G. Kenar

Ankylosing Spondylitis: HLA-B*27-Positive Versus HLA-B*27-Negative Disease

Purpose of ReviewWe review our current knowledge about the clinical features of patients with ankylosing spondylitis (AS) who possess HLA-B*27 versus those who lack this gene.Recent FindingsERAP1 association is present only in HLA-B*27+ patients, but other genetic associations are similar between the two groups. A genetic study supports the existence of an HLA-B27-independent common link between gut inflammation and AS. It is unusual to observe familial occurrence of primary AS among families of northern European extraction that show no segregation of HLA-B*27, psoriasis, or IBD.SummaryAlthough there are many similarities among AS patients possessing HLA-B*27 versus those lacking this gene, the former group has a younger age of onset, a shorter delay in diagnosis, a better clinical response to tumor necrosis factor inhibitors, a greater familial occurrence, a greater risk for occurrence of acute anterior uveitis, and a lower risk for occurrence of psoriasis and IBD. ERAP1 association is present only in HLA-B*27+ patients, but other genetic associations are similar between the two groups. It is unusual to observe occurrence of primary AS among families of northern European extraction that show no segregation of HLA-B*27, IBD, or psoriasis. A recent genetic study supports the existence of an HLA-B*27-independent common link between gut inflammation and AS.

Osteoprotegrin interacts with biomarkers and cytokines that have roles in osteoporosis, skin fibrosis, and vasculopathy in systemic sclerosis: A potential multifaceted relationship between OPG/RANKL/TRAIL and Wnt inhibitors

Abstract Objectives: We explored the interactions of osteoprotegerin (OPG) with biomarkers of bone turnover and cytokines, including soluble receptor activator for nuclear factor kappa beta ligand (sRANKL), tumor necrosis factor-related apoptosis-induced ligand (TRAIL), and Wnt inhibitors in osteoporosis, vasculopathy and fibrosis related to systemic sclerosis (SSc). Methods: The study included 46 SSc patients and 30 healthy controls. Skin thickness, pulmonary fibrosis and/or hypertension, digital ulcers, and calcinosis cutis of SSc patients were assessed. We determined bone mineral density (BMD), and OPG, sRANKL, TRAIL, secreted frizzled-related protein 1 (sFRP-1), Dickkopf-related protein 1 (DKK-1), sclerostin in the serum of both patients and controls. Results: OPG, sclerostin, and sFRP-1 levels were similar between patients and controls (P > 0.05). Femoral neck and lumbar spine BMD and vitamin D levels were lower, and the OC, NTX, sRANKL, DKK1 and TRAIL levels were significantly higher, in patients than in controls (p < 0.05). In subgroup analysis, patients with higher modified Rodnan skin score (mRodnan) had higher DKK-1, sclerostin, and TRAIL levels (p < 0.05); those with diffuse SSc subtype had lower BMD values than those with limited SSc (p < 0.05). Skin and pulmonary fibrosis linked negatively with BMD measures. Conclusion: we showed that sRANKL levels were higher and correlated with bone turnover markers. It may be related to osteoporosis in SSc. The OPG level was unaltered in SSc patients. Higher TRAIL levels associated with skin thickness may indicate vascular dysfunction or injury. Higher DKK-1 and sclerostin levels may be related to a reactive increase in cells and be prominently linked to fibrosis in SSc.

SAT0184 The effect of smoking on response to tumor necrosis factor-alpha inhibitor treatment in ankylosing spondylitis patients: results from the turkbio registry

