Long-term hepatic safety of lomitapide in homozygous familial hypercholesterolaemia
Autor: | Larrey, D., D'Erasmo, L., O'Brien, S., Arca, M., Italian Working Group on Lomitapide: Angelo Baldassare Cefalù, Alessia Di Costanzo, Simone, B., Antonina, G., Maurizio, A., Gabriella, I., Giuliana, F., Marco, G., Maria Donata Di Taranto, Arturo, P., Tiziana, M., Pavanello, C., Calabresi, L., Giovanni Battista Vigna, Marco, B., Katia, B., Tiziana, S., Francesco, S., Patrizia, S., Carlo, S., Fabio, F., Arturo, C., Paolo, C., Fulvio, V., Sergio, D., Livia, P., Stefano, B. |
---|---|
Přispěvatelé: | Larrey, Dominique, D'Erasmo, Laura, O'Brien, Sallyann, Arca, Marcello, Cefalù, Angelo Baldassare, Di Costanzo, Alessia, Bini, Simone, Giammanco, Antonina, Averna, Maurizio, Iannuzzo, Gabriella, Fortunato, Giuliana, Gentile, Marco, Di Taranto, Maria Donata, Pujia, Arturo, Montalcini, Tiziana, Pavanello, Chiara, Calabresi, Laura, Vigna, Giovanni Battista, Bucci, Marco, Bonomo, Katia, Sampietro, Tiziana, Sbrana, Francesco, Suppressa, Patrizia, Sabbà, Carlo, Fimiani, Fabio, Cesaro, Arturo, Calabrò, Paolo, Ventura, Fulvio, D’Addato, Sergio, Pisciotta, Livia, Bertolini, Stefano, Angelo Baldassare Cefalu', Alessia Di Costanzo, Simone Bini, Antonina Giammanco, Maurizio Averna, Gabriella Iannuzzo, Giuliana Fortunato, Marco Gentile, Maria Donata Di Taranto, Arturo Pujia, Tiziana Montalcini, Chiara Pavanello, Laura Calabresi, Giovanni Battista Vigna, Marco Bucci, Katia Bonomo, Tiziana Sampietro, Francesco Sbrana, Patrizia Suppressa, Carlo Sabbà, Fabio Fimiani, Arturo Cesaro, Paolo Calabrò, Fulvio Ventura, Sergio D'Addato, Livia Pisciotta, Stefano Bertolini |
Jazyk: | angličtina |
Rok vydání: | 2023 |
Předmět: | |
Popis: | Introduction: Lomitapide is a microsomal triglyceride transfer protein inhibitor for patients with homozygous familial hypercholesterolaemia. Due to its mechanism of action, potential hepatic effects of lomitapide are of clinical interest. This study aimed to determine the long-term hepatic safety of lomitapide. Methods: Data were aggregated from the pivotal phase 3 and extension phase clinical trial with lomitapide (median 5.1 years; serum total bilirubin, transaminases, cytokeratin-18 [CK-18] and enhanced liver fibrosis [ELF] score, fat-soluble vitamins and essential fatty acids), 8-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER) and real-world evidence from a cohort of patients treated with lomitapide in Italy (hepatic elastography, and FIB-4 score for hepatic fibrosis). Results: In the phase 3 trial and the LOWER registry, any asymptomatic excursions in liver transaminase levels were not associated with elevations in bilirubin, and no Hy's law cases were detected in up to 8 years follow-up. There were no clinically relevant increases among hepatic biomarkers CK-18, CK-18 fragments or ELF score and fat-soluble vitamins and essential fatty acids remained above normal levels. In 34 patients treated in Italy with lomita pide for more than 9 years, elevations in hepatic fat were mild-to-moderate; hepatic stiffness remained normal, and the mean FIB-4 score remained below the fibrosis threshold value of 2.67. Conclusions: These data indicate that the hepatic safety of lomitapide remains favourable with no clinically significant elevations in hepatic biomarkers and hepatic stiffness remained normal for more than 9 years follow-up. PHASE 3 TRIAL: NCT00730236; extension phase: NCT00943306; LOWER: NCT02135705. |
Databáze: | OpenAIRE |
Externí odkaz: |