC were magnetically purified from synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) stimulated and stained with a panel of fluorochrome conjugated antibodies for multicolour flow cytometry. CD141+ DC isolated and purified from IA synovial fluid were subsequently cocultured with allogenic CD3+ T cells for 6d after which intracellular cytokine production was assessed by flow cytometry. Supernatants from this DC-T cell cocultures were used to treat synovial fibroblasts & the expression of adhesion molecules, cytokines & MMPs was measured. Finally using sorted populations of CD141+ DC from SFMC and PBMC, RNA sequencing was performed and differentially expressed genes and interaction network analysis were identified using the DeSeq2 R package, Ingenuity® Pathway Analysis (IPA) and InnateDB and Cytoscape. Results Within IA synovial fluid (SF), CD141+ DC are significantly enriched compared to WB & express higher levels of the costimulatory activation markers CD80 CD86 and CD40. Following coculture of these SF CD141+ DC with CD3+ T cells, CD141+ DC induce both CD8+ & CD4+ T cell proliferation. SF CD141+ DC induce Granzyme B production from CD8+ T cells & TNFα, IFNγ & GMCSF from CD4+ T cells. The IA synovium consists of a complex interplay of multiple cell types. Therefore next we examined the effect of this CD141+ DC-T cell interaction on the key invasive cells in the synovium – synovial fibroblasts. Supernatants from CD141 activated T cells were cultured with fibroblasts & induced expression of ICAM-1, IL-6, IL-8, MMP1 & MMP3. SF CD141 expressed significantly higher levels of the the hypoxia marker TREM1, activation of which induces further expression of CD80, CD86 and CD40. Coculture of these TREM1 activated CD141 with CD3+T cells increases IFNγ and IL-17a production. Finally RNASeq analysis revealed that there are 2089 differentially expressed genes between SF CD141+DC & WB CD141+DC. These genes are involved in a number of key pathways such as energy metabolism, chemokine & cytokine signalling. Principal Component Analysis (PCA) revealed that CD141+ DC with the synovium are distinctly different from blood CD141+ DC Conclusions CD141+ DC are enriched in the IA joint in an active state. RNASeq analysis revealed they are distinct from blood CD141+DC and our in vitro data would support the hypothesis that these CD141+DC contribute to synovial inflammation and joint destruction. Disclosure of Interest None declared

Background Deep profiling of synovial tissue samples from rheumatoid arthritis (RA) patients may reveal the molecular underpinnings of phases of RA progression and provide new therapeutic targets to intervene earlier in disease pathogenesis. Objectives We sought to identify the molecular pathways expressed in different stages of disease (from seropositive subjects without clinically apparent synovitis to those with established disease) in synovial tissue compared to non-RA controls. Methods Transcriptomics profiling was performed on RNA isolated from synovial tissue biopsies. Normal synovium was collected from subjects with knee pain and without diagnosis of OA or RA (n=28). Arthralgia tissue was collected from ACPA-positive subjects without synovitis (n=10). Early RA tissue was collected from patients recently diagnosed (<1 year) with RA (n=57). Established RA tissue was collected from ACPA-positive subjects with >1 year of disease duration (n=95). Protein expression was confirmed on infiltrating immune cells from synovial biopsy cell suspensions by flow cytometry in separate RA subjects. Results Several pathways previously identified as important for RA pathogenesis (e.g., lymphocyte activation, osteoclast differentiation, NF-kappa B signaling) were enriched in differentially expressed genes in disease synovial biopsies compared to normal tissue samples. Interestingly, several genes known to function in T cell activation as signal 2 co-stimulatory or co-inhibitory molecules were differentially expressed, even in arthralgia and early RA subjects. 