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OBJECTIVE To investigate a role for insulin-resistant pathways in inflammation and therapeutic targeting for disease modification in rheumatoid arthritis (RA). METHODS RA disease activity and cardiovascular risk factors, including insulin resistance and body mass index (BMI), were assessed in an Irish RA cohort. Glucose transporter 1 (GLUT-1) and GLUT-4 activity in RA and osteoarthritis (OA) synovial tissue was examined using immunohistochemistry. Spontaneous release of proinflammatory mediators from ex vivo RA synovial explants and primary synovial fibroblast (SF) cell culture supernatants was quantified by enzyme-linked immunosorbent assay. Phosphorylated AMP-activated protein kinase (p-AMPK) and GLUT-1 protein expression was analyzed by Western blotting. Cellular glycolytic and oxidative phosphorylation was assessed using extracellular flux analysis. RESULTS Insulin resistance was independently associated with both BMI (unstandardized coefficient B 0.113 [95% confidence interval (95% CI) 0.059-0.167]; P < 0.001) (n = 61) and swollen joint count in 28 joints (SJC28) (B 0.114 [95% CI 0.032-0.197]; P = 0.008) (n = 61). Increased GLUT-1 expression in RA synovium (n = 26) versus OA synovium (n = 16) was demonstrated (P = 0.0003), with increased expression in the lining, sublining, and vascular regions. In contrast, decreased GLUT-4 expression in the RA lining layer (n = 21) versus the OA lining layer (n = 8) was observed (P = 0.0358). Decreased GLUT-1 protein expression was observed in parallel with increased p-AMPK protein expression in SFs in the presence of metformin (n = 4). Metformin increased glycolytic activity and decreased oxidative phosphorylation in RASFs (n = 7) (P < 0.05 for both). Metformin or aminoimidazole carboxamide ribonucleotide presence decreased spontaneous production of interleukin-6 (IL-6), IL-8, and monocyte chemotactic protein 1 in RA synovial explants and SFs (n = 5-7). CONCLUSION Insulin resistance is significantly associated with BMI and synovitis in RA, suggesting distinct interplay between glucose availability and inflammation in RA. Furthermore, the effect of metformin on proinflammatory mechanisms suggests a role for AMPK-modifying compounds in the treatment of RA.

ObjectiveMicroRNA (miRNA) are small endogenous regulatory RNA molecules that have emerged as potential therapeutic targets and biomarkers in autoimmunity. Here, we investigated serum miRNA levels in patients with psoriatic arthritis (PsA) and further assessed a serum miRNA signature in therapeutic responder versus nonresponder PsA patients.MethodsSerum samples were collected from healthy controls (HC; n = 20) and PsA patients (n = 31), and clinical demographics were obtained. To examine circulatory miRNA in serum from HC and PsA patients, a focused immunology miRNA panel was analyzed utilizing a miRNA Fireplex assay (FirePlex Bioworks Inc.). MiRNA expression was further assessed in responders versus nonresponders according to the European League Against Rheumatism response criteria.ResultsSix miRNA (miR-221-3p, miR-130a-3p, miR-146a-5p, miR-151-5p, miR-26a-5p, and miR-21-5p) were significantly higher in PsA compared to HC (all P < 0.05), with high specificity and sensitivity determined by receiver-operating characteristic curve analysis. Analysis of responder versus nonresponders demonstrated higher baseline levels of miR-221-3p, miR-130a-3p, miR-146a-5p, miR-151-5p, and miR-26a-5p were associated with therapeutic response.ConclusionThis study identified a 6-serum microRNA signature that could be attractive candidates as noninvasive markers for PsA and may help to elucidate the disease pathogenesis.

Objective.The Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials and longitudinal observational studies has recently been updated. The joint counts are central to the measurement of the peripheral arthritis component of the musculoskeletal (MSK) disease activity domain. We report the Outcome Measures in Rheumatology (OMERACT) 2018 meeting’s approaches to seek endorsement of the 66/68 swollen and tender joint count (SJC66/TJC68) for inclusion in the PsA Core Outcome Measurement Set (COS).Methods.Using the OMERACT Filter 2.1 Instrument Selection Process, the SJC66/TJC68 was assessed for (1) domain match, (2) feasibility, (3) numerical sense (construct validity), and (4) discrimination (test retest reliability, longitudinal construct validity, sensitivity in clinical trials, and thresholds of meaning). A protocol was designed to assess the measurement properties of the SJC66/TJC68 joint count. The results were summarized in a Summary of Measurement Properties table developed by OMERACT. OMERACT members discussed and voted on whether the strength of the evidence supported that the SJC66/TJC68 had passed the OMERACT Filter as an outcome measurement instrument for the PsA COS.Results.OMERACT delegates endorsed the use of the SJC66/TJC68 for the measurement of the peripheral arthritis component of the MSK disease activity domain. Among patient research partners, 100% voted for a “green” endorsement, whereas among the group of other stakeholders, 88% voted for a “green” endorsement.Conclusion.The SJC66/TJC68 is the first fully endorsed outcome measurement instrument using the OMERACT Filter 2.1 and the first instrument fully endorsed within the PsA COS.

Objective.To compare the association between different remission criteria and physical function in patients with rheumatoid arthritis followed in clinical practice.Methods.Longitudinal data from the METEOR database were used. Seventeen definitions of remission were tested: American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean-based; Simplified/Clinical Disease Activity Index (SDAI/CDAI); and 14 Disease Activity Score (DAS)-based definitions. Health Assessment Questionnaire (HAQ) ≤ 0.5 was defined as good functional status. Associations were investigated using generalized estimating equations. Potential confounders were tested and sensitivity analyses performed.Results.Data from 32,915 patients (157,899 visits) were available. The most stringent definition of remission was the ACR/EULAR Boolean-based definition (1.9%). The proportion of patients with HAQ ≤ 0.5 was higher for the most stringent definitions, although it never reached 100%. However, this also meant that, for the most stringent criteria, many patients in nonremission had HAQ ≤ 0.5. All remission definitions were associated with better function, with the strongest degree of association observed for the SDAI (adjusted OR 3.36, 95% CI 3.01–3.74).Conclusion.The 17 definitions of remission confirmed their validity against physical function in a large international clinical practice setting. Achievement of remission according to any of the indices may be more important than the use of a specific index. A multidimensional approach, targeted at wider goals than disease control, is necessary to help all patients achieve the best possible functional status.

ObjectiveThis study examines polyfunctional T-cells in psoriatic arthritis (PsA) synovial tissue and their associations with clinical disease and implications for therapy.MethodsPsA synovial tissue was enzymatically/mechanically digested to generate synovial tissue single cell suspensions. Frequencies of polyfunctional CD4, CD8, T-helper 1 (Th1), Th17 and exTh17 cells, using CD161 as a marker of Th17 plasticity, were determined by flow cytometry in matched PsA synovial tissue and peripheral blood. Synovial T-cell polyfunctionality was assessed in relation to Disease Activity in PSoriatic Arthritis (DAPSA) and in synovial cell suspensions cultured with a current mode of treatment, phosphodiesterase 4 (PDE4) inhibitor.ResultsPsA synovial tissue infiltrating CD4+ T-cells expressed higher levels of interleukin (IL)-17A, interferon gamma (IFN-γ), GM-CSF and CD161, with parallel enrichment of Th1, Th17 and exTh17 T-helper subsets (all p+/TNF+/IFN-γ+ (r=0.7, p+/TNF+/IL-17+ (r=0.6, p+/TNF+/IFN-γ+ (r=0.7, p=0.0096), with no associations observed for single cytokine-producing T-cells. Following ex vivo culture of PsA synovial tissue cell suspensions, polyfunctional GM-CSF+TNFα+IL-17A+ or/IFN-γ+-producing T-cells (pConclusionThese data demonstrate enrichment of polyfunctional T-cells in PsA synovial tissue which were strongly associated with DAPSA and ex vivo therapeutic response.

Giant cell arteritis (GCA) is the most common form of systemic vasculitis. Glucocorticoids are an effective treatment but have significant adverse events and relapses are common. Interleukins 12 (IL-12) and 23 (IL-23) stimulate TWe performed a prospective open label study of ustekinumab in patients with refractory GCA. Ustekinumab 90mg was administered subcutaneously every 12 weeks. The primary outcome was the comparison of the median glucocorticoid dose prior to commencement of ustekinumab and at 52 weeks. Secondary outcomes included physician assessed relapse, acute phase reactants, and imaging assessment of large vessel vasculitis (LVV).Twenty-five GCA patients received ustekinumab. All patients had failed to taper glucocorticoids despite addition of a median of 1 other immunosuppressive agent. At week 52, median (IQR) daily prednisolone dose decreased from 20 (15, 25)mg to 5 (2.5, 5)mg (p0.001). Six patients (24%) stopped prednisolone completely. No patient experienced a relapse of GCA while receiving ustekinumab. Median (IQR) CRP decreased significantly from 12.9 (5.3, 42) to 6 (2.6, 12.5)mg/L (p = 0.006). CT angiography demonstrated improvement of LVV in all patients studied. No unexpected adverse events were observed with ustekinumab.Ustekinumab may be effective for the treatment of GCA and warrants further assessment in a randomized controlled trial.

ObjectivesThis study investigates pathogenic and protective polyfunctional T-cell responses in patient with rheumatoid arthritis (RA), individuals at risk (IAR) and healthy control (HC) synovial-tissue biopsies and identifies the presence of a novel population of pathogenic polyfunctional T-cells that are enriched in the RA joint prior to the development of clinical inflammation.MethodsPathway enrichment analysis of previously obtained RNAseq data of synovial biopsies from RA (n=118), IAR (n=20) and HC (n=44) was performed. Single-cell synovial tissue suspensions from RA (n=10), IAR (n=7) and HC (n=7) and paired peripheral blood mononuclear cells (PBMC) were stimulated in vitro and polyfunctional synovial T-cell subsets examined by flow cytometric analysis, simplified presentation of incredibly complex evaluations (SPICE) and FlowSom clustering. Flow-imaging was utilised to confirm specific T-cell cluster identification. Fluorescent lifetime imaging microscopy (FLIM) was used to visualise metabolic status of sorted T-cell populations.ResultsIncreased plasticity of Tfh cells and CD4 T-cell polyfunctionality with enriched memory Treg cell responses was demonstrated in RA patient synovial tissue. Synovial-tissue RNAseq analysis reveals that enrichment in T-cell activation and differentiation pathways pre-dates the onset of RA. Switch from potentially protective IL-4 and granulocyte macrophage colony stimulating factor (GMCSF) dominated polyfunctional CD4 T-cell responses towards pathogenic polyfunctionality is evident in patient with IAR and RA synovial tissue. Cluster analysis reveals the accumulation of highly polyfunctional CD4+ CD8dim T-cells in IAR and RA but not HC synovial tissue. CD4+ CD8dim T-cells show increased utilisation of oxidative phosphorylation, a characteristic of metabolically primed memory T-cells. Frequency of synovial CD4+ CD8dim T-cells correlates with RA disease activity.ConclusionSwitch from potentially protective to pathogenic T-cell polyfunctionality pre-dates the onset of clinical inflammation and constitutes an opportunity for therapeutic intervention in RA.

