Anti-tnf tedavisi alan olgularda uygulama öncesi ve sonrasında serum inflamasyon belirteçlerinin seyrinin değerlendirilmesi
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Dosyalar
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Tümör nekroz faktörü (TNF) çoğunluğu makrofajlar tarafından üretilen, geniş sitokin ailesinin bir üyesidir. Farklı sitokinler farklı mesajlar iletir ancak sitokinler bağışıklık, inflamasyon, hücre büyümesi, hücre göçü, fibrozis, vaskülarizasyon dahil olmak üzere birçok önemli biyolojik süreçte kilit rol alır. Dolayısıyla bu kadar önemli görevleri olan sitokin ailesinin birçok hastalıkta da tedavi anlamında önemli görevleri bulunmaktadır.
Anti-TNF tedaviler çeşitli inflamatuvar hastalıklarda genellikle birinci sıra tedavilerden yarar görmeyen hastalarda kullanılmaktadır. Anti-TNF tedavinin başlıca kullanıldığı inflamatuvar hastalıklar Romatoid Artrit (RA), Ankilozan Spondilit (AS), İnflamatuvar Bağırsak Hastalıkları (İBH) ve Psöriatik Artrit (PSA)’tir. Şu anda onaylanmış beş anti-TNF ilaç bulunmaktadır: İnfliximab, Etanercept, Adalimumab, Golimumab ve Sertolizumab.
Akut veya kronik inflamasyonda kullanılan bazı inflamatuvar belirteçler vardır. Nötrofil-lenfosit oranı (NLR), trombosit-lenfosit oranı (PLR), sistemik immün inflamasyon indeksi (SII) ve CRP/albümin oranı (CAR) gibi çeşitli immün inflamatuvar temelli indeksler gösterilmiştir. Yapılan son çalışmalar bu biyobelirteçleri inflamasyonu belirlemek, tedavi yanıtını değerlendirmek, hastalık aktivitesini değerlendirmek için potansiyel birer belirteç olarak tanımlamaktadır.
Günümüzde hem romatolojik hem de İBH hastalarında anti-TNF tedavinin etkinliğini net olarak değerlendirebilecek spesifik bir belirteç yoktur. Bu çalışmada anti-TNF alan hastalarda uygulama öncesi ve sonrasında serum inflamasyon belirteçlerinin seyrinin değerlendirilmesiyle tedavi yanıtını ve/veya yanıt yetersizliğini öngörebilmeyi amaçladık.
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Çalışmaya, Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi Hastanesi İç Hastalıkları Anabilim Dalı Ayaktan Tedavi Ünitesine 10/2021 – 09/2022 tarihleri arasında anti-TNF-α tedavisi almak için başvuran 80 gönüllü hasta dahil edilmiştir. Çalışmaya dahil edilen hastalar Romatoloji ve Gastroenteroloji kliniklerinde takipli, en az 3 aydır anti-TNF-α tedavisi almakta olan ve remisyonda takip edilen hastalardan seçilmiştir. Çalışma prospektif yapılmıştır. Hastaların sosyodemografik ve karakteristik özellikleri hastane otomasyon sisteminden geriye dönük incelenmiştir. Hastalara ait kaynaklardan tanı konulma anındaki yaş (yıl), cinsiyet, hastalığın tanısı, hastalık süresi (ay), fistül ve/veya perianal apse varlığı (İBH hastalarında), anti-TNF-α kullanım sıklığı (hafta), anti-TNF-α kullanım süresi (ay), anti-TNF-α değişikliği, anti-TNF-α advers etki, steroid bağımlılığı, steroid direnci, ek hastalık varlığı ve İBH nedeni ile cerrahi tedavi öyküsü kaydedilmiştir. Hastalar kendi tedavi periyotlarına göre tedavilerini 8 haftalık, 4 haftalık, 2 haftalık ve 1 haftalık aralıklarla almıştır. 0. gün tedavi öncesi, 1. gün tedavi başı, 7. 14. ve 28. günler tedavi ortası olarak değerlendirilmiştir. Serum örneklerinin sonuçlarına göre NLR, PLR, SII ve CAR değerleri çalışmaya dahil edilmiştir.
Hastaların %20’si (n=16) İBH hasta grubunu oluştururken hastaların %80’i (n=64) İBH dışı hasta grubunu oluşturmuştur. İBH hasta grubunun yaş ortalaması 38,25 (±15,04) iken İBH dışı hasta grubunun ise 44,78 (±11,90) saptanmıştır. İBH grubunda hastaların %43,8’i (n=7) ADA, %37,5’i (n=6) İFX ve %18,8’i (n=3) Vedolizumab, İBH dışı grubun %37,5’i (n=24) İFX, %18,8’i (n=12) CZP, %15,6’sı (n=10) ETA, %15,6’sı (n=10) GOL ve %12,5’i (n=8) ADA kullanmıştır.