Background: Although there is good evidence that smoking has a dose-dependent impact on structural damage progression in ankylosing spondylitis (AS) the evidence is poor for its impact on disease activity, physical mobility, life quality and treatment response. Objectives: We aimed to investigate the impact of smoking on disease acitivity, treatment adherence and treatment response in Turkish patients with AS treated with their first tumour necrosis factor-alpha inhibitor (TNFi) therapy in a real-life cohort. Methods: 561 patients fulfilling the modified New York criteria for AS and treated with their first TNFi therapy since 2011 from 8 centers in Turkey were included in the analysis. Treatment response was evaluated as achievement of “BASDAI50” or “ASDAS Clinically important improvement (CII)” at the 3-months’ and 6 months’ visits. Clinical and demographic parameters were compared between current/never and current/previous smoker groups. Demographic and descriptive data are presented by medians/interquartile ranges (IQRs). Groups were compared by non- parametric tests (x2, Kruskal Wallis and Mann Whitney tests). Kaplan Meier plots, Cox and logistic regression analyses were calculated for treatment adherence and treatment response. Results: Among 561 AS patients included in the study, 506 (90%) had known smoking status (37% current, 35% never, 17% previous smokers). The median follow-up time was 1.9 years (IQR 0.85–3.5) and disease duration was 3.1 years (0,6–7,7). At baseline, current smokers were younger (34, IQR 29–41) compared with never (38, IQR 30–46 p=0.007) and previous smokers (42, IQR 34–49 p<0,001). Current smokers had male predominance (n=148, 43.9%; n=85, 25.2%); lower erythrocyte sedimentation rate (28 mm/h (13–42); 34 mm/h, (20–49) and higher change in BASMI (40, IQR 10–57.5; 10, IQR 4–30) compared with never smokers (all p<0.005). HLA status, body mass index, CRP, baseline disease indexes (BASDAI, BASFI, BASMI, HAQ, ASDAS) and treatment response was not found to be different between current and never smoker patients in our population (table 1). In multivariate analysis, male (OR:1,98; 95% CI (1,39–2,82), p<0,01), HLA positive (OR:1,54; 95%CI (1,08–2,18), p=0,016) and active DMARD user (OR:1,84; (95%CI 1,12–3,01) p=0,015) patients had better treatment response and treatment adherence ((HR:1,93; 95% CI (1,36–2,73); HR:1,60; 95% CI (1,13–2,27); HR:1,80; 95% CI (1,10–2,95) all p<0,005) but smoking status were not significant (p>0,05). Conclusions: In this study of TNFi-treated AS patients in clinical practice, smoking was not found to be associated with disease activity, treatment response and treatment adherence. Disclosure of Interest: None declared

Phenotype Differences in HLA-B27 Positive Versus Negative Patients with Ankylosing Spondylitis in a Population That Show Relatively Weaker Association with HLA-B27

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THU0314 Radiologic activity is the major determinant for physicians while deciding active disease in takayasu arteritis