Rheumatoid arthritis (RA) is a progressive erosive autoimmune disease that affects 1% of the world population. Anti-citrullinated protein autoantibodies (ACPA) are routinely used for the diagnosis of RA, however 20–30% of patients are ACPA negative. ACPA status is a delineator of RA disease endotypes with similar clinical manifestation but potentially different pathophysiology. Profiling of key peripheral blood and synovial tissue immune populations including B cells, T follicular helper (Tfh) cells and CD4 T cell proinflammatory cytokine responses could elucidate the underlying immunological mechanisms involved and inform a treat to target approach for both ACPA-positive and ACPA-negative RA. Detailed high dimensionality flow cytometric analysis with supervised and unsupervised algorithm analysis revealed unique RA patient peripheral blood B cell and Tfh cell profiles. Synovial tissue single cell analysis of B cell subpopulation distribution was similar between ACPA− and ACPA+ RA patients, highlighting a key role for specific B cell subsets in both disease endotypes. Interestingly, synovial tissue single cell analysis of CD4 T cell proinflammatory cytokine production was markedly different between ACPA− and APCA+ RA patients. RNAseq analysis of RA patient synovial tissue highlighted disease endotype specific gene signatures. ACPA status associates with unique immune profile signatures that reinforce the need for a treat to target approach for both endotypes of RA.

Background Biologic therapies have greatly improved outcomes in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Yet, our ability to predict long-term remission and persistence or continuation of therapy remains limited. This study explores predictors of remission and persistence of the initial biologic therapy in patients after 12 years. Furthermore, outcomes with adalimumab and etanercept are compared. Patients and methods RA and PsA patients were prospectively recruited from a biologic clinic. Outcomes on commencing therapy, at 1 year and 12 years were reviewed. Demographics, medications, morning stiffness, patient global health score, tender and swollen joint counts, antibody status, CRP and HAQ were collected. Outcomes at 1 year and 12 years are reported and predictors of biologic persistence and EULAR-defined remission (DAS28-CRP Results A total of 403 patients (274 RA and 129 PsA) were analysed. PsA patients were more likely to be male, in full-time employment and have completed higher education. PsA had higher remission rates than RA at both 1 year (60.3% versus 34.5%, p p p p = 0.041). Multivariate analysis showed 1-year continuation [OR 4.28 (1.28–14.38)] and 1-year low-disease activity [OR 3.90 (95% CI 1.05–14.53)] was predictive of a 12-year persistence. Persistence with initial biologic at 12 years [OR 4.98 (95% CI 1.83–13.56)] and male gender [OR 4.48 (95% CI 1.25–16.01)] predicted 12 year remission. Conclusions This is the first study to show better response to biologic therapy in PsA compared to RA at 12 years. Long-term persistence with initial biologic agent was high and was predicted by biologic persistence and low-disease activity at 1 year. Interestingly, PsA patients had higher levels of employment, educational attainment, and long-term remission rates compared to RA patients.

To evaluate the effects of alcohol consumption on disease activity in rheumatoid arthritis. EMBASE, Pubmed, the Cochrane Library, and Web of Science were searched until July 29, 2020. English language studies that reported disease activity outcomes in rheumatoid arthritis were included. Studies were excluded if they were reviews, case reports, had fewer than 20 patients, or reported on prevalence but not disease activity in RA. Forest plots were used to determine pooled mean difference and were generated on RevMan5.3. Linear regression was used to determine correlations between alcohol and antibody status, gender, and smoking status. The search identified 4126 citations of which 14 were included. The pooled mean difference in DAS28 (95% CI) was 0.34 (0.24, 0.44) (p −5) between drinkers and non-drinkers with lower DAS28 in non-drinkers, 0.33 (0.05, 0.62) (p = 0.02) between heavy drinkers and non-drinkers with lower DAS28 in heavy drinkers, and 0.00 (− 0.30, 0.30) (p = 0.98) between low- and high-risk drinkers. The mean difference of HAQ assessments was significantly different between those who drink alcohol compared to those who do not, with drinkers reporting lower HAQ scores (0.3 (0.18, 0.41), p −5). There was no significant correlation between drinking and gender, smoking status, or antibody positivity. Alcohol consumption is associated with lower disease activity and self-reported health assessment in rheumatoid arthritis. However, drinking has no correlation with smoking, gender, or antibody status.

The activation of antigen specific T cells during an immune response is a tightly regulated process at the level of both costimulatory and coinhibitory receptors. One such coinhibitory receptor or checkpoint inhibitor which has received much attention in the field of oncology is the programmed cell death protein 1 (PD-1). Blockade of PD-1 or its ligand PD-L1 has proven successful in the treatment of a wide variety of cancers, therefore highlighting an important role for this pathway in anti-tumour immune responses. However, a caveat of PD-1 therapy and boosting anti-tumour immune responses is the development of self-reactive T cells which can lead to the induction of various autoimmune or inflammatory diseases, referred to as immune- related adverse events (irAEs). The emergence of rheumatological irAEs such as Inflammatory Arthritis (IA) in recent years has highlighted the importance of PD-1 in maintaining self-tolerance. Furthermore, the emergence of rheumatology related irAEs raises an important question as to how defects in this pathway can contribute to spontaneous rheumatological disease. In this review, we describe the biological distribution, function and regulation of the PD-1 pathway, its potential role in IA and irAE related IA.

Introduction This study investigates the metabolic activity of circulating monocytes and their impact on pro‐inflammatory responses in RA and explores whether this phenotype is already primed for inflammation before clinical manifestations of disease. Methods Blood was collected and CD14+ monocytes isolated from healthy control donors (HC), individuals at‐risk (IAR) and RA patients. Monocyte frequency in blood and synovial tissue was assessed by flow cytometry. Inflammatory responses and metabolic analysis ± specific inhibitors were quantified by RT‐PCR, Western blot, migration assays, Seahorse‐XFe‐technology, mitotracker assays and transmission electron microscopy. Transcriptomic analysis was performed on HC, IAR and RA synovial tissue. Results CD14+ monocytes from RA patients are hyper‐inflammatory following stimulation, with significantly higher expression of cytokines/chemokines than those from HC. LPS‐induced RA monocyte migratory capacity is consistent with increased monocyte frequency in RA synovial tissue. RA CD14+ monocytes show enhanced mitochondrial respiration, biogenesis and alterations in mitochondrial morphology. Furthermore, RA monocytes display increased levels of key glycolytic enzymes HIF1α, HK2 and PFKFB3 and demonstrate a reliance on glucose consumption, blockade of which abrogates pro‐inflammatory mediator responses. Blockade of STAT3 activation inhibits this forced glycolytic flux resulting in metabolic reprogramming and resolution of inflammation. Interestingly, this highly activated monocytic phenotype is evident in IAR of developing disease, in addition to an enhanced monocyte gene signature observed in synovial tissue from IAR. Conclusion RA CD14+ monocytes are metabolically re‐programmed for sustained induction of pro‐inflammatory responses, with STAT3 identified as a molecular regulator of metabolic dysfunction. This phenotype precedes clinical disease onset and may represent a potential pathway for therapeutic targeting early in disease., In this study, we demonstrated that rheumatoid arthritis CD14+ monocytes are metabolically re‐programmed for sustained induction of pro‐inflammatory responses, an effect that is mediated by STAT3 signalling and precedes clinical disease onset.

BackgroundMicroRNAs (miRNAs) are small non-coding RNAs which have been implicated as potential biomarkers or therapeutic targets in autoimmune diseases. This study examines circulatory miRNAs in RA patients and further investigates if a serum miRNA signature precedes clinical manifestations of disease in arthralgia or “at-risk individuals”.MethodsSerum was collected from HC subjects (N = 20), RA patients (N = 50), and arthralgia subjects (N = 10), in addition to a subgroup of the RA patients post-methotrexate (MTX) (N = 18). The FirePlex miRNA Immunology-V2 panel was selected for multiplex analysis of 68 miRNAs in each sample. DNA intelligent analysis (DIANA)-mirPath and Ingenuity Pathway Analysis (IPA) software were used to predict pathways targeted by the dysregulated miRNAs.Results8 miRNA (miR-126-3p, let-7d-5p, miR-431-3p, miR-221-3p, miR-24-3p, miR-130a-3p, miR-339-5p, let-7i-5p) were significantly elevated in RA serum compared to HC (all p < 0.01) and 1 miRNA (miR-17-5p) was significantly lower in RA (p < 0.01). High specificity and sensitivity were determined by receiver operating characteristic (ROC) curve analysis. Both miR-339-5p and let-7i-5p were significantly reduced post-MTX (both p < 0.01). MiR-126-3p, let-7d-5p, miR-431-3p, miR-221-3p, miR-24-3p, miR-130a-3p were also significantly elevated in subjects “at risk” of developing RA (all p < 0.05) compared to HC. IPA analysis of this miRNA signature identified downstream targets including key transcription factors NF-κB, STAT-1, STAT-3, cytokines IL-1β, TNF-α, and matrix-metalloproteases all importantly associated with RA pathogenesis.ConclusionThis study identified six miRNAs that are altered in both RA and “at-risk individuals,” which potentially regulate key downstream pathways involved in regulating inflammation. These may have potential as predictive signature for disease onset and early progression.

