{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:12:33Z","timestamp":1783696353321,"version":"3.55.0"},"reference-count":26,"publisher":"Becaris Publishing Limited","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Comp. Eff. Res."],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by severe hypertriglyceridemia causing recurrent acute pancreatitis (AP). Since FCS is a genetic deficiency in functional lipoprotein lipase, conventional triglyceride-lowering therapies are ineffective in this metabolic disorder. Apolipoprotein C-III (apoC-III) inhibitors, including volanesorsen and olezarsen, have emerged as targeted treatments for FCS.\n                    <jats:bold>Aim:<\/jats:bold>\n                    To compare the efficacy and safety of olezarsen 80\u00a0mg every four weeks (Q4W) versus volanesorsen 300\u00a0mg weekly (QW) in patients with FCS using an anchored matching-adjusted indirect comparison.\n                    <jats:bold>Materials &amp; methods:<\/jats:bold>\n                    Individual patient data from the Balance trial of olezarsen (n\u00a0=\u00a045) were weighted to match baseline characteristics reported in the APPROACH trial of volanesorsen (n\u00a0=\u00a066). Outcomes included percent change in fasting triglycerides (TG) and apoC-III at 26 and 52\u00a0weeks, and risks of AP events and adverse events at 52\u00a0weeks.\n                    <jats:bold>Results:<\/jats:bold>\n                    At 52\u00a0weeks, mean differences in fasting TG and apoC-III were -27.4% (95% CI: -69.4, 14.5) and -21.3% (95% CI: -61.9, 19.3). Relative risks of AP, treatment-emergent adverse events, and serious adverse events were 0.23 (95% CI: 0.01, 5.02), 0.87 (95% CI: 0.66, 1.13) and 0.50 (95% CI: 0.08, 3.26) at week 52. The rate ratio for AP events per patient-year was 0.06 (95% CI: 0.003, 1.41). No comparisons were statistically significant.\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    In this matching-adjusted indirect comparison, no statistically significant differences in outcomes were observed between olezarsen and volanesorsen in patients with FCS. These findings provide important comparative context in a setting where head-to-head evidence is unavailable.\n                  <\/jats:p>","DOI":"10.57264\/cer-2026-0069","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:41:56Z","timestamp":1781880116000},"source":"Crossref","is-referenced-by-count":0,"title":["Comparative efficacy and safety of olezarsen versus volanesorsen for familial chylomicronemia syndrome: a matching-adjusted indirect comparison"],"prefix":"10.57264","volume":"15","author":[{"given":"Handrean","family":"Soran","sequence":"first","affiliation":[{"name":"NIHR\/Welcome Trust Clinical Research Facility &amp; Manchester University Hospital NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9417-6637","authenticated-orcid":false,"given":"Asia Sikora","family":"Kessler","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals Inc., Carlsbad, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0669-1657","authenticated-orcid":false,"given":"Montserrat","family":"Vera-Llonch","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals Inc., Carlsbad, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3729-5749","authenticated-orcid":false,"given":"Veronica J","family":"Alexander","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals Inc., Carlsbad, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9773-5837","authenticated-orcid":false,"given":"Paul","family":"Serafini","sequence":"additional","affiliation":[{"name":"Evidinno Outcomes Research Inc., Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6680-4074","authenticated-orcid":false,"given":"Divya","family":"Pushkarna","sequence":"additional","affiliation":[{"name":"Evidinno Outcomes Research Inc., Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabete","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, ULS Sao Joao, Faculty of Medicine, University of Porto (FMUP), Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7584-7677","authenticated-orcid":false,"given":"Erik","family":"Stroes","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8009-9482","authenticated-orcid":false,"given":"Ulrike","family":"Schatz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III of the University Hospital Dresden, Technical University of Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4536-7063","authenticated-orcid":false,"given":"Ursula","family":"Kassner","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Division of Lipid Disorders, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5835-8599","authenticated-orcid":false,"given":"Zalmai","family":"Hakimi","sequence":"additional","affiliation":[{"name":"Sobi, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aletta","family":"Falk","sequence":"additional","affiliation":[{"name":"Sobi, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8732-8249","authenticated-orcid":false,"given":"Koo","family":"Wilson","sequence":"additional","affiliation":[{"name":"Sobi, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"36897","reference":[{"issue":"8","key":"e_1_3_8_3_2","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1080\/00325481.2016.1243005","article-title":"Hypertriglyceridemia: the importance of identifying patients at risk","volume":"128","author":"Kushner PA","year":"2016","unstructured":"Kushner PA, Cobble ME. Hypertriglyceridemia: the importance of identifying patients at risk. Postgrad Med. 128(8), 848\u2013858 (2016).","journal-title":"Postgrad Med."},{"issue":"1","key":"e_1_3_8_4_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s11010-008-0005-1","article-title":"Hypertriglyceridemia: phenomics and genomics","volume":"326","author":"Hegele RA","year":"2009","unstructured":"Hegele RA, Pollex RL. Hypertriglyceridemia: phenomics and genomics. Mol. Cell. Biochem. 326(1\u20132), 35\u201343 (2009).","journal-title":"Mol. Cell. Biochem."},{"issue":"19","key":"e_1_3_8_5_2","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1177\/2047487319888054","article-title":"Prevalence of familial chylomicronemia syndrome in a quaternary care center","volume":"27","author":"Pallazola VA","year":"2020","unstructured":"Pallazola VA, Sajja A, Derenbecker R Prevalence of familial chylomicronemia syndrome in a quaternary care center. Eur. J. Prev. Cardiol. 27(19), 2276\u20132278 (2020).","journal-title":"Eur. J. Prev. Cardiol."},{"issue":"3","key":"e_1_3_8_6_2","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.jacl.2025.03.013","article-title":"Familial chylomicronemia syndrome: an expert clinical review from the National Lipid Association","volume":"19","author":"Javed F","year":"2025","unstructured":"Javed F, Hegele RA, Garg A Familial chylomicronemia syndrome: an expert clinical review from the National Lipid Association. J. Clin. Lipidol. 19(3), 382\u2013403 (2025).","journal-title":"J. Clin. Lipidol."},{"issue":"4","key":"e_1_3_8_7_2","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1080\/17446651.2024.2365787","article-title":"Etiology and emerging treatments for familial chylomicronemia syndrome","volume":"19","author":"Spagnuolo CM","year":"2024","unstructured":"Spagnuolo CM, Hegele RA. Etiology and emerging treatments for familial chylomicronemia syndrome. Expert Rev. Endocrinol. Metab. 19(4), 299\u2013306 (2024).","journal-title":"Expert Rev. Endocrinol. Metab."},{"issue":"12","key":"e_1_3_8_8_2","doi-asserted-by":"crossref","first-page":"e304","DOI":"10.1161\/ATV.0000000000000177","article-title":"Lipoprotein apheresis: utility, outcomes, and implementation in clinical practice: a scientific statement from the American Heart Association","volume":"44","author":"Gianos E","year":"2024","unstructured":"Gianos E, Duell PB, Toth PP Lipoprotein apheresis: utility, outcomes, and implementation in clinical practice: a scientific statement from the American Heart Association. Arterioscler. Thromb. Vasc. Biol. 44(12), e304\u2013e321 (2024).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"issue":"5","key":"e_1_3_8_9_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s11883-021-00914-7","article-title":"ANGPTL3 and apolipoprotein C-III as novel lipid-lowering targets","volume":"23","author":"Akoumianakis I","year":"2021","unstructured":"Akoumianakis I, Zvintzou E, Kypreos K, Filippatos TD. ANGPTL3 and apolipoprotein C-III as novel lipid-lowering targets. Curr. Atheroscler. Rep. 23(5), 20 (2021).","journal-title":"Curr. Atheroscler. Rep."