Orhan Kucuksahin

Anti-interleukin-1 treatment in 26 patients with refractory familial mediterranean fever

Abstract Objective: To investigate the effect of anti-interleukin-1 (anti-IL-1) treatment on the frequency and severity of attacks and other disease-related clinical parameters and to evaluate the adverse effects associated with anti-IL-1 treatment in 26 patients with refractory familial mediterranean fever (FMF). Methods: The study included 26 FMF patients followed up in our centre using colchicine for 4 months to 30 years. The treatment was switched to anti-IL-1 treatment for various reasons; 20 cases were resistant to colchicine, 8 were intolerant to colchicine, and 3 had prolonged arthritis under colchicine. Clinical response was monitored through the number of attacks, and laboratory inflammation was monitored through erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A concentrations. Colchicine resistance was defined as at least two attacks/month together with C-reactive protein and serum amyloid A levels above the normal range between attacks. The colchicine dose was increased to 2 mg/day before they were considered colchicine-resistant. Results: 24 patients used anakinra (100 mg/day), and 2 used canakinumab (150 mg/month), for –36 months. Sixteen patients with colchicine resistance had no attacks under anti-IL-1 treatment, and 4 had decreased frequency and duration of attacks. Seven of 8 patients intolerant to colchicine used anakinra, and 6 were attack-free under treatment, while 1 using canakinumab had attacks under treatment. One patient with prolonged arthritis used canakinumab but arthritis showed progression and the treatment was changed to IL-6 inhibitor. Three patients had injection site erythema and one had fatigue with anti-IL-1 treatment. Topical steroids with systemic antihistaminics were sufficient for symptom control in two cases, but canakinumab treatment was given due to severe injection site erythema in one case. Conclusion: Anti-IL-1 agents are rational treatment modalities in patients resistant or intolerant to colchicine. Anti-IL-1 agents can control FMF attacks quite effectively and they have a promising role in the treatment of FMF.

A Nationwide Experience With The Off‐label Use of Interleukin‐1 Targeting Treatment in Familial Mediterranean Fever Patients

Approximately 30–45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine‐unresponsive or colchicine‐intolerant FMF patients are limited; the most promising alternatives seem to be anti–interleukin‐1 (anti–IL‐1) agents. Here we report our experience with the off‐label use of anti–IL‐1 agents in a large group of FMF patients.

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.

Can the Thiol/Disulfide Imbalance Be a Predictor of Colchicine Resistance in Familial Mediterranean Fever?

Familial Mediterranean fever (FMF) is a chronic autoinflammatory condition characterized by fever attacks and recurrent polyserositis. Subclinical inflammation that persists during attack-free periods can result in oxidative stress (OS) damage. Thiol groups bind to reactive oxygen radicals and protect cells and tissues from OS damage. The aim of this study was to investigate the relationship between thiol-disulfide balance and colchicine resistance in FMF patients during an attack or attack-free period. A newly developed spectrophotometric method was used to measure native thiol (NT) and disulfide (DS) levels in FMF patients and an age-sex matched group of healthy controls. NT and DS levels were compared in FMF patients 1) with vs. without colchicine resistance; and 2) during an attack (FMF-AP) vs. attack-free period (FMF-AFP). A total of 118 FMF patients and 60 healthy controls were studied. NT (P < 0.001) and total thiol (TT) (P < 0.001) levels in FMF patients were significantly lower compared to healthy controls. NT (P = 0.030) and TT (P = 0.010) levels of FMF-AP patients were significantly lower than that of FMF-AFP patients. FMF-AP patients had significantly higher DS levels than FMF-AFP patients (P = 0.039). Compared to FMF patients without colchicine resistance, elevated levels of DS (P = 0.019) but not NT (P = 0.620) and TT (P = 0.718) were found in those with colchicine resistance. Thiol-disulfide homeostasis is altered in FMF patients during an attack period and this imbalance may be associated with colchicine resistance.

Incidence of sleep disturbances in patients with familial Mediterranean fever and the relation of sleep quality with disease activity

To evaluate the sleep quality and the relation of sleep quality with depression, anxiety, fatigue and disease activity in adult patients with familial Mediterranean fever (FMF).

Axial psoriatic arthritis: the impact of underdiagnosed disease on outcomes in real life

Psoriatic arthritis (PsA) may affect different joints, including the spine. The prevalence of spinal involvement is variable depending on the definition and a subset of patients have been identified in cohorts that do not have clinical features of axial disease and yet have imaging findings. Still, there is not a consensus on how and when to screen axial disease. In this study, we aimed to investigate factors associated with being underdiagnosed for axial psoriatic arthritis (axPsA) and its impacts on outcomes. Disease features and outcomes of axPsA according to the physician (n = 415) were compared with patients with imaging findings only (sacroiliitis fulfilling the modified New York criteria, n = 112), using data from a real-life PsA registry. Patients with imaging findings only were more frequently women (83/220 (37.7%) vs 29/122 (23.8%); p = 0.008). This group also had higher peripheral disease activity (imaging only vs clinical AxPsA: mean (SD) tender joint count 5.3 (6.1) vs 3.3 (4.7), swollen joint count 1.9 (2.9) vs 1.2 (2.4); p < 0.001 for both comparisons) and was less often treated using TNF inhibitors (16.1 vs 38.2%; p < 0.001) than patients who were classified as axPsA. Patient-reported outcomes were similar in both groups. PsA patients, especially women with more severe peripheral disease, have a higher risk of being underdiagnosed for axPsA. The severity of peripheral symptoms may be a risk factor to mask the spinal features of PsA.