Objective: \ud We undertook this study to examine microRNA (miRNA) expression across rheumatoid arthritis (RA) phenotypes, along with the effects and mechanisms of action of miRNA‐17‐5p (miR‐17).\ud \ud Methods: \ud A miRNA array was performed in synovial tissue biopsied from patients with naive erosive RA (n = 3) and patients with nonerosive RA (n = 3). MicroRNA‐17 lipoplex was delivered intraarticularly in the murine collagen‐induced arthritis model. Clinical, histologic, and structural effects were studied over the course of arthritis. In‐depth studies of the mechanisms of action of miR‐17 were performed in primary RA fibroblast‐like synoviocytes (FLS) isolated from synovial tissue.\ud \ud Results: \ud Fifty‐five miRNAs including miR‐17 were reduced in erosive RA. The miR‐17 transfection into arthritic paws reduced the clinical inflammation score between day 2 and day 7 (2.8 versus 1.9; P = 0.03). Synovial B cell, T cell, macrophage, and polynuclear neutrophil infiltration was significantly reduced. Structural damage was also decreased, as shown by a reduction in the number of osteoclasts detected using tartrate‐resistant acid phosphatase staining (osteoclast surface/bone surface 32% versus 18%; P = 0.005) and erosion score by computed tomography analysis (2.9 versus 1.7; P = 0.023). Proinflammatory cytokines from the interleukin‐6 (IL‐6) family and IL‐1β expression were also significantly reduced, but tumor necrosis factor was not. MicroRNA‐17 directly targeted the 3′‐untranslated regions of STAT3 and JAK1. STAT3 and JAK1 messenger RNA (mRNA) and protein expression were reduced in RA FLS following miR‐17 transfection. STAT3 and JAK1 mRNA and activation of STAT3, as assessed by immunohistochemistry, were also reduced in injected paws (% stained area 93% versus 62%; P = 0.035).\ud \ud Conclusion: \ud We demonstrate an antiinflammatory and antierosive role of miR‐17 in vivo. This effect involves the suppression of the IL‐6 family autocrine‐amplifying loop through the direct targeting of JAK1 and STAT3.

Objectives To establish, amongst Irish rheumatic musculoskeletal disease (RMD) patients, rates of COVID-19 symptoms and positive tests, DMARD adherence and attitudes to virtual clinics. Methods An online survey assessing COVID-19 status, RMD diagnoses, adherence and information sources was disseminated via the Arthritis Ireland website and social media channels. Results There were 1381 respondents with 74.8% on immunosuppressive medication. Symptoms of COVID-19 were reported by 3.7% of respondents of which 0.46% tested positive, consistent with the general Irish population. The frequency of COVID-19 symptoms was higher for respondents with spondyloarthropathy [odds ratio (OR) 2.06, 95% CI: 1.14, 3.70] and lower in those on immunosuppressive medication (OR 0.48, 95% CI: 0.27, 0.88), and those compliant with health authority (HSE) guidance (OR 0.47, 95% CI: 0.25, 0.89). Adherence to RMD medications was reported in 84.1%, with 57.1% using health authority guidelines for information on medication use. Importantly, adherence rates were higher amongst those who cited guidelines (89.3% vs 79.9%, P Conclusion The rate of COVID-19 positivity in RMD patients was similar to the general population. COVID-19 symptoms were lower amongst respondents on immunosuppressive medication and those adherent to medication guidelines. Respondents were supportive of HSE advice and virtual clinics.

ObjectiveTo update the European League Against Rheumatism (EULAR) recommendations for the pharmacological treatment of psoriatic arthritis (PsA).MethodsAccording to the EULAR standardised operating procedures, a systematic literature review was followed by a consensus meeting to develop this update involving 28 international taskforce members in May 2019. Levels of evidence and strengths of recommendations were determined.ResultsThe updated recommendations comprise 6 overarching principles and 12 recommendations. The overarching principles address the nature of PsA and diversity of both musculoskeletal and non-musculoskeletal manifestations; the need for collaborative management and shared decision-making is highlighted. The recommendations provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs and local glucocorticoid injections are proposed as initial therapy; for patients with arthritis and poor prognostic factors, such as polyarthritis or monoarthritis/oligoarthritis accompanied by factors such as dactylitis or joint damage, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumour necrosis factor (TNF), interleukin (IL)-17A or IL-12/23 should be initiated, taking into account skin involvement if relevant. If axial disease predominates, a TNF inhibitor or IL-17A inhibitor should be started as first-line disease-modifying antirheumatic drug. Use of Janus kinase inhibitors is addressed primarily after bDMARD failure. Phosphodiesterase-4 inhibition is proposed for patients in whom these other drugs are inappropriate, generally in the context of mild disease. Drug switches and tapering in sustained remission are addressed.ConclusionThese recommendations provide stakeholders with an updated consensus on the pharmacological management of PsA, based on a combination of evidence and expert opinion.

Background Osteoarthritis is the most common cause of disability in people over 65 years old. The readability of of online osteoarthritis information has never been assessed. A 2003 study found the quality of online osteoarthritis information to be poor. This study reviews the quality of online information regarding osteoarthritis in 2018 using three validated scoring systems. Readability is reviewed for the first time, again using three validated tools. Methods The term osteoarthritis was searched across the three most popular English language search engines. The first 25 pages from each search engine were analysed. Duplicate pages, websites featuring paid advertisements, inaccessible pages (behind a pay wall, not available for geographical reasons) and non-text pages were excluded. Readability was measured using Flesch Reading Ease Score (FRES), Flesch-Kincaid Grade Level (FKGL) and Gunning-Fog Index (GFI). Website quality was scored using the the Journal of the American Medical Association (JAMA) benchmark criteria and DISCERN criteria. Presence or absence of HONcode certification, age of content, content producer and author characteristics were noted. Results 37 unique websites were suitable for analysis. Readability varied by assessment tool from 8th to 12th grade level. This compares with the recommended 7- 8th grade level. One (2.7%) website met all four JAMA Criteria. Mean DISCERN quality of information for OA websites was “fair”, comparing favourably with the “poor” grading of a 2003 study. HONCode endorsed websites (43.2%) were of a statistically significantly higher quality. Conclusion Quality of online health information for OA is “fair”. 2.7% of websites met JAMA benchmark criteria for quality. Readability was equal to or more difficult than recommendations. HONcode certification was indicative of higher quality, but not readability. Disclosures K. Murray None. T. Murray None. C. Low None. A. O'Rourke None. D.J. Veale None.

Background Pneumococcal and influenza vaccination rates have been suboptimal in studies of immunosuppressed patients. We aimed to assess barriers to and increase rates of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and influenza vaccination in this group. Methods In 2017, Rheumatology outpatients completed an anonymous questionnaire recording vaccination knowledge, status and barriers. Simultaneously, a low-cost multifaceted quality improvement (QI) intervention was performed. All outpatients on oral steroids, immunosuppressant conventional synthetic disease modifying antirheumatic drugs (csDMARDs) or biologics (bDMARDs) were included in the study. In 2018, post-intervention, the clinic was re-assessed. Demographics, diagnosis, medications, smart phone access and willingness to use this for vaccination reminders were assessed for independent vaccination predictors using binary logistic regression analysis. Results 425 patients were included (72.6% rheumatoid arthritis, 74% women, 45.6% ≥60 years old). From 2017-2018, vaccination rates increased for PPSV23 {41.0% to 47.2% (p = 0.29)} and influenza {61.8% to 62.1% (p = 0.95)}. The most common reason for non-vaccination was lack of awareness. Following the intervention, this decreased for influenza (36.7% to 34.2%) and PPSV23 (82.1% to 76.4%). General Practitioners performed most vaccinations, only 3.6% were delivered in hospital. Significant predictors of PPSV23 vaccination were older age {≥80 years had an OR 41.66 (95% CI 3.69-469.8, P = 0.003), compared to ≤ 39 years}, bDMARD use (OR 2.80, 95% CI 1.24-6.32, P = 0.013) and adequate influenza vaccination (OR 9.01, 95% CI 4.40-18.42, P < 0.001). Up to date PPSV23 vaccination (OR 8.93, 95% CI 4.39-18.17, P < 0.001) predicted influenza vaccination. Conclusion PPSV23 and influenza vaccination rates were suboptimal and increased marginally. Point-of-care vaccination may be more effective. Disclosures K. Murray: None. C. Low: None. F. Young: None. A. O'Rourke: None. I. Callanan: None. E. Feeney: None. D. Veale: None.

Background Rheumatic disease (RD) patients when family planning must consider fertility, disease activity, and management from preconception to lactation. A clear understanding is necessary, especially for those receiving disease-modifying antirheumatic medications. Previous studies have highlighted unmet needs in the care of women with RDs with reproductive healthcare needs. This study describes, to our knowledge, the first published standardised reproductive care pathway for women with RDs and the outcomes of this approach. Methods We developed the care pathway with multidisciplinary input from rheumatologists, rheumatology nurse specialists, obstetricians, midwives, maternal medicine specialists, and pharmacists. We identified patients’ emotional and healthcare needs, ensured access to expert advice, maintenance of good disease control, and positive reproductive outcomes. We prospectively followed the patients and report the results of the service. Results Ninety-eight women with median age (range) of 35 years (19-48) were assessed. The majority had an inflammatory arthritis. Seventy-six babies were born to 62 mothers. There were 12 miscarriages and one perinatal death. Breastfeeding rates at 6 weeks were low (28%). Conclusion We describe the first published evidence-based integrated multidisciplinary reproductive care pathway for women with RDs and the results of this approach. Seventy percent of women successful in trying to conceive delivered a healthy baby, and 90% of patients were ‘very satisfied’ with the service. Disclosures K. Murray: None. L. Moore: None. C. O'Brien: None. A. Clohessy: None. C. Brophy: None. F. McAuliffe: None. D. Veale: None.

We read with interest the research letter by Raychaudhuri et al , which examines the frequencies of cytokine producing CD4+ memory T cells in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) synovial fluid mononuclear cells (SFMC) compared with peripheral blood mononuclear cells (PBMC).1 The authors examined the frequencies of single cytokine-producing T cells, specifically interleukin (IL)-17A+, IL-22+, tumour necrosis factor (TNF)+, interferon gamma (IFNγ)+ or IL-23R+ and report that Th17 cells are enriched in PsA SFMC, while RA is skewed to a Th1-like profile. In our previous publication, Wade et al ,2 we reported the frequencies of both single cytokine-producing and multiple cytokine (polyfunctional)-producing T cells, in addition to the frequencies of Th1, Th17 and exTh17 cells by using the Th17 lineage marker CD161. In our study, however, we reported these findings in synovial tissue biopsies from PsA patients, as opposed to …

Summary Psoriatic arthritis is a chronic, immune-mediated, inflammatory arthropathy that presents with inflammation of the joints and entheses, including those of the axial skeleton, and is associated with increased mortality from cardiovascular disease. Diagnosis is primarily based on clinical phenotype because of the diversity of the associated features, which can include skin and nail disease, dactylitis, uveitis, and osteitis. Improved understanding of the pathogenesis of psoriatic arthritis has led to the development of effective biologics and small-molecular drugs targeting specific cytokines and signalling pathways, which can prevent disease progression and improve quality of life. However, at least 40% of patients with psoriatic arthritis have only a partial response or fail to respond to such treatments. Cytokine inhibitors, mainly those specific for tumour necrosis factor and, more recently, the interleukin 23–T-helper-17 cell pathway, have been highly successful in the treatment of disease manifestations in several different tissues, although targeting the interleukin 23–T-helper-17 cell pathway might be more effective in psoriasis than in arthritis. However, the precise mechanisms underlying the pathogenesis of psoriatic arthritis—which include genetics, environmental factors, and immune-mediated inflammation—are complex, and the relationship between disease of the joint and that of other domains is poorly understood. Improving our understanding of psoriatic arthritis pathogenesis could help to establish validated biomarkers for diagnosis, predict therapeutic response and remission, develop precision medicines, and predict which patients will respond to which therapy. We discuss advances in pathogenetic translational research that could inform these issues.