Çalışmada, İBH grubunda yer alan hastaların anti-TNF tedavi döngülerinin başında NLR ve SII’da anlamlı azalmalar tespit edilmiştir. İBH dışı grupta tedavinin başında NLR ve PLR’de anlamlı azalmalar tespit edilmiş ve tedavi ortasına gelindiğinde NLR ve PLR’de anlamlı azalmaların devam ettiği, SII ve CAR’da da bu dönemde anlamlı azalmaların görüldüğü tespit edilmiştir. Hasta gruplarının anti-TNF ajanlara göre biyobelirteçlerinin değerlendirilmesinde özellikle İFX tedavisi sonrası anlamlı sonuçlar tespit edilmiştir. İBH grubunda yer alan hastaların anti-TNF tedavi döngülerinin başında NLR, PLR ve SII’da anlamlı azalmalar tespit edilmiştir. Tedavinin ortasında ise PLR ve SII’da anlamlı azalmaların devam ettiği tespit edilmiştir. İBH dışı grupta ise tedavinin başında PLR ve CAR’da anlamlı azalmalar tespit edilmiştir ve İFX tedavisini 8 haftada bir alan hastalarda tedavinin ortalarına gelindiğinde PLR’de anlamlı artışlar görülmüştür.
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Sonuç olarak hem İBH hem İBH dışı hasta gruplarında anti-TNF tedavilerin sonrasında tedavi yanıtının değerlendirilmesinde NLR ve SII’ın ortak olarak kullanılabileceği, PLR ve CAR’ın daha çok İBH dışı grup hastalarda anlamlı değerlendirmelerde kullanılabileceği tespit edilmiştir. Özellikle PLR’nin İBH dışı grupta tedavi başı ve ortasında tedavinin sürdürülmesi, ek ajanlara geçilmesi, tedavi sıklığının artırılması gibi değerlendirmelerde daha etkin kullanılabileceği tespit edilmiştir. İBH dışı grupta IFX tedavisi alan hastalarda PLR’nin tedavi ortasında artması, yoğunlaştırılmış anti-TNF tedavinin hastalıkların remisyonunda daha faydalı olabileceğini akla getirmektedir. Özellikle GOL tedavisi alan hastalarda tedavi sonrası yanıtın, tedavinin ortasında anlamlılık kazanması GOL tedavisinin etkinliğinin tedavinin ortalarına doğru ortaya çıktığını düşündürmektedir. Biyobelirteçlerin anti-TNF tedavi yanıt ve takibi bakımından klinik pratikte kullanımını öngörebilmek için yüksek volümlü hasta sayıları içeren daha ileri çalışmaların yapılması gerekmektedir ancak mevcut çalışmamızın da ileri çalışmalara referans olabilecek sonuçları olduğu görülmektedir.
Tumor necrosis factor (TNF) is a member of the large family of cytokines, mostly produced by macrophages. Different cytokines convey different messages, but cytokines play a key role in many important biological processes, including immunity, inflammation, cell growth, cell migration, fibrosis, vascularization. Therefore, the cytokine family has important duties in terms of treatment in many diseases. Anti-TNF therapies are used in various inflammatory diseases, usually in patients who does not benefit from the first-line treatments. Inflammatory diseases in which anti-TNF therapy is mainly used are Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Inflammatory Bowel Diseases (IBD) and Psoriatic Arthritis (PSA). There are currently five approved anti-TNF drugs: Infliximab, Etanercept, Adalimumab, Golimumab, and Sertolizumab. There are some inflammatory markers used in acute or chronic inflammation. Various immune-inflammatory-based indices have been demonstrated, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and CRP/viiespons ratio (CAR). Recent studies define these biomarkers as potential markers for determining inflammation, evaluating treatment viiesponse, and evaluating disease activity. Currently, there is no specific marker that can clearly evaluate the effectiveness of anti-TNF therapy in both rheumatologic and IBD patients. In this study, we aimed to predict the treatment response and/or lack of response by evaluating the course of serum inflammation markers before and after administration in patients receiving anti-TNF. viii Eighty volunteer patients who applied to Necmettin Erbakan University Meram Medical Faculty Hospital, Department of Internal Medicine, Outpatient Treatment Unit between 