Browsing by Author "Önen F."

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    Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis
    (Public Library of Science, 2019) Li Z.; Akar S.; Yarkan H.; Lee S.K.; Çetin P.; Can G.; Kenar G.; Çapa F.; Pamuk O.N.; Pehlivan Y.; Cremin K.; de Guzman E.; Harris J.; Wheeler L.; Jamshidi A.; Vojdanian M.; Farhadi E.; Ahmadzadeh N.; Yüce Z.; Dalkılıç E.; Solmaz D.; Akın B.; Dönmez S.; Sarı İ.; Leo P.J.; Kenna T.J.; Önen F.; Mahmoudi M.; Brown M.A.; Akkoc N.
    Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS. We aimed to identify AS susceptibility loci and also examine the association between MEFV and AS in Turkish and Iranian cohorts. We performed genome-wide association studies in 1001 Turkish AS patients and 1011 Turkish controls, and 479 Iranian AS patients and 830 Iranian controls. Serum IL-1β, IL-17 and IL-23 cytokine levels were quantified in Turkish samples. An association of major effect was observed with a novel rare coding variant in MEFV in the Turkish cohort (rs61752717, M694V, OR = 5.3, P = 7.63×10−12), Iranian cohort (OR = 2.9, P = 0.042), and combined dataset (OR = 5.1, P = 1.65×10−13). 99.6% of Turkish AS cases, and 96% of those carrying MEFV rs61752717 variants, did not have FMF. In Turkish subjects, the association of rs61752717 was particularly strong in HLA-B27-negative cases (OR = 7.8, P = 8.93×10−15), but also positive in HLA-B27-positive cases (OR = 4.3, P = 7.69×10−8). Serum IL-1β, IL-17 and IL-23 levels were higher in AS cases than controls. Among AS cases, serum IL-1β and IL-23 levels were increased in MEFV 694V carriers compared with non-carriers. Our data suggest that FMF and AS have overlapping aetiopathogenic mechanisms. Functionally important MEFV mutations, such as M694V, lead to dysregulated inflammasome function and excessive IL-1β function. As IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy. © 2019 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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    Prevalence of spondyloarthritis among patients who underwent lumbar disc herniation surgery
    (Turkish League Against Rheumatism (TLAR), 2020) Soysal Gündüz Ö.; Akar S.; Solmaz D.; Can G.; Önen F.; Akkoç N.
    Objectives: This study aims to estimate the prevalence of spondyloarthritis (SpA) among patients who had been surgically treated for lumbar disc herniation (LDH), according to the modified New York (mNY) criteria for the diagnosis of ankylosing spondylitis and Amor, the European Spondyloarthropathy Study Group (ESSG), the Assessment of Spondyloarthritis International Society (ASAS) classification criteria for SpA. Patients and methods: The study included 321 patients (142 males, 179 females; mean age 49±10.8 years; range, 18 to 79 years) who underwent LDH surgery between April 2008 and May 2012 in the neurosurgery clinic of our hospital. Patients were contacted by phone on at least two attempts. Totally, 123 patients accepted to come to the outpatient clinic, while the remaining 198 agreed to be interviewed on the phone. Patients who agreed to come to the outpatient rheumatology clinic underwent clinical examination, and pelvic X-ray and magnetic resonance imaging (MRI) scan of the sacroiliac joints when indicated. Results: Inflammatory back pain was diagnosed in 108 patients (34%) and 40 patients (13%) according to Calin criteria and the ASAS criteria, respectively. Prevalence of SpA among all patients was estimated as 17.7% according to the ESSG criteria, and 8.7% according to Amor criteria. Five of the 308 pelvic radiographs had definite radiographic sacroiliitis as required by the mNY criteria. Four patients had a characteristic pattern of bone marrow edema on MRI examination in accordance with the ASAS definitions. The overall prevalence of sacroiliitis (MRI sacroiliitis+X-ray sacroiliitis) among the patients who came to the clinic was 7.3% ([4+5]/123). Conclusion: The relatively increased prevalence of SpA among patients who underwent LDH surgery indicates the necessity of increasing awareness on the new concept of axial SpA for specialists treating patients with low back pain. © 2020 Turkish League Against Rheumatism. All rights reserved.
