Federica Fogacci1, Nicola Ferri2, Peter P Toth3,4, Massimiliano Ruscica5, Alberto Corsini5,6, Arrigo F G Cicero7. 1. Medical and Surgical Sciences Department, University of Bologna, Via Albertoni, 15, 40138, Bologna, Italy. 2. Drug Sciences Department, University of Padua, Padua, Italy. 3. CGH Medical Center, Sterling, IL, USA. 4. Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 5. Pharmacological and Biomolecular Sciences Department, University of Milan, Milan, Italy. 6. IRCCS Multimedica, Milan, Italy. 7. Medical and Surgical Sciences Department, University of Bologna, Via Albertoni, 15, 40138, Bologna, Italy. arrigo.cicero@unibo.it.
Abstract
AIM: Our aim was to assess the efficacy and safety of mipomersen through a systematic review of the literature and a meta-analysis of the available clinical studies. METHODS: A systematic literature search in SCOPUS, PubMed Medline, ISI Web of Science and Google Scholar databases was conducted up to January 20, 2019, in order to identify clinical trials assessing the effect of mipomersen on lipoproteins, and the safety profile of mipomersen. Effect sizes for lipid changes were expressed as weighted mean differences (WMD) and 95% confidence intervals (CI). For safety analysis, odd ratios (OR) and 95% CI were calculated using the Mantel-Haenszel method. Data were pooled from 13 clinical studies comprising 49 arms, which included 1053 subjects overall, with 729 in the active-treated arm and 324 in the control arm. RESULTS: Meta-analysis of data suggested that mipomersen significantly reduced low-density lipoprotein cholesterol (WMD - 1.52, 95% CI - 1.85 to - 1.19; p < 0.001), total cholesterol (WMD - 1.55, 95% CI - 1.97 to - 1.13; p < 0.001), non-high-density lipoprotein cholesterol (non-HDL-C) (WMD - 1.66, 95% CI - 2.06 to - 1.27; p < 0.001), lipoprotein(a) (WMD - 0.99, 95% CI - 1.37 to - 0.62; p < 0.001), apolipoprotein B (WMD - 1.66, 95% CI - 2.04 to - 1.27; p < 0.001), triglycerides (WMD -0.61, 95% CI - 0.76 to - 0.46, p < 0.001), very-low-density lipoprotein cholesterol (WMD - 0.58, 95% CI - 0.73 to - 0.43; p < 0.001) and apolipoprotein A-I (WMD - 0.25, 95% CI - 0.51 to - 0.001; p = 0.049) without affecting HDL-C levels (WMD 0.11, 95% CI - 0.03 to 0.26; p = 0.124). However, treatment with mipomersen was positively associated with an increased risk of discontinuation of treatment (OR 3.02, 95% CI 1.96-4.65; p < 0.001), injection-site reaction (OR 11.41, 95% CI 7.88-16.52; p < 0.001), hepatic steatosis (OR 4.96, 95% CI 1.99-12.39; p = 0.001), hepatic enzymes elevation (OR 3.61, 95% CI 2.09-6.24; p < 0.001) and flu-like symptoms (OR 2.02, 95% CI 1.45-2.81; p < 0.001). CONCLUSION: Despite favourable effects on the lipid profile, some concerns are reinforced from the safety profile. As a matter of fact, mipomersen therapy is more likely discontinued and associated with increased risk of injection-site reactions, hepatic steatosis, hepatic enzyme elevation, and flu-like symptoms.
