D. Solmaz

Different disease subtypes with distinct clinical expression in familial Mediterranean fever: results of a cluster analysis

OBJECTIVE The aim of this study was to evaluate whether there are clinical subgroups that may have different prognoses among FMF patients. METHODS The cumulative clinical features of a large group of FMF patients [1168 patients, 593 (50.8%) male, mean age 35.3 years (s.d. 12.4)] were studied. To analyse our data and identify groups of FMF patients with similar clinical characteristics, a two-step cluster analysis using log-likelihood distance measures was performed. For clustering the FMF patients, we evaluated the following variables: gender, current age, age at symptom onset, age at diagnosis, presence of major clinical features, variables related with therapy and family history for FMF, renal failure and carriage of M694V. RESULTS Three distinct groups of FMF patients were identified. Cluster 1 was characterized by a high prevalence of arthritis, pleuritis, erysipelas-like erythema (ELE) and febrile myalgia. The dosage of colchicine and the frequency of amyloidosis were lower in cluster 1. Patients in cluster 2 had an earlier age of disease onset and diagnosis. M694V carriage and amyloidosis prevalence were the highest in cluster 2. This group of patients was using the highest dose of colchicine. Patients in cluster 3 had the lowest prevalence of arthritis, ELE and febrile myalgia. The frequencies of M694V carriage and amyloidosis were lower in cluster 3 than the overall FMF patients. Non-response to colchicine was also slightly lower in cluster 3. CONCLUSION Patients with FMF can be clustered into distinct patterns of clinical and genetic manifestations and these patterns may have different prognostic significance.

The Psoriatic Arthritis Registry of Turkey: results of a multicentre registry on 1081 patients.

Objective. The aim was to assess the characteristics of PsA, find out how well the disease is controlled in real life, demonstrate the treatments and identify the unmet needs. Methods. The PsA registry of Turkey is a multicentre Web-based registry established in 2014 and including 32 rheumatology centres. Detailed data regarding demographics for skin and joint disease, disease activity assessments and treatment choices were collected. Results. One thousand and eighty-one patients (64.7% women) with a mean (S.D.) PsA duration of 5.8 (6.7) years were enrolled. The most frequent type of PsA was polyarticular [437 (40.5%)], followed by oligoarticular [407 (37.7%)] and axial disease [372 (34.4%)]. The mean (S.D.) swollen and tender joint counts were 1.7 (3) and 3.6 (4.8), respectively. Of these patients, 38.6% were on conventional synthetic DMARD monotherapy, 7.1% were on anti-TNF monotherapy, and 22.5% were using anti-TNF plus conventional synthetic DMARD combinations. According to DAS28, 86 (12.4%) patients had high and 105 (15.2%) had moderate disease activity. Low disease activity was achieved in 317 (45.7%) patients, and 185 (26.7%) were in remission. Minimal disease activity data could be calculated in 247 patients, 105 of whom (42.5%) had minimal disease activity. The major differences among sexes were that women were older and had less frequent axial disease, more fatigue, higher HAQ scores and less remission. Conclusion. The PsA registry of Turkey had similarities with previously published registries, supporting its external validity. The finding that women had more fatigue and worse functioning as well as the high percentage of active disease state highlight the unmet need in treatment of PsA.

Do major histocompatibility complex tag single nucleotide polymorphisms accurately identify HLA-B27 in the Turkish population?

To evaluate the performance of human leukocyte antigen (HLA)‐B27 tag single nucleotide polymorphisms (SNPs) by polymerase chain reaction – restriction fragment length polymorphism (PCR–RFLP).

Update on the epidemiology, risk factors, and disease outcomes of psoriatic arthritis

Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects different structures of the musculoskeletal system in addition to the skin and the nail. The complexity of the disease had been a barrier to understand the pathogenesis and define valid outcome tools; however, our understanding about the disease has considerably increased with time mainly because of the advances in imaging, new discoveries in genetics and underlying inflammatory pathways, and better understanding of the epidemiology of the disease and environmental risk factors. The purpose of this review is to summarize developments and changes in epidemiology, risk factors for developing PsA, and outcome measures with a focus on data obtained in the last 10 years.