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    The prevalence of sjögren’s syndrome and sicca symptoms in patients with systemic sclerosis and alpha-smooth muscle actin expression in biopsy specimens from minor salivary glands
    (Turkiye Klinikleri, 2021) Can G.; Sarioğlu S.; Birlik M.; Kenar G.; Soysal Ö.; Solmaz D.; Gerdan V.; Önen F.; Akkoç N.; Akar S.
    Background/aim: This study aimed to investigate the prevalence of sicca symptoms and secondary Sjögren’s syndrome (SjS) in patients with systemic sclerosis (SSc). Also this study aimed to evaluate the expression of α-smooth muscle actin (α–SMA) in minor salivary gland (MSG) specimens, a possible marker of fibrosis responsible for myofibroblastic transformation. Materials and methods: Patients with SSc who were followed in Rheumatology outpatient clinic at a university hospital evaluated. The questionnaire of sicca symptoms and classification of SjS were evaluated according to the American–European Consensus Group (AECG) criteria. Histopathologic evaluations were done in MSG specimens investigating the presence of focal lymphocytic sialadenitis and glandular fibrosis, also assessing the expression of α–SMA. Results: This cross-sectional study included 102 patients with SSc [91 females (89%), mean age 52.5 ± 12 years]. In this cohort 76 (75%) patients had sicca symptoms and 36 (35.3%) patients fulfilled the AECG criteria for SjS; all with limited form. Having SjS found to be associated with older age and the presence of positive anti-SS-A antibodies. On histopathologic examinations, glandular fibrosis was observed in 67 (80%) and lymphocytic sialadenitis was detected in 38 (45%) patients; but only 7 samples were positive for α–SMA. Conclusion: This study suggested sicca symptoms were found to be very common among patients with SSc. Also secondary SjS was detected in nearly one-third of patients with SSc; especially in limited subtype. Anti SS-A positivity and older age were detected as predictors for SjS. Histopathologic evaluations showed significant glandular fibrosis but rare α-SMA staining in patients with SSc. © TÜBİTAK.
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    A patient-driven registry on Behçet’s disease: the AIDA for patients pilot project
    (Frontiers Media SA, 2023) Gaggiano C.; Del Bianco A.; Sota J.; Gentileschi S.; Ruscitti P.; Giacomelli R.; Piga M.; Crisafulli F.; Monti S.; Emmi G.; De Paulis A.; Vitale A.; Tarsia M.; Caggiano V.; Nuzzolese R.; Parretti V.; Fabiani C.; Lopalco G.; Maier A.; Cattalini M.; Rigante D.; Govoni M.; Li Gobbi F.; Guiducci S.; Parronchi P.; Marino A.; Ciccia F.; Maggio M.C.; Aragona E.; Bartoloni E.; Iagnocco A.; Viapiana O.; Sebastiani G.D.; Guerriero S.; Insalaco A.; Del Giudice E.; Conti G.; Barone P.; Olivieri A.N.; Brucato A.; Carubbi F.; Triggianese P.; Mauro A.; Tosi G.M.; Fonollosa A.; Giardini H.A.M.; Ragab G.; Tharwat S.; Hernández-Rodríguez J.; Sfikakis P.P.; Laskari K.; Karamanakos A.; Espinosa G.; Shahram F.; Direskeneli H.; Hinojosa-Azaola A.; Opris-Belinski D.; AlMaghlouth I.A.; Hatemi G.; Eksin M.A.; Önen F.; Więsik-Szewczyk E.; Akkoç N.; Tufan A.; Şahin A.; Erten Ş.; Ozen S.; Batu E.D.; Frediani B.; Balistreri A.; Cantarini L.