10/2021 and 09/2022 for anti-TNF-α treatment were included in the study. The patients were selected from who were followed up in Rheumatology and Gastroenterology Clinics, were receiving anti-TNF-α therapy for at least 3 months, and were followed up in remission. The study was conducted prospectively. Sociodemographic and characteristic features of the patients were analyzed retrospectively from the hospital automation system. Age at diagnosis (years), gender, diagnosis of disease, duration of disease (months), presence of fistula and/or perianal abscess (in IBD patients), frequency of use of anti-TNF-α (weeks), use of anti-TNF-α from patient sources Duration (months), anti-TNF-α change, anti-TNF-α adverse effects, steroid dependence, steroid refractoriness, presence of comorbid disease, and history of surgical treatment for IBD were recorded. Patients received treatments at 8-week, 4-week, 2-week and 1-week intervals according to their own treatment periods. Day 0 was evaluated as pre-treatment, day 1 as beginning of treatment, and days 7, 14 and 28 as mid-treatment. By the help of serum samples, NLR, PLR, SII and CAR values were calculated. While 20% (n=16) of the patients constituted the IBD patient group, 80% (n=64) of the patients constituted the non-IBD patient group. The mean age of the IBD patient group was 38.25 (±15.04), and the non-IBD patient group was 44.78 (±11.90). In the IBD group, 43.8% (n=7) of the patients had ADA, 37.5% (n=6) IFX, and 18.8% (n=3) Vedolizumab. In the non-IBD group, 37.5% (n=24) had IFX, 18.8% (n=12) CZP, 15.6% (n=10) ETA, 15.6% (n) =10) GOL and 12.5% (n=8) had ADA. Significant decreases in NLR and SII were detected at the beginning of the anti-TNF treatment cycles of the patients included in the study and in the IBD group. Significant decreases were observed in NLR and PLR at the beginning of the treatment in the non-IBD group, and significant decreases were observed in NLR and PLR by the middle of the treatment, and significant decreases were observed in SII and CAR in this period. In the evaluation of biomarkers of the patient groups participating in the study according to anti-TNF agents, significant results were found especially after IFX treatment. Significant reductions in NLR, PLR and SII were detected at the beginning of the anti-TNF treatment cycles of patients in the IBD group. In the middle of the treatment, significant decreases in PLR and SII continued. In the non-IBD group, significant decreases in PLR and CAR were detected at the beginning of ix treatment, and significant increases in PLR were observed by mid-treatment in patients who received IFX treatment every 8 weeks. As a result, it has been determined that NLR and SII can be used jointly in the evaluation of treatment response after anti-TNF treatments in both IBD and non-IBD patient groups, and PLR and CAR can be used in meaningful evaluations mostly in non-IBD patients. It has been determined that PLR can be used in more accurate evaluations in the non-IBD group, such as maintaining the treatment at the beginning and mid-treatment, switching to additional agents, and increasing the frequency of treatment. The increase in PLR mid-treatment in patients receiving IFX therapy in the non-IBD group suggests that intensified anti-TNF therapy may be more beneficial in remission of the disease. The fact that the post-treatment response became significant in the middle of the treatment, especially in patients who received GOL treatment, suggests that the effectiveness of GOL treatment emerges towards the middle of the treatment. In order to predict the use of biomarkers in clinical practice in terms of anti-TNF treatment response and follow-up, further studies with high-volume patient numbers are required, but it can be postulated that our current study has results in terms of being as a reference for further studies.
