Jmw Hazes

Modification of a sonographic enthesitis score to differentiate between psoriatic arthritis and young healthy volunteers

Objectives: We aimed to describe sonographic structural and inflammatory changes in entheses of patients with recently diagnosed psoriatic arthritis (PsA), patients with established PsA, and young healthy volunteers, and to investigate whether the MAdrid Sonographic Enthesitis Index (MASEI) enables us to distinguish these groups in an extreme comparison. Method: New and established PsA patients and healthy volunteers (aged 20–30 years) were recruited. The triceps, quadriceps, patellar, Achilles and elbow extensor tendon insertion, and plantar fascia entheses were investigated sonographically for structural changes, erosions, calcifications, increased thickness, bursitis, and power Doppler (PD) signal according to the MASEI. Results: The study included 25 new and 25 established PsA patients, and 25 healthy volunteers. Increased thickness and PD signal in knee entheses were common for patients and healthy volunteers, while changes at other locations predominantly occurred in patients only. PD was recoded (1, one spot; 1.5, two or three spots; 2, confluent signal; 3, severe confluent signal) and thickness of knee entheses excluded. This resulted in different modified MASEI scores between PsA patients and young healthy controls: median (interquartile range) modified MASEI of 13 (10–22.5) in new PsA, 13.5 (9.5–18) in established PsA, and 3 (1–8.5) in healthy volunteers (p = 0.002). Conclusions: Structural ultrasound changes and PD in entheses are common in both new and established PsA and healthy controls. MASEI score did not differentiate PsA patients from young healthy volunteers. After recoding of PD severity and excluding thickness of knee entheses, marked differences between PsA patients and healthy controls were observed.

Effects of psychosocial factors on monitoring treatment effect in newly diagnosed rheumatoid arthritis patients over time: response data from the tREACH study

Objectives: To investigate whether, apart from effects of patient- and disease-related factors, psychosocial factors have additional effects on disease activity; and which factors are most influential during the first year of treatment in early rheumatoid arthritis (RA). Method: The study assessed 15 month follow-up data from patients in tREACH, a randomized clinical trial comparing initial triple disease-modifying anti-rheumatic drug therapy to methotrexate monotherapy, with glucocorticoid bridging in both groups. Patients were evaluated every 3 months and treated to target. Associations between Disease Activity Score (DAS) at 3, 9, and 15 months and psychosocial factors (anxiety, depression, fatigue, and coping with pain) at the previous visit were assessed by multivariable linear regression correcting for demographic, clinical, and treatment-related factors. Results: At 3, 9, and 15 months of follow-up, 265, 251, and 162 patients, respectively, were available for analysis. Baseline anxiety and coping with pain were associated with DAS at 3 months; coping with pain at 6 months was associated with DAS at 9 months, and fatigue at 12 months with DAS at 15 months. Psychosocial factors were moderately correlated. Effects on DAS were mainly due to tender joint count and global health. Conclusion: Psychosocial factors have additional effects on DAS throughout the first year of treatment in early RA. A change was observed from anxiety and coping with pain at baseline being associated with subsequent DAS towards fatigue being associated with subsequent DAS at 12 months. Owing to the explorative nature of this study, more research is needed to confirm this pattern.

AB1047 Can the acr/eular 2010 classification criteria be used as diagnostic tool for rheumatoid arthritis in real life?