66 of 81 known co-stimulatory or co-inhibitory genes profiled were differentially expressed (FDR <5% and absolute fold-change >2) in disease samples from at least one cohort. The genes encoding co-stimulatory proteins that were increased compared to normal included CD28, CD40LG, CD40 and ICOS. Interestingly, some of the genes encoding co-inhibitory proteins were increased (PDCD1/PD-1, CD274/PD-L1, HAVCR2/TIM3, TIGIT, BTLA), whereas others showed decreased expression (C10orf54/VISTA and LAG3) compared to normal controls. We focused on CD28 expression, which is elevated in “pre-RA” arthralgia samples, proposing that anti-CD28 therapeutics could be candidates for RA disease prevention. By flow cytometry we demonstrated that a majority of CD4+ (>90%) and CD8+ (>60%) T cells from RA synovial biopsy cell suspensions (n=4) showed surface expression of CD28. Conclusions We have generated a unique dataset from different phases of RA progression. Our results provide guidance for the selection of co-signaling molecules as therapeutic targets as well as for preventing the progression to RA. In particular, CD28 expression was elevated in synovial tissue biopsies before the development of RA and it was also expressed on the majority of synovial tissue infiltrating CD4+ and CD8+ T cells from RA patients. These observations provide rationale to target CD28 for both RA treatment and disease interception. Disclosure of Interest A. Walsh Shareholder of: Johnson & Johnson, Employee of: Johnson & Johnson, M. Canavan: None declared, Y. Guo Shareholder of: Johnson & Johnson, Employee of: Johnson & Johnson, T. McGarry: None declared, X. Yin Shareholder of: Johnson & Johnson, Employee of: Johnson & Johnson, M. Wechalekar Grant/research support from: Johnson & Johnson, M. Smith Consultant for: Johnson & Johnson, S. Proudman: None declared, C. Orr: None declared, S. Kelly: None declared, C. Pitzalis Grant/research support from: Johnson & Johnson, Consultant for: Abbott, Astellas, MedImmune, BMS, Celgene, Grunenthal, GSK, MSD, Pfizer, Sanofi, Roche, UCB, D. Veale: None declared, U. Fearon: None declared, S. Nagpal Shareholder of: Johnson & Johnson, Employee of: Johnson & Johnson

Background Rheumatoid arthritis (RA) is a chronic joint disease, characterised by synovial inflammation and a shift in the metabolic profile of cells to a more destructive phenotype. The JAK-STAT signalling pathway is implicated in the pathogenesis of RA. Objectives To examine the effect of tofacitinib, a selective JAK inhibitor, on synovial cellular bioenergetics, mitochondrial function and subsequent pro-inflammatory mechanisms in RA. Methods Ex-vivo RA whole tissue synovial explants and primary RA synovial fibroblasts (RASFC) and were cultured with tofacitinib (1μM) for 24–72hrs. RASFC metabolism was assessed by the XF24-Flux-analyser and mitochondrial mutagenesis was quantified using a mitochondrial random mutation capture assay. Mitochondrial function was assessed for reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and mitochondrial mass (MM) using the specific cell fluorescent probes and differential gene expression by mitochondrial gene arrays or RT-PCR. Mitochondrial structural morphology was assessed by transmission electron microscopy. Lipid peroxidation (4HNE) was measured by specific ELISA. Dual staining of pSTAT3 and mitochondrial marker Cox-IV was demonstrated by confocal microscopy. The effect of tofacitinib (1μM) in RA synovial explant on markers of cellular bioenergetics and pro-inflammatory mediators, including cytokines and growth factors were quantified by ELISA, MSD multiplex assays and Real-time PCR. Results An initial screen demonstrated alterations in 18 key genes involved in mitochondrial function in RA synovial tissue in response to tofacitinib. Supporting this, tofacitinib inhibited ROS production, decreased the MMP and MM (all p<0.05), coupled with altered mitochondrial morphology. No effect observed for mtDNA mutations or 4HNE levels. Tofacitinib significantly inhibited the expression of glycolytic genes HIF1α, HK2, LDHA, GSK3A and PDK1 (all p<0.05) suggesting altered energy metabolism. This was paralleled by inhibition of baseline ECAR (glycolysis) with a concomitant increase in baseline OCR (oxidative phosphorylation), ATP production, maximal respiratory capacity and in the respiratory reserve in RASFC, confirming a bioenergetic switch in synovial cells in response to tofacitinib. Furthermore, we demonstrated co-localisation of pSTAT3 with Cox-IV in RASFC, suggested that in addition to nuclear transcription, pSTAT3 may also act as a mitoTF, regulating mitochondrial function directly. Finally, in RA whole tissue explants, tofacitinib significantly inhibited glycolytic genes HK2, GSK3A and PDK1 which was paralleled by a significant decrease in the spontaneous secretion of inflammatory mediators IL-6, IL-8, IL-1β, ICAM-1, VEGF, Tie2 and MMP1 (all p<0.05). Conclusions In this study, we describe a potential mechanism of action for tofacitinib, through reversing mitochondrial dysfunction and subsequent switch in cellular bioenergetics, in favour of a less glycolytic microenvironment leading to the reduction of inflammatory mediators. Thus, we have demonstrated that pathological cellular metabolism may be reversed by therapeutic treatment with tofacitinib. Disclosure of Interest None declared

