Browsing by Author "Pehlivan, Y"

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    A real-life analysis of patients with rheumatologic diseases on biological treatments: Data from TURKBIO Registry
    Önen, F; Can, G; Çapar, S; Dalkiliç, E; Pehlivan, Y; Senel, S; Akar, S; Koca, SS; Tufan, A; Yazici, A; Yilmaz, S; Inanç, N; Sari, I; Birlik, M; Solmaz, D; Cefle, A; Öztürk, MA; Yolbas, S; Krogh, NS; Yilmaz, N; Erten, S; Bes, C; Gündüz, ÖS; Göker, B; Haznedaroglu, S; Yavuz, S; Çetin, GY; Yildiz, F; Direskeneli, H; Akkoç, N
    Objective: TURKBIO registry, established in 2011, is the first nationwide biological database in Turkey. This study aimed to provide an overview of TURKBIO data collected by June 2018. Methods: The registry included adult patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis (nr-AxSpA), and psoriatic arthritis (PsA). Demographic and clinical features, disease activity markers, and other follow-up parameters, current and previous treatments, and adverse events were registered electronically at each visit using open-source software. The registration of patient-reported outcome measures was carried out electronically by the patients using touch screens. Results: TURKBIO registry included a total of 41,145 treatment series with biologicals. There were 2,588 patients with axSpA (2,459 AS and 129 nr-axSpA), 2,036 with RA, and 428 with PsA. The total number of patients, including those with other diagnoses, was 5,718. In the follow-up period, the number of patients and also visits steadily increased by years. The yearly mean number of visits per patient was found to be 2.3. Significant improvements in disease activity and health assessment parameters were observed following the biological treatments. Biologics were often given in combination with a conventional synthetic disease-modifying antirheumatic drug in patients with RA. Infections were the most commonly seen adverse events, followed by allergic reactions. Tuberculosis was observed in 12 patients, malignancy in 18, and treatment-related mortality in 31. Conclusion: TURKBIO provided a valuable real-life experience with the use of biologics in rheumatic diseases in Turkey.
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    UNINTENTIONAL MONOTHERAPY IN RHEUMATOID ARTHRITIS PATIENTS RECEIVING TOFACITINIB AND DRUG SURVIVAL RATE OF TOFACITINIB
    Inanc, N; Abacar, K; Ozturk, MA; Tufan, A; Karadeniz, H; Sari, I; Can, G; Erez, Y; Pehlivan, Y; Dalkiliç, E; Ocak, T; Cefle, A; Yazici, A; Senel, A; Akar, S; Ediboglu, ED; Koca, SS; Sagir, RP; Yilmaz, S; Gulcemal, S; Gündüz, ÖS; Basibüyük, CS; Alkan, S; Cesur, TY; Onen, F
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    A national, multicenter, secondary data use study evaluating efficacy and retention of first-line biologic treatment with tocilizumab in patients with rheumatoid arthritis in real-life setting: results from TURKBIO registry
    Yazici, A; Isik, ÖÖ; Dalkiliç, E; Koca, SS; Pehlivan, Y; Senel, S; Inanc, N; Akar, S; Yilmaz, S; Gündüz, ÖS; Cefle, A; Karakas, ÖF; Onen, F
    Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody that targets the IL-6 receptor. TCZ found to be efficacious and has a good tolerated safety profile in rheumatoid arthritis (RA) patients. The aim of this study was to describe the disease activity and retention rate in Turkish RA patients who were prescribed TCZ as first-line biologic treatment in a real-world setting. Secondary data obtained from adult RA patients' files was used in a multicenter and retrospective context. Clinical Disease Activity Index (CDAI), Disease Activity Score in 28 joints with ESR (DAS28-ESR), and retention rates of TCZ were evaluated at related time points. 130 patients (87.7% female) with a mean age of 53 years (SD; 15.0) were included in the study. Mean RA duration was 14 years and median duration of follow-up was 18.5 months. Number of patients with ongoing TCZ treatment at 6, 12, and 24 months were 121 (93%), 85 (65%), and 46 (35%), respectively. Remission rates at 6, 12, and 24 months per CDAI (<2.8) and DAS28-ESR (<2.6) scores were 61.5, 44.6, 30%, and 54.6, 40.8, 27.7%, respectively. Both CDAI and DAS28-ESR scores significantly improved at 6, 12 and 24 months (p<0.001 for both). At 24 months, 23 patients (17.6%) discontinued TCZ, of whom majority (17/23) were due to unsatisfactory response. Retention rates of TCZ at 6, 12, and 24 months were 93, 84.3, and 72.2%, respectively. In this real-world study, TCZ as a first-line biologic therapy was found to be efficacious and showing high retention rates. These real-world study results are in line with previous randomized studies.