To assess the association between smoking, anti-cyclic citrullinated peptide (anti-CCP) antibody status, and clinical efficacy of biological therapies in rheumatoid arthritis (RA) patients.This retrospective clinical practice setting study included 1349 RA patients from the METEOR database (aged18 years). We collected data on sociodemographics, smoking status (smoker,10, 10-19, and20 cigarettes/day; ex-smoker; non-smoker), baseline disease activity parameters and anti-CCP, previous disease-modifying anti-rheumatic drugs (DMARDs), biological therapy, combined therapy (steroids and DMARDs), and follow-up disease activity. Clinical efficacy was assessed by European League Against Rheumatism (EULAR) good/moderate response rates for all aggregated biological therapies, based on both smoking and anti-CCP status.The non-smoking RA patients were more often female at biological therapy initiation than the ex-smokers and smokers (91.1% vs 60.4% and 67.9%, respectively, p 0.001), and ex-smokers were older than non-smokers and smokers (mean ± sd 56.5 ± 11.1, 53.5 ± 13.3 and 51.3 ± 11.0 years old, respectively; p 0.001). In total, 845 (62.6%) were non-smokers, 214 (15.9%) ex-smokers, and 290 (21.5%) smokers [daily cigarettes smoked: 148 (11%)11; 61 (4.5%) 11-20; and 81 (6%)20]. Anti CCP-antibody status was similar in both groups. Non-smokers showed higher baseline DAS28 than ex-smokers and smokers (5.0 ± 1.5 vs 4.7 ± 1.4 and 4.7 ± 1.4, respectively; p 0.001) and used more baseline steroids and DMARDs. A higher EULAR response rate was observed in non-smokers than in ex-smokers and smokers (73% vs 65% and 64.1%, respectively; p = 0.004). Drug survival was higher in non-smokers compared to ex-smokers and smokers [57.7 months (46.4-53.8), 38.6 (30.3-46.8), and 50.1 (41.8-58.4); p0.001, respectively].In daily clinical practice, non-smokers respond better than smokers to biological therapy, but this does not result in better drug survival.

Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field. orcid-numbers: Machado, Pedro/0000-0002-8411-7972 Inman, Robert/0000-0002-4750-1422 unique-id: ISI:000417778700007 ispartof: Annals Of The Rheumatic Diseases vol:77 issue:1 pages:3-17 ispartof: location:England status: published

There are now high-quality data showing rheumatoid arthritis improves in pregnancy and flares post partum, and that active disease in pregnancy may be associated with adverse fetal outcomes such as low birth weights. However, in psoriatic arthritis (PsA), the data are less clear. Previous studies examining the disease course of PsA, in and around pregnancy, have found conflicting results.1–3 Only one of those studies was prospective and many lack disease activity scores. Much of the data also predate the widespread use of biologic disease-modifying antirheumatic drugs (bDMARDs) in pregnancy and so may not reflect current clinical practice. A recent abstract reviewing a Swedish patient registry reported increased odds of preterm birth, induction of labour and caesarean section in PsA pregnancies compared with population comparators.4 Consecutive female patients with PsA planning pregnancy or were …

Objective Serum anti–citrullinated peptide antibodies (ACPAs) may be present before the development of rheumatoid arthritis (RA) and may be predictive of more severe, erosive disease. This study was undertaken to examine the synovial tissue immunophenotype according to ACPA status in patients with RA, as well as the response to treatment and erosion status. Methods Consecutive RA patients were prospectively recruited and underwent clinical and serologic assessments before and after treatment. Radiologic assessment was performed at the time of clinical follow-up. Synovial tissue was immunostained for specific markers of B cells (CD19), T cells (CD3, CD4, and CD8), macrophages (CD68), and blood vessels (factor VIII). Serum CXCL13 levels were quantified by enzyme-linked immunosorbent assay. Synovial tissue sections were analyzed for immunophenotype according to ACPA status, using a validated semiquantitative scoring method, and also analyzed for the presence of lymphoid aggregates. Response to treatment with nonbiologic or biologic disease-modifying antirheumatic drugs was assessed using the European League Against Rheumatism (EULAR) response criteria. Results In total, 123 subjects (78 ACPA+) were included. Compared to ACPA– RA patients, synovium from ACPA+ RA patients was characterized by significantly higher levels of CD19+ B cells and CD3+ and CD8+ T cells (each P < 0.05), and CD19+ B cell levels were significantly higher in patients who were naive to treatment. The CD19+ B cell infiltrate level was higher in patients with erosions at follow-up (P = 0.0128). Levels of lymphoid aggregates of CD19+ B cells were significantly higher in ACPA+ patients (P < 0.05), and this was associated with increased serum CXCL13 levels. The EULAR response was significantly associated with the level of CD3+ T cell infiltrates (P < 0.05), while CD68+ macrophage and CD8+ T cell levels were predictive of the response to tumor necrosis factor inhibitors (P < 0.05). Conclusion The results of this prospective study demonstrate that the levels of synovial B cell infiltrates and lymphoid aggregates were significantly higher in ACPA+ RA patients, especially those who were naive to treatment. In addition, ACPA+ subjects developed more erosions during progression of the disease and had higher serum levels of CXCL13. The EULAR response to therapy in ACPA+ RA patients was associated with increased levels of T cell and macrophage markers.

Objective Patient-physician discordance in global assessment of disease activity concerns one-third of patients, but what does it reflect? We aimed to assess patient-physician discordance in psoriatic arthritis (PsA) and patient-reported domains of health (physical and psychological) associated with discordance. Methods We analyzed the PsAID (Psoriatic Arthritis Impact of Disease), a cross-sectional, multicenter European study of patients with PsA according to expert opinion. Patient global assessment (PGA) and physician global assessment (PhGA) were rated on a 0–10 numeric rating scale. Discordance was defined as the difference (PGA−PhGA) and as the absolute difference |PGA−PhGA| ≥3 points. Determinants of PGA−PhGA were assessed by a stepwise multivariate linear regression among 12 physical and psychological aspects of impact: pain, skin problems, fatigue, ability to work/leisure, functional incapacity, feeling of discomfort, sleep disturbance, anxiety/fear, coping, embarrassment/shame, social participation, and depressive affects. Results In 460 patients (mean ± SD age 50.6 ± 12.9 years, 52.2% female, mean ± SD disease duration 9.5 ± 9.5 years, mean ± SD Disease Activity Index for Psoriatic Arthritis score 30.8 ± 32.4, and 40.4% undergoing treatment with biologic agents), the mean ± SD PGA was higher than the mean PhGA, with a mean absolute difference of 1.9 ± 1.8 points. Discordance defined by |PGA−PhGA| ≥3 of 10 concerned 134 patients (29.1%), and 115 patients (85.8% of the patients with discordance) had PGA>PhGA. Higher fatigue (β = 0.14), lower self-perceived coping (β = 0.23), and impaired social participation (β = 0.16) were independently associated with a higher difference (PGA−PhGA). Conclusion Discordance concerned 29.1% of these patient/physician dyads, mainly by PGA>PhGA. Factors associated with discordance were psychological rather than physical domains of health. Discordance was more frequent in patients in remission, indicating more work is needed on the patient perspective regarding disease activity.

Objective To examine the prevalence of α1-antitrypsin deficiency (AATD) in rheumatoid arthritis (RA), and to determine whether AATD is associated with higher levels of rheumatoid factor (RF), antinuclear antibodies (ANAs), and anti–citrullinated peptide autoantibodies (ACPAs). Methods RF, ANAs, and ACPAs were measured by standard immunoturbidimetry, immunofluorescence assay, and enzyme-linked immunosorbent assay, respectively. Characterization of AAT phenotypes was performed by isoelectric focusing and immunofixation. The chi-square test with Yates' correction and the Mann-Whitney U test were used to assess the prevalence of alleles associated with AATD in RA and to compare mean antibody titers, respectively. Results Of 246 patients with RA, 24 who were heterozygous for AATD were identified, with no statistically significant difference in the prevalence of AATD between RA patients and the general population (P = 0.39). A positive association between heterozygosity for AATD and the production of ACPAs was observed (P

The inflammatory CD40–CD40L pathway is implicated in various autoimmune diseases, but the activity status of this pathway in various stages of rheumatoid arthritis (RA) progression is unknown. In this study, we used gene signatures of CD40L stimulation derived from human immature dendritic cells and naive B cells to assess the expression of CD40-downstream genes in synovial tissues from anti-citrullinated protein Ab–positive arthralgia, undifferentiated arthritis (UA), early RA, and established RA cohorts in comparison with healthy donors. Interestingly, the expression of CD40LG and active full-length CD40 was increased in the disease tissues, whereas that of a dominant-negative CD40 isoform was decreased. Gene set variation analysis revealed that CD40L-responsive genes in immature dendritic cells and naive B cells were significantly enriched in synovial tissues from UA, early RA, and established RA patients. Additionally, CD40L-induced naive B cell genes were also significantly enriched in synovial tissues from arthralgia patients. In our efforts to characterize downstream mediators of CD40L signaling, we have identified GPR120 and KDM6B as novel components of the pathway. In conclusion, our data suggest that therapeutic CD40–CD40L blocking agents may prove efficacious not only in early and established RA, but also in inhibiting the progression of the disease from arthralgia or UA to RA.