Background There are no valid follow-up parameters in the assessment of disease activity in Takayasu arteritis (TA). Objectives We investigated the impact of incorporation of vascular imaging into ITAS in the assessment of disease activity in TA. Methods 52 patients who fulfilled the ACR criteria were included in the study. PGA, Kerr et al.s criteria and ITAS2010/ITAS-A scores were evaluated in all patients in serial visits. All the patients were followed using 3–6 monthly B-mode/Doppler ultrasonography (USG) and 6–12 monthly magnetic resonance angiography (MRA). Radiological activity (Rad) was defined based on the presence of any of the 3 parameters including new vessel involvement by any technique (5 points),increase in vessel wall thickness on USG (3 points) and vessel wall edema on MRA (3 points).Then we incorporated these scores with ITAS-A to obtain a composite disease activity index (ITAS2010-A-Rad) (Table 1). Active disease was defined as ITAS-A-Rad >4 points. Results Total 410 visits of 52 TA patients (mean age 50.7 yrs, F: 92.3%, mean follow-up duration:6.4±2.9 yrs) were evaluated. Radiological assessment was done in 359 visits (by USG in 271 and by MRA in 190). Patients were categorized as having active disease in 194 visits (47.4%) according to PGA and 72 visits (17.5%) according to Kerr et al. criteria.The agreement between them was fair (66%, κ: 0.29). Radiological activity was determined in 105 out of 359 visits (29.2%). The total agreement between radiological activity and Kerr at al. criteria was 83% (κ: 0.58). It was found to be 76% (κ: 0.52) between radiological activity and PGA. Mean ITAS-A-Rad scores were found to be significantly higher in visits with active disease compared to visits with inactive disease according to both PGA and Kerr et al. criteria (Table 2). The ITAS-A-Rad was significantly correlated with all the other activity parameters including ITAS2010, ITAS-A, and APRs. There were 43 visits with new vessel involvement by any radiologic technique; all visits included patients with active disease based on both PGA and Kerr et al. criteria. Whereas in 50% of these visits, patients had normal CRP, and %49 had normal ESR. The agreement between ITAS2010 and PGA was fair (69%, κ: 0.38).When APR was added (ITAS-A), it did not improve (68%, κ: 0.34). But the agreement between ITAS-A-Rad and PGA (72%, κ: 0.50) and also Kerr et al. criteria (82%, κ: 0.56)was found to be moderate. Interestingly, when only USG (ITAS-A-USG) or only MRA (ITAS-A-MRA) was used, the agreement with PGA was remained unchanged (73%, κ: 0.45 and 76%, κ: 0.52, respectively). When responsiveness to change of ITAS-A-Rad score was evaluated by serial visits of patients, it was found that the mean value of the score was discriminative for activity according to PGA in 9 of 11 visits (Figure 1).Table 1. The definition of ITAS-A-Rad Score Clinical ITAS2010 0– Laboratory APR ESR 0 for ESR<20 1 for 21–39 2 for 40–59 3 for >60 mm/h 0–3 CRP 0 for CRP≤5 1 for 6–10 2 for 11–20 3 for >20mg/l Radiology Radiological activity New vessel involvement with any radiological method 5 B-mode Doppler USG Progression on vessel wall thickness 3 MRA Presence of vessel wall edema 3 Total ITAS-A-RAD Score ITAS-A-Rad Score >4 –> Activity. Conclusions The results of this study suggest that ITAS-A-Rad may be used to be a valuable foIlow-up parameter in the assessment of disease activity. Disclosure of Interest None declared

THU0714 Investigating the effects of hypermobility on balance variables

Background Hypermobility syndrome (HMS) is a clinical syndrome in which the range of motion of the joint is observed above normal ranges without being associated with a rheumatic disease. Excessive joint motion in HMS reduces joint stability and joint position sense and also can cause pain. Decreased muscle tone and tensile forces of the tendons cause decreased locomotor system stiffness and impairment of proprioception mechanisms. These problems in proprioceptive mechanisms can lead to balance-related disorders in individuals with hypermobility syndrome Objectives The aim of this study was to investigate the possible effects of hypermobility on balance variables. Methods 50 hypermobile (5 males and 45 females) volunteers diagnosed with Brighton Scale and 50 healthy (21 males and 29 females) volunteers were included in this cross sectional study. Participants with a score of 4 or over according to the Beighton scale were referred to a rheumatologist and were administered Brighton scale. Participants who were diagnosed by the physician were included in the hypermobile group. The objective balance evaluation was conducted using a balance platform. Evaluation variables were; static balance on single foot, static balance on both feet, limits of stability test and tandem walking. analysis was performed using independent samples t-test. Results The mean age was found 21,69±2,13 years old for the control group and 20,09±2,65 years old for the HMS group. Body Mass Index was found 22,13±3,54 kg/m2 in the control group and 21,54±3,50 kg/m2 in the HMS group. HMS group showed significant wider step width in tandem walking (p=0,001), significantly longer reaction time (p=0,23, p=0.030), significantly higher end-point excursion (p=0.003, p=0,026, p=0,049), significant higher mean maximum excursions (p=0.018) (Table 1).Table 1. Comparison of Groups About Balance Variables HMS Group Control Group p (Mean ± SD) (Mean ± SD) Tandem Walking  Step-Width (cm) 6,52±0,89 7,20±1.10 0.001* Limits Of Stability  Reaction Time 2 (sec) 0,91±0.44 0,72±0.37 0.023*  Reaction Time 6 (sec) 0,78±0,36 0,64±0,25 0.030*  End-Point Excursion 1 (°/sec) 86,69±17,73 73,19±26,17 0.003*  End-Point Excursion 4 (°/sec) 76,56±17,36 83,92±14,91 0.026*  Maximum Excursion 5 (°/sec) 76,54±18,31 82,69±11,50 0.049*  Mean Maximum Excursion (°/sec) 94,56±6,51 97,25±4,29 0.018* *p<0.05. Conclusions In this study it was found that hypermobility has significant effects on the stability limits test and tandem walking. In previous studies it was found that hypermobility affects the static balance assessment variables (1, 2), but in this study dynamic balance assessment variables were affected. References Iatridou K, Mandalidis D, Chronopoulos E, Vagenas G, Athanasopoulos S. Static and dynamic body balance following provocation of the visual and vestibular systems in females with and without joint hypermobility syndrome. J Bodyw Mov Ther. 2014 Apr;18(2):159–64. doi: 10.1016/j.jbmt.2013.10.003. Juul-Kristensen B, Johansen K, Hendriksen P, Melcher P, Sandfeld J, Jensen BR. Girls with generalized joint hypermobility display changed muscle activity and postural sway during static balance tasks. Scand J Rheumatol. 2015 Sep 1:1–9. Disclosure of Interest None declared