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    DISEASE DURATION AND HLA-B27 POSITIVITY ALTER LONGTERM RETENTION RATE OF CERTOLIZUMAB PEGOL IN PATIENTS WITH PSORIATIC ARTHRITIS
    Koca, SS; Pehlivan, Y; Akar, S; Senel, S; Karadeniz, H; Sosyal, O; Yazici, A; Yilmaz, S; Sagir, RP; Inanc, N; Karatas, A; Cetin, GY; Onen, F
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    INCIDENCE OF ANTERIOR UVEITIS IN AXIAL SPONDYLOARTHRITIS DURING SECUKINUMAB TREATMENT: TWO YEARS REAL LIFE EXPERIENCE FROM TURKBIO REGISTRY
    Akleylek, C; Akar, S; Cinakli, H; Sagir, RP; Coskun, BN; Karakas, A; Apaydin, H; Kardas, RC; Isik, OO; Hakbilen, S; Okyar, B; Sosyal, O; Koca, SS; Pehlivan, Y; Dalkiliç, E; Can, G; Sari, I; Birlik, M; Onen, F; Erten, S; Ozturk, MA; Yazici, A; Cefle, A; Yilmaz, S; Cetin, GY; Akkoc, N; Yilmaz, N
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    LONGTERM RETENTION RATE OF CERTOLIZUMAB PEGOL IN AXIAL SPONDYLOARTHRITIS IS HIGHER: DATA FROM TURKBIO
    Koca, SS; Pehlivan, Y; Akar, S; Senel, S; Guler, AA; Sosyal, O; Yazici, A; Yilmaz, S; Sagir, RP; Inanc, N; Karatas, A; Cetin, GY; Atagündüz, P; Onen, F
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    Body mass index does not affect response of rituximab in patients with rheumatoid arthritis: results from the TURKBİO registry
    Karatas, A; Piskin Sagir, R; Koca, SS; Dalkiliç, E; Can, G; Pehlivan, Y; Yazici, A; Inanç, N; Cefle, A; Ertürk, Z; Akar, S; Senel, 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 databse. Patients with a BMI >= 30 kg/m(2) were classified as obese, and patients with a BMI <30 kg/m(2) 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/m(2). 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 Delta DAS28 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.
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    LONG-TERM SURVIVAL OF THE FIRST BIOLOGIC TREATMENT IN PSORIATIC ARTHRITIS AND THE EFFECT OF THE SELECTED TREATMENT ON DRUG SURVIVAL; TURKBIO REGISTRY
    Kocaer, SB; Inel, TY; Erez, Y; Avsar, AK; Uslu, S; Karakas, A; Gulle, S; Can, G; Sari, I; Birlik, M; Dalkiliç, E; Pehlivan, Y; Akar, S; Cefle, A; Öztürk, MA; Yolbas, S; Yilmaz, N; Erten, S; Akkoc, N; Onen, 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
    Li, ZX; Akar, S; Yarkan, H; Lee, SK; Çetin, P; Can, G; Kenar, G; Çapa, F; Pamuk, ON; Pehlivan, Y; Cremin, K; De Guzman, E; Harris, J; Wheeler, L; Jamshidi, A; Vojdanian, M; Farhadi, E; Ahmadzadeh, N; Yüce, Z; Dalkiliç, E; Solmaz, D; Akin, B; Dönmez, S; Sari, I; Leo, PJ; Kenna, TJ; Önen, F; Mahmoudi, M; Brown, MA; 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-1, 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 = 7.63x10(-12)), Iranian cohort (OR = 2.9, P = 0.042), and combined dataset (OR = 5.1, P = 1.65x10(-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 = 8.93x10(-15)), but also positive in HLA-B27-positive cases (OR = 4.3, P = 7.69x10(-8)). Serum IL-1, IL-17 and IL-23 levels were higher in AS cases than controls. Among AS cases, serum IL-1 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-1 function. As IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy. Author summary Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis. To identify new genetic associations with AS, we performed genome-wide association studies in Turkish and Iranian AS patients and controls. We identified a novel rare coding MEFV variant associated with AS. Rare polymorphisms of MEFV, which encodes the protein pyrin, are known to cause Familial Mediterranean Fever (FMF), a monogenic, autosomal recessive, autoinflammatory disease which can be complicated by arthritis. 99.6% of Turkish AS cases, and 96% of those carrying the MEFV variant, did not have FMF, and the association with AS remains excluding cases with FMF. In Turkish subjects, the MEFV variant association was particularly strong in HLA-B27-negative cases, but also positive in HLA-B27-positive cases. This represents the first rare variant association with AS, and has the highest odds ratio for AS of any non-MHC reported hitherto, indicating a major effect on disease pathogenesis. We assessed serum cytokine levels in the cohort, and found that IL-1, IL-17 and IL-23 levels were higher in AS cases. Furthermore, among AS cases, IL-1 and IL-23 levels were increased in MEFV variant carriers compared with non-carriers. This study has therapeutic implications; as IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy.