Evaluation of periostin and factors associated with new bone formation in ankylosing spondylitis: Periostin may be associated with the Wnt pathway

Periostin has been shown to be involved in bone anabolism through the regulation of Wnt‐β‐catenin signaling. It may be one of the pathogenic mechanisms in syndesmophyte formation in ankylosing spondylitis (AS). The aim of this study was to evaluate serum periostin levels in patients with AS and to assess relationships among biomarkers of bone formation and periostin in disease outcomes, particularly radiographic changes.

AB0678 A Comparison of Depression and Anxiety Levels in Patients with Non-Radiographic Axial Spondyloarthropathy with Those in Patients with Ankylosing Spondylitis: Table 1.

Background The concept of axial spondyloarthropathy (SpA) recently recommended by the ASAS includes patients comprising the early and late stages of the disease. This concept also includes patients not meeting the criteria for ankylosing spondylitis (AS) but classified as non-radiographic SpA on the basis of chronic lumbar back pain and other characteristics of SpA. Although this group is more heterogeneous and distinct from AS in terms of some characteristics, it still has a similar burden in terms of disease activity. Psychiatric symptoms can often be seen in patients during the course of AS. Depressive symptoms are seen at levels of 27.4–55.5% and anxiety symptoms at levels of 19.5–60.9%. Few studies have investigated this situation in the non-radiographic SpA group. Objectives To assess depression and anxiety levels in AS and non-radiographic SpA groups and to review potentially associated factors. Methods One hundred fifty-five (114 AS, 41 non-radiographic SpA) patients with axial SpA according to the ASAS definition were included in the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess activity, visual anolog scale (VAS) for spinal pain, the Bath Ankylosing Spondylitis Functional Index (BASFI) for functional capacity and the Ankylosing Spondylitis Quality of Life (ASQOL) for quality of life. The State-Trait Anxiety inventory (STAI), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were used to determine psychiatric symptoms. Results The AS patient group (mean age 39±10.8, male 73.4%) was older than the non-radiographic SpA group (mean age 35±10.1, male 54.8%), and had a greater preponderance of males. No difference was determined between the two groups in terms of BASDAI, VAS spinal pain, ASQOL or BASFI scores. Psychiatric measurements were also similar between the AS and non-radiographic SpA groups. The STAI, BDI and BAI exhibited good correlated with BASDAI, BASFI, ASQOL and VAS spinal pain (Table).Table 1. Correlations between psychiatric symptoms and disease, functional capacity and quality of life scales BASDAI BASFI VAS spinal pain ASQOL STAI-I (state anxiety) r 0.432 0.343 0.373 0.481 p <0.001 <0.001 <0.001 <0.001 STAI-II (trait anxiety) r 0.375 0.342 0.234 0.420 p <0.001 <0.001 0.005 <0.001 Beck anxiety inventory r 0.430 0.375 0.326 0.508 p <0.001 <0.001 <0.001 <0.001 Beck depression inventory r 0.427 0.432 0.410 0.595 p <0.001 <0.001 <0.001 <0.001 Conclusions Despite the presence of some clinical differences between the AS group and the non-radiographic SpA group, regarded as the early stage of the disease, the two group exhibit similar features in terms of psychiatric symptoms and disease activity. Psychiatric symptoms are closely associated with disease activity, functional capacity and quality of life. 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

AB0944 Vitamin D Deficiency Might Contribute Fatigue and Disease Activity in Patients with Fibromyalgia