},{"issue":"1","key":"e_1_3_8_10_2","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1194\/jlr.M900346-JLR200","article-title":"Expression of apolipoprotein C-III in McA-RH7777 cells enhances VLDL assembly and secretion under lipid-rich conditions","volume":"51","author":"Sundaram M","year":"2010","unstructured":"Sundaram M, Zhong S, Bou Khalil M Expression of apolipoprotein C-III in McA-RH7777 cells enhances VLDL assembly and secretion under lipid-rich conditions. J. Lipid Res. 51(1), 150\u2013161 (2010).","journal-title":"J. Lipid Res."},{"issue":"12","key":"e_1_3_8_11_2","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1007\/s40265-019-01168-z","article-title":"Volanesorsen: first global approval","volume":"79","author":"Paik J","year":"2019","unstructured":"Paik J, Duggan S. Volanesorsen: first global approval. Drugs 79(12), 1349\u20131354 (2019).","journal-title":"Drugs"},{"issue":"5","key":"e_1_3_8_12_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s11883-020-00836-w","article-title":"Efficacy and safety of volanesorsen (ISIS 304801): the evidence from Phase II and III clinical trials","volume":"22","author":"Fogacci F","year":"2020","unstructured":"Fogacci F, Norata GD, Toth PP, Arca M, Cicero AFG. Efficacy and safety of volanesorsen (ISIS 304801): the evidence from Phase II and III clinical trials. Curr. Atheroscler. Rep. 22(5), 18 (2020).","journal-title":"Curr. Atheroscler. Rep."},{"issue":"4","key":"e_1_3_8_13_2","doi-asserted-by":"crossref","first-page":"982","DOI":"10.3390\/jcm11040982","article-title":"Volanesorsen: a new Era in the treatment of severe hypertriglyceridemia","volume":"11","author":"Kolovou G","year":"2022","unstructured":"Kolovou G, Kolovou V, Katsiki N. Volanesorsen: a new Era in the treatment of severe hypertriglyceridemia. J. Clin. Med. 11(4), 982 (2022).","journal-title":"J. Clin. Med."},{"issue":"4","key":"e_1_3_8_14_2","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s40265-025-02166-0","article-title":"Olezarsen: first approval","volume":"85","author":"Syed YY","year":"2025","unstructured":"Syed YY. Olezarsen: first approval. Drugs 85(4), 571\u2013576 (2025).","journal-title":"Drugs"},{"key":"e_1_3_8_15_2","unstructured":"European Medicines Agency. Summary of opinion - initial authorization - Tryngolza (olezarsen). (2025). Available from: https:\/\/www.ema.europa.eu\/en\/documents\/smop-initial\/chmp-summary-positive-opinion-tryngolza_en.pdf"},{"key":"e_1_3_8_16_2","unstructured":"US Food and Drug Administration. FDA approves drug to reduce triglycerides in adult patients with familial chylomicronemia syndrome: FDA. (2024). Available from: https:\/\/www.fda.gov\/drugs\/news-events-human-drugs\/fda-approves-drug-reduce-triglycerides-adult-patients-familial-chylomicronemia-syndrome"},{"issue":"19","key":"e_1_3_8_17_2","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1056\/NEJMoa2400201","article-title":"Olezarsen, acute pancreatitis, and familial chylomicronemia syndrome","volume":"390","author":"Stroes ESG","year":"2024","unstructured":"Stroes ESG, Alexander VJ, Karwatowska-Prokopczuk E Olezarsen, acute pancreatitis, and familial chylomicronemia syndrome. N. Engl. J. Med. 390(19), 1781\u20131792 (2024).","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_8_18_2","unstructured":"European Medicines Agency. Waylivra (volanesorsen) EU SmPC\/EPAR product information. (2025). Available from: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/waylivra-epar-product-information_en.pdf"},{"issue":"2","key":"e_1_3_8_19_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1177\/0272989X17725740","article-title":"Methods for population-adjusted indirect comparisons in health technology appraisal","volume":"38","author":"Phillippo DM","year":"2018","unstructured":"Phillippo DM, Ades AE, Dias S, Palmer S, Abrams KR, Welton NJ. Methods for population-adjusted indirect comparisons in health technology appraisal. Med. Decis. Making. 38(2), 200\u2013211 (2018).","journal-title":"Med. Decis. Making."},{"key":"e_1_3_8_20_2","doi-asserted-by":"crossref","DOI":"10.1002\/9781119536604","volume-title":"Cochrane handbook for systematic reviews of interventions","author":"Higgins JPT","year":"2019","unstructured":"Higgins JPT, Thomas J, Chandler Jet al. (Eds). Cochrane handbook for systematic reviews of interventions. 2nd Edition. John Wiley & Sons, Chichester (UK) (2019).","edition":"2"},{"issue":"6","key":"e_1_3_8_21_2","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1056\/NEJMoa1715944","article-title":"Volanesorsen and triglyceride levels in familial chylomicronemia syndrome","volume":"381","author":"Witztum JL","year":"2019","unstructured":"Witztum JL, Gaudet D, Freedman SD Volanesorsen and triglyceride levels in familial chylomicronemia syndrome. N. Engl. J. Med. 381(6), 531\u2013542 (2019).","journal-title":"N. Engl. J. Med."