| Abstract | Ulcerozni kolitis (UC) je autoimuna bolest crijeva karakterizirana kroničnom upalom. Lokalizacijski se može podijeliti na ulcerativni proktitis, ulcerativni proktosigmoiditis, lijevostrani kolitis i pankolitis, dok ovisno o kliničkoj težini bolesti razlikujemo blagi, umjereni i teški oblik. Stope prevalencije su više u sjevernim i razvijenim zemljama, a niže u manje razvijenim, u kojima pak bilježimo porast stopa incidencije. Glavni patofiziološki čimbenici rizika za razvoj UC-a su: genetski, okolišni, mikrobiološki i imunološki. Međudjelovanje istih, pretpostavlja se, vodi ka narušavanju funkcije intestinalne barijere i kroničnoj upali. Klinička očitovanja variraju od lokalnih intestinalnih, ekstraintestinalnih do sistemskih, a tipična klinička slika obuhvaća: abdominalne bolove, promjene u ritmu pražnjenja crijeva, kolorektalno krvarenje, anemiju, malaksalost, gubitak teka, povišenu tjelesnu temperaturu i artralgije. Metode kojima se koristimo u postavljanju dijagnoze bolesti uključuju: laboratori jske, proceduralne i
histološke testove. Osnovni terapijski cilj kojemu težimo je duga i stabilna remisija temeljem postignutog mukozalnog i/ili histološkog cijeljenja, čime osiguravamo manju vjerojatnost od komplikacija, hospitalizacija, kolorektalnog karcinoma te postižemo dulji i kvalitetniji ži vot. U liječenju UC-a svoju primjenu nalazi konvencionalna terapija – kortikosteroidi, aminosalicilati, imunomodulatori, inhibitori kalcineurina; biološka terapija – anticitokinska i anti-integrinska protutijela te niskomolekulska oralna precizna terapija – inhibitori Janus kinaze, S1PR modulatori/agonisti, inhibitori fosfodiesteraze i drugi. Tofacitinib je predstavnik među inhibitorima Janus kinaze koji svoj protuupalni učinak postiže kompetitivnom inhibicijom Janus kinaze, daljnjom inhibicijom STAT transkripcijskih faktora te posljedično smanjenjem sinteze proupalnih citokina. Među S1PR modulatorima/agonistima posebno se ističe ozanimod – funkcionalni antagonist koji putem internalizacije i degradacije receptora onemogućava
izlazak limfocita iz limfoidnih organa, cirkulaciju limfocita i time uzrokuje limfopeniju. Ostali niskomolekulski oralni precizni lijekovi su: inhibitori fosfodiesteraze 4 (pr. apremilast), analozi fosfatidilkolina (pr. LT-02), anti-integrini (pr. AJM300), antiviralni imunomodulatori (pr. ABX464), antisense oligonukleotidi (pr. alicaforsen) i drugi. |
| Abstract (english) | Ulcerative colitis (UC) is an autoimmune bowel disease, characterized by chronic inflammation. UC is classified by localization into ulcerative proctitis, ulcerative proctosigmoiditis, left-sided colitis and pancolitis and by clinical severity into mild, moderate and severe form. The prevalence rates are higher in the northern and developed countries and lower in the developing countries, but latter also experience incidence growth. Major pathophysiological risk factors for developing UC are: genetic, environmental, microbiological and immunological. Interraction among those leads to impaired intestinal barrier function and chronic inflammation. Clinical manifestations vary from local intestinal, extraintestinal to systemic manifestations. Typical symptoms are abdominal pain, irregular bowel movements, colorectal bleeding, anemia, malaise, loss of appetite, increased body temperature and arthralgias. Most commonly used diagnostic tools are laboratory, procedural and histopathological studies. The main therapeutic goal represents a long and stable remission based on the achieved mucosal and/or histological healing, which reduces the risk of complications, hospitalizations, colorectal cancer and ensures a better quality of life. Therapeutic strategies used in UC treatment are: conventional therapy – corticosteroids, aminosalicylates, immunomodulators, calcineurin inhibitors; biological therapy – anti-cytokine and anti-intregrin antibodies
and small molecule oral targeted therapies – Janus kinase inhibitors, S1PR modulators/agonists, phosphodiesterase inhibitors and others. Tofacitinib is a lead Janus kinase inhibitor which exerts its anti-inflammatory effect by competitive inhibition of Janus kinase, further inhibition of STAT transcription factors and a subsequent decrease in the synthesis of inflammatory cytokines. One of the key S1PR modulators/agonists is ozanimod – a functional antagonist that prevents lymphocyte egress from lymphoid organs, lymphocyte circulation and thus causes lymphopenia by the mechanism of internalization and degradation of receptors. Other small molecule oral targeted therapies are: phosphodiesterase-4 inhibitors (e.g. apremilast), phosphatidylcholine analogues (e.g. LT-02), anti-integrins (e.g. AJM300), antiviral immunomodulators (e.g. ABX464), antisense oligonucleotides (e.g. alicaforsen) and others. |
