{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:46:22Z","timestamp":1787165182246,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Ibrutinib is metabolized by cytochrome P450 3A (CYP3A) and poses challenges with drug interactions. We conducted a population\u2010based cohort study of Ontario residents aged \u226566\u2009years who initiated ibrutinib for chronic lymphocytic leukaemia (CLL) to evaluate the frequency of potential drug interactions involving moderate\/strong CYP3A inhibitors and inducers and their association with overall survival (OS). Secondary analyses employed a nested case\u2013control design examining hospitalizations for haemorrhage or infection as potential markers of ibrutinib toxicity. Among 642 ibrutinib recipients (median age 74\u2009years, 34.4% female), 70 (10.9%) received a concomitant CYP3A inducer while 404 (62.9%) received a concomitant CYP3A inhibitor. In the primary analysis, we found no association between death (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009162) and concurrent use of either moderate\/strong CYP3A inducers or inhibitors. In secondary analyses, 86 patients (13.4%) were admitted to hospital for bleeding and 287 patients (44.7%) for infection. Receipt of moderate\/strong CYP3A inhibitors was associated with an increased odds of hospitalization for infection (odds ratio 2.88, 95% confidence intervals [CI] 1.29\u20136.43) but not haemorrhage. Among older patients receiving ibrutinib for CLL, concomitant use of CYP3A\u2010modulating drugs is common. We found no association between use of interacting drugs and OS, but CYP3A inhibitors were strongly associated with hospitalization for infection, underscoring the importance of pharmacovigilance.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70131","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T09:14:05Z","timestamp":1756458845000},"page":"1893-1901","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Outcomes following exposure to drug interactions with ibrutinib in patients with chronic lymphocytic leukaemia"],"prefix":"10.1111","volume":"207","author":[{"given":"Tuan","family":"Hoang","sequence":"first","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3193-5872","authenticated-orcid":false,"given":"Matthew C.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"ICES  Toronto Ontario Canada"},{"name":"Odette Cancer Centre Sunnybrook Health Sciences Centre  Toronto Ontario Canada"},{"name":"Sunnybrook Research Institute  Toronto Ontario Canada"},{"name":"Canadian Cancer Trials Group Queen's University  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Juurlink","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"ICES  Toronto Ontario Canada"},{"name":"Sunnybrook Research Institute  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin K. W.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"ICES  Toronto Ontario Canada"},{"name":"Odette Cancer Centre Sunnybrook Health Sciences Centre  Toronto Ontario Canada"},{"name":"Sunnybrook Research Institute  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Lau","sequence":"additional","affiliation":[{"name":"ICES  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"ICES  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Husam","family":"Abdel\u2010Qadir","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"ICES  Toronto Ontario Canada"},{"name":"Peter Munk Cardiac Center University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5621-9261","authenticated-orcid":false,"given":"Anca","family":"Prica","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Division of Medical Oncology &amp; Hematology Princess Margaret Cancer Centre  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4581-3390","authenticated-orcid":false,"given":"Annette E.","family":"Hay","sequence":"additional","affiliation":[{"name":"Canadian Cancer Trials Group Queen's University  Kingston Ontario Canada"},{"name":"Department of Medicine Queen's University  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abi","family":"Vijenthira","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Division of Medical Oncology &amp; Hematology Princess Margaret Cancer Centre  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3436-3849","authenticated-orcid":false,"given":"Lee","family":"Mozessohn","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"ICES  Toronto Ontario Canada"},{"name":"Odette Cancer Centre Sunnybrook Health Sciences Centre  Toronto Ontario Canada"},{"name":"Sunnybrook Research Institute  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215637"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1400376"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.12.007"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102018\u201011\u2010846808"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.419"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.156"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1460474"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2016.1251592"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13651"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy175"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190701724785"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.096792"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102019\u2010122673"},{"key":"e_1_2_11_15_1","unstructured":"Johns Hopkins ACG System. Accessed February 20 2024. Available from:https:\/\/www.hopkinsacg.org\/"},{"key":"e_1_2_11_16_1","first-page":"246","article-title":"Cancer registration in Ontario: a computer approach","volume":"95","author":"Clarke EA","year":"1991","journal-title":"IARC Sci Publ"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g6196"},{"key":"e_1_2_11_18_1","unstructured":"U.S. Food and Drug Administration.Drug development and drug interactions. Accessed January 9 2024. Available from:https:\/\/www.fda.gov\/drugs\/drug\u2010interactions\u2010labeling\/drug\u2010development\u2010and\u2010drug\u2010interactions\u2010table\u2010substrates\u2010inhibitors\u2010and\u2010inducers"},{"key":"e_1_2_11_19_1","unstructured":"FlockhartD.Drug interactions: cytochrom P450 drug interaction Table.2007Accessed January 9 2024. Available from:https:\/\/drug\u2010interactions.medicine.iu.edu\/MainTable.aspx"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2018.07.287"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.00693"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102016\u201006\u2010722991"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix687"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.04.012"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13928"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2021.1967139"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24490"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V128.22.233.233"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509388"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.182907"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.450"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/epirev\/mxs009"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2014.58.7550"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.78.8687"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2025.7029"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1908213"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(16)30029\u20108"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010019\u20100602\u2010x"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/1078155210389217"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509981"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009617"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(22)00293\u20105"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211582"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2213093"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1513257"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.70131","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.70131","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.70131","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:07:15Z","timestamp":1783015635000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.70131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,29]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/bjh.70131"],"URL":"https:\/\/doi.org\/10.1111\/bjh.70131","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,29]]},"assertion":[{"value":"2025-04-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}