Pneumococcal and influenza vaccination rates have been suboptimal in studies of immunosuppressed patients. We aimed to assess barriers to and increase rates of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and influenza vaccination in this group. The primary endpoint was a statistically significant increase in adequate PPSV23 and influenza vaccination.In 2017, rheumatology outpatients completed an anonymous questionnaire recording vaccination knowledge, status, and barriers. Simultaneously, a low-cost multifaceted quality improvement (QI) intervention was performed. All outpatients on oral steroids, immunosuppressant conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologics disease-modifying antirheumatic drugs (bDMARDs) were included in the study. In 2018, post-intervention, the clinic was re-assessed. Demographics, diagnosis, medications, smart phone access, and willingness to use this for vaccination reminders were assessed for independent vaccination predictors using binary logistic regression analysis.Four hundred twenty-five patients were included (72.6% rheumatoid arthritis, 74% women, 45.6% ≥ 60 years old). From 2017 to 2018, PPSV23 vaccination rates changed from 41.0 to 47.2% (P = 0.29) and influenza from 61.8 to 62.1% (P = 0.95). The most common reason for non-vaccination was lack of awareness. Following the intervention, this changed for influenza (36.7 to 34.2%) and PPSV23 (82.1 to 76.4%). General practitioners performed most vaccinations, only 3.6% were delivered in the hospital. Significant predictors of PPSV23 vaccination were older age {≥ 80 years had an OR 41.66 (95% CI 3.69-469.8, P = 0.003), compared with ≤ 39 years}, bDMARD use (OR 2.80, 95% CI 1.24-6.32, P = 0.013), and adequate influenza vaccination (OR 9.01, 95% CI 4.40-18.42, P 0.001). Up-to-date PPSV23 vaccination (OR 8.93, 95% CI 4.39-18.17, P 0.001) predicted influenza vaccination.PPSV23 and influenza vaccination rates were suboptimal. The intervention did not cause a statistically significant change in vaccination rates. Point-of-care vaccination may be more effective.Key Points• Low vaccination rates amongst immunosuppressed inflammatory arthritis outpatients• Less than 5% of vaccinations occurred in hospital• There was no statistically significant difference in the rates of adequate PPSV23 (41.0 to 47.2%) or influenza (61.8 to 62.1%) vaccination following our intervention.

Background Several biologic disease modifying anti-rheumatic drugs (bDMARDs) are currently available, but comparisons among these different drugs in clinical trials are rare and follow-up duration in trials is often limited. A comparison of these bDMARDs in daily practice can provide clinically relevant knowledge on treatment survival of all currently available bDMARDs. Objectives To assess the survival of each and every one of the biological therapies available in patients with rheumatoid arthritis (RA). Methods The METEOR registry is a multinational project that includes data on> 40,000 patients with RA from its diagnosis and prospectively, with proven reliability, in clinical practice. Inclusion criteria: patients> 18 years in biological treatment (bDMARD). Variables under study: disease onset date, bDMARD initiation and discontinuation date, bDMARD type (infliximab, certolizumab, adalimumab, golimumab, etanercept, rituximab, tocilizumab and abatacept), concomitant treatment, line of treatment. Clinical variables: TJC, SJC, ESR, CRP, BMI, patient‘s VAS, and RF and ACPA levels; smoking status. Cox regression analysis that was adjusted for several potential confounders. Results From the 47,263 patients registered in the total METEOR database, 11,132 were eligible for inclusion of the current study. Of these, 9,516 had sufficient data available and were included in the analyses. Included patients (n=9,516) less often smoked than non-included patients (n=1,616), but other baseline characteristics were very similar between groups (data not shonw). Baseline features of all patients were similar. Median time on bDMARD as 1st line treatment for each drug is shown in Table 1, infliximab showed the longest median time on treatment. Using infliximab as ‘reference’ treatment, Table 2 shows abatacept, certolizumab, rituximab and tocilizumab showed higher hazard risk to finish the treatment prematurely, while adalimumab, golimumab or etanercept had similar results than infliximab. Conclusion: after adjusting by several confounders, analysed data showed that most anti-TNF (infliximab, adalimumab, etanercept and golimumab) had a similar hazard to stop treatment in clinical practice. Other than anti-TNF bDMARD showed higher hazard to switch treatment than infliximab. Disclosure of Interests Vicenc Torrente-Segarra Speakers bureau: Roche, GSK, UCB, Thomas Huizinga Consultant for: Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, GSK, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience Inc., Nycomed, Boeringher, Takeda, Zydus, Epirus, Eli Lilly, Karen Solomon-Escoto: None declared, Jose Antonio P. da Silva: None declared, Douglas Veale: None declared, Samar Al Emadi: None declared, Sytske Anne Bergstra Grant/research support from: Bristol-Myers Squibb provided funding for the completion of this study and the development of the abstract.

Background: Appropriate management can reduce the increased perioperative infection risk in RA patients(1). In 2017, American College of Rheumatology (ACR) and the American Association of Hip and Knee Surgeons released Guidelines for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty(1). Atlanto-axial subluxation at induction of general anaesthetic (GA) is another concern. Preoperative C-spine X-rays with flexion-extension views are recommended(2). Objectives: Assess compliance with medication guidelines and C-spine imaging practices for RA patients undergoing arthroplasty under GA. Methods: An anonymous 24 question paper-based survey was distributed at Irish Society of Rheumatology Meeting (September 2017) and Irish Institute of Trauma and Orthopaedic Surgery Curriculum Day (January 2018) examining clinician demographics, imaging and prescribing practices. Results: 33 orthopaedists and 23 rheumatologists responded. The majority (n=46) were trainees and The guideline advocates cDMARD continuation perioperatively(1). Rheumatologists are more likely than orthopaedists to continue cDMARDs (Pearson Chi squared, 0.001). 8 (36%) rheumatologists continue cDMARDs, 6 (27%) stop one week preoperatively and 8 (36%) at two weeks. 1 orthopaedist never stops cDMARDs. 8 (24%) stop at one week preoperatively, 13 (39%) at 2 weeks, 5 (15%) at 4 weeks. 6 (18%) were unsure. The guideline advocates stopping bDMARDs 1 dosing cycle preoperatively and restarting after wound healing. Depending on the agent, 2 to 4 rheumatologists never stop bDMARDs preoperatively. Responses varied by medication half-life. 18 hold etanercept for 8 weeks. 2 orthopaedists never stop bDMARDs preoperatively. Depending on the agent, 14-15 would stop 8 weeks 0-1 times. Regarding patients on glucocorticoids for RA, the guideline advocates continuing current dosing perioperatively. 6 orthopaedists always increase steroids (13 sometimes, 9 never, 5 unsure). 7 never stop (13 sometimes, 6 always, 5 unsure). 12 rheumatologists sometimes increased steroids (8 always, 1 never, 1 not sure, 1 no answer). 14 never stop steroids (8 sometimes, one not sure). In RA patients undergoing GA, 22 orthopaedists always perform C spine imaging prior (10 sometimes, 1 never). 11 rheumatologists always do C spine imaging prior (11 sometimes, 1 never). Orthopaedists are more likely than rheumatologists to always perform spinal imaging preoperatively (P value=0.002, Fisher’s exact test). Conclusion: There is poor compliance with guidelines and variability and uncertainty in prescribing. Orthopaedists often discontinue sDMARDs preoperatively despite guidelines to the contrary. Orthopaedists are more likely than rheumatologists to perform preoperative C spine imaging as per recommendations. References: [1] Goodman SM, Springer B, Guyatt G, Abdel MP, Dasa V, George M, et al. 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty. Arthritis care & research. 2017;69(8):1111-24. [2] Wasserman BR, Moskovicich R, Razi AE. Rheumatoid arthritis of the cervical spine. Bull NYU Hosp Joint Dis.2011;69:136-48. Disclosure of Interests: Kieran Murray Grant/research support from: Newman Research Fellowship (Abbvie), Tristan Cassidy: None declared, Abuelmagd Abdalla: None declared, Timothy Murray: None declared, Anna O’Rourke: None declared, Douglas Veale: None declared

Background: The single nucleotide variant rs26232 has been associated with both the susceptibility to, and severity of, rheumatoid arthritis (RA). There is an allele dose response between rs26232 and radiological damage, with the minor, T, allele being protective against disease severity. Rs26232 is situated in the first intron of C5orf30, which is a negative regulator of tissue damage and inflammation in RA. Objectives: The objective of this study is to elucidate the mechanism by which rs26232 may mediate disease severity. We also aimed to determine the genotype-phenotype association of rs26232 in rheumatoid arthritis synovial fibroblasts (RASF). Methods: RASF were derived from knee biopsies of RA patients taken at arthroscopy (n=33). RASFs were used between passages 3-8. Matrigel-coated Boyden transwell chambers were used to measure invasion. Wound healing (scratch assays) were used to measure migration, whereas proliferation was measured via crystal violet staining of fixed RASF. Intracellular cytokine staining and cell surface markers were measured via flow cytometry. Secreted cytokines were measured in the supernatant of RASF using ELISA. Rs26232 genotype was determined by PCR genotyping assay with allelic discrimination analysis. Anticitrullinated protein antibody (ACPA) status was measured for each participant. Quantitative real-time PCR was used to measure gene expression. Mann-Whitney U test was used to compare two independent groups, Kruskal-Wallis test was used to compare groups of greater than two. Results: 49% (n=16) of our RASF cohort where homozygous for the major allele CC, 42% (n=14) were heterozygous CT, 9% (n=3) were TT. Rs26232 is associated with invasion of RASFs with the CC genotype being more invasive than the CT genotype (p=0.021). RASFs with the CC genotype had increased ICAM1 and VEGF cell surface expression compared to CT genotype (p=0.001, p=0.05 respectively). MCP1/CCL2 was decreased in CC compared to CT (p=0.013). No association was found between rs26232 genotype and migration, proliferation, or expression of MMP3, TIMP3, IP10 or MIP1a. rs26232 is located in the first intron of C5orf30. There was no differential expression of total C5orf30 or with any of the 3 individual transcript variants in rs26232 genotype groups. In silico analysis of the region in which rs26232 is located on chromosome 5 identified a DNase Hypersensitivity cluster. Furthermore, mining of the Genotype-Tissue Expression (GTEX) expression quantitative trait loci (eQTL) database revealed a cluster of genes located upstream on chromosome 5 (102,850,000-103,150,000) associated with rs26232. This region upstream from rs26232 contains 4 genes (EIF3KF1, PPIP5K2, PAM and GIN1), of which three are eQTLs of rs26232. In silico analysis revealed that the 3 eQTLs (EIF3KF1, PPiP5K2 and PAM) also contain the active enhancer mark H3K27Ac, whereas GIN1 does not. Conclusion: The CC genotype of rs26232 is associated with both increased invasiveness of RASFs and increased adhesion markers compared to CT genotype. Rs26232 does not mediate its affect via its nearest gene, C5orf30. Rather, in silico analysis predicts rs26232 may function as a distal regulator of EIF3KF1, PPIP5K2 and PAM. Future work will test the hypothesis that rs26232 genotype phenotype association is mediated by EIF3KF1, PPIP5K2 and PAM. Disclosure of Interests: None declared