Background Fibromyalgia syndrome (FMS) is a chronic musculoskeletal system disease characterized by widespread pain and allodynia in at least 11/18 anatomic regions. Other important symptoms are fatigue, sleep disturbance and cognitive impairment. Widespread pain and fatigue can also be seen in patients with vitamin D deficiency. The association between low levels of 25-hydroxy (OH) vitamin D and non-specific musculoskeletal pain, including fibromyalgia syndrome, is controversial. Objectives The aim of this study is to assess fatigue and health quality in patients with isolated FMS, isolated vitamin D deficiency and FMS in together with vitamin D deficiency. Methods Patients followed by rheumatology clinic and classified as FMS according to ACR 2010 criteria were included in this study. 25- OH vitamin D levels below 20 ng/ml were accepted as vitamin D deficiency. Study groups classified as first group; patient with isolated FMS, second group; isolated vitamin D deficiency and third group was FMS in together with vitamin D deficiency. Patients with known calcium abnormality, hyperparathyroidism and osteomalacia were excluded. Fatigue level was measured by the visual analog scale (VAS) and functional assessments were determined by using BASFI and HAQ. Routine laboratory data were recorded. Widespread Pain Index (WPI); by evaluation of 0-19 tender points and Symptom Severity Score (SS); by the sum of fatigue, sleep, cognitive disturbances with general somatic symptoms were obtained. Results Patients distribution according to groups and properties were summarized in the table. As expected, in all groups, the majority of patients were female. While fatigue levels were similar between isolated vitamin D deficiency group and isolated FMS group, in FMS together with vitamin D deficiency group fatigue level was measured higher than the other two groups. Moderate and negative correlation was detected between fatigue level and vitamin D level (r:- 413, p:0,002). Negative relation was also detected between widespread pain index and symptom severity score with vitamin D level (r: -0.325, p: 0.023; r: -0.315, p: 0.037 respectively). HAQ and BASFI scores were higher with D vitamin deficiency between FMS patients (respectively p: 0.018, p<0.001). Group 1: Group 2: Group 3: Isolated vitamin D deficiency (n=37) Isolated FMS (n=21) FMS and vitamin D deficiency (n=43) Age, mean ± SD 49±13.0 45±6.6 47±9.9 Gender, female % 32, 86.5 21, 100 43, 100 ESR mm/h; mean ± SD 15±8.8 19±10.5 18±9.5 CRP mg/L; mean ± SD 2.3±2.4 3.9±3.1 4.1±1.8 25-Hydroxy vitamin D, ng/ml; mean ± SD 11.6±5.3 34.6±12.0 11.3±4.7 Ca mg/dl; mean ± SD 9.7±0.3 9.6±0.2 9.6±0.3 P mg/dl; mean ± SD 3.3±0.4 3.4±0.5 3.6±1.1 PTH pg/ml; mean ± SD 54±20.0 52±9.9 52±25.1 ALP IU/L ; mean ± SD 74±21.2 69±19.2 83±24.5 BASFI; mean ± SD 2.0±0.9 2.6±1.5 4.5±1.8* HAQ; mean ± SD 0.6±0.9 0.8±0.4 1.2±0.3* VAS fatigue; mean ± SD 54±22 59±10 76±15* WPI score; mean ± SD N/A 10±1.5 12±2.1 SS score; mean ± SD N/A 6±1.2 8±1.5 Conclusions Vitamin D deficiency may contribute disease severity, fatigue and disturbances in health quality in FMS patients. Based on this, in FMS screening the level of vitamin D and correction may be helpful in symptom control. Disclosure of Interest None declared

AB0157 Serum Level of the Vascular Endothelial Growth Factor is Elevated in Ankylosing Spondylitis and Osteocalcin May be Related Wth Osteoproliferation

