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Adverse events of biologic therapy in psoriasis
Marques, Emanuel Carvalheiro ; Paluch, Zoltán (advisor) ; Kančeva, Radmila (referee) ; Farghali, Hassan (referee)
1 Adverse events of biologic therapy in psoriasis Abstract This doctoral thesis focuses on psoriasis vulgaris and its therapy, especially biologic agents and their safety profiles. The objectives of this research were to identify prognostic factors of severe psoriasis, compare the safety profiles of different therapy types (topical compounds, non-biologic systemic agents and biologic agents) and those of biologic agents themselves (adalimumab, etarnecept, infliximab, secukinumab, ustekinumab). A total of 289 psoriatic patients were followed up for 30 months; these were divided into 3 groups according to therapy type. Comorbidities, epidemiological parameters, and rates of adverse events were compared between the three groups and, also, between each of the 5 biologic agents, and the data were statistically analysed. It was concluded that psoriasis severity is directly related to an increased risk of cardiovascular disease, depression, hyperuricemia, and nonspecific noninfectious liver disease. Male gender, increased height, early age at disease onset, viral upper respiratory infections and periods of hormonal changes seem to be prognostic of higher levels of psoriasis severity. When comparing therapy types, biologic agents were the most effective therapies; however, they were associated with higher rates of...
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Metabolism of immunosuppressants in children with inflammatory bowel disease
Pospíšilová, Kristýna ; Bronský, Jiří (advisor) ; Leníček, Martin (referee) ; Dědek, Petr (referee)
Metabolism of immunosuppressants in children with inflammatory bowel disease Abstract Thiopurines are still used as the main immunosuppressants in the maintenance therapy of paediatric Crohn's disease. According to official guidelines, in case of failure, biological therapy (mainly infliximab or adalimumab) is generally commenced. The present thesis focuses on the possibilities of therapy optimization in children in whom the conventional Crohn's disease therapy has failed based on the metabolism of administered immunosuppressive medications. We confirmed that the knowledge of thiopurine metabolites concentration in red blood cells may help to monitor patients' adherence to therapy. However, according to our observations in children on combination therapy of infliximab and thiopurine lower concentrations of 6- thioguanine (the active metabolite of thiopurines) seems to be effective compared to what has been expected. We presented a web application designed to partially substitute for the thiopurine metabolite measurements based on easily available laboratory data. Last, but not least, we confirmed that the clinical effect and safety profile of both adalimumab and infliximab are similar in the treatment of paediatric Crohn's disease. Only in case of family history of atopic dermatitis adalimumab may be preferred.
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