Aims: Lomitapide is a lipid-lowering agent indicated as an adjunct therapy for adult homozygous familial hypercholesterolaemia (HoFH). This study evaluated the medium-term effectiveness and safety of lomitapide in a large cohort of HoFH patients in Europe. Methods and results: In a multicentre retrospective, observational study including 75 HoFH patients treated with lomitapide in a real-world clinical setting from 9 European countries, low-density lipoprotein cholesterol (LDL-C) changes, adverse events (AEs), and major adverse cardiovascular events (MACE) were assessed. After a median 19 months (interquartile range 11-41 months) of treatment with a mean dosage of 20 mg of lomitapide. Low-density lipoprotein cholesterol decreased by 60%, from baseline 280.5 mg/dL (191.8-405.0 mg/dL) to 121.6 mg/dL (61.0-190.5 mg/dL). At the last visit, 32.0% of patients achieved LDL-C <100 mg/dL and 18.7% <70 mg/dL. At baseline, 38 HoFH patients were receiving LDL apheresis (LA), but after initiation of lomitapide 36.8% of patients discontinued LA. During follow-up, lomitapide was permanently interrupted in 13% of patients. Gastrointestinal AEs occurred in 40% and liver transaminases increased (3-5 × upper limits of normal) in 13% of patients. Among patients with liver ultrasound evaluation (n = 45), a modest increase in hepatic steatosis was noted during treatment; however, liver stiffness measured by elastography in 30 of them remained within the normal range. Among HoFH patients exposed to lomitapide for at least 2 years, MACE incident rate was 7.4 per 1000 person-years in the 2 years after as compared to 21.2 per 1000 person-years before treatment with lomitapide. Conclusion: In this medium-term real-world experience, lomitapide proved to be very effective in reducing LDL-C in HoFH. Gastrointestinal AEs were common, but liver safety was reassuring with no sign of increased risk of liver fibrosis. A signal of cardiovascular protection was also observed.

Efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia: the pan-European retrospective observational study / D'Erasmo, Laura; Baldassare Cefalù, Angelo; Di Costanzo, Alessia; Bini, Simone; Giammanco, Antonina; Averna, Maurizio; Iannuzzo, Gabriella; Fortunato, Giuliana; Gentile, Marco; Puja, Arturo; Montalcini, Tiziana; Pavanello, Chiara; Calabresi, Laura; Battista Vigna, Giovanni; Bucci, Marco; Bonomo, Katia; Nota, Fabio; Sampietro, Tiziana; Sbrana, Francesco; Suppressa, Patrizia; Sabbà, Carlo; Fimiani, Fabio; Cesaro, Arturo; Calabrò, Paolo; Ventura, Fulvio; D'Addato, Sergio; Pisciotta, Livia; Bertolini, Stefano; Arca, Marcello; Kolovou, Genovefa; Liberopoulos, Evangelos; Daphnis, Eugene; Roeters van Lennep, Jeanine; Rutten, Joost; Boersma, Eric; Steward, Kim; Vogt, Anja; Cegla, Jaimini; Walji, Shahenaz; Kayikcioglu, Meral; Real, José; Martínez-Hervás, Sergio; Ellis, Avishay; Littmann, Karin. - In: EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY. - ISSN 2047-4881. - 29:5(2022), p. 832-841. [10.1093/eurjpc/zwab229]

Efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia: the pan-European retrospective observational study

Maurizio Averna;Gabriella Iannuzzo;Giuliana Fortunato;Marco Gentile;
2022

Abstract

Aims: Lomitapide is a lipid-lowering agent indicated as an adjunct therapy for adult homozygous familial hypercholesterolaemia (HoFH). This study evaluated the medium-term effectiveness and safety of lomitapide in a large cohort of HoFH patients in Europe. Methods and results: In a multicentre retrospective, observational study including 75 HoFH patients treated with lomitapide in a real-world clinical setting from 9 European countries, low-density lipoprotein cholesterol (LDL-C) changes, adverse events (AEs), and major adverse cardiovascular events (MACE) were assessed. After a median 19 months (interquartile range 11-41 months) of treatment with a mean dosage of 20 mg of lomitapide. Low-density lipoprotein cholesterol decreased by 60%, from baseline 280.5 mg/dL (191.8-405.0 mg/dL) to 121.6 mg/dL (61.0-190.5 mg/dL). At the last visit, 32.0% of patients achieved LDL-C <100 mg/dL and 18.7% <70 mg/dL. At baseline, 38 HoFH patients were receiving LDL apheresis (LA), but after initiation of lomitapide 36.8% of patients discontinued LA. During follow-up, lomitapide was permanently interrupted in 13% of patients. Gastrointestinal AEs occurred in 40% and liver transaminases increased (3-5 × upper limits of normal) in 13% of patients. Among patients with liver ultrasound evaluation (n = 45), a modest increase in hepatic steatosis was noted during treatment; however, liver stiffness measured by elastography in 30 of them remained within the normal range. Among HoFH patients exposed to lomitapide for at least 2 years, MACE incident rate was 7.4 per 1000 person-years in the 2 years after as compared to 21.2 per 1000 person-years before treatment with lomitapide. Conclusion: In this medium-term real-world experience, lomitapide proved to be very effective in reducing LDL-C in HoFH. Gastrointestinal AEs were common, but liver safety was reassuring with no sign of increased risk of liver fibrosis. A signal of cardiovascular protection was also observed.
2022
Efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia: the pan-European retrospective observational study / D'Erasmo, Laura; Baldassare Cefalù, Angelo; Di Costanzo, Alessia; Bini, Simone; Giammanco, Antonina; Averna, Maurizio; Iannuzzo, Gabriella; Fortunato, Giuliana; Gentile, Marco; Puja, Arturo; Montalcini, Tiziana; Pavanello, Chiara; Calabresi, Laura; Battista Vigna, Giovanni; Bucci, Marco; Bonomo, Katia; Nota, Fabio; Sampietro, Tiziana; Sbrana, Francesco; Suppressa, Patrizia; Sabbà, Carlo; Fimiani, Fabio; Cesaro, Arturo; Calabrò, Paolo; Ventura, Fulvio; D'Addato, Sergio; Pisciotta, Livia; Bertolini, Stefano; Arca, Marcello; Kolovou, Genovefa; Liberopoulos, Evangelos; Daphnis, Eugene; Roeters van Lennep, Jeanine; Rutten, Joost; Boersma, Eric; Steward, Kim; Vogt, Anja; Cegla, Jaimini; Walji, Shahenaz; Kayikcioglu, Meral; Real, José; Martínez-Hervás, Sergio; Ellis, Avishay; Littmann, Karin. - In: EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY. - ISSN 2047-4881. - 29:5(2022), p. 832-841. [10.1093/eurjpc/zwab229]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/885541
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