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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.
Detailed record
Immunosuppression in active multiple sclerosis: combination treatment with interferon beta and azathioprine and fingolimod monotherapy
Tichá, Veronika
;
Kubala Havrdová, Eva
(advisor) ;
Vymazal, Josef
(referee) ;
Laczó, Jan
(referee)
Introduction: Addition of a second drug used to be a strategy to achieve clinical stabilization of multiple sclerosis in many patients with on-going activity despite monotherapy. Modern immunosuppressive drugs used in monotherapy exert more specific mode of action. Methods: This retrospective observational study evaluated 5-year data from 85 patients with active multiple sclerosis despite monotherapy with either interferon beta or azathioprine, who received add-on azathioprine or interferon beta, respectively. In a subgroup of 23 patients 10- year data were analysed. In a second part of the study, a group of 126 patients switched either from interferon beta or glatiramer acetate to fingolimod was followed-up for one after the change of their treatment and a in a subgroup of 53 patients the 2-year data were assessed. Clinical (relapse frequency, disability) parameters were compared preceding and following the addition of second drug or the switch of treatment. Laboratory results and potential serious adverse events were evaluated in a group of patients with combination therapy. Results: The add-on treatment triggered a drop in annualised relapse rate by approximately 1.5 points sustained over 5 and 10 years. No effect on disability was observed. Simultaneously, white blood cell and lymphocyte counts...
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