Background Psoriatic Arthritis (PsA) is a chronic immune-mediated inflammatory disease, characterised by proliferation of synovial tissue and destruction of articular cartilage/bone with associated psoriasis. Dysregulated angiogenesis is one of the key early pathogenic processes in PsA. Monocyte subpopulations are increasingly recognized contributors to angiogenesis. Circulating monocytes can differentiate into tissue resident macrophages, monocyte derived dendritic cells and osteoclasts, which orchestrate both pro-inflammatory and pro-angiogenic signalling. These processes may be governed by microRNA (miRNA), a class of evolutionary conserved short non-coding RNAs which function as post-transcriptional repressors of gene expression. On such miRNA is miR-125a-5p, which in cancer, has been previously associated with altered angiogenesis, invasion and migration. Objectives To examine the expression and angiogenic associations of miR-125a-5p in PsA. Methods Synovial tissue biopsies were obtained from patients with PsA and osteoarthritis (OA). In parallel, CD14+ monocytes and CD3+ T cells were isolated from peripheral blood mononuclear cells. MiR-125a-5p levels were analysed by real-time PCR. To examine possible factors involved in regulating miR-125a-5p expression in endothelial cells,microvascular endothelial cells (HMVEC) were cultured with candidate pro-inflammatory stimuli including; TLR ligands (PAM, PolyIC, LPS), pro-inflammatory cytokines (TNFa, IL-1b, IL-17) and growth factors (VEGF, Ang2). Matrigel tube formation assays were performed with pre- and anti- 125a treated HMVEC to elucidate angiogenic function. Immunoistochemical analysis of synovial vasculature was performed using factor VIII (DAKO).Cliical markers assertained at the time of arthroscopy, includding synovitis and vascularity were correlated with synovial miRNA expression. Results Expression of miR-125a-5p was significantly decreased in PsA synovial biopsies (n=8) compared to OA (n=4) (p<0.05). CD14+ peripheral blood monocytes showed a significant decrease in miR-125a-5p compared to whole PBMC (p<0.05). No difference was observed for CD3+ T cells. Anti-125a-5p treated HMVEC displayed increased tube formations. Angiogenic growth factor, Ang2, induced miR-125a-5p in HMVEC (p<0.05). Lower synovial expression of miR-125a-5p displayed a higher degree of factor VIII staining compared to patients with higher miR-125a-5p expression. This was further demonstrated in representative arthroscopic images. Conclusions Our data demonstrates decreased expression of miR-125a in the joint and peripheral CD14+ monocytes in PsA patients. MiR-125a expression was associated with joint vascularity, a hallmark of PsA, suggesting its important role in mediating key pro-angiogenic and thereby pro-inflammatory mechanisms in the synovium. Correcting these microRNA deficiencies, either by conventional pharmacological agents or as novel targets, may provide a therapeutic benefit, especially in early disease stages. Disclosure of Interest None declared

Background and objectives Rheumatoid Arthritis (RA) is a chronic inflammatory autoimmune disease which leads to progressive joint destruction. RA is characterised by synovial hyperplasia and invasion of the synovium into the adjacent bone and cartilage. The precise aetiology of RA is not known, but both genetic and environmental influences play a role. Methotrexate (MTX) is the most commonly used disease modifying anti-rheumatic drug in the management of RA, however its mechanism of action remains poorly understood. In this study, we aim to identify the functional effects of MTX on primary RA synovial fibroblasts (RASFC) and to determine if the epigenetic signature of RASFC/CD14+ monocytes can predict clinical response to MTX. Materials and methods Primary RASFC were