{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:41:57Z","timestamp":1790707317769,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Multiple sclerosis (MS) is associated with significant early morbidity, reduced life expectancy and substantial healthcare and societal costs. The primary objective of this study is to assess the early cost\u2010effectiveness potential of a novel gene therapy, IMMUTOL, for MS compared with current high\u2010efficacy treatment sequences. The secondary objective is to explore value\u2010based pricing thresholds in line with Dutch health economic guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using the ErasmusMC\/iMTA MS microsimulation model, we compared IMMUTOL gene therapy against various high\u2010efficacy and escalation\u2010based disease\u2010modifying therapy sequences. Analyses considered a lifetime horizon, societal and healthcare perspectives, and uncertainty through probabilistic sensitivity analysis. The IMMUTOL gene therapy scenarios varied in efficacy parameters (relapse and disability reduction) and adverse event profiles. Cost assumptions incorporated projected market dynamics, including future price reductions due to generics and biosimilars.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IMMUTOL gene therapy demonstrated dominance (higher quality\u2010adjusted life years, lower costs) at price points \u2264\u20ac200\u2009000 and remained cost\u2010effective at \u20ac500\u2009000 under realistic clinical scenarios (incremental cost\u2010effectiveness ratio \u20ac26\u2009570\u2013\u20ac40\u2009615\/quality\u2010adjusted life year). Its cost\u2010effectiveness threshold depended on sustained reductions in relapse rates and disability progression (incidence rate ratio\u2009\u22640.2, relative risk\u2009\u22640.1). Indirect societal costs improved gene therapy's economic attractiveness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>IMMUTOL gene therapy shows promising cost\u2010effectiveness at a value\u2010based price up to approximately \u20ac500\u2009000, contingent on achieving curative clinical efficacy. These findings inform strategic development and pricing considerations for emerging gene therapies in MS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bcp.70204","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T02:09:33Z","timestamp":1755569373000},"source":"Crossref","is-referenced-by-count":6,"title":["Early\u2010stage health technology assessment of a curative gene therapy for multiple sclerosis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0110-8395","authenticated-orcid":false,"given":"Attila","family":"Imre","sequence":"first","affiliation":[{"name":"Center for Health Technology Assessment Semmelweis University  Budapest Hungary"},{"name":"Center for Pharmacology and Drug Research &amp; Development Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4125-7905","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"Nagy","sequence":"additional","affiliation":[{"name":"Center for Health Technology Assessment Semmelweis University  Budapest Hungary"},{"name":"Center for Pharmacology and Drug Research &amp; Development Semmelweis University  Budapest Hungary"},{"name":"Syreon Research Institute  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rok","family":"Hren","sequence":"additional","affiliation":[{"name":"Syreon Research Institute  Budapest Hungary"},{"name":"Faculty of Mathematics and Physics University of Ljubljana  Ljubljana Slovenia"},{"name":"Institute of Mathematics, Physics, and Mechanics  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517708663"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200150"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.1015256"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2024.1448377"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.15171\/ijhpm.2019.36"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm14060599"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737167.2017.1271325"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2009.00550.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s41669\u2010023\u201000439\u20106"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/20016689.2021.1889841"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/20016689.2019.1601484"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2020.09.021"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vhri.2024.02.002"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2021.11.1363"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2023.105100"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/20552173231189398"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/13524585241258692"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2025.03.002"},{"key":"e_1_2_9_20_1","volume-title":"Richtlijn voor het uitvoeren van economische evaluaties in de gezondheidszorg (versie 2024) [guideline for economic evaluations in healthcare (2024 version)]","author":"Zorginstituut Nederland","year":"2024"},{"key":"e_1_2_9_21_1","volume-title":"Richtlijn voor het uitvoeren van economische evaluaties in de gezondheidszorg [guideline for conducting economic evaluations in healthcare]","author":"Zorginstituut Nederland","year":"2016"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s41669\u2010022\u201000363\u20101"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70204","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T02:09:35Z","timestamp":1755569375000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,18]]},"references-count":21,"alternative-id":["10.1002\/bcp.70204"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70204","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,18]]},"article-number":"bcp.70204"}}