Background To date, due to the large variability in its clinical manifestations, early identification of rheumatoid arthritis (RA) relies on practice-based evidence. Moreover, this variation hampers the comparability and accurate stratification of the base population within and between RA trials. In 2010 the ACR/EULAR working group developed RA classification criteria that were primarily intended for research purposes. Despite its use in scientific settings, one can speculate on the effectiveness of these criteria when used in the routine clinical practice of diagnosing RA. Objectives In this study we aimed to investigate the degree of concordance between the diagnosis of RA in routine clinical practice and the ACR/EULAR 2010 classification criteria. Methods All patients who received a diagnosis of RA between 2010–2016 within our hospital were identified according to the financial diagnosis treatment combination (DTC) code, which corresponds to the ICD-10. Clinical and demographic data were extracted from our digital patient records of which 10% of the data were cross-checked by random selection. In retrospect we collected variables at time of RA diagnosis such as: number and type of swollen/painful joints, inflammatory markers, rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), disease duration and patients primary/secondary/tertiary diagnosis according to the rheumatologist. Additionally, all patients were classified according to the ACR/EULAR 2010 criteria for RA. The degree of concordance was determined by descriptive statistics. Results The database included 977 patients with a DTC RA of which 673 (69%) had RA according to the rheumatologist. From the patients who were clinically diagnosed with RA, 463 (69%) fulfilled the ACR/EULAR 2010 criteria (see figure 1), this is 47% of the total DTC RA patients. The majority of the population was female (72%) and the mean age was 59. A number of 161 (24%) patients were diagnosed with RA according to the rheumatologists, but did not fulfil the ACR criteria. These patients had less inflammation, were more often RF and/or ACPA negative, and had less involved joints. About 5% of the data were missing. Conclusions It can be concluded that the DTC codes are not the most reliable source of information in terms of the diagnosis. There is a discrepancy between the DTC code, the diagnosis according to the rheumatologist and the classification criteria. The degree of concordance between rheumatologist and the ACR criteria is comparable to the numbers described in literature. Since in our practice aspects of the ACR classification are used for diagnostic purposes, we will investigate factors that drive the specificity. Furthermore, reasons for the ICD-10/ DTC and final diagnostic mismatch is of great importance and will be studied as well. These factors will indicate opportunities on the use of the ACR/EULAR criteria in clinical practice. Acknowledgements None Disclosure of Interest None declared

AB0769 Sonographic signs of enthesitis in established psoriatic arthritis and healthy volunteers

Background Previous research in our group showed that sonographic signs of enthesitis are present in early and established PsA, but in young healthy volunteers as well. The Madrid Sonographic Enthesitis Index (MASEI) was only able to differentiate between patients and healthy volunteers after excluding knee enthesis thickness from the score and semi-quantitative scoring of Power Doppler (PD) signal (1). Objectives We aim to validate the modified MASEI in a larger cohort of established PsA patients and healthy volunteers. Methods Established PsA patients and healthy volunteers aged 35–55 were asked to participate in this cross-sectional study, irrespective of presence of enthesitis complaints. The triceps, quadriceps, proximal and distal patellar and Achilles tendon and plantar fascia (i.e. the locations of the MASEI) and the common extensor insertion at the lateral epicondyle of the elbow were evaluated sonographically for structural changes (i.e. erosions, calcifications and structure) and active inflammation (thickness, bursitis and PD). Results 84 established PsA patients and 25 healthy volunteers participated. Sonographic structural changes and one or two spots of PD signal were common in both groups. The modified MASEI was significantly higher in PsA patients (median 12 (IQR 7.25–17) vs. 7.5 (5–9), P<0.001), while the original MASEI did not differ significantly (Table 1). Confluent PD over a larger area was only seen in 8% of the established PsA patients. Structural damage on ultrasound was more pronounced in the patients compared to the healthy volunteers. Number of PD locations and PD score did not distinguish the two groups.Table 1. Participant characteristics and sonographic enthesitis scores PsA patients (n=84) Healthy Volunteers (n=25) Male, n (%) 45 (54) 12 (48) Age, mean (SD) 55 (11) 47 (6)* Disease duration, median years (IQR) 8.0 (4.9–12.3) LEI, median (IQR) 0.5 (0–2) 0 (0–0)** Ultrasound MASEI, median (IQR) 15.5 (11–22) 13 (9–18) Modified MASEI, median (IQR) 12 (7.25–17) 7.5 (5–9)** structural components 7 (3–10) 3 (1–6)** inflammatory components 6 (3.5–8.5) 3.5 (2–5.5) Power Doppler in any enthesis, n (%) 74 (88) 22 (88) score 3, n (%) 7 (8%) 0 (0%) locations, median (IQR) 2 (1–3) 2 (1–3) if positive, median (IQR) 1.5 (1.25–1.75) 1.5 (1.25–1.5) PsA: Psoriatic Arthritis; SD: standard deviation, IQR: interquartile range; LEI: Leeds Enthesitis Index; MASEI: Madrid Sonographic Enthesitis Score; modified MASEI: MASEI with new PD scoring method (1: one spot of PD, 1.5: some spots of PD, 2: confluent signal, 3: severe signal) and without knee entheses thickness. Structural components: erosions, calcifications, structure. Inflammatory components: bursitis, thickness and PD signal. PD: Power Doppler. *P<0.01, **P<0.001 (Wilcoxon rank sum test). Conclusions Inflammatory and structural changes of the enthesis measured with ultrasound are common in both unselected PsA patients and healthy volunteers, but more pronounced in established PsA patients. References Wervers K, Rasappu N, Vis M, Tchetverikov I, Kok MR, Gerards AH, et al. AB0733 Masei Shows Substantial Changes in The Entheses of Young Healthy Volunteers – Amending Its PD Score and Excluding Knee Entheses Thickness Provides Better Discrimination of Enthesitis in Psoriatic Arthritis Patients. Ann Rheum Dis 2016;75:1155. Disclosure of Interest None declared