Background: Disease-related immune dysfunction and medications cause immunosuppression in inflammatory arthritis (IA)(1). EULAR and Centers for Disease Control (CDC) recommend influenza and 23-valent pneumococcal polysaccharide (PPSV23) vaccination. Previous studies show suboptimal coverage. Objectives: To increase influenza (annual) and PPSV23 (5 yearly) vaccination in immunosuppressed IA patients through a multifaceted quality improvement intervention. Methods: Between April and September 2017, IA patients completed an anonymous paper 23 question worksheet recording demographics, medical history, medications, vaccination knowledge, status and barriers. All patients on oral steroids, bDMARDs or immunosuppressant cDMARDs were included. Simultaneously, we introduced staff education sessions, point-of-care paper “Arthritis and Infection Worksheets” and “Vaccination Advice Letters”. In 2018, the clinic was re-assessed. Results: 163 patients met inclusion criteria in 2017 and 262 in 2018. Patients were typical of an IA clinic (74% women, 45.4%≥60 years old, 72.7% had RA, 61.1% on cDMARDs, 53.6% on methotrexate, 46.6% on bDMARDs, 23.1% on cDMARD plus bDMARD). In 2017, 104 (65.4%) knew of the increased infectious risk of IA. In 2018, 168 (65.6%) were aware. Awareness of infection risk with medications increased from 111 (69.8%) to 172 (66.9%). Table 1 shows vaccination rates. PPSV23 rates increased from 41.0% to 47.2% (P value=0.29. Pearson Chi squared), and influenza from 61.8% to 62.1% (P value=0.95, Pearson Chi squared). Vaccination awareness was higher for influenza (Table 2). Most patients were informed of requirements and vaccinated by general practitioners (GPs), with Conclusion: This study shows suboptimal vaccination awareness and uptake. Our interventions increased PPSV23 and influenza vaccination rates. There is debate about who is responsible for vaccinations. Guidelines advocate specialists sharing responsibility with GPs. 57% of rheumatologists considered GPs responsible (2). Perhaps, we should take a more active approach. References [1] Doran MF, Crowson CS, Pond GR, O’Fallon WM, Gabriel SE. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis & Rheumatism.2002;46(9):2287-93 [2] McCarthy EM, Azeez MA, Fitzpatrick FM, Donnelly S. Knowledge, attitudes, and clinical practice of rheumatologists in vaccination of the at-risk rheumatology patient population. JCR: Journal of Clinical Rheumatology. 2012;18(5):237-41 Disclosure of Interests: Kieran Murray Grant/research support from: Newman Research Fellowship (Abbvie), Francis Young: None declared, Candice Low: None declared, Anna O’Rourke: None declared, Ian Callanan: None declared, Eoin Feeney: None declared, Douglas Veale: None declared

Rheumatic disease (RD) patients when family planning must consider fertility, disease activity, and management from preconception to lactation. A clear understanding is necessary, especially for those receiving disease-modifying antirheumatic medications. Previous studies have highlighted unmet needs in the care of women with RDs with reproductive healthcare needs. This study describes the first published standardized reproductive care pathway for women with RDs and the outcomes of this approach. We developed the care pathway with multidisciplinary input from rheumatologists, rheumatology nurse specialists, obstetricians, midwives, maternal medicine specialists, and pharmacists. We identified patients’ emotional and healthcare needs, ensured access to expert advice, maintenance of good disease control, and positive reproductive outcomes. We prospectively followed the patients and report the results of the service. Ninety-eight women with median age (range) of 35 years (19–48) were assessed. The majority had an inflammatory arthritis. Seventy-six babies were born to 62 mothers. There were 12 miscarriages and one perinatal death. Breastfeeding rates at 6 weeks were low (28%). We describe the first published evidence-based integrated multidisciplinary reproductive care pathway for women with RDs and the results of this approach. Seventy percent of women successful in trying to conceive delivered a healthy baby, and 90% of patients were ‘very satisfied’ with the service.

Career situation of first and presenting author Post-doctoral fellow. Introduction RF and ACPA have been used extensively for the diagnosis of RA, however no clear mechanism of action towards disease pathogenesis and progression has been identified. Importantly, both seropositive and seronegative RA patients experience significant improvement in disease severity following B cell depletion. Therefore, we hypothesized that B cells have a central role in ACPA+ and ACPA- RA irrespective of their capacity to produce auto-antibodies. Objectives To characterize B and T cell populations, their recruitment to the inflamed joint, B cell cytokine production and CD4+ T cell polarization in RA synovial tissue biopsies and peripheral blood of ACPA+, ACPA- RA and arthralgia subjects. Methods Synovial tissue biopsies from ACPA+ and ACPA- RA and ACPA+ arthralgia subjects, with paired blood/synovial fluid, were obtained through key-hole arthroscopy and were enzymatically digested. B cell invasion assays and B and CD4+ T cell in vitro stimulation were conducted under hypoxic conditions simulating the unique environment of the inflamed joint. Flow cytometric analysis was performed. Results Significant accumulation, compared to peripheral blood, of pro-inflammatory B cells and pro-inflammatory cytokine-producing CD4+ T cells in the synovial tissue and fluid of RA patients, irrespective of ACPA status, as well as the synovial tissue of arthralgia subjects. SPICE analysis of peripheral blood B cells, for a panel of chemokine receptors, revealed a disease-specific expression pattern detected in RA and arthralgia subjects. Importantly, the tissue-invading B cells expressed CXCR3, with in vitro blockade of CXCR3 resulting in reduced B cell invasion in response to RA synovial tissue biopsy-conditioned media. Under the unique hypoxic conditions of the inflamed joint, RA patient but not healthy subject-derived B cells produce several pro-inflammatory cytokines including TNF-a and IL-6 and are capable of polarizing CD4+ T cells towards a pro-inflammatory phenotype. Conclusions Accumulation of pro-inflammatory B cell subpopulations in the synovium of both ACPA+ and ACPA- RA patients underlines a common, antibody-independent, contribution of B cells in synovial inflammation. Arthralgia early in disease, specific chemokine receptor expression and the accumulation of CXCR3+ B cells in the inflamed joint offers an opportunity for therapeutic intervention. Once in the hypoxic environment of the inflamed RA joint, B cells show altered activation, cytokine production and T cell polarization capacity that could prove important for understanding the role of B cells in disease pathogenesis of RA. Disclosure of Interest None declared.

The pathogenesis of SpA is multifactorial and involves a range of immune cell types and cytokines, many of which utilize Janus kinase (JAK) pathways for signaling. In this review, we summarize the animal and pre-clinical data that have demonstrated the effects of JAK blockade on the underlying molecular mechanisms of SpA and provide a rationale for JAK inhibition for the treatment of SpA. We also review the available clinical trial data evaluating JAK inhibitors tofacitinib, baricitinib, peficitinib, filgotinib and upadacitinib in PsA, AS and related inflammatory diseases, which have demonstrated the efficacy of these agents across a range of SpA-associated disease manifestations. The available clinical trial data, supported by pre-clinical animal model studies demonstrate that JAK inhibition is a promising therapeutic strategy for the treatment of SpA and may offer the potential for improvements in multiple articular and extra-articular disease manifestations of PsA and AS.

Objective The aim of this study was to examine the pro-inflammatory effects of IL-6 in ex vivo temporal artery explant cultures. Methods Patients meeting 1990 ACR classification criteria for GCA were prospectively recruited. Temporal artery biopsies were obtained and temporal artery explants cultured ex vivo with IL-6 (10-40 ng/ml) in the presence or absence of its soluble receptor (sIL-6R; 20 ng/ml) for 24 h. Explant supernatants were harvested after 24 h and assayed for IFN-γ, TNF-α, Serum amyloid A, IL-1β, IL-17, IL-8, angiotensin II and VEGF by ELISA. Myofibroblast outgrowths, cytoskeletal rearrangement and wound repair assays were performed. Results IL-6 augmented production of VEGF, but not of any of the other pro-inflammatory mediators assayed. No differences were observed in the explants cultured in the presence or absence of the sIL-6R or between those with a positive (n = 11) or negative (n = 17) temporal artery biopsy. IL-6 did not enhance myofibroblast proliferation or migration. Western blot analysis confirmed signalling activation, with increased expression of pSTAT3 in response to IL-6+sIL-6R. Conclusion IL-6 stimulation of temporal artery explants from patients with GCA neither increased expression of key pro-inflammatory mediators nor influenced myofibroblast proliferation or migration.

Background: The aim of this global collaboration was to develop a consensual set of items for the analysis of synovial biopsies in clinical practice and translational research through the EULAR Synovitis Study Group (ESSG) and OMERACT Synovial Tissue Biopsy Group. Methods: Participants were consulted through a modified Delphi method. Three sequential rounds occurred over 12 months. Members were sent a written questionnaire containing items divided into two parts. Items were identified and formulated based on a scoping review. The first part of the questionnaire referred to synovial biopsies in clinical practice including five subsections, and the second part to translational research with six subsections. Every participant was asked to score each item on a 5-point Likert scale. Items with a median score above 3.5 and a ≥ 70% agreement were selected for the next round. The last round was conducted orally at EULAR in June 2017. Results: Twenty-seven participants from 19 centers were contacted by email. Twenty participants from 17 centers answered. Response rates for next rounds were 100%. For the first part relating to clinical practice, 20/44 items (45.5%) were selected. For the second part relating to translational research, 18/43 items (41.9%) were selected for the final set. Conclusions: We herein propose a consensual set of analysis items to be used for synovial biopsies conducted in clinical practice and translational research.

Several inflammatory, proteolytic, angiogenic and bone-associated factors play a role in the development of autoimmune, accelerated atherosclerosis in rheumatic diseases. Some of these may serve as biomarkers of vascular pathology and may be useful in the follow-up of vascular damage and outcome. Multi-biomarker profiles rather than a single markers would likely be optimal in this respect.

