Primerjava bolnikov v redni klinični praksi in tistih, vključenih v randomizirana klinična preskušanja tarčnih zdravil za ulcerozni kolitis: pomen vključitvenih in izključitvenih kriterijev

Hameršak, Erika (author), Vovk, Tomaž (mentor), Hanžel, Jurij (comentor)

Ulcerozni kolitis je dolgotrajna in imunsko pogojena kronična vnetna črevesna bolezen, ki prizadene rektum ter debelo črevo v različno dolgih odsekih. Čeprav vzrok nastanka ni natančno poznan, študije dokazujejo, da na njegov razvoj vpliva prepletanje genetskih in okoljskih dejavnikov. Kaže se kot krvavo blato tekoče konsistence, povečana frekvenca odvajanja blata, nujni pozivi na blato, lahko pa tudi bolečine v spodnjem delu trebuha ali celo povišana telesna temperatura. Za ocenitev aktivnosti ulceroznega kolitisa se uporablja skupna Mayo ocena, ki temelji na endoskopski Mayo oceni, znakih in simptomih bolnika ter splošni oceni zdravnika. Najbolj razširjena in specifična metoda diagnosticiranja ulceroznega kolitisa je endoskopski pregled, zraven pa se še lahko opravi histološki pregled in določi vrednost fekalnega kalprotektina iz vzorca blata. Cilj zdravljenja ulceroznega kolitisa je doseči globoko remisijo bolezni. Za indukcijo remisije se uporabljajo zdravila iz skupine 5-aminosalicilatov ter kortikosteroidi, za vzdrževanje remisije pa 5-aminosalicilati, tiopurini ter tarčna zdravila. Zaradi izgube kliničnega odziva na odobrena tarčna zdravila ostaja nenehna potreba po novih tarčnih zdravilih za zdravljenje ulceroznega kolitisa. Podatke o njihovi učinkovitosti in varnosti pridobimo iz randomiziranih kliničnih preskušanj, vendar so rezultati le teh lahko potencialno pristranski zaradi izbire idealne študijske populacije, kar je določeno z vključitvenimi in izključitvenimi kriteriji študijskega protokola. Posledično je učinkovitost novih tarčnih zdravil na klinični populaciji vprašljiva, saj je ta pogosto iz kliničnih študij izključena zaradi drugih pridruženih obolenj, polifarmacije, nestabilnih odmerkov zdravil ali neustreznega časovnega intervala zdravljenja z ostalimi zdravili, previsoke starosti, itd. Namen magistrske naloge je bilo raziskati delež bolnikov z diagnosticiranim ulceroznim kolitisom, ki bi izpolnjevali pogoje za vključitev v izbrane klinične študije tarčnih zdravil. Opravljena je bila neintervencijska retrospektivna raziskava v Univerzitetnem kliničnem centru Ljubljana, na Kliničnem oddelku za gastroeneterologijo. V raziskavo so bili vključeni polnoletni bolniki, ki so bili v letu 2022 zdravljeni in obravnavani na kliničnem oddelku za gastroenterologijo, Ljubljana. Ugotovili smo, da od 131 bolnikov, ki so bili vključeni v raziskavo, 52,7% ne bi ustrezalo pogojem za vključitev v študije. Najpogostejši razlogi za izključitev bolnikov iz kliničnih preskušanj so bili prenizka aktivnost ulceroznega kolitisa, neuspešno zdravljenje z že obstoječi tarčnim zdravilom ali konvencionalno terapijo, previsoka starost bolnikov, prisotnost ulceroznega proktitisa, klinično pomembno pridruženo zdravstveno stanje in potrditev diagnoze ulceroznega kolitisa manj kot 3 mesece.

• Language: Slovenian
• Keywords: ulcerozni kolitis, tarčna zdravila, klinična preskušanja, vključitveni in izključitveni kriteriji
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2024
• PID: 20.500.12556/RUL-161426
• Publication date in RUL: 11.09.2024

Secondary language

• Language: English
• Title: Comparison of patients in routine clinical practice and those enrolled in randomized clinical trials of target drugs for ulcerative colitis: importance of inclusion and exclusion criteria

Abstract

Ulcerative colitis is a long-term and immune-related chronic inflammatory bowel disease that affects rectum and colon in varying lenghts. Although the exact cause is not known, studies show that its development is influenced by genetic and environmental factors. It is recognized by bloody stools with liquid consistency, increased frequency of bowel movements, urgent defecations, pain in the lower abdomen or even a fever. The total Mayo score is used to assess the activity of ulcerative colitis, which is based on the endoscopic Mayo score, the patient's signs and symptoms, and the physician's global assessment. The most widespread and specific methods of diagnosing ulcerative colitis is and endoscopic examination. Histological examination or determination of fecal calprotectin values from stool sample can also be performed. The goal of ulcerative colitis treatment is to achieve deep remission. Drugs from 5-aminosalicylates group and corticosteroids are used to induce remission, while 5-aminosalicylates, thiopurines and target drugs are intended to maintain remission. Due to the loss of clinical response of approved target drugs, there remains an ongoing need for new targeted drugs for ulcerative colitis treatment. Data on their efficacy and safety are obtained from randomized clinical trials, but the results of these could be potentially biased by the selection of the ideal study population, which is determined by the inclusion and exclusion criteria of the study protocol. As a result, the effectiveness of new target drugs on the clinical population is questionable, as this is often excluded from clinical studies due to other associated diseases, polypharmacy, unstable drug doses or inadequate treatment time interval, older patients, etc. The purpose of the master's thesis was to investigate the proportion of patients diagnosed with ulcerative colitis who would meet the conditions for inclusion in selected clinical studies of targeted drugs. A non-interventional etrospective study was performed at the University Clinical Center of Ljubljana, at the Clinical Department of Gastroenterology. In the reserch were included adult patients, who were treated at the Clinical Department of Gastroenterology, Ljubljana in 2022. Results show that of the 131 patients who were included in the study, 52.7% would not meet the conditions for inclusion in clinical studies. The most common reasons for excluding patients from clinical trials were too low activity of ulcerative colitis, unsuccessful treatment with previous target drugs or conventional therapy, too high age of patients, presence of ulcerative proctitis, clinically significant associated medical condition and confirmation of the diagnosis of ulcerative colitis for less than 3 months.

• Keywords: ulcerative colitis, targeted drugs, clinical trials, inclusion and exclusion criteria