Background Ankylosing spondylitis (AS) is a chronic rheumatic disease characterized by sacroiliac and spinal inflammation and new bone formation (syndesmophyte). Molecular mechanisms underlying this process have not been yet fully understood however differentiation of mesenchymal cells into bone-forming osteoblasts appears to be a key pathogenic event. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor and have some pro-inflammatory activity. It has also been suggested that VEGF may be relevant for new bone formation in AS. Objectives To evaluate the serum VEGF and osteocalcin levels in patients with AS. We also assessed the relationship among VEGF/osteocalcin levels and disease related parameters including radiographic outcomes. Methods In total 98 consecutive AS patients (77 males [79%]; with a mean age of 39.3±10.0 years) according to the modified New York criteria and 49 healthy controls (37males [76%]; with a mean age of 39.0±5.9 years) from two centers were included in the study. Serum VEGF, osteocalcin, interleukin (IL)-8, IL-6 levels were measured by commercially available ELISA kits. We also determined the serum high-sensitivity C-reactive protein (hs-CRP) levels. Disease related characteristics of patients were assessed by using BASDAI, BASFI, BASMI. Radiographs of the pelvis, cervical and lumbar spine were scored by using the modified New York and modified Stokes ankylosing spondylitis spinal score (mSASSS). Results Age and sex distribution were not different between AS patients and control subjects. As expected hs-CRP levels and erythrocyte sedimentation rate were higher in AS patients in comparison with controls. Serum VEGF level was found to be significantly higher in our AS patients compared with controls. In our study group serum VEGF levels were correlated with hs-CRP (rho=0.285 and P=0.005), ESR (rho=0.247 and P=0.015), IL-6 level (rho=0.380 and P<0.001), IL-8 (rho=0.400 and P<0.001) and ASDAS-CRP (rho=0.203 and P=0.048). Serum VEGF level was found to be not associated with hip involvement, sacroiliac joint ankylosis or presence of the syndesmophyte. Our study showed that although serum osteocalcin level was not statistically different in AS patients and controls it was significantly higher in patients with sacroiliac joint ankylosis and hip involvement.Table 1 AS patients (n=98) Controls (n=49) P Age at disease onset 27.7±8.6 N/A N/A Mean BASDAI 4.2±2.1 N/A N/A Mean BASFI 3.4±2.4 N/A N/A Mean BASMI 3.8±1.7 N/A N/A ASDAS-CRP 3.0±0.9 N/A N/A Median mSASSS score 6 (0-72) N/A N/A Serum VEGF (pg/mL) 1591.71±753.55 995.70±611.23 <0.001 Osteocalcin (mg/dL) 5.8±7.3 6.3±8.4 0.0507 IL-6 (pg/mL) 22.3±161.6 6.6±31.2 <0.001 IL-8 (pg/mL) 103.9±270.9 66.9±60.1 0.390 hsCRP (μg/mL) 5.2±8.4 0.7±1.3 <0.001 ESR 25.6±22.5 10.8±9.2 <0.001 Conclusions The results of the present study showed that VEGF may be a good indicator of disease activity in AS and osteocalcin may have a role in new bone formation. Disclosure of Interest None declared

AB0803 Obesity is Associated with Psoriatic Arthritis and Contributes to the Increased Use of Biologics

Background An increased prevalence of obesity and metabolic syndrome (Mets) has been reported in psoriatic arthritis (PsA) as compared with the general population suggesting an association between the inflammation and atherosclerotic risk factors. Takayasu arteritis (TA) is a systemic inflammatory disease which affects mostly the aorta and its main branches. Increased atherosclerosis has also been reported in Takayasu patients. Objectives In this study, we aimed to investigate the prevalances of obesity and Mets in patients with PsA and to compare the results with those in patients with TA. Methods This cross-sectional study included patients with PsA and age matched control patients with TA who were followed in the Rheumatology out-patient clinic at Dokuz Eylul University. Patients with body mass index (BMI; kg/m2) between 25.0 and 29.99 were classified as overweight and those with ≥30 as obese. The NCEP-ACT III criteria were used to identify subjects with MetS. Disease activity was assessed in patients with PsA using the Composite Psoriatic Disease Activity Index (CPDAI), BASDAI and DAS28. HAQ and DLQI were used for the health assessment and BASFI for the functional status. Results There were 117 PsA patients (78 female; mean age: 47.2±12.0 years; disease duration: 8.0±8.4 years) who fulfilled the CASPAR criteria and 32 TA patients (29 female; mean age: 43.5±11.3 years; disease duration: 8.3±8.7 years) who fulfilled the ACR 1990 classification criteria for TA.The prevalence of obesity and overweight was found to be higher in PsA compared with TA (29.9% versus 18.8% and 40.2% versus 28.0%, respectively; p=0.03). The prevalence of MetS was 28.2% in PsA and 18.8% in TA (p0.05).In the further analysis of obese, overweight patients and patients with normal BMI, no differences were found regarding disease activity, functional status, health assessment, disease duration, and glucocorticoid and DMARD use (p0.05). However there was a higher frequency of biologic use in the obese and overweight patients compared with those with normal BMI (42.9% and 23.4%, respectively vs 11.4%, p0.05) Conclusions This study demonstrates a higher prevalence of obesity in PsA compared with TA. The increased use of biologics in obese patients suggests the association of obesity with worse disease severity in PsA. Disclosure of Interest None declared