Mustafa Ferhat Oksuz

Investigation of MEFV gene polymorphisms (G138G and A165A) in adult patients with familial Mediterranean fever

AIM Various mutations have been identified in the Mediterranean fever (MEFV) gene which is reported to be responsible from Familial Mediterranean fever (FMF). In our study, we aimed to determine the frequency of the MEFV mutations in our region and to investigate the impact of G138G (rs224224, c.414A>G) and A165A (rs224223, c.495C>A) gene polymorphisms on the clinical findings of the disease. METHODS One hundred and sixteen patients diagnosed with FMF and 95 control subjects were included in this study. We used the DNA sequence analysis method to identify the most prevailing 10 mutations located in exon 2 and 10 of MEFV gene. RESULTS As a result of the MEFV mutation analysis, the most common mutation was the M694V mutation allele with a frequency rate of 41.8%. When the patients group and control group were compared in terms of frequency of both polymorphic alleles (G polymorphic allele, observed in G138G and the A polymorphic allele, observed in A165A), the variation was observed to be statistically significant (p<0.001). It was found that the MEFV mutation types have no relation with clinical findings and amyloidosis (p>0.05). CONCLUSIONS To our knowledge, our study is the first study in the Southern Marmara region that reports the frequency of MEFV mutations. Our findings imply that the polymorphisms of G138G and A165A may have an impact on progress of the disease. We think that more studies, having higher number of cases and investigating the polymorphisms of MEFV gene, are needed.

Comparing female-based contraceptive methods in patients with systemic lupus erythematosus, rheumatoid arthritis and a healthy population

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is 10 times more prevalent in women, particularly those of reproductive age. The varying effects of pregnancy on SLE and the differences between available SLE treatments make pregnancy timing and contraceptive methods significant. We aimed to determine the contraceptive methods used by SLE patients in the north‐west part of Turkey, and compared them with those used by rheumatoid arthritis (RA) patients and healthy controls.

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.

Hairy cell leukemia presenting initially with symptoms of Behçet's disease

Vasculitis is relatively uncommon in lymphoproliferative disease and may predate the diagnosis of lymphoproliferative disease. Many vasculitides have been associated with hairy cell leukemia (HCL), including polyarteritis nodosa (PAN) and leukocytoclastic vasculitis. We herein report a case whose initial presentation was like Behçets disease (BD) (arthritis, oral and genital ulcerations, papulopustular skin lesions) in addition to pancytopenia, but turned out to have HCL. Because of the overlap between their symptoms, like oral ulcerations, skin lesions, arthritis and constitutional findings, HCL and BD may mimic each other. We should keep in mind other reasons for vasculitis such as lymphoproliferative disease, especially whose who have hematological abnormalities such as pancytopenia.

SAT0526 Is relapse rate of giant cell arteritis in real-life experience lower than in the controlled trials? results of a retrospective, multi-centre cohort study

Objectives Corticosteroids (CS) are accepted as the standard first-line treatment for giant cell arteritis (GCA). However, controlled trials of tocilizumab and abatacept demonstrated relapse rates of up to 70%–80% in patients on CS-only protocols in 12–24 months. Though level of evidence is low and not suggested by guidelines (except for methotrexate), conventional immunosuppressives (ISs) are also commonly used. We aimed to assess the relapse rates in patients with GCA in routine practice, retrospectively. Methods We assembled a retrospective cohort of patients with GCA from Turkey. All data was abstracted from records. Relapse was defined as any new manifestation or increased acute-phase response leading to the change of the CS dose or use of a new therapeutic agent by the treating physician. Results The study included 156 (F/M: 95/61) patients with GCA (table 1). The mean age at disease onset was 67.8±9.1 years. Polimyalgia Rheumatica was also present in 48 (30,8%) patients. Diagnosis was proven histopathologically in 99 patients.All patients received 1 mg/kg/day CS for remission induction, additional CS pulses were given to 36 (23.1%) patients. Conventional ISs including methotrexate and azathioprine were used in 89 (56.1%) and 26 (16.6%) patients respectively, while 10 (6.4%) patients received biologic treatments (8 tocilizumab,2 etanercept). Fourty-four (28.2%) patients used only CS during follow-up. Follow-up of at least 6 months was available for 132 patients, and median follow-up duration was 35 (6–268) months. Relapses occurred in 27 (20.5%) patients during follow-up. Mortality rate was 7.5% (n=10) during follow-up. VDI score was 2.4±1.7. Main causes of damage were related to CS treatments such as cataract, osteoporosis and diabetes mellitus. Conclusions In this first multi-centre series of GCA from Turkey, we observed that only one fifth of patients had relapses during a mean follow-up of 35 months. This lower relapse frequency suggests a different clinical spectrum in routine practice compared to patients included in controlled trials. Our results also suggest that there is a clear need for a steroid sparing agent in patients with GCA, that is a older aged population prone to CS side effects. Disclosure of Interest None declared

