Sistemska izloženost i nuspojave, te mjere smanjenja rizika nakon bevacizumaba primijenjenoga intravitrealno u liječenju senilne makularne degeneracije

doctoral thesis

• Title (english): Systemic exposure, systemic adverse reactions and risk minimization measures of bevacizumab applied intravitreally in senile macular degeneration treatment
• Author: Ivana Mikačić
• Mentor: Damir Bosnar (mentor)
• Committee member: nije dostupno (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2017-04-07, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

Tema ove doktorske disertacije je minimizacija rizika primjene IVT bevacizumaba od
sustavnih neželjenih događaja u liječenju AMD. Učinjen je sustavni pregled svih publiciranih
kliničkih studija kojim se ne može utvrditi da li postoji i koliki je rizik KV/CV događaja.
Evaluirana je kohorta bolesnika liječenih u KBSD s primjenom postupnika u kojoj je nađeno
4,1% KV/CV događaja (vs. 12,4% u sličnoj kohorti bez probira u literaturnoj kontroli) i 4,1%
ne-okularnih krvarenja. Više vrijednosti kreatinina i dulje trajanje liječenja IVT
bevacizumabom nezavisno su združeni s većim rizikom ozbiljnih kardio-/cerebrovaskularnih
štetnih događaja. Više vrijednosti kreatinina i više vrijednosti D-dimera nezavisno su
združene s većim rizikom krvarenja. Dulje vrijeme trajanja (povremene) izloženosti IVT
bevacizumabu nezavisno je združeno s višim razinama kreatinina i D-dimera tijekom
vremena. Koncentracije VEGF-a i bevacizumaba određivanih PEA metodom povezane su
linearno - porast koncentracije bevacizumaba dovodi do pada koncentracije VEGF-a. Opaženi
odnos između sistemskih koncentracija bevacizumaba i VEGF-a očekivan je, no valja uočiti
da je opažen nakon IVT primjene svega 1,25 mg bevacizumaba. VEGF pokazuje kompleksan
odnos koji odražava kompleksnu molekularnu biologiju molekule i brojne (pato)fiziološke
učinke koji se još moraju detaljnije istraživati. Predloženi postupnik mjera je minimizacije
rizika sustavnih štetnih događaja intravitrealno primijenjenoga bevacizumaba i služi odabiru
bolesnika u kojih će omjer koristi i rizika terapije biti povoljan.

Abstract (english)

The main objective of this doctoral dissertation is risk minimisation measures of systemic
adverse events of IVT bevacizumab in AMD treatment. We did a systematic review of all
published clinical studies and, based on the results, we cannot determine whether IVT
bevacizumab affects cardio-/cerebrovascular risk and in which direction. Treated patients
were evaluated through a 3-year period at University Hospital Sveti Duh with selection
protocol applied. Adverse cardio-/cerebrovascular events and non-ocular bleeding events
occurred each in 4.1% patients (vs. 12.4% patients in bibliographic control). Higher serum
creatinine levels and longer IVT bevacizumab treatment were independently associated with

higher cardio-/cerebroascular adverse event risk. Higher serum creatinine and D-dimer levels
were independently associated with higer bleeding risk. Longer treatment exposure was
independetly associated with higher serum creatinine and D-dimer levels in time. VEGF and
bevacizumab plasma concentrations, measured by PEA, were associated in linear relationship
– increase in bevacizumab concentration decreased VEGF concentration. This is in
accordance with the known mechanism of action, but achieved after intravitreal application of
only 1.25 mg bevacizumab. VEGF had shown complex relationship with measured laboratory
parameters, which mirrors complex (patho)-physiological and molecular biology, yet to be
elucidated. The recommended selection protocol is the risk minimisation measure for IVT
bevacizumab and could be a useful tool for patients with positive benefit/risk ratio in off-label
setting.

• Keywords: medicina
• Keywords (english): medicine
• Language: croatian
• URN:NBN: urn:nbn:hr:105:039887
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
• Type of resource: Text
• Extent: 100 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-05-05 08:43:37