Analiza sigurnosnog profila JAK inhibitora na temelju zaprimljenih prijava sumnji na nuspojave

master's thesis

• Title (english): Analysis of the safety profile of JAK inhibitors based on the received reports of suspected side effects
• Author: Lora Pavlinović
• Mentor: Nikica Mirošević Skvrce (mentor)
• Committee member: Nikica Mirošević Skvrce (predsjednik povjerenstva)
• Committee member: Lidija Bach-Rojecky (član povjerenstva)
• Committee member: Iva Mucalo (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2022-03-25, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Citokini i faktori rasta su proteini koji posreduju aktivnost i preživljavanje brojnih stanica u organizmu. Jedan od
načina kojim se to posredovanje odvija je i JAK/STAT signalizacijski put. Citokini se vežu za svoje receptore na
površini stanica, konformacijskom promjenom se pokreće signalizacijska kaskada te nastavlja fosforilacijom. Janus
(JAK) kinaze su unutarstanične tirozin kinaze, vezane uz citokinske receptore, zadužene za uzastopnu fosforilaciju
nizvodnih molekula. Obzirom na širok utjecaj kojeg JAK/STAT put ima na imunosne i krvne stanice, ne čudi da su
Janus kinaze postale atraktivna terapijska meta u liječenju autoimunih i hematoloških bolesti. Velik broj nizvodnih
ciljeva na koje utječe inhibicija Janus kinaza ima i jednu manu, a to je sigurnosni profil ovih potentnih lijekova. Cilj
ovog rada bio je analizirati nuspojave JAK inhibitora prijavljene Agenciji za lijekove i medicinske proizvode u
razdoblju od 1. siječnja 2013. godine do 11. srpnja 2021. godine te povećati svijest o sigurnosnom profilu ovih
lijekova, kao i mjerama minimizacije rizika. Zaprimljene prijave sumnji na nuspojave analizirane su u odnosu na
ukupan broj zaprimljenih prijava u zadanom razdoblju, prema vrsti prijavitelja, dobi i spolu pacijenta, ozbiljnosti
reakcije, kriteriju ozbiljnosti, najčešće prijavljenim rekacijama, pripadnosti prema klasifikaciji organskih sustava
Medicinskog rječnika za regulatorne poslove (MedDRA) te najčešće istodobno primijenjivanim lijekovima. Dobiveni
rezultati i znanje o sigurnosnom profilu JAK inhibitora te mjerama minimizacije rizika omogućuju dodatnu edukaciju
zdravstvenih radnika o učinkovitijoj prevenciji, otkrivanju i liječenju mogućih nuspojava, a sve sa svrhom poboljšanja
kvalitete života pacijenata.

Abstract (english)

Cytokines and growth factors are proteins that mediate the activity and survival of many cells in human body. One of the ways in which this mediation takes place is via JAK / STAT signaling path. Cytokines bind to their receptors on the cell surface and, by conformational change, trigger a signaling cascade which is continued by phosphorylation. Janus (JAK) kinases are intracellular tyrosine kinases which are associated with cytokine receptors. Kinases are responsible for the consequential phosphorylation of downstream molecules. Given the wide range of effects that JAK / STAT pathway has on immune and blood cells, the fact that Janus kinases have become an attractive therapeutic target in the treatment of autoimmune and hematological diseases is not surprising. A number of downstream targets affected by Janus kinase inhibition also has one disadvantage which is the safety profile of these potent drugs. The aim of this study was to analyze the side effects of JAK inhibitors reported to the Agency for Medicinal Products and Medical Devices of Croatia in the period from 1 January 2013 to 11 July 2021. Also, another intention was to increase awareness of the safe profile of these drugs and risk minimization measures. Received reports of suspected adverse reactions were analyzed in relation to the total number of received reports in a given period, reporter qualification, age and sex of the patient, seriousness of reactions, seriousness criteria, most commonly reported reactions, reported reactions by MEdDRA organic classification (Medical Dictionary for Regulatory Affairs) and most commonly applied medicines.The obtained results and knowledge about the safe profile of JAK inhibitors and risk minimization measures enable additional education of healthcare professionals on effective prevention, detection and treatment of possible side effects, all with the purpose of improving the quality of life of patients.

• Keywords: Janus kinaze; JAK inhibitori; Jakinibs; nuspojave; sigurnosni profil; mjere minimizacije rizika
• Keywords (english): Janus kinases; JAK inhibitors; Jakinibs; side effects; safety profile; risk minimization measures
• Language: croatian
• URN:NBN: urn:nbn:hr:163:806801
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-05-26 11:38:03