Synovial tissue is a key structure in diarthrodial joints and is the primary target of inflammation in autoimmune arthritis. The study of synovial tissue has developed significantly in the last two decades as arthroscopic and ultrasonographic techniques have allowed visualization and access to synovial biopsy. Further progress in synovial tissue processing and analysis has improved studies of disease pathogenesis, biomarker discovery, and molecular therapeutic targeting with increasingly specialized analytical and technological approaches. In September 2018 the first course on Synovial Tissue Biopsies was convened in Brussels, in this Mini Review these approaches will be described and I will summarize how synovial tissue research advanced.

Background: Patient engagement with clinicians results in shared decision making and increased adherence to medication. However, in order for strong patient: clinician partnerships to be achieved, communication barriers need to be identified. Therefore, the aim of this study was to examine the level of understanding of inflammatory arthritis patients and the need for strong patient-partnership in research. Methods: An online anonymous survey was distributed to patients living with inflammatory arthritis which addressed questions about diagnosis, routine tests, medications and how they work, medication adherence, disease flare, heredity, pregnancy, and patient involvement in research. Results: There were 1,873 respondents, 1416 of which had inflammatory arthritis (IA)- rheumatoid arthritis (RA) (65.8%) and psoriatic arthritis (PsA) (34.2%). They were predominantly female (RA 86%, PsA 85 %), aged 55±13 and 50±12 years. Less than 35% of patients had an understanding of diagnostic tests, what was measured and the implication for disease, with 75.5% also concerned about heredity. There was a high level of understanding of how specific medications treat inflammatory arthritis (72.9%). Adherence was also very high (>87%), with the main reasons for stopping medication without the advice of their clinician, ‘feeling better’ and ‘side effects’ however a significant proportion of patients (69.9%) reported a disease-flare following cessation of medication. Patients (31%) were also concerned that inflammatory arthritis reduced their chances of getting pregnant, with only 8% believing arthritis medications were safe to take during pregnancy. Finally, only 9% of patients had ever been asked to participate in a research study. Conclusions: This study demonstrates a need for the development of stronger patient-partnerships with clinicians and researchers in relation to patient education and engagement with research, to create a platform where patients can have meaningful input and involvement in future research studies.

Background:Myeloid Dendritic Cells (DC) are potent antigen presenting cells that can be subdivided into CD141 and CD1c+ DC. We have previously reported an unacknowledged role for CD141+DC in the IA synovium. However, the identification and function of CD1c+ DC in the IA synovium has yet to be fully elucidated.Objectives:To investigate if CD1c+DC reside in the IA synovium and ascertain if they represent a unique population, distinct from peripheral CD1c+DC and if they contribute to synovial inflammation.Methods:Synovial tissue (ST) biopsies and synovial fluid mononuclear cells (SFMC) were obtained via arthroscopy and healthy control (HC) ST was obtained during ACL surgery. Synovial tissue single cells suspensions were generated following enzymatic and mechanical digestion. Single cell analysis of synovial tissue cell suspensions, along with PBMC and SFMC was performed by multicolour flow cytometry. CD1c+DC were sorted from IA synovial fluid and peripheral blood and bulk RNA sequencing was performed. CD1c+DC functionality and maturation was assessed using OVA DQ phagocytosis assays, multiplex ELISA and DC: T cell cocultures.Results:Within the circulation the frequency of CD1c+DC are significantly decreased in IA peripheral blood compared to HC (p+ DC were identified in IA ST and were significantly enriched compared to IA peripheral blood (p+DC express significantly higher levels of the activation marker CD80 compared to IA peripheral blood (p+DC are enriched in synovial fluid compared to PB (p+DC revealed distinct transcriptional variation between both sites. Functionally, synovial CD1c+DC express higher levels of the maturation markers CD80, CD83, CD40, PD-L1 and BTLA (all p+DC are less phagocytic compared to peripheral blood DC, have decreased production of MMP1 and MMP9 and importantly are still capable of additional activation in-vitro. Finally, synovial CD1c+DC induce the proinflammatory cytokines TNFα, GMCSF, IL-17a and IFNγ from CD4+ T-cells in allogeneic DC: T cells cocultures.Conclusion:Mature circulatory CD1c+DC migrate and accumulate in the IA synovium. Synovial DC are present in the IA synovium in a mature state, have distinct tissue specific characteristics and can induce proinflammatory CD4+T cell responses.Acknowledgements:We would like to thank all the patients who contributed to this studyDisclosure of Interests:Mary Canavan: None declared, Viviana Marzaioli: None declared, Vipul Bhargava Employee of: Janssen Research and Development, Sunil Nagpal Employee of: Janssen Research and Development, Phil Gallagher: None declared, Conor Hurson: None declared, Ronan Mullan: None declared, Douglas Veale Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, MSD, UCB, Consultant of: Abbvie, Janssen, Novartis, Pfizer, MSD, UCB, Grant/research support from: Pfizer, Janssen, AbbVie, UCB, Ursula Fearon Speakers bureau: Abbvie, Grant/research support from: Pfizer, Janssen, Abbvie, UCB

Background:Rheumatoid arthritis (RA) is a progressive erosive autoimmune disease that affects 1% of the world population. Anti-citrullinated protein autoantibodies (ACPA) are routinely used for the diagnosis of RA, however 20-30% of patients are ACPA negative. ACPA status is a delineator of RA disease endotypes with similar clinical manifestation but potentially different pathophysiology. Elucidating the underlying mechanisms of disease pathogenesis could inform a treat to target approach for both ACPA-positive and ACPA-negative RA patients.Objectives:To identify peripheral blood and synovial tissue immune population differences that associate with RA disease endotype.To identify unique RA patient synovial tissue gene signatures and enriched pathways that correlate with ACPA status.Methods:Detailed high dimensionality flow cytometric analysis with supervised and unsupervised algorithm analysis of ACPApos and ACPAneg RA patient peripheral blood and synovial tissue single cell suspensions. Ex vivo peripheral blood and synovial tissue T cell stimulation and cytokine production characterisation. RNAseq analysis with specific pathway enrichment analysis of APCApos and ACPAneg RA patient synovial tissue biopsies.Results:Detailed profiling based on high dimensionality flow cytometric analysis of key peripheral blood and synovial tissue immune populations including B cells, T follicular helper (Tfh) cells, T peripheral helper cells (Tph) and CD4 T cell proinflammatory cytokine responses with supervised and unsupervised algorithm analysis revealed unique RA patient peripheral blood B cell and Tfh cell profiles. ACPApos RA patients were characterised by significantly (*P=0.03) increased frequency of Tfh (CXCR5+CD4+) cells and distinct clustering influenced by increased switched (IgD-CD27+) and DN (IgD-CD27-) memory B cells compared to APCAneg RA patients. Surprisingly synovial tissue B cell subpopulation distribution was similar between ACPAneg and ACPApos RA patients, with significant accumulation of switched and double negative memory B cells, highlighting a key role for specific B cell subsets in both disease endotypes. Interestingly, synovial tissue CD4 T cell proinflammatory cytokine (TNF-α, IFN-γ, IL-2, GM-CSF, IL-17A, IL-22, IL-4) production was markedly different between ACPAneg and APCApos RA patients with hierarchical clustering and PCA analysis revealing endotype specific cytokine profiles with ACPAneg RA patient synovial T cells showing increased TNF-α (P=0.01) expression. RNAseq analysis of RA patient synovial tissue revealed significant disease endotype specific gene signatures with specific enrichment for B cell receptor signalling and T cell specific pathways in ACPApos compared to ACPAneg RA patients. Additionally, significantly different chemokine receptor expression based on RA patient ACPA status was observed with increased CXCR3 (PConclusion:ACPA status associates with unique synovial tissue immune cell and gene profile signatures highlighting differences in the underlying immunological mechanisms involved, therefore reinforcing the need for a treat to target approach for both endotypes of RA.Figure 1.RNAseq analysis of synovial tissue biopsies revealed specific T cell related pathway enrichment in ACPA positive compared to ACPA negative RA patients (n=50, analysis performed with the DESq2 and pathfindeR pipelines in R).Disclosure of Interests:Achilleas Floudas: None declared, Mary Canavan: None declared, Trudy McGarry Employee of: Novartis, Vinod Krishna Employee of: Janssen, Sunil Nagpal Employee of: Janssen, GSK, Douglas Veale Speakers bureau: Abbvie, Janssen, Novartis, MSD, Pfizer, UCB, Consultant of: Abbvie, Janssen, Novartis, MSD, Pfizer, UCB, Grant/research support from: Janssen, Abbvie, Pfizer, UCB, Ursula Fearon Speakers bureau: Abbvie, Grant/research support from: Janssen, Abbvie, Pfizer, UCB

Background:Axial spondyloarthritis (axSpA) is an umbrella term for types of inflammatory arthritis that primarily affect the spine and the sacroiliac joints. It is comprised of patients with both radiographic (r-axSpA) and non-radiographic features (nr-axSpA). R-axSpA was historically known as Ankylosing Spondylitis. Previous studies have shown the burden of disease to be largely similar in patients with radiographic versus non-radiographic axial spondyloarthritis in cohorts both in the US and Europe [1]. The Ankylosing Spondylitis Registry of Ireland (ASRI) was formed with the objective to measure the burden of axial spondyloarthritis in the population and identify early predictors of a poor outcome. All patients in the registry are 18 years or older and meet Assessment of Spondyloarthritis International Society (ASAS) criteria for a diagnosis of SpA.Objectives:To compare the characteristics and burden of disease in patients with radiographic versus non-radiographic axial spondyloarthritis in the ASRI cohort.Methods:Patients with radiographic axial spondyloarthritis (r-axSpA) were defined as those with x-ray evidence of sacroiliitis. Patients with non-radiographic axial spondyloarthritis (nr-axSpA) were defined as having MRI evidence of sacroiliitis but no x-ray evidence of sacroiliitis. A standardised clinical assessment was performed on each patient and structured interviews provided patient-reported data. For each patient the following scores were captured: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Health Assessment Questionnaire (HAQ) assesses the self-reported functional status for performing activities of daily living, and the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. Categorical variables were summarized as percentages with frequency counts, and continuous variables with a mean and standard deviation. Statistical comparisons between subgroups were evaluated using 2 sample t-tests for continuous variables and chi-square tests for categorical variables.Results:764 patients were available for analysis. Analysis of radiographic status showed 88.1% (n=673) of patients with r-axSpA and 11.9% (n=91) with nr-axSpA. Patients with nr-axSpA were younger (41.3 vs. 46.6 years, pConclusion:This study provides evidence that the burden of disease is less in patients with non-radiographic axial spondyloarthritis than radiographic axial spondyloarthritis, as demonstrated by better BASDAI, BASFI, BASMI, HAQ and ASQoL scores.References:[1]López-Medina C, et al. Characteristics and burden of disease in patients with radiographic and non-radiographic axial Spondyloarthritis: a comparison by systematic literature review and meta-analysis. RMD Open, 2019. 5(2) p1108.Table 1.r-axSpAnr-axSpAp valuen67391Age (years)46.6 (+/-12.4)41.3 (+/-12.4)Disease duration (years)20.2 (+/-12.4)14.8 (+/-11.7)Delay to diagnosis (years)8.41 (+/-8.6)6.34 (+/-7.2)0.03Males78.8% (528)65.9% (60)0.02Females21.5% (145)34.1% (31)0.02HLA-B27+90.50%(440 of 486 available results)73.60%(53 of 72 available results)BASDAI4.05 (+/-2.39)3.37 (+/-2.31)0.01BASFI3.88 (+/-3.00)2.46 (+/-2.39)BASMI4.34 (+/-2.08)2.33 (+/-1.42)ASQoL6.67 (+/-5.55)5.2 (+/-5.53)0.02HAQ0.57 (+/-0.54)0.38 (+/-0.44)Psoriasis17.8% (120)15.4% (14)0.31IBD11% (74)8.8% (8)0.58Uveitis33.9% (228)34.1% (31)0.54Disclosure of Interests:Sean Quinn: None declared, Sinead Maguire: None declared, Finbar Barry O’Shea: None declared, Lorraine O’Neill: None declared, Eamonn Molloy: None declared, Ursula Fearon Speakers bureau: Abbvie, Grant/research support from: Janssen, Abbvie, Pfizer, UCB, Phil Gallagher: None declared, Douglas Veale Speakers bureau: AbbVie, BMS, Celgene, Pfizer, MSD, Roche, Consultant of: AbbVie, Actelion, BMS, Novartis, Pfizer, MSD, Roche, Regeneron/Sanofi, Grant/research support from: AbbVie, Pfizer, MSD, Novartis, Roche, Janssen.