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    Does obesity affect treatment response to secukinumab and survival in ankylosing spondylitis? Real-life data from the TURKBIO Registry
    Karakas, A; Gulle, S; Can, G; Dalkilic, E; Akar, S; Koca, SS; Pehlivan, Y; Senel, S; Tufan, A; Ozturk, MA; Yilmaz, S; Yazici, A; Cefle, A; Inel, TY; Erez, Y; Sari, I; Birlik, M; Direskeneli, H; Akkoc, N; Onen, F
    Objectives The aim of this study was to evaluate the impact of obesity on the treatment response to secukinumab and drug survival rate in patients with ankylosing spondylitis (AS). Methods We performed an observational cohort study that included AS patients based on the biological drug database in Turkey (TURKBIO) Registry between 2018 and 2021. The patients were divided into three groups: normal [body mass index (BMI) < 25 kg/m(2)], overweight (BMI: 25-30 kg/m(2)), and obese (BMI & GE; 30 kg/m(2)). Disease activity was evaluated at baseline, 3, 6, and 12 months. Drug retention rates at 12 months were also investigated. Results There were 166 AS patients using secukinumab (56.6% male, mean age: 44.9 & PLUSMN; 11.6 years). The median follow-up time was 17.2 (3-33.2) months. Forty-eight (28.9%) patients were obese. The mean age was higher in the obese group than in others (P = .003). There was no statistically significant difference in Bath Ankylosing Spondylitis Disease Activity Index 50, Assessment of SpondyloArthritis international Society 20 (ASAS20), ASAS40, Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity, and ASDAS clinically important improvement responses between the three groups at 3, 6, and 12 months, although they were numerically lower in obese patients. Drug retention rates at 12 months were similar in all groups (P > .05). Conclusions This study suggested that obesity did not affect secukinumab treatment response and drug retention in AS patients.
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    Unintentional Monotherapy in Rheumatoid Arthritis Patients Receiving Tofacitinib and Drug Survival Rate of Tofacitinib
    Inanc, N; Abacar, KY; Ozturk, MA; Tufan, A; Karadeniz, H; Sari, I; Can, G; Erez, Y; Pehlivan, Y; Dalkilic, HE; Ocak, T; Cefle, A; Yazici, A; Senel, AS; Akar, S; Durak-Ediboglu, E; Koca, SS; Piskin-Sagir, R; Yilmaz, S; Gulcemal, S; Soysal-Gunduz, O; Basibuyuk, CS; Alkan, S; Cesur, TY; Onen, F
    ObjectiveTo determine the rate of unintentional monotherapy (UM; switching to monotherapy from combination therapy of patients' own volition) in rheumatoid arthritis patients receiving tofacitinib and to evaluate tofacitinib survival rate.MethodsThis national, multicenter study included patients' data from the TURKBIO Registry. Demographics, clinical characteristics, disease duration and activity, comorbidities, and treatments were analyzed.ResultsData of 231 rheumatoid arthritis patients (84.8% female, median age, 56 years) were included; 153 were initially prescribed combination therapy and continued to their therapies; 31 were initially prescribed combination therapy but switched to monotherapy on their own volition (UM); 21 were initially prescribed monotherapy and switched to combination therapy; 26 were initially prescribed monotherapy and continued to their therapies. The rate of comorbidities at the time of data retrieval was higher in the UM group than in the combination group (83.3% vs. 60.3%, p = 0.031). Presence of comorbidities was a significant factor affecting switching to monotherapy (p = 0.039; odds ratio, 3.29; 95% confidence interval, 1.06-10.18). The combination and UM groups did not differ regarding remission rate assessed by Disease Activity Score 28-joint count C-reactive protein (60.5% and 70%, respectively; p = 0.328). Drug survival rates of the UM and combination groups did not differ. The median drug survival duration of tofacitinib was 27+ months with 1- and 4-year drug survival rates of 89.6% and 60.2%, respectively, in the UM group.ConclusionsAlthough 13.4% of the study population started monotherapy unintentionally, drug survival and remission rates of the UM and combination groups were not different. Comorbidity was a factor affecting transition from combination therapy to monotherapy.
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    DO COMORBIDITIES IMPACT PERSISTENCE OF FIRST TUMOR NECROSIS FACTOR INHIBITOR TREATMENT IN RHEUMATOID ARTHRITIS? DATA FROM TURKBIO
    Inel, TY; Kocaer, SB; Erez, Y; Gulle, S; Karakas, A; Avsar, AK; Uslu, S; Can, G; Sari, I; Birlik, M; Dalkiliç, E; Pehlivan, Y; Akar, S; Goker, B; Cetin, GY; Haznedaroglu, S; Yavuz, S; Pirildar, T; Direskeneli, H; Akkoc, N; Onen, F
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    DO COMORBIDITIES DECREASE THE FIRST TNF-INHIBITOR RETENTION AND TREATMENT RESPONSE IN AXIAL SPONDYLOARTHRITIS PATIENTS? DATA FROM TURKBIO
    Erez, Y; Karakas, A; Kocaer, SB; Inel, TY; Gulle, S; Avsar, AK; Uslu, S; Can, G; Sari, I; Birlik, M; Dalkiliç, E; Pehlivan, Y; Senel, S; Akar, S; Koca, SS; Tufan, A; Yazici, A; Yilmaz, S; Inanc, N; Solmaz, D; Akkoc, N; Onen, F