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

SAT0353 Geographical differences in psoriatic arthritis: a transatlantic comparison

Background The environmental and genetic factors play a crucial role in the pathogenesis of psoriatic arthritis (PsA) which may cause a difference in disease characteristics for patients from different geographical regions. Objectives The aim of the study was to explore the disease characteristics, treatment choices and comorbidities in patients with PsA in different countries to see the impact of geographic factors. Methods PsArt-ID (Psoriatic Arthritis- International Database) is a prospective, multicentre registry in PsA, which was initially developed in Turkey in 2014, with participation of Canada since 2015 and Italy since 2017. Patients with PsA are consecutively registered to this registry with the aim of investigating the real-life data. Patient characteristics across Turkey (n=1283) and Canada (n=119) are compared for this analysis.Abstract SAT0353 – Table 1 The demographics and clinical characteristics in two countries TURKEY CANADA p value Female* 827/1283 (64.5) 60/119 (50.4) 0.002 Age (years) 47 (36–56.7) 49 (34–61) <0.001 BMI (kg/m2) 27.47 (24.5–31.2) 29 (23.7–33.5) 0.013 At onset age for PsA 36 (29–49.7) 39 (30–48) 0.058 Smoking (package/years) 10 (3–19.7) 14.5 (5–26.25) 0.007 Education years 8 (5–12) 15 (13–16) <0.001 SJC 2 (1–5) 2 (1–7) 0.461 TJC 4 (2–8) 6.5 (2–17) 0.340 TEP 2 (1–2) 1 (1–2) 0.021 BSA 5 (1–13.75) 1 (0–5) <0.001 BASDAI 37 (20–54) 38 (22–58) 0.027 Pt GA 45 (20–60) 31 (12–70) <0.001 PGA 30 (20–50) 34 (18–66) <0.001 Pain VAS 40 (20–60) 33 (18–78) <0.001 TJC: tender joint counts; TEP: tender entheseal points; BSA: body surface area; PtGA: patient global activity; PGA: physician global activity. All data were given n/total n (percentage (%))* or median (first-third percentiles).Abstract SAT0353 – Figure 1 The distribution of the treatment choices in Turkey and Canada, excluding patients with new diagnosis at the time of recruitment. DMARD: Disease-modifying anti-rheumatic drug; anti-TNF: anti-tumour necrosis factor. All data were given n/total n (percentage (%). Results Canadian patients were older at the time of recruitment (Table). They also were more frequently smokers, had higher duration of education and higher BMI than patients in Turkey. Patients in Canada had more frequent polyarthritis (66.7% vs 39.6%, p<0.001), DIP joint disease (34.2% vs 16%, p<0.001), dactylitis (38.1% vs 29%, p=0.037) nail involvement (55.9% vs 45.7%, p=0.008) and higher number deformed joints (29.3% vs 20.7%, p=0.035) whereas Turkish patients had oligoarthritis more often (37.6% vs 24.8%, p=0.016). For disease activity, tender and swollen joint counts were similar for whereas the skin activity was higher in Turkish patients. There were no major differences between countries regarding treatment choices with similar frequencies of patients on biologic therapies (34.5% vs 30.2%, p=0.339) (figure 1). Although the numbers were very low, there was more frequent cancer in Canada than Turkey (4.3% vs 1.4%, p=0.022) whereas all the other comorbidities were similar. Conclusions Geographical differences have impacts on the disease features in PsA, which may be due to genetic, environmental and cultural differences. The treatments are comparable suggesting a similar approach by the physicians. Disclosure of Interest None declared

THU0329 Budd-chiari syndrome in behÇet's disease: a retrospective multicenter study

