Title Azatioprin u liječenju bolesnika s ulceroznim kolitisom Title (english) Azathioprine in the treatment of patients with ulcerative colitis Author Franjo Barun Mentor Neven Ljubičić (mentor)Committee member Lucija Virović Jukić (predsjednik povjerenstva)Committee member Jasenka Markeljević (član povjerenstva)Committee member Neven Ljubičić (član povjerenstva)Granter University of Zagreb Defense date and country 2021-09-25, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Abstract Ulcerozni kolitis (UC) kronična je upalna bolest za koju su karakteristične ulceracije sluznice debelog crijeva. Zajedno s Crohnovom bolešću spada u skupinu idiopatskih upalnih bolesti crijeva. Riječ je o netransmuralnoj upalnoj bolesti ograničenoj na debelo crijevo, s kliničkim tijekom obilježenim razdobljima remisije i relapsa bolesti. Prema Montrealskoj klasifikaciji, ovisno o tome koji je dio debelog crijeva zahvaćen bolešću, razlikujemo: proktitis, lijevostrani kolitis i ekstenzivni kolitis, te ovisno o aktivnosti, odnosno težini bolesti: blagi, umjereni, teški UC i kliničku remisiju. Klinički se UC najčešće očituje učestalim sluzavo-krvavim proljevima. Razlikujemo njegovo medikamentno i kirurško liječenje. Medikamentno liječenje nije kurativno, već je usmjereno na postizanje kliničke, endoskopske i histološke remisije bolesti te sprječavanje kirurških intervencija. Ono se provodi uporabom aminosalicilata, kortikosteroida, imunomodulatornih lijekova, kao što je azatioprin (AZA) te biološkom terapijom. Azatioprin je tiopurin koji imunosupresiju postiže putem svojih aktivnih metabolita. Oni potiču apoptozu T-limfocita te, inkorporirajući se u replicirajući lanac DNA i blokirajući de novo sintezu purina, smanjuju njihovu proliferaciju. Mjerenjem aktivnosti TPMT-a te praćenjem metabolita tiopurina, uspješno se postiže optimizacija terapije. Time se poboljšava klinička djelotvornost liječenja te se sprječava neuspjeh liječenja uzrokovan štetnim nuspojavama azatioprina, kao što je pankreatitis. Zbog intenzivnog razvoja biološke terapije, stručnjaci smatraju da se azatioprin u budućnosti više neće koristiti u liječenju bolesnika s ulceroznim kolitisom. Unatoč prepostavkama, azatioprin ostaje i dalje jedan od osnovnih lijekova u liječenju bolesnika s ulceroznim kolitisom. Nove smjernice ACG-a, ECCO-a te Toronto consensusa podržavaju uporabu tiopurina u liječenju bolesnika s UC-om u sljedećim slučajevima: 1) u svrhu održavanje remisije u bolesnika s ograničenom ekstenzijom bolesti i blagim do umjerenim UC-om koji ne podnose ili prestaju reagirati na liječenje aminosalicilatima; 2) u svrhu održavanja remisije u bolesnika s teškim akutnim UC-om u kojih je indukcija remisije postignuta ciklosporinom; te 3) u kombinaciji s TNF-α antagonistima u liječenju bolesnika s umjerenim do teškim UC-om.
Abstract (english) Ulcerative colitis (UC) is a chronic inflammatory disease characterized by ulcerative lesions of the colon mucosa. Together with Crohn's disease, it belongs to a group of conditions known as inflammatory bowel diseases. It is a nontransmural inflammatory disease with a clinical course characterized by periods of remissions and relapses. According to the Montreal classification, depending on the part of the affected colon, it can be defined as: proctitis, left colitis, or extensive colitis, whereas according to the activity or severity, as: mild, moderate, severe UC and clinical remission. The most common clinical symptom of UC is frequent bloody diarrhea usually accompanied by mucus. UC can be managed by medicaments and surgical treatment. Conservative treatment is focused on achieving clinical, endoscopic and histological remission. It is carried out by using aminosalicylates, corticosteroids, immunomodulatory drugs, such as azathioprine (AZA) and the biological therapy. Azathioprine is a thiopurine which achieves immunosuppression through its active metabolites. They induce apoptosis of T-lymphocytes and, by incorporating into the replicating DNA chain and blocking de novo purine synthesis, reduce its proliferation. The measurement of TPMT activity as well as thiopurine metabolite monitoring successfully lead to a therapy optimization. Thus, improving clinical effectiveness of the therapy and reducing management failure from adverse effects, such as pancreatitis. Due to the intensive development of biological therapy, experts believe that thiopurines will in future no longer be used as therapy in patients with UC. Despite these assumptions, thiopurines are still one of the basic therapies in the treatment of patients with UC. Recent guidelines from the ACG, ECCO and Toronto Consensus support the use of thiopurines in the treatment of patients with ulcerative colitis in the following cases: 1) maintenance of remission in patients with confined extension of disease and mild-to-moderate UC who are intolerant to or fail aminosalicylates; 2) as a maintenance therapy after using cyclosporine for acute severe UC; and 3) as combination therapy with TNF-α antagonists in patients with moderate to severe UC.
Keywords
ulcerozni kolitis
azatioprin
TPMT
biološka terapija
Keywords (english)
ulcerative colitis
azathioprine
TPMT
biological therapy
Language croatian URN:NBN urn:nbn:hr:105:376298 Study programme Title: Medicine Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2022-01-21 08:05:12