},{"issue":"5","key":"e_1_3_8_22_2","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/S2213-8587(21)00046-2","article-title":"Efficacy and safety of volanesorsen in patients with multifactorial chylomicronaemia (COMPASS): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial","volume":"9","author":"Gouni-Berthold I","year":"2021","unstructured":"Gouni-Berthold I, Alexander VJ, Yang Q Efficacy and safety of volanesorsen in patients with multifactorial chylomicronaemia (COMPASS): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 9(5), 264\u2013275 (2021).","journal-title":"Lancet Diabetes Endocrinol."},{"issue":"10","key":"e_1_3_8_23_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v011.i10","article-title":"Econometric computing with HC and HAC covariance matrix estimators","volume":"11","author":"Zeileis A","year":"2004","unstructured":"Zeileis A. Econometric computing with HC and HAC covariance matrix estimators. J. Stat. Softw. 11(10), 1\u201317 (2004).","journal-title":"J. Stat. Softw."},{"issue":"6","key":"e_1_3_8_24_2","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S0895-4356(97)00049-8","article-title":"The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials","volume":"50","author":"Bucher HC","year":"1997","unstructured":"Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J. Clin. Epidemiol. 50(6), 683\u2013691 (1997).","journal-title":"J. Clin. Epidemiol."},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vhri.2025.101088"},{"issue":"1","key":"e_1_3_8_26_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s12944-024-02389-2","article-title":"Safety and efficacy of antisense oligonucleotides on triglyceride, apolipoprotein C-III, and other lipid parameters levels in hypertriglyceridemia; a network meta-analysis of randomized controlled trials","volume":"24","author":"Mahmoud A","year":"2025","unstructured":"Mahmoud A, Abdelsayed K, Mohamed AA Safety and efficacy of antisense oligonucleotides on triglyceride, apolipoprotein C-III, and other lipid parameters levels in hypertriglyceridemia; a network meta-analysis of randomized controlled trials. Lipids Health Dis. 24(1), 109 (2025).","journal-title":"Lipids Health Dis."},{"issue":"1","key":"e_1_3_8_27_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s44337-025-00329-2","article-title":"Efficacy and safety of olezarsen in treating hypertriglyceridemia: a systematic review and meta-analysis of randomized controlled trials","volume":"2","author":"Saddique MN","year":"2025","unstructured":"Saddique MN, Thapa R, Khan Y Efficacy and safety of olezarsen in treating hypertriglyceridemia: a systematic review and meta-analysis of randomized controlled trials. Discov. Med. 2(1), 117 (2025).","journal-title":"Discov. Med."},{"issue":"3","key":"e_1_3_8_28_2","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.jacl.2024.12.018","article-title":"Differential effects of volanesorsen on apoC-III, triglycerides, and pancreatitis in familial chylomicronemia syndrome diagnosed by genetic or nongenetic criteria","volume":"19","author":"Tsimikas S","year":"2025","unstructured":"Tsimikas S, Ginsberg HN, Alexander VJ Differential effects of volanesorsen on apoC-III, triglycerides, and pancreatitis in familial chylomicronemia syndrome diagnosed by genetic or nongenetic criteria. J. Clin. Lipidol. 19(3), 422\u2013431 (2025).","journal-title":"J. Clin. Lipidol."}],"container-title":["Journal of Comparative Effectiveness Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/becarispublishing.com\/doi\/pdf\/10.57264\/cer-2026-0069","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T14:13:41Z","timestamp":1783692821000},"score":1,"resource":{"primary":{"URL":"https:\/\/becarispublishing.com\/doi\/10.57264\/cer-2026-0069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":26,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.57264\/cer-2026-0069"],"URL":"https:\/\/doi.org\/10.57264\/cer-2026-0069","relation":{},"ISSN":["2042-6305","2042-6313"],"issn-type":[{"value":"2042-6305","type":"print"},{"value":"2042-6313","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"article-number":"e260069"}}