isolated from synovial biopsies obtained from patients undergoing arthroscopic examination. RASFC were cultured in the presence or absence of MTX (10–100 μM). Cell migration, invasion, viability/proliferation, adhesion and pro-inflammatory cytokine expression were assessed by: wound repairs assays, transwell matrigelTM invasion chambers, MTT/ Crystal violet cell growth assay, xCELLigence Real Time Cell Analyser and ELISA respectively. In parallel, CD14+ monocytes were isolated from peripheral blood mononuclear cells from RA patients both pre- and 12 weeks post-MTX therapy and global methylation was assessed. Results MTX (10 μM) inhibited RASFC repopulation of the wound margins in comparison to vehicle control where migration across the wound was clearly evident (n = 7, p = 0.03). In parallel, MTX (100 μM)significantly decreased RASFC invasion (n = 7, p = 0.01) and altered cytoskeletal dynamics through inhibition of lamellopodia and filopodia formation, which are indicative of cell movement. MTX had no inhibitory effect on the expression of IL-6, IL-8 and RANTES. Importantly, we determined that the effect of MTX on RASFC migration and invasion were independent of both cell viability (p = 0.37) and proliferation (p = 0.18). Finally preliminary results demonstrated altered DNA methylation in CD14+ monocytes from RA patients (n = 11) at 3 months post MTX treatment. Conclusions MTX inhibits RASFC migration, invasion and cytoskeletal re-arrangement, mechanisms which are critically involved in the pathogenesis of RA. Further preliminary data suggests that the effect of MTX on pro-inflammatory mechanisms in RA, maybe be mediated through alterations in epigenome.

Background and purpose Psoriatic Arthritis (PsA) is amultifaceted disease associated with Psoriasis. Key pathogeneic mechanisms seen at all disease sites include angiogenesis, invasion, migration, proliferation and more specifically to joint involvement, osteoclastogenesis. These aberrant processes have been previously associated with dysregulated miRNA expression, a class of small non-coding RNAs which exert their function through suppression of specific target genes. More specifically, the miR-23a Cluster (miR-23a, miR-27a and miR-24–2) as in other chronic conditions, such as cancer. Methods Synovial tissue biopsies and/or peripheral blood mononuclear cells (PBMC) were obtained from PsA (n = 8), osteoarthritis (OA) (n = 7), and healthy controls (n = 8). To determine factors involved in regulating miRNA expression, primary PsA synovial fibroblasts (SFC) were isolated and cultured with candidate pro-inflammatory stimuli including TLR ligands: Pam3CSK4 (1 µg/ml), LPS (1 µg/ml), polyIC (10 µg/ml) and pro-inflammatory cytokines: IL-1β (1 ng/ml), TNFα (10 ng/ml) and IL-17 (20ng/ml). MiR-23a, miR-27a and miR-24–2 expression was quantified by RT-PCR using RNU48 as an endogenous control. Clinical demographics such as synovitis, vascularity, DAS-28 CRP, TJC, SJC and patient global were also assessed. Results All members of the miR-23a cluster, miR-23a, miR-27a and miR-24–2, were significantly decreased PsA synovial tissue versus OA (p = 0.0172). Synovial miR-23a expression negatively correlated with matched PBMC miR-23a (r=-1.00, p = 0.0167), demonstrating a dissociation in miR-23a expression between systemic and local inflammation. In addition, miR-23a expression in PsA synovial biopsies inversely correlated with DAS28-CRP (r= -0.5294, p = 0.035) and distinguished patient synovial vascularity and synovitis into high versus low groupings (all < 0.05). TLR activation via PolyIC (TLR3) and LPS (TLR4), but not Pam3CSK4 (TLR2), significantly decreased miR-23a expression in PsA SFC (all p < 0.05), with no effect observed for pro-inflammatory cytokines. Finally, in silico analysis identified putative targets for miR-23a, including PDE4B and PTK2B, which are known mediators in immune pathways, osteoclast function and angiogenic mechanisms. Conclusion Our data provides evidence that the miR-23a cluster is significantly decreased in PsAsynovium. Synovial miR-23a levels, regulated by TLRs, correlate and distinguish clinical markers. Both previously confirmed and new potential targets identified here may have putative pathogenic implications for PsA pathogenesis. Thereby, the miR-23a cluster may represent a potential novel biomarker for disease activity or elucidate new therapeutic strategies.

