RT info:eu-repo/semantics/doctoralThesis
T1 Sobre el beneficio de tratar con inhibidores del complemento: Evaluación farmacométrica  piloto
A1 Bernuy Guevara, Coralina Melissa
A2 Universidad de Valladolid. Escuela de Doctorado
K1 Farmacología
K1 Inhibidores
K1 Farmacométrica
K1 32 Ciencias Médicas
AB This PhD manuscript presents quantitative findings on the actual benefit of terminalcomplement component 5 (C5) inhibitors and complement component 1 (C1) esterase inhibitorsthrough their formal and common ¿off-label¿ indications. The results emanated from pairwiseand network meta-analyses to present evidence until September 2019. Clinical trials (CT) andreal-life non-randomized studies of the effects of interventions (NRSI) are consistent on thebenefits of C5 inhibitors and of the absence of effects of C1 esterase inhibitors (n = 7484):Mathematically, eculizumab (surface under the cumulative ranking area (SUCRA) >0.6) andravulizumab (SUCRA ¿ 0.7) were similar in terms of their protective effect on hemolysis inparoxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathy (TMA) in atypicalhemolytic uremic syndrome (aHUS), and acute kidney injury (AKI) in aHUS, in comparison topre-/off-treatment state and/or the standard of care (SUCRA < 0.01), and eculizumab had apositive effect on thrombotic events in PNH (odds ratio (OR)/95% confidence interval (95% CI)in CT and real-life NRSI, 0.07/0.03 to 0.19, 0.24/0.17 to 0.33) and chronic kidney disease(CKD) occurrence/progression in PNH (0.31/0.10 to 0.97, 0.66/0.44 to 0.98). In addition, metaanalysison clinical trials shows that eculizumab mitigates a refractory generalized myastheniagravis (rgMG) crisis (0.29/0.13 to 0.61) and prevents new acute antibody-mediated rejection(AMR) episodes in kidney transplant recipients (0.25/0.13 to 0.49). The update of findings fromthis meta-analysis will be useful to promote a better use of complement inhibitors in thoseaffected by the conditions may be treated by these drugs.
YR 2022
FD 2022
LK https://uvadoc.uva.es/handle/10324/69448
UL https://uvadoc.uva.es/handle/10324/69448
LA spa
NO Escuela de Doctorado
DS UVaDOC
RD 01-sep-2024