AB0597 Adaptation of Ucla Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 Questionnaire into Turkish

Background Nearly 90% of patients with scleroderma (SSc) have gastrointestinal tract (GIT) involvement in variable severities and is a challenging process for clinicians. The University of California Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) is a questionnaire including 34 items, 7 multi-item scales: reflux, distention/bloating, diarrhea, fecal soilage, constipation, emotional well-being and social functioning. By these parameters, a total GIT score is calculated (1). This scale translated in German, Italian, French, Polish, Spanish, Swedish, Dutch before, they are available in http://www.uclascleroderma.researchcore.org/website (1–3). There is no Turkish version of this scale yet. Objectives Our aim is to make translation, cultural adaptation of the UCLA SCTC GIT 2.0 into Turkish, and assess reliability of the scale in patients speaking Turkish. Methods UCLA SCTC GIT 2.0 scale was translated into Turkish according to international guidelines and applied to 97 SSc patients. The questionnaire repeated in 29 patients after an interval of 15 days for determining reliability. For internal consistency, Cronbachs alpha was calculated, reliability coefficient if item deleted and test-retest reliability also determined. External consistency was measured by comparing with the Short Form (SF)-36 by Spearmans correlation analysis (rho: ≤0.29 weak, 0.30–0.49 middle, ≥0.50 strong). Results 97 scleroderma patients were included in this study (female:87.6%, mean age:55.4±11.4). Internal consistency Cronbachs alpha was calculated as 0.89, reliability coefficient if item deleted was 0.89–0.90. External consistency of UCLA SCTC GIT 2.0 was measured by comparing with the SF-36, correlation was meaningful in medium level (Table 1,2).Table 1. Descriptive statistics and internal consistency statistics UCLA SCTC GIT 2.0 Scale n Mean score (SD) Minimum score Maximum score Cronbach alpha Floor effect % Ceiling effect % Reflux 97 0.64 (0.54) 0.0 2.6 0.83 17.5 0.0 Distension 97 1.02 (0.75) 0.0 3.0 0.58 7.2 1.0 Soilage 97 0.30 (0.72) 0.0 3.0 0.68 82.5 3.1 Diarrhea 97 0.28 (0.47) 0.0 1.5 0.36 69.1 0.0 Social Functioning 97 0.17 (0.32) 0.0 1.3 0.47 67.0 0.0 Emotional Wellbeing 97 0.30 (0.43) 0.0 2.2 0.73 41.2 0.0 Constipation 97 0.63 (0.69) 0.0 2.5 0.56 34.0 0.0 Total GIT score 97 0.45 (0.37) 0.0 1.6 0.82 3.1 0.0 All scales are scored from 0.00 (better HRQOL) to 3.00 (worse HRQOL) except the diarrhea and constipation (range from 0.00–2.00 and 0.00–2.50, respectively). The UCLA GIT 2.0 provides a total score of GIT severity and calculated by summation of all scales (except constipation) and ranges from 0.00 to 2.83. Conclusions UCLA SCTC GIT 2.0 scale had strong internal consistency, good reliability and acceptable validity when adapted into Turkish. Turkish-speaking patients with scleroderma, this scale will be useful to assess GIT symptoms. The basic constraint of our study was, not using image procedures for objective GIT involvement evidences. References Khanna D,Reliability and validity of the UCLA SCTC GIT Instrument.Arthritis Rheum,2009. Bae S,Development and validation of French version of the UCLA SCTC GIT Instrument.Clin Exp Rheumatol, 2011. Meijs J,Translation,cross-cultural adaptation,and validation of the UCLA SCTC GIT 2.0 into Dutch. Clin Exp Rheumatol,2014. Disclosure of Interest None declared