Background Arthroscopy, by allowing direct visualization of the synovial membrane, is the gold standard for the assessment of knee synovitis. Given the fact that it is an invasive procedure, other reliable ways to assess synovitis has developed over the past few years. Ultrasonography (US) is a fast, available and low cost imaging tool and has been validated for detecting knee synovitis (1). Ultrasonographic and arthroscopic findings have been shown to correlate (2). However, few studies have yet assessed the correlation between ultrasonographic and histological findings. Objectives The aim of this study was to assess the correlation between ultrasonographic scores, arthroscopic scores and histological scores for inflammation and vascularity in knee joint synovitis. Methods Patients with knee pain and/or effusion were prospectively included. Knee was divided in three compartments (medial, lateral and superior). 1 operator (AN) performed a knee ultrasonography (B mode and Doppler mode) prior to the arthroscopy with a semi-quantitative assessment for degree of synovitis. 1 operator then performed a knee arthroscopy (CO, DJV) and scored macroscopic aspects with a 100-mm visual analogic scale (VAS) blindly from US findings and retrieved biopsies from each compartment. Biopsies were analyzed by 1 operator (UF) blindly from both US and arthroscopic findings and scored for: lining layer hyperplasia, inflammation and vascularity. Statistical analysis was made with non parametric Spearman correlation test. Results 23 patients were included. 16 had rheumatoid arthritis (RA) (ACR/EULAR 2010 criteria). 3 patients had psoriatic arthritis (PsA) (CASPAR criteria), 3 had osteoarthritis (OA) and 1 had gout. Mean ultrasonographic, arthroscopic and histological scores for both synovitis and vascularity were calculated for each patient. A strong correlation was observed between: US synovitis grade and histological inflammation score (r=0.71; p=0.001), US Doppler grade and histological score for vascularity (r=0.6; p=0,0003); US measured synovial thickness and lining layer hyperplasia (r=0.61; p=0,002). Moreover, high positive correlations were observed for both histological lining layer hyperplasia and inflammation between lateral and medial compartments (r=0,90; p=0,00005 and r=0,66; p=0,014 respectively), lateral and superior compartments (r=0,75; p=0,001 and r=0,51; p=0,048, respectively) and medial et superior compartments (r=0,61; p=0,012 and r=0,62; p=0,010, respectively). Conclusions B mode and Power Doppler US findings strongly correlate with histological inflammation and vascularity scores in actively inflamed knee joints. Ultrasound is therefore a reliable tool for knee joint assessment of the four most common rheumatological diagnoses - RA, PsA, OA and gout -. Moreover, the histological inflammation and hyperplasia scores highly correlate between the superior, medial and lateral compartments of the knee, highlighting the homogeneity of synovial membrane features within the same joint. References Karim Z, Wakefield RJ, Quinn M, Conaghan PG, Brown AK, Veale DJ et al. Validation and reproducibility of ultrasonography in the detection of synovitis in the knee: a comparison with arthroscopy and clinical examination. Arthritis Rheum. 2004;50(2):387–94. Rubaltelli JL, Fiocco U, Cozzi L, Baldovin M, Rigon C, Bortoletto P et al. Ultrasound Med. 1994;13(11):855–62. Disclosure of Interest None declared

