Background: Lomitapide is a lipid-lowering agent indicated as adjunct therapy for adult HoFH. Objectives: This study evaluated the medium-term effectiveness and safety of lomitapide in a large cohort of HoFH patients in Europe. Methods: In a multicenter retrospective, observational study including 75 HoFH patients treated with lomitapide in a real-world clinical setting from 9 European countries, LDL-C changes, adverse events (AEs) as well as major adverse cardiovascular events (MACE) were assessed. Results: After a median 19 months (IQR 11-41 months) of treatment with a mean dosage of 20 mg of lomitapide. LDL-C 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 < 100mg/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 (GI) AEs occurred in 40% and liver transaminases increased (3-5 x ULN) 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. Conclusions: In this medium-term real-world experience, lomitapide proved to be very effective in reducing LDL-C in HoFH. GI 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.

d'Erasmo, L., Steward, K., Cefalù, A.B., Di Costanzo, A., Boersma, E., Bini, S., et al. (2021). EFFICACY AND SAFETY OF LOMITAPIDE IN HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA: THE PAN-EUROPEAN RETROSPECTIVE OBSERVATIONAL STUDY. EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY, 29, 832-841 [10.1093/eurjpc/zwab229].

EFFICACY AND SAFETY OF LOMITAPIDE IN HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA: THE PAN-EUROPEAN RETROSPECTIVE OBSERVATIONAL STUDY

Cefalù, Angelo Baldassare
Secondo
Conceptualization
;
Antonina Giammanco;Maurizio Averna;
2021-12-31

Abstract

Background: Lomitapide is a lipid-lowering agent indicated as adjunct therapy for adult HoFH. Objectives: This study evaluated the medium-term effectiveness and safety of lomitapide in a large cohort of HoFH patients in Europe. Methods: In a multicenter retrospective, observational study including 75 HoFH patients treated with lomitapide in a real-world clinical setting from 9 European countries, LDL-C changes, adverse events (AEs) as well as major adverse cardiovascular events (MACE) were assessed. Results: After a median 19 months (IQR 11-41 months) of treatment with a mean dosage of 20 mg of lomitapide. LDL-C 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 < 100mg/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 (GI) AEs occurred in 40% and liver transaminases increased (3-5 x ULN) 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. Conclusions: In this medium-term real-world experience, lomitapide proved to be very effective in reducing LDL-C in HoFH. GI 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.
Settore MED/09 - Medicina Interna
d'Erasmo, L., Steward, K., Cefalù, A.B., Di Costanzo, A., Boersma, E., Bini, S., et al. (2021). EFFICACY AND SAFETY OF LOMITAPIDE IN HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA: THE PAN-EUROPEAN RETROSPECTIVE OBSERVATIONAL STUDY. EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY, 29, 832-841 [10.1093/eurjpc/zwab229].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/534839
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