AB1120 Comparison of Long-Term Drug Survival of Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis and Psoriatic Arthritis: A Single Center Turkish Experience Over a Decade

Background The studies from different national biologics registries provide data on long term efficacy and safety of tumor necrosis factor inhibitors inhibitors (TNFi) for the treatment of rheumatic diseases in diverse patient populations. The data in this regard is lacking in Turkish population. Objectives To assess and compare the long term drug survival rates of TNFi in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic Arthritis (PsA) and to identify potential reasons for treatment discontinuation. Methods The analysis included all the patients treated with TNFi at our center since 2004. Persistence on anti-TNF in patients who were lost to follow-up were analyzed using the national prescription database. Patients with no prescription over the last 6 months were considered to have discontinued the treatment. The date of the last prescription was accepted as the date of discontinuation. These patients were tried to be contacted by phone to identify the reason for discontinuation. Kaplan-Meier plots and log rank tests were used to assess drug survival. Results Of the 351 patients in the study 222 had AS (26.1% females, mean age: 44.3±11.7 years, mean disease duration: 20±9.9 years, HLA-B27:(+): 71.1%), 96 had RA (78.2% females, mean age: 53±13.9 years, mean disease duration: 15.1±7.7 years, RF (+): 59.1%, anti-CCP (+): 67.9%) and 32 had PsA (62.2% females, mean age: 47±14.2, mean disease duration: 12.2±8.7). Etanercept (ETA) was started in 123 (35.1%) patients, infliximab in 116 (33.1%), adalimumab (ADA) in 98 (28%) and golimumab (GOL) in 13 (%3,7). Over an observational period of up to 10 years, biologic treatment was discontinued in 198 (56.4%) patients, of whom 137 (69%) were switched to another TNFi. Drug survival rate for all of the three anti-TNF-α agents is 48.6% for AS, 37.5% for RA, and 40.6% for PsA. Median drug survival time in AS was 67.4 (95% CI, 58.5-76.3) and seemed to be longer than in RA (51.6 months, 95%CI 37.8-65.4) and PsA (45.5 months, 95% CI 30.0-61.0). No difference was observed between different TNFi within the same disease category. In patients with RA, female patiens had a longer drug survival than male patients. The reasons for discontinuation were inefficacy in 86 patients (44.3%), adverse events in 45 (23.2%) (tuberculosis in 2 patients, malignancy in 4 patients), remission in 10 (5.2%) and other or unclear reasons in 55 (29.3%). During the observational period four patients died, one due to lymphoma which developed during anti-TNF therapy, one due to metastatic germ cell tumor which developed one year after the cessation of antiTNF therapy, two due to possibly not related to the anti-TNF therapy. Conclusions Our single center study indicate generally similar long term drug survival rates for TNFi within a disease category. The trend for a better long term drug survival in this study is in line with some previously published. Disclosure of Interest G. Can: None declared, S. Capar: None declared, P. Cetin: None declared, D. Solmaz: None declared, G. Kenar: None declared, H. Yarkan: None declared, S. Akar: None declared, M. Birlik: None declared, I. Sari: None declared, F. Onen: None declared, N. Akkoc Grant/research support from: Pfizer UCB, Consultant for: Pfizer UCB Abbvie MSD BMS, Speakers bureau: Pfizer UCB Abbvie MSD

FRI0229 Evaluation of Patient Acceptable Symptom State in Patients with Axial Spondylarthritis; Similar Thresholds for Radiographic and Non-Radiographic Subgroups