A2.19 IL-17A-low CCR6+ TH cell populations of patients with rheumatoid arthritis are pathogenic, multidrug resistant and associated with dmard and glucocorticoid treatment response

Background and objectives CCR6+ T-helper (Th) cells and their pro-inflammatory cytokines, including IL-17A, are implicated in the pathogenesis of rheumatoid arthritis (RA). However, within CCR6+ Th cells various subpopulations are present and their clinical relevance in RA is unclear. Therefore, we characterised CCR6+ Th subpopulations with regard to pathogenic potential and disease-modifying antirheumatic drugs (DMARDs) and glucocorticoid (GC) therapy outcome in RA. Material and methods Within total CCR6+ Th cells from patients with RA, CCR4+CXCR3- (Th17), CCR4-CXCR3+ (Th17.1), CCR4/CXCR3 double-positive (DP) and double-negative (DN) cells were distinguished and/or sorted by flow cytometry. These subpopulations were: analysed for Th17/Th1-associated factors; co-cultured with RA-derived synovial fibroblasts (RASF); related to disease-modifying antirheumatic drugs (DMARDs) and glucocorticoid (GC) therapy response; analysed regarding the expression of multidrug transporters MDR1 and MRP1 and drug efflux potential. Results All these populations expressed the transcription factor RORC and were present in RA peripheral blood and synovial fluid. Despite differential IL-17A, IL-17F, IFNg and TBX21 expression, all subpopulations, including the IL-17A low-producing Th17.1, DP and DN cells, showed pathogenic activity in the induction of IL-1β, IL-6, IL-8, COX-2 and MMP-3 expression by synovial fibroblasts. MDR1 (ABCB1) and MRP1 (ABCC1) are cellular efflux transporters of glucocorticoids and the DMARD methotrexate. In particular Th17.1 and DN cells expressed relatively high levels of MDR1, whereas MRP1 was expressed at similar levels among the subpopulations. Interestingly, increased drug efflux potential by CCR6+ Th cells, as measured by rhodamine123 and calcein transport, was associated with the lack of DMARD/GC therapy response. Conclusions Therefore, we conclude that in addition to IL-17-high Th17 cells, IL-17-low CCR6+ Th cells display pathogenic activity in the context of RA. Moreover, we identified efflux transporter expression and efflux activity by RA CCR6+ Th cells. These findings suggest that pathogenic and multidrug resistant CCR6+ Th cells are associated with the lack of DMARD/GC therapy response in patients with RA.