    Introduction: This paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet’s disease (BD). Methods: The project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry. Results: Respondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet’s Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0–30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1–50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range – 1.8–4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p < 0.001), the presence of any major organ involvement (p < 0.031), the presence of gastro-intestinal (p < 0.001), neurological (p = 0.012) and musculoskeletal (p = 0.022) symptoms, recurrent fever (p = 0.002), and headache (p < 0.001) were associated to a higher number of accesses to the healthcare system. Multiple linear regression showed that the BDQoL score could significantly predict the global socioeconomic impact of BD (F = 14.519, OR 1.162 [CI 0.557–1.766], p < 0.001). Discussion: Preliminary results from the AIDA for Patients BD registry were consistent with data available in the literature, confirming that PROs and PREs could be easily provided by the patient remotely to integrate physician-driven registries with complementary and reliable information. Copyright © 2023 Gaggiano, Del Bianco, Sota, Gentileschi, Ruscitti, Giacomelli, Piga, Crisafulli, Monti, Emmi, De Paulis, Vitale, Tarsia, Caggiano, Nuzzolese, Parretti, Fabiani, Lopalco, Maier, Cattalini, Rigante, Govoni, Li Gobbi, Guiducci, Parronchi, Marino, Ciccia, Maggio, Aragona, Bartoloni, Iagnocco, Viapiana, Sebastiani, Guerriero, Insalaco, Del Giudice, Conti, Barone, Olivieri, Brucato, Carubbi, Triggianese, Mauro, Tosi, Fonollosa, Giardini, Ragab, Tharwat, Hernández-Rodríguez, Sfikakis, Laskari, Karamanakos, Espinosa, Shahram, Direskeneli, Hinojosa-Azaola, Opris-Belinski, AlMaghlouth, Hatemi, Eksin, Önen, Więsik-Szewczyk, Akkoç, Tufan, Şahin, Erten, Ozen, Batu, Frediani, Balistreri and Cantarini.
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    The impact of smoking on response to tumor necrosis factor-α inhibitor treatment in patients with ankylosing spondylitis
    (Turkiye Klinikleri, 2023) Yarkan Tuğsal H.; Kenar G.; Can G.; Çapar S.; Zengin B.; Akar S.; Dalkiliç E.; Şenel S.; Koca S.S.; Göker B.; Yazici A.; İnanç N.; Ellidokuz H.; Akkoç N.; Önen F.
    Background/aim: To investigate the impact of smoking on disease activity, treatment retention, and response in patients with ankylosing spondylitis (AS) treated with their first tumor necrosis factor-α inhibitor (TNFi). Materials and methods: AS patients who started their first TNFi treatment for the active axial disease (BASDAI ≥ 4) from TURKBIO Registry were included. Treatment response of smoker (current and ex-smokers) and nonsmoker (never smoker) patients were primarily evaluated as achievement of BASDAI50 or improvement in BASDAI at least 20 mm at 3 months and 6 months compared to baseline. Results: There were 322 patients with AS (60% male, 59% smoker, mean age: 38.3 years). The median follow-up time was 2.8 years (Q1– Q3: 1.3–3.8), and disease duration was 3.5 years (Q1–Q3: 0.7–8.2). Smokers had male predominance (p < 0.001), lower ESR (p = 0.03), higher BASDAI (p = 0.02), BASFI (p = 0.05), HAQ-AS (p = 0.007), and ASDAS-CRP (p = 0.04) compared with nonsmokers at baseline. In the multivariate analysis, male gender [OR 2.7 (95%CI 1.4–5), p = 0.002], and concomitant conventional synthetic disease-modifying antirheumatic drug use [OR 2.4 (95%CI 1.1–5.2), p = 0.03] were associated with better treatment response. There was an association of male gender [HR 2.4 (95%CI 1.6–3.7), p < 0.001], older age (≥30years) [HR 1.8 (95%CI 1.1–2.8), p = 0.01], and response to treatment [HR 1.8 (95%CI 1.2–2.9), p = 0.008] with better treatment retention. No impact of smoking status was found on treatment retention and response in univariate and multivariate analyses. Conclusion: This study suggested that smoking was associated with poorer patient-reported outcomes in biologic naïve AS patients initiating their first TNFi treatment, but it had no impact on the TNFi treatment response and retention rate. © TÜBİTAK.
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    Body mass index does not affect response of rituximab in patients with rheumatoid arthritis: results from the TURKBİO registry
    (Turkiye Klinikleri, 2023) Karataş A.; Pişkin Sağir R.; Koca S.S.; Dalkiliç E.; Can G.; Pehlivan Y.; Yazici A.; İnanç N.; Cefle A.; Ertürk Z.; Akar S.; Şenel S.; Birlik M.; Akkoç N.; Önen F.
