Efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia: the pan-European retrospective observational study
Laura D’Erasmo, Kim Steward, Angelo B. Cefalù, Alessia Di Costanzo, Eric Boersma, Simone Bini, Marcello Arca, Jeanine E. Roeters van Lennep, the Italian and European Working Group on Lomitapide in HoFH, Laura D’Erasmo, Angelo Baldassare Cefalù, Alessia Di Costanzo, Simone Bini, Antonina Giammanco, Maurizio Averna, Gabriella Iannuzzo, Giuliana Fortunato, Marco Gentile, Arturo Puja, Tiziana Montalcini, Chiara Pavanello, Laura Calabresi, Giovanni Battista Vigna, Marco Bucci, Katia Bonomo, Fabio Nota, Tiziana Sampietro, Francesco Sbrana, Patrizia Suppressa, Carlo Sabbà, Fabio Fimiani, Arturo Cesaro, Paolo Calabrò, Fulvio Ventura, Sergio D’Addato, Livia Pisciotta, Stefano Bertolini, Marcello Arca, Genovefa Kolovou, Evangelos Liberopoulos, Eugene Daphnis, Jeanine E. Roeters van Lennep, Joost H.W. Rutten, Eric Boersma, Kim Steward, Anja Vogt, Jaimini Cegla, Shahenaz Walji, Meral Kayıkçıoğlu, José Manuel Fernández‐Real, Sergio Martínez‐Hervás, Avishay Ellis, Karin Littmann
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.