Background:The effect of alcohol on disease activity in inflammatory arthritis remains poorly understood. Studies of alcohol and the incidence or risk of inflammatory arthritis are conflicting [1,2]. Alcohol does downregulate pro-inflammatory cytokines and may therefore reduce immune-mediated disease activity.Objectives:This study investigates the relationship between alcohol consumption and disease activity in our inflammatory arthritis patient cohort and performs a systematic review with meta-analysis.Methods:Cohort Study Design and data analysisPatients attending a rheumatology clinic between 2010-2020 were prospectively followed. Information on demographics, alcohol use, smoking habits, and disease outcome measures were collected. Statistical analysis included univariate and multivariate linear and binary logistic regressions, Mann Whitney-U tests, and one-way ANOVA with Tukey’s HSD.Meta-analysisEMBASE, Pubmed, the Cochrane library, and Web of Science were searched. Studies reporting on alcohol consumption and disease activity in a cohort of RA patients were included for further investigation. Forest plots were generated from 95% confidence intervals of extracted data using mean differences. Linear regression was used to determine correlations between alcohol and antibody status, gender, and smoking status.Results:Cohort StudyOf the 979 analysed patients, 62% had RA, 26.7% had PsA, and 11.2% had AS. Mean DAS28-CRP in RA and PsA at one year was 2.96 ± 1.39, and 64.2% of patients were in remission (DAS28-CRP ≤ 2.6 or BASDAI ≤ 4). Both male gender and risky drinking (>15 units of weekly alcohol) were both significantly associated with remission. Compared to women, men had an odds ratio of 1.78 [1.04, 2.52] (p=0.034) for any alcohol consumption and 6.9 [4.7, 9.1] (p=0.001) for drinking at least 15 weekly drinks. when adjusted for gender, there was no significant association between alcohol and disease activity. Yet, when adjusted for alcohol consumption, gender still influenced disease activity.Meta-analysisThe search identified 4126 citations of which 14 were included. The pooled mean difference in DAS28 (95% CI) was 0.34 (0.24,0.44) (pConclusion:While it appears that alcohol is linked to remission in inflammatory arthritis, this association is lost when adjusted for gender. Men with inflammatory arthritis drink significantly more than women and men generally have less severe disease activity. However, the meta-analysis suggests alcohol consumption is associated with lower disease activity and self-reported health assessment in rheumatoid arthritis.References:[1]Bae S-C, Lee YH. Alcohol intake and risk of rheumatoid arthritis: a Mendelian randomization study. Z Rheumatol 2019;78:791–6. doi:10.1007/s00393-018-0537-z[2]Scott IC, Tan R, Stahl D, et al. The protective effect of alcohol on developing rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology (Oxford) 2013;52:856–67. doi:10.1093/rheumatology/kes376Figure 1.Mean differences in DAS28 between drinking groups. A between non-drinkers and drinkers. B between non-drinkers and high-risk drinkers. C between low-risk and high-risk drinkers.Disclosure of Interests:None declared

Background:Synovial tissue macrophages are an exquisitely plastic pool of innate cells that play a key role in RA disease progression. However, the precise nature, diversity, and function of macrophage subsets within the inflamed joint remains unexplored.Objectives:Therefore, the aims of this study are to phenotypically, transcriptionally and functionally characterise synovial tissue macrophages residing within the inflamed joint.Methods:Rheumatoid Arthritis, Psoriatic Arthritis, Osteoarthritis and healthy control synovial-tissue biopsies and synovial-fluid mononuclear cells were analysed using the following panel (CD40,-CD45,-CD64,-CD68,-CD163,-CD206,-CD253,-CCR4,-CCR7,-CXCR1,-CXCR3). CD206+CD163+ and CD206-CD163- macrophages were sorted from RA synovial-tissue by FACSAria sorter; RNAseq and FLIM analysis, autologous T-cell co-culture and heathy fibroblast experiments performed. Cytokine expression was measured by MSD immunoassay.Results:RA synovial tissue and fluid macrophages display markers typical of both M1 (CD40+CD253+) and M2 (CD206+CD163+) macrophages with a spectrum of macrophage activation states identified. Within this spectrum, significant enrichment of dominant CD206+CD163+ macrophage-subtype is present in synovial tissue versus fluid (pConclusion:This data identifies for the first-time enrichment of a previously undescribed dysfunctional dominant and transcriptionally distinct macrophage subtype in RA synovial tissue. Taken together, this data provides a greater understanding of the critical role tissue-resident macrophages play in perpetuating inflammation in RA. Further investigation of the molecular patterns and cues that shape specific synovial macrophage subsets may provide opportunities to reinstate RA joint homeostasis.Disclosure of Interests:Megan Hanlon: None declared, Mary Canavan: None declared, Qingxuan Song Employee of: Janssen Research & Development, Nuno Neto: None declared, Phil Gallagher: None declared, Ronan Mullan: None declared, Conor Hurson: None declared, Michael Monaghan: None declared, Sunil Nagpal Employee of: Janssen Research & Development, Douglas Veale Speakers bureau: Abbvie, Janssen, Novartis, MSD, Pfizer, UCB, Consultant of: Abbvie, Janssen, Novartis, MSD, Pfizer, UCB, Grant/research support from: Janssen, Abbvie, Pfizer, UCB, Ursula Fearon Speakers bureau: Abbvie, Grant/research support from: Janssen, Abbvie, Pfizer, UCB

Background:Despite recent therapeutic advances, our ability to predict prognosis and therapeutic response in RA remains imprecise.Objectives:To determine biomarkers predictive of outcome at one year following arthroscopy.Methods:RA patients were prospectively recruited and underwent knee arthroscopy performed under local anaesthetic. Each patient underwent a careful systematic assessment of demographic, clinical, and serologic factors on the day of arthroscopy and were reviewed at 2 weeks, 3, 6 and 12 months post arthroscopy. Erosive disease was defined based on plain-film radiographs of hands and feet. Disease activity at one year was used to define treatment response into responders (moderate/good EULAR Response) and non-responders.Clinical characteristics, synovial tissue cell profiles and immunohistochemistry were analysed for T Cells (CD3), B Cells (CD20, CD138), macrophages (CD68) and vascularity (Factor VIII) to establish predictors of treatment response. All areas of each biopsy section were examined and the sub-lining layer independently scored by 2 observers using a well-validated semiquantitative scoring method, ranging from 0 to 4 (0=no staining, 1=Results:There were no significant differences between responders and non-responders regarding gender, age, disease duration, medications, erosive status, ESR, CRP or synovitis or vascularity at arthroscopy (Table 1). Interestingly, rates of RF and ACPA positivity, tender and swollen joint counts, DAS28 and DAS28CRP were all higher amongst treatment responders. Immunohistochemistry was a very poor predictor of treatment response. There were no significant differences between the two groups in CD3, CD20, CD138, CD68 or Factor 8 score.Table 1.Baseline CharacteristicsResponder(n=30)Non-responder (n=18)p valueFemale20 (66.7%)14 (77.8%)NSAge51.5 (11.2)54.2 (10.9)NSDisease duration0.5 (0-16)0.5 (0-10)NSRF positive22 (73.3%)5 (27.8%)0.003ACPA positive22 (73.3%)8 (44.4%)0.045Erosions8 (26.7%)5 (27.8%)NSMedications No DMARD23 (76.7%)10 (55.6%)NS csDMARD only4 (13.3%)3 (16.7%)NS TNFi2 (6.7%)3 (16.7%)NS Other bDMARD1 (3.3%)2 (11.1%)NSPatient global health, VAS (mm)54.2 (10-100)51.5 (0-90)NSSJC (28 Joints)4.5 (0-16)1 (0-18)0.001TJC (28 Joints)7 (1-25)1 (0-15)0.001ESR, mm/hr23 (2-120)24 (2-81)NSCRP, mg/L5 (1-95)6.5 (1-64)NSDAS285.01 (1.95-7.36)3.93 (1.40-6.62)0.003DAS28CRP4.78 (2.82-7.13)3.39 (1.21-6.26)0.002Synovitis, VAS65 (10-100)70 (30-100)NSVascularity, VAS60 (10-90)70 (30-100)NSConclusion:In this small study, seropositivity and disease activity were higher in responders. Baseline immunohistochemical staining was not a good discriminator of treatment responsDisclosure of Interests:Kieran Murray Grant/research support from: Bresnihan Molloy and Newman fellowships, Candice Low: None declared, Francis Young: None declared, Monika Bienicka: None declared, EImear Mylod: None declared, Ursula Fearon: None declared, Douglas Veale: None declared