    Background/aim: Adipose tissue produces several inflammatory mediators. Thus, obesity affects the disease course and the responses to the antirheumatic agents in inflammatory diseases. The aim of the study was to determine whether the body mass index (BMI) is involved in the response to rituximab in rheumatoid arthritis (RA). Materials and methods: This multicenter retrospective study included 206 RA patients who received rituximab from the Turkish Biologic (TURKBIO) registry between 2011 and the end of May 2017. Demographic and clinical data including age, sex, disease type, disease duration, and previous or current treatment with disease-modifying antirheumatic drugs (DMARDs) and biological drug durations are stored in the database. Patients with a BMI ≥30 kg/m2 were classified as obese, and patients with a BMI <30 kg/m2 were classified as nonobese. Kaplan-Meier survival analysis was performed to estimate the drug survival. The subgroups were compared using the log-rank test. Results: The mean BMI of 206 patients included in the study was 27.05 (17.2–43.4) kg/m2. There were 59 (28.6%) patients in the obese group and 147 (71.4%) patients in the nonobese group. The mean age, female percentage, and baseline disease activity score 28 (DAS28) were higher in the obese group than in the nonobese group. However, the ΔDAS28 at both 6 and 12 months were not significantly different between the groups (p = 0.785 and p = 0.512, respectively). Patient pain Visual Analogue Scale (VAS), patient fatigue VAS, and patient global VAS scores were also significantly higher at baseline in the obese group (p = 0.003, p = 0.006, and p = 0.006, respectively). However, no significant difference was found in terms of changes in patient pain VAS, patient fatigue VAS, patient global VAS and physician global VAS scores at 6 and 12 months compared to those at baseline. Rituximab treatment was ongoing for 71.2% of the obese and 63.3% of the nonobese patients (p = 0.279). The median drug survival duration was 77 months in the obese group and 62 months in the nonobese group (p = 0.053). The estimated drug survival rates for rituximab were not statistically significantly different in the obese and nonobese groups. Rituximab-related side effects were also similar between the groups. Conclusion: In obese and nonobese patients with RA, rituximab treatment exhibits similar side effects and similar long-term efficacy. These results suggest that obesity does not alter drug survival for rituximab and response rates, in RA and rituximab may be a favorable treatment agent in patients with RA and obesity. © TÜBİTAK.
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    Biological treatment in elderly and young patients with ankylosing spondylitis: TURKBIO real-life data results
    (Turkish League Against Rheumatism (TLAR), 2024) Uslu S.; Gülle S.; Urak Ö.; Şen G.; Dalkılıç E.; Şenel S.; Akar S.; İnanç N.; Cefle A.; Avşar A.K.; Yolbaş S.; Yılmaz S.; Gündüz Ö.S.; Sarı İ.; Birlik M.; Akkoç N.; Önen F.
    Objectives: This study aims to investigate the effect of age on disease activity and biological treatment in patients with ankylosing spondylitis (AS). Patients and methods: A total of 811 AS patients registered in the TURKBIO registry database between 2011 and 2019 were categorized according to their age at the time of entry into the registry and assigned to one of two groups: young patients, defined as <60 years of age (n=610), and those aged ≥60 years (n=201) were recorded as elderly patients. Demographic, clinical, and laboratory characteristics, along with disease activity markers and other follow-up parameters, as well as current and prior treatments, were electronically recorded during each visit using open-source software. Results: The mean age of the elderly patients was 67±5.8 years, while the mean age of the younger patients was 49.2±10.9 years. Male predominance was lower in the older AS group compared to the younger AS group (p=0.002). During follow-up period, 397 patients (comprising 318 young and 79 elderly individuals) had a history of using at least one biological disease-modifying agent (bDMARD). There was no significant difference between the groups in terms of DMARD and bDMARD-use distributions. First tumor necrosis factor inhibitor (TNFi) retention rates were found to be similar in both groups over 10 years of follow-up. Adverse events were found to be similar in young (19.9%) and elderly (26.8%) AS patients. Conclusion: Research in the TURKBIO cohort reveals that both older and younger patients with AS exhibited similar disease activity levels with comparable treatment approaches. Moreover, the results of TNFi treatments in elderly patients were the same as those observed in younger patients, with no notable increase in safety concerns. © 2024, Turkish League Against Rheumatism (TLAR). All rights reserved.