Clinical outcomes and survival in AA amyloidosis patients

AIM Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. METHODS A total of 81 patients (51 males, 30 females) with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. RESULTS Most of the patients (55.6%) had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2%) and rheumatoid arthritis (10.6%) in the good outcome group and malignancy (20%) in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively). Median duration of renal survival was 65±3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p=0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p=0.006) and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p=0.027) were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3±16 months. CONCLUSION Our study indicated that familial Mediterranean fever constituted a large proportion of cases and increased number of patients with idiopathic amyloid A amyloidosis. Additionally, it was observed that patient survival was not affected by different etiological causes in amyloid A amyloidosis.

THU0586 Agreement of Patient and Physician Global Assessment of Disease Activity in Adult Onset Still's Disease

Background There is not valid outcome measures for assessment Adult onset Stills disease (AOSD) activity. The patients or physicians global view is relevant way to assess this kind of complex diseases. However, it is well known that there is discordance between patient and physician perspective for disease activity in different inflammatory diseases. Objectives Objective of this study was to evaluate agreement of patient and physician perspective in AOSD patients. Methods We conducted a cross-sectional, multicenter study for assessment of disease activity in AOSD patients. All AOSD patients were fulfilled Yamaguchi criteria. For every center, at least 20% of AOSD patients had to be an active state according to physician assessment. Age, sex, disease duration, current disease symptoms was recorded. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), leucocyte, and ferritin level also recorded. Visual analog scale (VAS) (0–10 cm) used for physician and patient global assessment of disease activity. Disease activity status were also assessed by likert scale (as remission, low, moderate, severe, and more severe disease activity) for both patients and physician perspective. Patient global assessment VAS and physician global assessment were correlated by correlation coefficient (r). Agreement of disease activity level for patient and physician perspective were calculated with kappa. Kappa >0.6 was accepted as significant. Results One hundred thirty (83, 63.4% female) AOSD patients were enrolled. Mean age was 38 (14) years old and median disease duration was 3 years (0–29). Currently AOSD symptoms followed; fever 34 (26.2%), rash 28 (21.5%), arthritis 31 (23.8%), arthralgia 60 (46.2%), sore throat 28 (21.5), myalgia 42 (32.3), lympadenopathy 12 (9.2%), splenomegaly 17 (13.1%), hepatomegaly 7 (5.4%), pleuritic 3 (2.3%), hemophagocytic syndrome 2 (1.5%). ESR 47.7%, CRP 43.8%, ferritin 27.0%, and leucocyte 43.1% were higher than upper limit. Mean patient global assessment VAS was 3.53 (3.25), and mean physician global assessment VAS was 2.71 (2.95). Correlation coefficient (r) of patient and physican global VAS was 0.89. There was excellent agreement according to severe/more severe disease activity at patient and physician level (kappa 0.88 (CI 95% 0.79–0.98). There was also good to excellent agreement according to low disease activity/remission at patient and physician level (kappa 0.74 (CI 95% 0.62–0.86). Conclusions Although, features of AOSD seems more complex with constitutional symptoms, joint or reticuloendothelial system involvement, patients and physicians assess level of disease activity similarly. We thought, this results will be helpful for procedure of new composite index in AOSD. Disclosure of Interest None declared

AB0432 Dose Escalation and Switching Patterns of Anti-TNF Drugs in Rheumatoid Arthritis: A Retrospective Chart – Review Study in Turkey