Background The aim of this study was to determine the demographic, clinical, laboratory and management characteristics along with the clinical course of Budd-Chiari syndrome (BCS) associated with Behçets disease (BD). Methods Sixty patients with BD with BCS (40 male, 20 female) were identified in 23 rheumatology centers (Group I). A total of 169 consecutive patients (100 male, 69 female) with BD who did not have clinically apparent BCS during the follow-up were evaluated as the control group (Group II). Results Comparison of the demographic and clinical findings between the Group I and the Group II were as follows: The mean age of disease onset was 23.1 +/- 6.7 years vs. 26.8±0.6 years (p=0.013), mean age at diagnosis was 27.2±0.9 vs. 30.4±0.6 years (p=0.008), arthritis was 10% vs. 28.4% (p=0.002), papulopustular skin lesion was 48.3% vs 69.2% (p=0.003), central nervous system (CNS) involvement 10% vs. 3% (p=0.03), cardiac involvement was 16.7% vs. 2.4% (p<0.001), superficial thrombophlebitis was 23.3% vs. 4.7% (p<0.001), and deep vein thrombosis was 58.3% vs. 15.4% (p<0.01). On diagnosis 50% of BD patients with BCS were classified as Child-Pugh A. Inferior vena cava obstruction was observed in 38.3% and portal vein thrombosis was seen in 3.3% of the patients with BCS. Mortality in BCS patients with BD was 18.3%. BCS related treatment after diagnosis in patients with BD were as follows: 71.7% of patients were treated with monthly cyclophosphamide intravenous pulses, 53.3% received intravenous pulse corticosteroids, 55.9% used azathioprine, 54.2% had warfarine treatment, and 50.8% were treated with low molecular weight heparin. Conclusions This study shows a higher frequency of cardiac and CNS involvement, superficial thrombophlebitis, papulopustular skin lesion, deep vein thrombosis in BD patients with BCS. Arthritis was observed less common in BD patients with BCS. The mean age onset was lower in patients with BCS. Medical treatment with immunosuppressive agents and anticoagulation appears to be the treatment of choice in BD patients with BCS. The majority of the patients with BCS were Child–Pugh class A on diagnosis. The inferior vena cava is frequently involved and, often associated with deep vein thrombosis and cardiac involvement. Disclosure of Interest None declared

SAT0570 An ignored disease in adults: acute rheumatic fever

Background Acute rheumatic fever (ARF) is a delayed, inflammatory sequela of pharyngitis secondary to Group A Streptococcus infection. ARF remains one of the most important causes of cardiovascular morbidity and mortality in developing countries. Although it is mainly known as a childhood disease, it is also encountered in adult clinics in developing countries. Objectives To investigate the clinical and laboratory characteristics of patients who were diagnosed with ARF in two rheumatology outpatient clinics from June 2015 to January 2017. Methods The data of 20 patients (12 female; median age 29.5 (21–40) years) were evaluated. The diagnosis of ARF was based on the 2015 Jones criteria. The data collected included patient age, gender, arthralgia, arthritis, erythema marginatum (EM), subcutaneous nodules (SN), ECG/ Doppler transthoracic echocardiography findings, and other rare findings. The erythrocyte sedimentation rate (ESR), antistreptolysin O (ASO) and CRP levels of the patients and the drugs initiated were also recorded. Anti-streptolysin O (ASO) test or throat culture were used for the evidence of preceding Streptococcus infection. Patients with post-streptococcal reactive arthritis were differentiated and excluded by clinically. Patients with positive rheumatoid factor or ACPA were also excluded. Joint fluid examination was done to exclude septic arthritis in patients with monoarthritis. Results All patients were referred to rheumatology for arthralgia or arthritis. Patients were taking some sort of nonsteroidal antiinflammatory (NSAI) drugs before the referral. The median follow-up time was 9 months (0–18). Sixteen out of 20 patients had mono-, oligo- or poliarthritis (25%, 25% and 30%, respectively). Knees and ankles were the most common involved joints. The median duration of arthritis was 1 week (1–50 weeks). Six out 20 patients had subclinical carditis (30%). Nine out of 20 patients had a history of ARF attack previously. Three patients had chronic rheumatic mitral valve thickening without any severe insufficiency. EM and SN were observed in 15% and 60% of patients, respectively. Chorea was diagnosed in one patient. NSAI drugs were given to all patients with maximum dosages. High dose salicylate therapy were not given to patients due to intolerance or side effects. Nine patients were given prednisolone therapy (5–20 mg/d). The median duration of prednisolone therapy was 2 weeks (0–6 weeks). Sulfasalazine was given to two patients for the prolonged arthritis. All patients received secondary prophylaxis with penicillin. Conclusions ARF should be considered in the differential diagnosis of arthritis in young adults in developing countries. Arthritis of ARF in adults seems to be resistant to classical NSAI drugs. Our data show that steroid therapy can be given safely instead of salicylates in carditis or arthritis. References GewitzMH,BaltimoreRS,TaniLY,etal. AmericanHeart Association Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease of the Council on Cardiovascu- lar Disease in the Young. Revision of the Jones criteria for the diagnosis of the rheumatic fever in the era of Doppler echocardiography: a scientific statement of the American Heart Association. Circulation 2015; 131: 1806–18. He VY, Condon JR, Ralph AP, et al. Long-Term Outcomes From Acute Rheumatic Fever and Rheumatic Heart Disease: A Data-Linkage and Survival Analysis Approach. Circulation. 2016 Jul 19;134(3):222–32. Disclosure of Interest None declared