A1.2 Prominent role of pathogenic memory CCR6+ TH17 cell populations in the pathogenesis of ACPA+ patients with rheumatoid arthritis

Background and objectives Patients with rheumatoid arthritis (RA) positive for serum anti-citrullinated protein antibodies (ACPAs) have a worse disease course than ACPA- patients. Association of ACPA and HLA-DRB1 suggests the involvement of T cells in ACPA+ RA. Therefore we examined possible differences in memory CD4+ T (Th) cell distribution between ACPA+ and ACPA- patients and their functional relevance. Materials and methods Th cell distribution profiles from ACPA+ and ACPA- patients with early RA were generated based on chemokine receptor, cytokine and transcription factor expression. On the basis of CXCR3 and CCR4 expression, four CCR6+ subpopulations were distinguished: Th17, Th17.1, CCR4/CXCR3 double positive (DP) and double negative (DN) cells. These Th cell populations were analysed for their pathological potential. Results ACPA+ patients had higher proportions of peripheral CCR6+ Th cells, notably Th22, Th17.1 and DP cells. All CCR6+ subpopulations were also present in RA synovial fluid. These subpopulations shared Th17 characteristics including RORC and CD161 expression. However, expression of IL-17A, IL-17F, IFNg and the Th1-associated transcription factor TBX21 differed markedly between CCR6+ subpopulations. Nevertheless, all CCR6+ Th cell subpopulations showed higher pathological activity than naive and Th1 cells, as they were more effective in stimulating IL-1β, IL-6, IL-8, COX-2 and MMP-3 expression by synovial fibroblasts. Interestingly, CCR6+ Th populations are inverse correlated with disease duration in ACPA- patients but not in ACPA+ patients. Conclusions ACPA+ and ACPA- patients can be distinguished by differences in pathogenic memory CCR6+ Th cell proportions, suggesting that these cells are involved in the worse disease course observed in ACPA+ RA.

A4.1 1.25(OH)2D3 Modulates Gene Expression Involved in Phenotype Stability and Migration of Th17 Cells from Patients with Rheumatoid Arthritis

Background and Objectives Vitamin D has suppressive effects on autoimmune diseases, such as rheumatoid arthritis (RA). Within these diseases, T-helper-17 (Th17) cells have been implicated to play a crucial role in the development and progression of chronic inflammation. Recently, we have found that the active vitamin D compound, 1.25(OH)2D3, has direct suppressive effects on both human and mouse Th17 cytokine expression and activity. Using gene-expression profiling, we aim to identify molecular targets of 1.25(OH)2D3 signalling underlying this suppressive action of 1.25(OH)2D3 in Th17 cells. Methods Primary Th17 cells were sorted from peripheral blood of treatment naïve patients with early RA and cultured with or without 1.25(OH)2D3. From these cultures gene-expression profiles were generated. Expression of genes of interest was confirmed by Q-PCR and/or specific ELISA. Results In the presence of 1.25(OH)2D3, protein expression of Th17 associated cytokines IL-17A and IL-22 was inhibited, while in contrast the anti-inflammatory cytokine IL-10 was induced. These findings were supported by the gene-expression profiles from these cultures. Furthermore, 1.25(OH)2D3 inhibited transcription of the cytokine receptors IL-23R and IL-7R, which are involved in Th17 survival and proliferation. Chemokines CCL20 and CXCL10 were down-regulated and chemokine receptors CCR2, CXCR6, CXCR3 and CCR10 were up-regulated. Importantly, RORγ t, which is critically involved in Th17 differentiation and function and the cell-size regulator and oncogene c-Myc were down-regulated by 1.25(OH)2D3. Conclusions From these findings, we concluded that 1.25(OH)2D3 modulates the expression of genes involved in cytokine production, proliferation, and migration of Th17 cells. These data indicate that 1.25(OH)2D3 not only suppresses Th17 cell activity but also regulates Th17 phenotype stability and migration of these cells to sites of tissue inflammation in RA.