Background There is not enough data on the dosing patterns and switching rates of the most frequently used TNFis infliximab, adalimumab and etanercept in Turkey. Objectives The aim of this retrospective chart review is to compare the proportion of rheumatoid arthritis (RA) subjects requiring treatment modification between the TNFis (etanercept, infliximab and adalimumab). Methods Inclusion criterias; a) Consecutive patients diagnosed with RA who were newly started on TNFis as the first biologic treatment. b) Have received continuous treatment with the index TNFi (the date of initial prescription of a TNFi is considered index date and the TNFi itself is the index TNFi) for at least 3 months following the index date and with a biologic (either the index drug or other biologic to which he/she was switched due to inefficacy) for at least 18 months. DMARDs and corticosteroids doses, dosing regimens and reasons for dose changes collected for 18 months following the index date. The primary end point is the proportion of patients with treatment modification which is defined as either one of the following: The first occurrence of any upward adjustment in dose or dosing frequency of each TNFi from the label/indicated dose and unit of time (etanercept 25 milligram [mg] biweekly or 50 mg once weekly, adalimumab 40 mg once every other week or infliximab 3mg/kilogram [kg] every 8 weeks after the 3rd infusion) within the 12 month period following index date. The first occurrence of any switch to another biologic agent due to inefficacy or loss of efficacy Results Overall 400 patients (79.3% female) were enrolled to this study. TNFi drugs were etanercept (240 patients), adalimumab (80 patients) and infliximab (80 patients) respectively. Mean age was 53±12 years old, mean disease duration was 11.3±7.5 years. Anti-CCP antibody was positive at 115/201 (57.2%), and rheumatoid factor was positive at 178/311 (57.2%) of patients. Baseline DAS-28 score was 5.75±0.79, baseline ESR and CRP were 45±26 mm/hour and 3.4±2.8 mg/dl, respectively. The distribution of modifications such as change of TNFi duration or dosage (modification 1), change of TNFi due to inefficacy or lost of efficacy (modification 2), increase of DMARDs or steroid dosage (modification 3) and add of DMARDs or steroid (modification 4) were shown at table 1.Table 1. Modification of TNFi or DMARDs according to different TNFi drugs Etanercept Adalimumab Infliximab p Modification 1 1.4 0 20 <0.001*,** Modification 2 10.4 11.2 25 0.001*, 0.024** Modification 3 14.5 12.5 13.7 >0.05 Modification 4 15.3 11.3 16.3 >0.05 Modification Total 30.2 26.3 45.0 0.017*, 0.013** Mod 1: Change TNFi duration or dosage; Mod 2: Change of TNFi due to inefficacy or lost of efficacy; Mod 3: Dosage increase at DMARDs or steroid; Mod 4: Add to DMARDs or steroid.* ETA vs. INF** ADA vs. INF. Conclusions Dose escalation was prominent at infliximab than other anti-TNF drugs. Patients with infliximab also had more frequent switch of TNFi due to inefficacy or loss of efficacy. However, increase or add of DMARD or steroid were similar at whole anti-TNF drugs. Acknowledgements This study was supported by Phizer, Inc. Disclosure of Interest None declared

SAT0582 Psoriasis Symptom Inventory is a Valid Patient-Reported Instrument for the Assessment of Skin Severityin Psoriatic Arthritis

Background Skin involvement in psoriatic arthritis (PsA) has significant impacts on health-related quality of lives in addition to the joint involvement. Due to this impact, its important to assess the severity of psoriasis to fully capture disease activity in PsA. In this study we aimed to test the validity of “Psoriasis symptom inventory” (PSI) in a cohort of patients with PsA. Methods PsART (Psoriatic Arthritis Registry of Turkey) is a prospective, multicentre, nationwide study in Turkey on patients with PsA. Patients are consecutively recruited to this registry, if they are diagnosed as PsA, regardless of any other disease characteristics. In this registry, PSI data was available in 237 patients. For the PSI the following items were scored on a scale between 0-4, by the patient: itching, redness, scaling, burning, stinging, cracking,flaking and pain. The PSI score was calculated as a sum of these items and ranged between 0-32. The correlations between PSI and other outcome measures were investigated. Results The mean (SD) age and BMI were 44.7 (12.3) and 28.7 (5.6), respectively. Sixty-six percent of the patients were female. The duration of psoriasis in this group was 167.3 (124.2) months. Mean (SD) PSI scores were 6.7 (6.7) with a range of 0-32. PSI scores were found to be significantly correlated to patient (R=0.338) and physician global assessments (R:0.342), fatique (R=0.226), pain (R=0.334) (p<0.001 for all comparisons) and HAQ (R=0.198; p=0.007). PSI was also correlated to body surface area involved, measured by the physician (R=0.256, p=0.07). Conclusions PSI has a good construct validity in comparison to other clinical assessment tools. Due to its high feasibility, PSI can be a useful tool to investigate and record the severity of psoriasis in PsA in clinical practice. Disclosure of Interest None declared