BACKGROUND:Psoriatic arthritis (PsA) is a chronic inflammatory disease, characterised by synovitis and destruction of articular cartilage/bone. Janus-kinase and signal transducer and activator of transcription (JAK-STAT) signalling pathway is implicated in the pathogenesis of PsA. OBJECTIVES:To examine the effect of tofacitinib (JAK inhibitor) on proinflammatory mechanisms in PsA. METHODS:Primary PsA synovial fibroblasts (PsAFLS) and ex vivo PsA synovial explants were cultured with tofacitinib (1 µM). PhosphoSTAT3 (pSTAT3), phosphoSTAT1 (pSTAT1), suppressor of cytokine signaling-3 (SOCS3), protein inhibitor of activated Stat3 (PIAS3) and nuclear factor kappa B cells (NFκBp65) were quantified by western blot. The effect of tofacitinib on PsAFLS migration, invasion, Matrigel network formation and matrix metallopeptidase (MMP)2/9 was quantified by invasion/migration assays and zymography. Interleukin (IL)-6, IL-8, IFN-gamma-inducible protein 10 (IP-10) monocyte chemoattractant protein (MCP)-1, IL-17, IL-10, MMP3 and tissue inhibitor of metalloproteinases 3 (TIMP3) were assessed by ELISA. RESULTS:Tofacitinib significantly decreased pSTAT3, pSTAT1, NFκBp65 and induced SOCS3 and PIAS3 expression in PsAFLS and synovial explant cultures (p<0.05). Functionally, PsAFLS invasion, network formation and migration were inhibited by tofacitinib (all p<0.05). In PsA explant, tofacitinib significantly decreased spontaneous secretion of IL-6, IL-8, MCP-1, MMP9/MMP2, MMP3 (all p<0.05) and decreased the MMP3/TIMP3 ratio (p<0.05), with no effect observed for IP-10 or IL-10. CONCLUSIONS:This study further supports JAK-STAT inhibition as a therapeutic target for the treatment of PsA.

Background and aims Psoriatic Arthritis (PsA) is a chronic immune-mediated inflammatory disease, characterised by proliferation of synovial tissue and destruction of articular cartilage/bone with associated psoriasis. Dysregulated angiogenesis is one of the key early pathogenic processes in PsA. These processes may be governed by microRNA (miRNA), a class of evolutionary conserved short non-coding RNAs which function as post-transcriptional repressors of gene expression. On such miRNA is miR-125a-5p which, in cancer, has been previously associated with altered angiogenesis, invasion and migration. Objectives To examine the expression and angiogenic associations of miR-125a-5p in PsA. Methods Synovial tissue biopsies and peripheral blood mononuclear cells were obtained from patients with PsA, osteoarthritis (OA) and/or healthy controls (HC). MiR-125a-5p levels were analysed by real-time PCR using RNU48 as an endogenous control. To examine possible factors involved in regulating miR125a-5p expression, primary synovial fibroblasts (SFC) and microvascular endothelial cells (HMVEC) microvascular endothelial cells (HMVEC) were cultured with candidate pro-inflammatory stimuli including; TLR ligands (PAM, PolyIC, LPS), pro-inflammatory cytokines (TNFa, IL-1b, IL-17) and growth factors (VEGF, Ang2). Immunoistochemical analysis was performed using factor VIII (DAKO) and appropriate IgG controls, on cryostat synovial tissue sections. Clinical markers, including synovitis, vascularity, ESR, CRP, DAS28, ascertained at the time of arthroscopy were correlated with synovial miRNA expression. Results Expression of miR-125a-5p was significantly decreased in PsA synovial biopsies (n = 8) compared to OA (n = 4) (p < 0.05). No significant difference was observed at the PBMC level across PsA (n = 6), RA (n = 5) and Healthy controls (n = 5). Angiogenic growth factor, Ang2, induced miR-125a-5p in HMVEC (p < 0.05). Lower synovial expression of miR-125a-5p displayed a higher degree of factor VIII staining compared to patients with higher miR-125a-5p expression. This was further demonstrated in representative arthroscopic images. Conclusion Decreased expression of miR-125a-5p in the joint and it’s association with vascularity, which is a hallmark of PsA, suggests it may be important in mediating key pro-angiogenic/pro-inflammatory mechanisms in the synovium. Correcting these microRNA deficiencies, either by conventional pharmacological agents or as novel targets, may provide a therapeutic benefit, especially in early disease stages.