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    Influence of gender on Behçet's disease phenotype and irreversible organ damage: Data from the International AIDA Network Behçet's Disease Registry
    (Elsevier Masson s.r.l., 2025) Sota J.; Ragab G.; AlMaglouth I.; Lopalco G.; Tufan A.; Direskeneli H.; Hinojosa-Azaola A.; Mayrink Giardini H.A.; Guerriero S.; Triggianese P.; Sfikakis P.P.; Piga M.; Ruscitti P.; Govoni M.; Iagnocco A.; Carubbi F.; Hernández-Rodríguez J.; Laymouna A.H.; Mahmoud A.A.-M.A.; Ghanema M.; Aboabat A.A.; Asfina K.N.; Alanazi F.; Morrone M.; Spedicato V.; Kucuk H.; Kardas R.; Alibaz Öner F.; Sevik G.; Torres-Ruiz J.; Kawakami-Campos P.A.; Parente de Brito Antonelli I.; Dammacco R.; Chimenti M.S.; Arida K.; Floris A.; Gentile M.; Ruffilli F.; Bellis E.; Alunno A.; Espinosa G.; Gentileschi S.; Gaggiano C.; Vitale A.; Caggiano V.; Lopez R.; Tarsia M.; Monti S.; Hatemi G.; Karakoç A.; Frassi M.; Giacomelli R.; Tharwat S.; Thabet M.; Ciccia F.; Emmi G.; Viapiana O.; Şahin A.; Sebastiani G.D.; Batu E.D.; Ozen S.; Sener S.; Opris-Belinski D.; Costi S.; Conforti A.; Cattalini M.; Bartoloni E.; Akkoç N.; Gunduz O.S.; Conti G.; Maier A.; Giardina A.; Li Gobbi F.; Parronchi P.; Sarzi Puttini P.; Breda L.; De Paulis A.; Carreño E.; La Torre F.; Więsik-Scewczyk E.; de-la Torre A.; Mejía-Salgado G.; Shahram F.; Guiducci S.; Maggio M.C.; Aragona E.; Rigante D.; Ciavarro A.; Önen F.; Erten; Insalaco A.; Del Giudice E.; Barone P.; Gicchino F.; Brucato A.; Lo Gullo A.; Mauro A.; Karamanakos A.; Balistreri A.; Mazzei M.A.; Frediani B.; Fabiani C.; Cantarini L.
    Objectives: Gender impact on phenotypical expression of Behçet's disease (BD) has been specifically investigated only in a few large-scale studies. The main goal of the study was to examine gender differences in a large cohort of patients affected by BD. Methods: Data were retrieved from the International AIDA Network Registry for BD. We assessed differences between males and females in terms of Behçet's syndrome Overall Damage Index (BODI), differences in the disease manifestations at onset and in the cumulative manifestations throughout disease course, as well as differences in the cardiovascular risk. Finally, predictive factors leading to major organ involvement were investigated. Results: In total, 1024 BD patients (567 males, 457 females) were enrolled in the study, with a male-to-female ratio of 1.24/1. Males displayed a significantly higher mean ± SD BODI (1.92 ± 2.09) at the last follow-up, compared to female patients (1.25 ± 1.87) (P < 0.0001). Uveitis (P < 0.0001) and vascular involvement (P = 0.0076) were significantly more frequent among males whereas female patients were significantly over-represented in arthralgia (P < 0.0001), arthritis (P = 0.00025), isolated headache (P < 0.0001), central nervous system (CNS) involvement (P = 0.040), and gastrointestinal involvement (P = 0.00046). Regarding cardiovascular risk, no differences between the two groups emerged (P = 0.617). Four variables were associated with the development of major organ involvement: male gender (OR = 2.104, P = 0.001), current treatment with biologic agents (OR = 2.257, P = 0.0003), origin from endemic countries (OR = 2.661, P = 0.0009), and disease duration (OR = 1.002, P = 0.024). Conclusion: BD displays a more severe course among males. This subgroup develops more irreversible damage and presents more frequently ocular and vascular involvement during disease course. On the other hand, female patients are prone to experience articular involvement, headache, CNS and gastrointestinal involvement. These data suggest the existence of a gender-driven disease expression. © 2024 The Author(s)