{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:38:46Z","timestamp":1781311126710,"version":"3.54.1"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with Crohn's disease (CD) who lose response to biologics experience reduced quality of life (QoL) and costly hospitalizations. Precision\u2010guided dosing (PGD) provides a comprehensive pharmacokinetic (PK) profile that allows for biologic dosing to be personalized. We analyzed the cost\u2010effectiveness of infliximab (IFX) PGD relative to two other dose intensification strategies (DIS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We developed a hybrid (Markov and decision tree) model of patients with CD who had a clinical response to IFX induction. The analysis had a US payer perspective, a base case time horizon of 5\u2009years, and a 4\u2010week cycle length. There were three IFX dosing comparators: PGD; dose intensification based on symptoms, inflammatory markers, and trough IFX concentration (DIS1); and dose intensification based on symptoms alone (DIS2). Patients that failed IFX initiated ustekinumab, followed by vedolizumab, and conventional therapy. Transition probabilities for IFX were estimated from real\u2010world clinical PK data and interventional clinical trial patient\u2010level data. All other transition probabilities were derived from published randomized clinical trials and cost\u2010effectiveness analyses. Utility values were sourced from previous health technology assessments. Direct costs included biologic acquisition and infusion, surgeries and procedures, conventional therapy, and lab testing. The primary outcomes were incremental cost\u2010effectiveness ratios (ICERs). The robustness of results was assessed via one\u2010way sensitivity, scenario, and probabilistic sensitivity analyses (PSA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PGD was the cost\u2010effective IFX dosing strategy with an ICER of 122,932 $ per quality\u2010adjusted life year (QALY) relative to DIS1 and dominating DIS2. PGD had the lowest percentage (1.1%) of patients requiring a new biologic through 5\u2009years (8.9% and 74.4% for DIS1 and DIS2, respectively). One\u2010way sensitivity analysis demonstrated that the cost\u2010effectiveness of PGD was most sensitive to the time between IFX doses. PSA demonstrated that joint parameter uncertainty had moderate impact on some results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PGD provides clinical and QoL benefits by maintaining remission and avoiding IFX failure; it is the most cost\u2010effective under conservative assumptions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2915","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T02:24:00Z","timestamp":1712283840000},"page":"331-342","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Simulated cost\u2010effectiveness of a novel precision\u2010guided dosing strategy in adult patients with Crohn's disease initiating infliximab maintenance therapy"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9561-9567","authenticated-orcid":false,"given":"Elmar R.","family":"Alizadeh","sequence":"first","affiliation":[{"name":"Prometheus Laboratories  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3799-4438","authenticated-orcid":false,"given":"Thierry","family":"Dervieux","sequence":"additional","affiliation":[{"name":"Prometheus Laboratories  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severine","family":"Vermeire","sequence":"additional","affiliation":[{"name":"Katholieke Universiteit Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marla","family":"Dubinsky","sequence":"additional","affiliation":[{"name":"Mount Sinai Medical Center  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"D'Haens","sequence":"additional","affiliation":[{"name":"University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Laharie","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Shim","sequence":"additional","affiliation":[{"name":"Prometheus Laboratories  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5081-3761","authenticated-orcid":false,"given":"Byron P.","family":"Vaughn","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2018.27"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i1.31"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0156-2"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000977"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000413"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.01.048"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-014-3368-z"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2012.12.035"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0254548"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-016-1266-1"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjy076"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.01.004"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izab285"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izz113"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2009.04033.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjv090"},{"key":"e_1_2_8_19_1","unstructured":"National Institute For health and Care Excellence (NICE).TA456: Ustekinumab for Moderately to Severely Active Crohn's Disease after Previous Treatment.2017Accessed July 27 2023.https:\/\/www.nice.org.uk\/guidance\/ta456"},{"key":"e_1_2_8_20_1","unstructured":"National Institute For health and Care Excellence (NICE).TA352: Vedolizumab for treating moderately to severely active Crohn's disease after prior therapy.2015Accessed July 27 2023.https:\/\/www.nice.org.uk\/guidance\/ta352"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2208"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(76)80163-1"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjad124"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1602773"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000979"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(82)90786-0"},{"issue":"12","key":"e_1_2_8_27_1","first-page":"1","article-title":"United States life tables, 2018","volume":"69","author":"Arias E","year":"2020","journal-title":"Natl Vital Stat Rep"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-019-07160-x"},{"key":"e_1_2_8_29_1","unstructured":"Bureau of Labor Statistics USD of L.BLS Medical Component of the Consumer Price Index.2022Accessed June 29 2022.https:\/\/data.bls.gov\/"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2010.04356.x"},{"key":"e_1_2_8_31_1","unstructured":"Centers for Medicare and Medicaid Services.Medicare Part B Drug Average Sales Price.2022Accessed June 29 2022.https:\/\/www.cms.gov\/medicare\/medicare\u2010part\u2010b\u2010drug\u2010average\u2010sales\u2010price\/2022\u2010asp\u2010drug\u2010pricing\u2010files"},{"key":"e_1_2_8_32_1","unstructured":"Prometheus Laboratories.EMPOWER CEP Results."},{"key":"e_1_2_8_33_1","unstructured":"Centers for Medicare and Medicaid Services.Medicare Reimbursement Files.2021."},{"key":"e_1_2_8_34_1","unstructured":"Institute for Clinical and Economic Review (ICER).JAK Inhibitors and Monoclonal Antibodies for the Treatment of Atopic Dermatitis: Effectiveness and Value.2021."},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/crocol\/otac021"},{"key":"e_1_2_8_36_1","unstructured":"Veterans Administration.VA Federal Supply Schedule (FSS)\u2010Pharmaceutical Pricing.2022Accessed June 29 2022.https:\/\/www.va.gov\/opal\/docs\/nac\/fss\/vaFssPharmPrices.xlsx"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/oso\/9780198526629.001.0001"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.2915","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:34:32Z","timestamp":1761042872000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.2915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/phar.2915"],"URL":"https:\/\/doi.org\/10.1002\/phar.2915","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2023-09-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}