Urška Koren (Author), Matjaž Jeras (Mentor), Nada Kecelj (Co-mentor)

Abstract

Kronična vnetna črevesna bolezen je bolezen prebavil z akutnimi zagoni. Patofiziološki mehanizmi in vzroki za njen pojav še niso povsem razjasnjeni, med poglavitnimi sprožilnimi dejavniki pa omenjajo imunsko neravnovesje, genetsko predispozicijo in sestavo črevesne flore obolelih posameznikov. Kronična vnetna črevesna bolezen se najpogosteje pojavlja v dveh oblikah, in sicer kot ulcerozni kolitis ali Crohnova bolezen. Trenutno je še neozdravljiva, v zadnjih letih pa predstavljajo veliko pridobitev biološka zdravila, s katerimi dosegamo večjo uspešnost pri zdravljenju. Z zdravili poskušamo doseči trajno remisijo bolezni in zmanjšati število hospitalizacij, kar vodi v boljšo kakovost življenja bolnikov s kronično vnetno črevesno boleznijo. Pri približno 20 % bolnikov pri zdravljenju hude oblike kronične vnetne črevesne bolezni uporabljamo zdravilo infliksimab, ki je himerno monoklonsko protitelo, sestavljeno iz mišjega in človeškega dela. Poznamo dva mehanizma delovanja infliksimaba. Veže se na dejavnik tumorske nekroze alfa (TNF-α) ali pa na receptorje za TNF-α na imunskih celicah in tako nevtralizira oziroma prepreči njegovo delovanje. Bolniki lahko proti infliksimabu razvijejo protitelesa, ki nato izzovejo neželene učinke, med katerimi se pogosto pojavljajo tudi spremembe na koži. Na osnovi teh dejstev smo se v okviru našega dela osredotočili na morebiten vpliv odmerka in koncentracije infliksimaba v krvi na pojav kožnih sprememb pri bolnikih s kronično vnetno črevesno boleznijo, saj lahko s povečevanjem odmerka in skrajšanjem intervala med posameznimi odmerki pogosto optimiziramo zdravljenje. V raziskavo smo, po njihovem predhodnem pristanku, vključili 171 bolnikov, ki se z infliksimabom zdravijo v Ambulanti za kronično vnetno črevesno bolezen Kliničnega oddelka za gastroenterologijo na Univerzitetnem kliničnem centru (UKC) Ljubljana. Potrebne podatke smo pridobili s pomočjo anketnega vprašalnika in iz bolnišnične dokumentacije. Koncentracije infliksimaba v serumu smo določali z metodo ELISA. Kožne spremembe smo fotografirali in na osnovi fotodokumentacije postavili okvirne diagnoze, ki smo jih nato fenotipsko klasificirali. Izračunali smo stopnje povezanosti (korelacije) med serumskimi koncentracijami in odmerki infliksimaba pri bolnikih s kožnimi spremembami ter pri tistih brez njih. Poleg tega smo statistično primerjali serumske koncentracije in odmerke infliksimaba med bolniki s kožnimi lezijami in tistimi brez, za kar smo uporabili neparametrični Mann-Whitneyev U test s 5-odstotno stopnjo tveganja.Kožne spremembe je razvilo 23,4 % bolnikov, ki se zdravijo z infliksimabom. Statistično značilnih razlik v koncentraciji zdravila v krvi med tistimi s kožnimi spremembami in tistimi brez njih nismo ugotovili (p = 0,389). Enako velja tudi za uporabljene odmerke infliksimaba (p = 0,741). Za vsak posamezen fenotip kožne spremembe smo preverjali tudi, ali obstaja povezava med njegovo pojavnostjo in uporabljenim odmerkom infliksimaba ter doseženo koncentracijo zdravila v krvi. Pri vseh prisotnih fenotipih kožnih sprememb (psoriaza, psoriaziformni ekcem, ekcem, kseroza, drugo) so bile vrednosti p ≥ 0,05, kar pomeni, da nismo zaznali statistično značilnih razlik. Pri bolnikih, ki so razvili kožne spremembe, smo ocenjevali tudi vpliv kožnih manifestacij na kakovost njihovega življenja. Na osnovi prejetih anketnih odgovorov smo ugotovili, da kožne spremembe ne vplivajo na kakovost življenja.

