Therapeutic possibilities in treatment of Crohn's disease

Crohnova bolest (CB), jedna od dva glavna tipa upalnih bolesti crijeva, kronična je, progresivna i potencijalno onesposobljavajuća bolest. Incidencija CB povećala se u zapadnom svijetu u drugoj polovici dvadesetog stoljeća zajedno s industrijalizacijom i socioekonomskim razvitkom te posljednje epidemiološke studije pokazuju značajni porast u zemljama u razvoju Može zahvatiti bilo koji dio gastrointestinalnog trakta od usta do anusa, a glavna patofiziološka obilježja su diskontinuirana, transmuralna upala, kaldrmasti izgled crijeva, granulomi, fistule, fibrotičan i sužen crijevni zid. Tipični simptomi i znakovi su proljev, malaksalost, vrućica, bol u abdomenu, često pražnjenje crijeva, krv u stolici, fistula, gubitak težine, malnutricija, a česti su i simptomi izvan gastrointestinalnog sustava. U dijagnozi se koristi fizikalni pregled, endoskopske i radiološke pretrage crijeva. Trenutna je teorija da u genetički predodređenih pojedinaca (npr. gen NOD2) interakcijom intestinalne mikrobiote i imunološkog sustava domaćina (barijerna funkcija intestinalnih epitelnih stanica, urođena i stečena imunost) dolazi do kronične upale koja je modificirana okolišnim čimbenicima (pušenje, prehrana, neki lijekovi...). Imunološka podloga bolesti je neodgovarajući odgovor regulatornih T stanica naspram pretjeranog odgovora pomagačkih T limfocita, Th1 i Th17 stanica. Crohnova bolest trenutno je neizlječiva, a cilj terapije je smanjivanje upale, očuvanje crijevne funkcije, sprječavanje komplikacija i omogućavanje normalne kvalitete života. Za indukciju remisije najčešće se koriste kortikosteroidi, ali mogu se koristiti i aminosalicilati, antibiotici, TNF α inhibitori, anti integrini, ustekinumab ili ciklosporin. Za održavanje remisije najuspješniji su tiopurini, a mogu se koristiti i aminosalicilati, metotreksat, TNF α inhibitori, anti integrini ili ustekinumab, ovisno o težini bolesti. Postoji i niz lijekova koji su pokazali obećavajuće rezultate u kliničkim istraživanjima faze 2, kao što su etrolizumab, ozanimod, risankizumab, brazikumab, mirikizumab, filgotinib, upadacitinib i mongersen. Prevalencija trenutnih ili bivših korisnika komplementarne i alternativne medicine (engl. complementary and alternative medicine, CAM) u odrasloj populaciji oboljelih od upalnih bolesti crijeva iz Sjeverne Amerike i Europe u rasponu je od 21% do 60%. Bitan aspekt liječenja CB je i nutritivna podrška.Crohn's disease (CB), one of the two main types of inflammatory bowel disease, is chronic, progressive and potentially disabling disease. CB incidence increased in the western world in the second half of the twentieth century with industrialization and socioeconomic development and the latest epidemiological studies show a significant increase in developing countries. It can affect any part of the gastrointestinal tract from mouth to anus, and the major pathophysiological features are discontinuous, transmural inflammation, cobblestone appearance of the intestine, granuloma, fistula, fibrotic and narrowed intestinal wall. Typical symptoms and signs are diarrhea, malaise, fever, abdominal pain, frequent bowel movements, hematochezia, fistula, weight loss, malnutrition. Extraintestinal manifestations also occur frequently. Diagnostic tools are physical, serologic, endoscopic and radiological examinations of the intestines. Current theory is that in genetically predisposed individuals (e.g. gene NOD2) interaction between intestinal microbiota and immune system of the host (intestinal epithelial cells barrier function, innate and adaptive immune function) lead to chronic inflammation which is further modified by environmental factors (smoking, nutrition, some drugs. ..). Immunological background of the disease is an inadequate regulatory T cells response in the face of an overly exuberant response involving T helper lymphocytes, Th1 and Th17 cells. Crohn's disease is currently incurable, and goal of the therapy is reduction of inflammation, preservation of intestinal function, prevention of complications and enabling normal quality of life. For the induction of remission, corticosteroids are most commonly used, but aminosalicylates, antibiotics, TNF α inhibitors, anti integrins, ustekinumab or cyclosporin can also be used and remission remedies are the most successful thiopurine. Aminosalicylates, methotrexate, TNF α inhibitors, anti integrins or ustekinumab, depending on the severity of the disease, can all be used for the remission maintenance. There is also a number of drugs that has shown promising results in Phase 2 clinical trials, such as etrolizumab, ozanimod, risankizumab, brazikumab, mirikizumab, filgotinib, upadacitinib and mongersen. The prevalence of current or past complementary and alternative medicine (CAM) use in adult inflammatory bowel disease population from North America and Europe ranges from 21% to 60%. Nutritional support is also an important aspect of CB treatment