20.500.12556/RUL-172924 Mehanizmi delovanja bioloških zdravil pri kronični vnetni črevesni bolezni Biologic drug mechanisms in chronic inflammatory bowel disease Namen diplomskega dela je bil raziskati mehanizme delovanja bioloških zdravil pri kronični vnetni črevesni bolezni (KVČB), med katere spadata Crohnova bolezen in ulcerozni kolitis. V tej nalogi sem naredila tudi primerjavo učinkovitosti na potek zdravljenja ter vključila primerjavo učinkovitosti glede na predhodna zdravljenja z biološkimi zdravili. Med biološka zdravila, namenjena zdravljenju KVČB, spadajo zaviralci TNF-α (infliximab, adalimumab, certolizumab pegol), zaviralci integrina α4β7 (vedolizumab) in zaviralci interlevkinov IL12, IL23 (ustekinzmab, risankizumab). Ta zdravila tarčno ciljajo molekule, ki povzročajo patološko stanje bolnika, kot so kronična vnetja črevesne stene, ulceracije in strikture črevesnega lumna. Mehanizmi delovanja bioloških zdravil vključujejo nevtralizacijo provnetnih citokinov, povratno signalizacijo prek transmembranskih oblik tarčnih molekul, induciranje apoptoze celic T, preprečevanje migracije imunskih celic v črevesno sluznico ter modulacijo ravnovesja med pro- in protivnetnimi imunskimi potmi. Uporabila sem pregled in analizo znanstvene literature ter mrežno meta-analizo naključnih kliničnih študij. Rezultati pri biološko naivnih bolnikih so pokazali, da je bila najučinkovitejša kombinacija infliximaba z azatioprinom, z 88 % verjetnostjo indukcije klinične remisije. Pri predhodno zdravljenih bolnikih pa so najučinkovitejše delovali ustekinumab, adalimumab in zaviralci IL-23. Vzdrževanje klinične remisije je bilo uspešno z vsemi trenutno dostopnimi biološkimi zdravili, brez pomembnih razlik v varnostnem profilu. Poznavanje mehanizmov delovanja in imunoloških tarč omogoča boljšo izbiro terapije ter podpira personaliziran pristop pri zdravljenju KVČB. The aim of the thesis was to investigate the mechanisms of action of biological drugs in chronic inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis. In this work, I also compared the effectiveness of treatments in influencing disease progression, and included a comparison of efficacy based on previous treatments with biological drugs. Biological drugs used for the treatment of IBD include TNF-α inhibitors (infliximab, adalimumab, certolizumab pegol), α4β7 integrin inhibitors (vedolizumab), and interleukin IL-12 and IL-23 inhibitors (ustekinumab, risankizumab). These drugs specifically target molecules responsible for the patient’s pathological condition, such as chronic inflammation of the intestinal wall, ulcerations, and strictures of the intestinal lumen. The mechanisms of action of biological drugs include neutralizing pro-inflammatory cytokines, reverse signaling through transmembrane forms of target molecules, inducing apoptosis of T cells, preventing the migration of immune cells into the intestinal mucosa, and modulating the balance between pro- and anti-inflammatory immune pathways. I used a review and analysis of scientific literature, as well as a network meta-analysis of randomized clinical trials. Results in biologically naïve patients showed that the most effective combination was infliximab with azathioprine, with an 88 % probability of inducing clinical remission. In previously treated patients, the most effective were ustekinumab, adalimumab, and IL-23 inhibitors. Maintenance of clinical remission was successful with all currently available biological drugs, without significant differences in safety profiles. Understanding the mechanisms of action and immunological targets allows for better therapy selection and supports a personalized approach in the treatment of IBD. kronična vnetna črevesna bolezen Crohnova bolezen ulcerozni kolitis biološka zdravila monoklonska protitelesa imunski mehanizmi inflammatory bowel disease Crohn’s disease ulcerative colitis biological drugs monoclonal antibodies immune system mechanisms true false false Slovenski jezik Angleški jezik Diplomsko delo/naloga 2025-09-12 07:19:00 2025-09-12 07:19:02 2025-10-28 03:47:14 0000-00-00 00:00:00 2025 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 263663 249005827 51059.pdf 51059.pdf 1 DDB99EC48B9B3B5E3A6075D647FF7E0C c5fc9f86777806969d86b5378fb3f9ab93eff628ae48d3f3a836c565ed38d6df d47e6e04-8f97-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=217058 Biotehniška fakulteta 0 0 0