Introduction Dendritic cells (DC) are a heterogeneous population of professional antigen presenting cells. Currently their classification within blood and skin has been well characterised however their identification within other tissues, in particular in the context of autoimmunity is limited. This work aims to identify DC within the inflamed synovium and elucidate how DC are altered by the microenvironment within the joint. Methods DC immunophenotyping was assessed in whole blood (WB), synovial fluid (SF) and synovial tissue (ST) using 9 colour flow cytometry. CD141+ DC were isolated from SF, cultured overnight +/- TLR3 ligands and stained with a panel of antibodies. Monocyte derived DC were cultured in the presence of explant conditioned media (ECM) or SF. MoDC treated with SF were also cocultured with CD4+ T cells for 5 days, after which T cell proliferation and intracellular cytokines were examined. Results RA patients have a significant decrease (p < 0.05) in mDC in WB compared to HC. CD11c+ HLADR+ myeloid cells are increased in the ST compared to WB, express higher levels of CD80/CD40 and express CD64, CD14 and CD16. These cells may represent a myeloid subset of cells unique to inflammatory tissues. DC in SF are more mature than PB DC (increased CD80/CD40; p < 0.05). SF is enriched in CD141+CLEC9A+DC compared to PB (p < 0.005). These cells are rare in WB and previously unidentified in SF. SF CD141+ DC express TREM1 while blood CD141+ DC do not. SF CD141+ DC express higher levels of CD80/CD86 and CD40 compared to blood CD141+ DC. To examine the effect of the synovial microenvironment on DC, MoDC were cultured in the presence of ECM or SF. Both induced a significant increase in the expression of CD80 (p < 0.05 and p < 0.0001). Finally DC treated with SF and subsequently cocultured with CD4+ T cells have enhanced IFNγ production and T cell proliferation. Conclusion Unique DC subsets are found in both ST and SF within the joint. These cells display a more activated phenotype than DC in circulation and the inflammatory nature of the joint contributes to this activation. These uniquely activated DC induce T cell proliferation and cytokine production.

Background The utility of synovial biopsy has been confirmed as an important research tool in increasing our understanding of the pathogenesis of RA, evaluating new treatments and identifying potential therapeutic targets.1,2 The utility of this safe and well-tolerated minimally invasive investigation in routine clinical practice is less well established, but in selected cases it can be useful in diagnosis.3 How macroscopic scores of synovitis as graded by the operator at arthroscopy relate to histology findings of the synovial biopsies retrieved has not been previously reported. Furthermore, the opportunity that macroscopic findings at arthroscopy may have to allow stratification of patients into disease phenotypes with respect to progression of erosive disease has not been reported. Objectives To examine how macroscopic scores of synovitis relate to CRP, histology findings and bone erosions. Methods A macroscopic score of synovitis, graded at 5 unit intervals between 0-100, is recorded by the operator at arthroscopy. How this score relates to the variables described below was examined in a cohort of 111 RA patients who underwent arthroscopy. The Wilcoxon matched-paired signed rank test was employed to test for a correlation between serum CRP concentrations at the time of arthroscopy, and synovitis scores. The Chi-squared test was employed to test for a correlation between categorical synovitis scores (4 quartiles), and categorical data for histology findings (no inflammation, mild inflammation, and moderate-severe inflammation) and the presence or absence of erosions on plain film radiographs of hands and feet. Results A strong correlation was observed between synovitis scores and CRP (n=103, p<0.001). Higher synovitis scores correlated with inflammatory findings on histology (n=90, p=0.02), and with the presence of erosions on radiographs (n=96, P=0.01). There was also a strong correlation between CRP at time of arthroscopy and histology findings (n=87, p=0.009). Conclusions We have demonstrated that synovitis can be reliably assessed by scores, by demonstrating a correlation with a systemic marker of inflammation and microscopic findings. Furthermore, those with high synovitis scores are more likely to have erosions on later radiographs. This demonstrates that arthroscopy is clearly a useful diagnostic investigation for patients in where it is not clear whether there is synovitis, and in assisting to stratify those who may have a worse disease phenotype. References Gerlag DM, Tak PP. Novel approaches for the treatment of rheumatoid arthritis: lessons from the evaluation of synovial biomarkers in clinical trials. Best Practice & Research Clinical Rheumatology. 