Background The Patient Acceptable Symptom State (PASS), a single-question outcome, has been defined as an absolute level of patient well-being. A few studies have assessed PASS in patients with ankylosing spondylitis (AS), but it is not known whether the results of those studies apply also to the group of non-radiographic (nr) axial spondylarthritis (axSpA) Objectives To estimate the PASS values for disease activity and several patient reported outcomes both in the whole group of axSpA and in the two subgroups of AxSpA. Methods This single-center cross-sectional analysis included patients fulfilling the ASAS criteria for axSpA, who have been registered in our local database. All patients responded to the global yes/no question for PASS. A variety of other outcome measures in regard with global scales, disease activity, functional status, health status and quality of life were collected at the same time. The thresholds at which patients rated themselves in PASS for disease activity (BASDAI and ASDAS) and for each of the assessed patient self-reported outcome measures were estimated using the 75th centile (25th centile for SF 36)estimation and receiver operating characteristic (ROC) analyses in the whole group, as well as in each subgroup of axSpA. Contributors which can affect PASS were evaluated with logistic regression analysis. Results The analysis was based on 356 axSpA patients (261 AS, 95 nr-axSpA) with a mean age of 42.2±12.0 years and mean disease duration of 14.7±10.8 years. Of the patients with axSpA, 271 (%76.1) considered themselves in PASS (76.6% in AS, 74.7% in nr-axSpA). PASS thresholds for disease activity and all other assessed outcome measures were shown in table and there were not significant difference between AS and nr-axSpA group. PASS cut-off points for BASDAI, BASFI and HAQ identified by the 75th percentile method were slightly higher than those determined by the ROC analysis, but similar for the rest of the outcome measures. The patients with an acceptable status had significantly lower mean disease activity scores and good results with the all outcome measures. PASS had no relationship with age, sex, disease duration and education (years) in logistic regression analysis. Of the axSpA patients with BASDAI (≥4), 61.4% and those with ASDAS (>3.5), 50% rated themselves in PASS, whereas 5.5% of the patients with a BASDAI score <2, and 4.5% of those with ASDAS <1.2 were not in PASS. Conclusions PASS thresholds for disease activity and outcome measures were similar to the figures previously reported in some studies with no apparent difference between patients with AS and nr-axSpA. However, more than half the Turkish axSpA patients considered themselves in PASS, which needs to be evaluated in further studies. Disclosure of Interest None declared

FRI0210 A Lower Frequency of Inflammatory Back Pain in Male Patients with Ankylosing Spondylitis Compared with Female Patients

Background Inflammatory back pain (IBP) is the first and most common symptom of ankylosing spondylitis (AS). In daily rheumatology practice, we noticed that a considerable number of male patients with AS did not experience IBP. Objectives The aim of this study was to investigate the frequency of IBP in male AS patients and compare it with that in female AS patients. Methods The study included patients with AS. A face-to-face interview was performed with all the participants by using a standardized questionnaire addressing all the components of IBP. IBP was defined based on the Berlin criteria which have been previously reported as having the highest specificity among all the current IBP criteria sets. To evaluate the specificity of the Berlin criteria in each of the male and female AS patient groups, 63 patients with chronic (>3 months) mechanical back pain (MBP) were also enrolled in the study. Results There were 181 patients with AS (124 male, mean age: 41.2 yrs; 57 female, mean age: 44.6 yrs) who fulfilled the modified New York criteria and 63 patients with chronic MBP (28 male, mean age: 47.2 yrs; 35 female, mean age: 43.5 yrs). There were no significant differences in mean ages and mean education durations between males and females in both AS and MBP groups. The prevalence of IBP was found to be 87.7% in female patients with AS and 66.1% in male patients with AS based on the Berlin criteria (p=0.002). The specificity of the criteria was determined to be high both in females (85.7%) and males (89.2%). Female patients with AS had higher BASDAI levels than males (p=0.048) but no difference was determined in BASFI and serum CRP levels between females and males. Conclusions The results of this study suggested that a considerable proportion of male patients with AS did not experience IBP although they had similar CRP levels compared with females. Disclosure of Interest None declared