AIM: Our aim was to assess the efficacy and safety of mipomersen through a systematic review of the literature and a meta-analysis of the available clinical studies. METHODS: A systematic literature search in SCOPUS, PubMed Medline, ISI Web of Science and Google Scholar databases was conducted up to January 20, 2019, in order to identify clinical trials assessing the effect of mipomersen on lipoproteins, and the safety profile of mipomersen. Effect sizes for lipid changes were expressed as weighted mean differences (WMD) and 95% confidence intervals (CI). For safety analysis, odd ratios (OR) and 95% CI were calculated using the Mantel-Haenszel method. Data were pooled from 13 clinical studies comprising 49 arms, which included 1053 subjects overall, with 729 in the active-treated arm and 324 in the control arm. RESULTS: Meta-analysis of data suggested that mipomersen significantly reduced low-density lipoprotein cholesterol (WMD - 1.52, 95% CI - 1.85 to - 1.19; p < 0.001), total cholesterol (WMD - 1.55, 95% CI - 1.97 to - 1.13; p < 0.001), non-high-density lipoprotein cholesterol (non-HDL-C) (WMD - 1.66, 95% CI - 2.06 to - 1.27; p < 0.001), lipoprotein(a) (WMD - 0.99, 95% CI - 1.37 to - 0.62; p < 0.001), apolipoprotein B (WMD - 1.66, 95% CI - 2.04 to - 1.27; p < 0.001), triglycerides (WMD -0.61, 95% CI - 0.76 to - 0.46, p < 0.001), very-low-density lipoprotein cholesterol (WMD - 0.58, 95% CI - 0.73 to - 0.43; p < 0.001) and apolipoprotein A-I (WMD - 0.25, 95% CI - 0.51 to - 0.001; p = 0.049) without affecting HDL-C levels (WMD 0.11, 95% CI - 0.03 to 0.26; p = 0.124). However, treatment with mipomersen was positively associated with an increased risk of discontinuation of treatment (OR 3.02, 95% CI 1.96-4.65; p < 0.001), injection-site reaction (OR 11.41, 95% CI 7.88-16.52; p < 0.001), hepatic steatosis (OR 4.96, 95% CI 1.99-12.39; p = 0.001), hepatic enzymes elevation (OR 3.61, 95% CI 2.09-6.24; p < 0.001) and flu-like symptoms (OR 2.02, 95% CI 1.45-2.81; p < 0.001). CONCLUSION: Despite favourable effects on the lipid profile, some concerns are reinforced from the safety profile. As a matter of fact, mipomersen therapy is more likely discontinued and associated with increased risk of injection-site reactions, hepatic steatosis, hepatic enzyme elevation, and flu-like symptoms.
Authors: Abel A Pavía-López; Marco A Alcocer-Gamba; Edith D Ruiz-Gastelum; José L Mayorga-Butrón; Roopa Mehta; Filiberto A Díaz-Aragón; Jorge A Aldrete-Velasco; Nitzia López-Juárez; Ivette Cruz-Bautista; Adolfo Chávez-Mendoza; Nikos C Secchi-Nicolás; Francisco J Guerrero-Martínez; Jorge E Cossio-Aranda; Victoria Mendoza-Zubieta; Guillermo Fanghänel-Salmon; Martha Valdivia-Proa; Luis Olmos-Domínguez; Carlos A Aguilar-Salinas; Luis Dávila-Maldonado; Armando Vázquez-Rangel; Vanina Pavia-Aubry; María de Los A Nava-Hernández; Carlos A Hinojosa-Becerril; Juan C Anda-Garay; Manuel O de Los Ríos-Ibarra; Ana C Berni-Betancourt; Julio López-Cuellar; Diego Araiza-Garaygordobil; Romina Rivera-Reyes; Gabriela Borrayo-Sánchez; Mónica Tapia-Hernández; Claudia V Cano-Nigenda; Arturo Guerra-López; Josué Elías-López; Marco A Figueroa-Morales; Bertha B Montaño-Velázquez; Liliana Velasco-Hidalgo; Ana L Rodríguez-Lozano; Claudia Pimentel-Hernández; María M Baquero-Hoyos; Felipe Romero-Moreno; Mario Rodríguez-Vega Journal: Arch Cardiol Mex Date: 2022
Authors: Arrigo F G Cicero; Cormac Kennedy; Tamara Knežević; Marilisa Bove; Coralie M G Georges; Agnė Šatrauskienė; Peter P Toth; Federica Fogacci Journal: Nutrients Date: 2021-02-16 Impact factor: 5.717