Tumor necrosis factor (TNF) is a member of the large family of cytokines, mostly produced by macrophages. Different cytokines convey different messages, but cytokines play a key role in many important biological processes, including immunity, inflammation, cell growth, cell migration, fibrosis, vascularization. Therefore, the cytokine family has important duties in terms of treatment in many diseases. Anti-TNF therapies are used in various inflammatory diseases, usually in patients who does not benefit from the first-line treatments. Inflammatory diseases in which anti-TNF therapy is mainly used are Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Inflammatory Bowel Diseases (IBD) and Psoriatic Arthritis (PSA). There are currently five approved anti-TNF drugs: Infliximab, Etanercept, Adalimumab, Golimumab, and Sertolizumab. There are some inflammatory markers used in acute or chronic inflammation. Various immune-inflammatory-based indices have been demonstrated, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and CRP/viiespons ratio (CAR). Recent studies define these biomarkers as potential markers for determining inflammation, evaluating treatment viiesponse, and evaluating disease activity. Currently, there is no specific marker that can clearly evaluate the effectiveness of anti-TNF therapy in both rheumatologic and IBD patients. In this study, we aimed to predict the treatment response and/or lack of response by evaluating the course of serum inflammation markers before and after administration in patients receiving anti-TNF. viii Eighty volunteer patients who applied to Necmettin Erbakan University Meram Medical Faculty Hospital, Department of Internal Medicine, Outpatient Treatment Unit between 10/2021 and 09/2022 for anti-TNF-α treatment were included in the study. The patients were selected from who were followed up in Rheumatology and Gastroenterology Clinics, were receiving anti-TNF-α therapy for at least 3 months, and were followed up in remission. The study was conducted prospectively. Sociodemographic and characteristic features of the patients were analyzed retrospectively from the hospital automation system. Age at diagnosis (years), gender, diagnosis of disease, duration of disease (months), presence of fistula and/or perianal abscess (in IBD patients), frequency of use of anti-TNF-α (weeks), use of anti-TNF-α from patient sources Duration (months), anti-TNF-α change, anti-TNF-α adverse effects, steroid dependence, steroid refractoriness, presence of comorbid disease, and history of surgical treatment for IBD were recorded. Patients received treatments at 8-week, 4-week, 2-week and 1-week intervals according to their own treatment periods. Day 0 was evaluated as pre-treatment, day 1 as beginning of treatment, and days 7, 14 and 28 as mid-treatment. By the help of serum samples, NLR, PLR, SII and CAR values were calculated. While 20% (n=16) of the patients constituted the IBD patient group, 80% (n=64) of the patients constituted the non-IBD patient group. The mean age of the IBD patient group was 38.25 (±15.04), and the non-IBD patient group was 44.78 (±11.90). In the IBD group, 43.8% (n=7) of the patients had ADA, 37.5% (n=6) IFX, and 18.8% (n=3) Vedolizumab. In the non-IBD group, 37.5% (n=24) had IFX, 18.8% (n=12) CZP, 15.6% (n=10) ETA, 15.6% (n) =10) GOL and 12.5% (n=8) had ADA. Significant decreases in NLR and SII were detected at the beginning of the anti-TNF treatment cycles of the patients included in the study and in the IBD group. Significant decreases were observed in NLR and PLR at the beginning of the treatment in the non-IBD group, and significant decreases were observed in NLR and PLR by the middle of the treatment, and significant decreases were observed in SII and CAR in this period. In the evaluation of biomarkers of the patient groups participating in the study according to anti-TNF agents, significant results were found especially after IFX treatment. Significant reductions in NLR, PLR and SII were detected at the beginning of the anti-TNF treatment cycles of patients in the IBD group. In the middle of the treatment, significant decreases in PLR and SII continued. In the non-IBD group, significant decreases in PLR and CAR were detected at the beginning of ix treatment, and significant increases in PLR were observed by mid-treatment in patients who received IFX treatment every 8 weeks. As a result, it has been determined that NLR and SII can be used jointly in the evaluation of treatment response after anti-TNF treatments in both IBD and non-IBD patient groups, and PLR and CAR can be used in meaningful evaluations mostly in non-IBD patients. It has been determined that PLR can be used in more accurate evaluations in the non-IBD group, such as maintaining the treatment at the beginning and mid-treatment, switching to additional agents, and increasing the frequency of treatment. The increase in PLR mid-treatment in patients receiving IFX therapy in the non-IBD group suggests that intensified anti-TNF therapy may be more beneficial in remission of the disease. The fact that the post-treatment response became significant in the middle of the treatment, especially in patients who received GOL treatment, suggests that the effectiveness of GOL treatment emerges towards the middle of the treatment. In order to predict the use of biomarkers in clinical practice in terms of anti-TNF treatment response and follow-up, further studies with high-volume patient numbers are required, but it can be postulated that our current study has results in terms of being as a reference for further studies.
Açıklama
Anahtar Kelimeler
Anti-TNF Tedavi, Serum İnflamasyon Biyobelirteçleri, İnflamatuvar Bağırsak Hastalıkları, Anti-TNF Treatment, Serum Inflammation Biomarkers, Inflammatory Bowel Diseases
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WoS Q Değeri
Scopus Q Değeri
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Künye
Öz. A. (2023). Anti-tnf tedavisi alan olgularda uygulama öncesi ve sonrasında serum inflamasyon belirteçlerinin seyrinin değerlendirilmesi. (Yayınlanmamış tıpta uzmanlık tezi) Necmettin Erbakan Üniversitesi, Meram Tıp Fakültesi Dahili Tıp Bilimleri Bölümü İç Hastalıkları Anabilim Dalı, Konya.