AB0829 Demographics of Patients with New-Onset Psoriatic Arthritis: Real Life Data from an Inception Cohort: Table 1.

Background Psoriatic arthritis is a complex disease with a wide range of manifestations. In this inception cohort of PsA patients we aimed to identify the initial manifestations as well as disease activity characteristics and compare with an unselected group of patients with longstanding disease. Methods PsART (Psoriatic Arthritis Registry of Turkey) is a prospective, multicentre study in Turkey on patients with PsA. Patients are consecutively recruited to this registry. Patients who have been newly diagnosed with PsA have been identified, and their characteristics were compared with longstanding disease. Results Within 746 patients recruited, 111 (14.9%) had a new diagnosis for PsA. Patients in the inception cohort were significantly younger than the rest of the cohort (p=0.03) (table). Females were 53.2% of the inception and 66.8% of the non-inception cohort (p=0.007). For types of joint patterns, 14.4% of the inception cohort had only axial involvement whereas this was seen in 8.2% for the other group (p=0.05). The other joint patterns were comparable among groups. Both groups had similar tender and swollen joint counts, BASDAI and BASFI. Patient (p=0.002) and physician global assessments (p<0.001), fatigue (p=0.02), duration of morning stiffness (p=0.02) and CRP (p=0.05) were higher in the inception cohort. Female patients had higher patient global assessment and fatigue scores despite similar physician global assessment, swollen and tender joint counts, BASDAI, BASFI and CRP with males in non-inception cohort. For the inception cohort, there were no differences between the 2 genders.Table 1. Disease characteristics of the groups Inception cohort Non-inception cohort Whole group Females Males Whole group Females Males n 111 59 52 635 424 211 age 42.5 (12.3) 44.4 (12.5) 40.4 (11.7) 45.5 (12.9) 46.7 (13) 43.1 (12.4) SJC 2.7 (3.4) 2.5 (3.2) 3 (3.6) 1.6 (2.8) 1.5 (2.8) 1.6 (2.7) TJC 4.1 (4) 3.8 (3.7) 4.5 (4.2) 3.4 (4.7) 3.5 (4.8) 3.4 (4.2) BASDAI* 4.5 (2.4) 4.3 (2.2) 4.8 (2.5) 3.7 (3.8) 3.8 (4.3) 3.5 (2.6) BASFI* 3.2 (2.4) 3 (2.3) 3.4 (2.4) 2.8 (2.7) 2.7 (2.7) 2.8 (2.7) Patient global* 4.9 (2.5) 4.7 (2.3) 5.1 (2.6) 3.9 (2.3) 4 (2.3) 3.5 (2.4) Physician global* 4.2 (1.9) 4 (1.6) 4.4 (2.1) 3.1 (2.1) 3.1 (2) 3 (2.2) fatigue* 4.9 (2.5) 5 (2.3) 4.9 (2.7) 4.2 (2.6) 4.5 (2.5) 3.7 (2.8) CRP (mg/lt) 13. 4 (23.4) 9.5 (16.5) 18 (29.1) 8.7 (16.2) 8.6 (16.1) 9 (16.5)* Data given on a scale between 0–10. There were missing data. The number of cases with available information are: BASDAI: 434, BASFI: 413; patient global assessment: 493; physician global assessment 440, fatigue: 506, CRP: 717, tender joint count: 677, swollen joint count: 672. Conclusions More patients present with sole axial involvement at the beginning, which may explain the higher disease activity agreed by the patient and the physician despite similar tender and swollen joint counts. Females may have a different perception of the disease with worse patient global assessments and fatigue in longstanding disease. Disclosure of Interest None declared