Keywords

infliksimab;kakovost življenja;neželeni učinki zdravil;

Data

Language: Slovenian
Year of publishing:
Typology: 2.11 - Undergraduate Thesis
Organization: UL FFA - Faculty of Pharmacy
Publisher: [U. Koren]
UDC: 615.32:616.34-002(043.2)
COBISS: 4610673 Link will open in a new window
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Downloads: 84
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Other data

Secondary language: English
Secondary title: ǂThe ǂanalysis of side effects of infliximab therapy on skin of patients suffering from inflammatory bowel disease
Secondary abstract: Inflammatory bowel disease (IBD) is a disease of a gastrointestinal tract with periods of acute exacerbation and remissions. Pathophysiological mechanisms and the cause of the disease are yet unknown. Immunological misbalance, genetic predisposition and the composition of the intestinal flora may be just one of them. IBD consists out of two forms: ulcerative colitis and Crohn’s diseass. At the moment we still do not know how to cure people with inflammatory bowel disease but in the last few years a lot of biological medicines (biopharmaceuticals) were presented which has opened new possibilities for treatment of many serious chronic diseases. With biopharmaceuticals we try to achieve the phase of remission, reduce the number of days spent in hospital and improve the quality of life of people with inflammatory bowel disease. The most used biopharmaceutical is infliximab which is a chimeric monoclonal antibody and it is used in almost 20 % of all the patients with IBD and consists of murine and human part. Infliximab works in two ways – it can bind to a tumor necrosis factor alpha (TNF – α) and neutralizes his activity or it can bind on a tumor necrosis factor receptors on immune cells. Side effects that occur are mostly because of the formation of antibodies against the components of the medicine. Often the side effects include the formation of skin lesions which is a reason why we decided to concentrate on a possible connection between infliximab concentration and dose of infliximab on a formation of skin disease in patients with inflammatory bowel disease. Increasing the dose and shortening intervals between the applications is a common way to optimize the treatment. 171 patients with inflammatory bowel disease who are treated with infliximab has given us a signed consent for cooperation in our research which took place in the Department of Gastroenterology in the University Medical Centre Ljubljana. Patient's data were collected with the questionnaire and patient’s hospital data. The infliximab concentration in blood was determinate with ELISA method.All skin lesions were photographed and based on the pictures we tried to determinate a framework diagnosis. Then we calculated and compared the correlation between the serum concentration and the dosage of infliximab among patients with and without skin lesions. Non parametric Mann – Whitney U Test with 5 % confidence interval was used. Skin lesions appeared in 23,4 % of all the observed patients whose main therapy is infliximab. Statistically significant differences in concentration of the medicine among patients with and without skin lesions was not detected (p = 0,389). Statistically significant differences in the dosage of infliximab among patients with and without skin lesions was not detected either (p = 0,741). Moreover, we calculated the correlation between the concentration and the dosage of the medicine among patients with skin lesions for each phenotype of the skin lesion. There were 5 phenotypes of skin lesions: psoriasis, psoriasphic eczema, eczema, xerose and the group we called other. All statistically significant differences were higher than 0,05 (p ≥ 0,05) which means that the concentration and dosage of infliximab does not impact the skin lesions. The quality of life was observed in patients who developed skin lesions. According to their answers we conclude that skin lesions do not have an impact on ones everyday life.
Secondary keywords: Biološka zdravila;Kronična vnetna črevesna bolezen;Crohnova bolezen;Ulcerozni kolitis;
Type (COBISS): Bachelor thesis/paper
Thesis comment: Univ. v Ljubljani, Fak. za farmacijo, študij kozmetologije
Pages: VIII, 45 str., I-XIII f. pril.
ID: 12038959