2008;22(2):311-23. Kraan MC, Reece RJ, et al. Modulation of inflammation and metalloproteinase expression in synovial tissue by leflunomide and methotrexate in patients with active rheumatoid arthritis: Findings in a prospective, randomized, double-blind, parallel-design clinical trial in thirty-nine patients at two centers. Arthritis & Rheumatism. 2000;43(8):1820-30. Bresnihan B. Are synovial biopsies of diagnostic value? Arthritis Research and Therapy 5, no. 6 (2003): 271-278. Disclosure of Interest None declared

Background Treatment decisions in clinic, in line with the EULAR Treat-to Target recommendations,1 require access in the clinic to CRP/ESR, the patient global assessment (visual analogue scale), in addition to joint counts. In practice, the CRP/ESR are often not readily available, thus preventing the calculation of disease activity scores (DAS) at that time. In addition, radiographic progression of erosive disease is also helpful to inform decisions. The potential benefits of using an empirical method to treat patients and compare DAS between visits and after commencing new therapies are readily apparent.2 Changing practice to calculating DAS28-CRP scores for all return IA patients will therefore result in a demonstrable increase in quality of care. Objectives To increase consult quality and efficiency by: Ensuring the availability at the time of consultation of recent inflammatory markers, full serology where relevant, and radiographs of hands and feet taken within the last 36 months. Routinely calculating DAS for all IA patients in clinic. Methods Returning IA patients where identified 2 weeks before their scheduled visit. The patient's blood results were accessed through the hospital's laboratory database. If the patient had an ESR and CRP within the last two weeks (and so within 4 weeks of their clinic visit), it was accepted that this likely represents an accurate result for the purposes of their clinic visit. If the results were more than 2 weeks old, or abnormal, new blood ordering forms for these tests were prepared and sent to the patient by post. RF and anti-CCP, were also requested if appropriate and not yet done. The last set of hands and feet plain film radiographs were identified for each patient by searching the hospital's radiology database. If they were performed anytime within the last 36 months, they were recorded as such, but if not, the patients were posted a request form. An explanatory letter accompanied these forms was also sent. Results 131 patients (85 female) were included. 77 had RA, 43 PsA, 2 undifferentiated arthritis, 1 connective tissue disease, 1 gout, 1 juvenile idiopathic arthritis, 4 OA (erosive), and 2 had no diagnosis recorded. 120 (91.6%), patients had with DAS28-CRP scores calculated, 7 (5.34%) did not have scores calculated because of a piece of essential missing data, and it was thought not appropriate to calculate a score for those 4 (3.05%) who had osteoarthritis. No radiographs were available for 68/131 (51.9%) in the three 3 years before the clinic visit. Of these, 49 (72.1%) had radiographs directly as a result of this change project. The overall compliance with the policy of obtaining staging radiographs every two years is now 92.4%, which represents an improvement of 40.5%. Conclusions This new system for reviewing patients has ensured that clinicians have access to full DAS and radiographic profiling of the pathology. This has improved the quality and efficiency of clinic decisions. References Smolen, J. S. et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Annals of the Rheumatic Diseases (2010)., 69(4), 631-637 Mierau M, et al. Assessing remission in clinical practice. Rheumatology (Oxford) 2007;46:975–9. Disclosure of Interest None declared