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In this study, we contrasted the reporting patterns of PML for two biologicals for which the risk was identified at different points in their lifecycle: natalizumab (before reapproval) and rituximab (nine years postapproval). We found that, apart from the differences in clinical characteristics (age, gender, indication, time to event, fatality), which reflect the diversity in context of use, PML reports for natalizumab were more complete and were received sooner after occurrence. This study serves as an important reminder that spontaneous reports should only be used with great caution to quantify and compare safety profiles across products over time. The observed variability in reporting patterns and heterogeneity of PML cases presents challenges to such comparisons. Lumping uncharacterized PML reports together without taking these differences into account may result in biased comparisons and flawed conclusions about differential safety.<\/jats:p>","DOI":"10.1002\/cpt.207","type":"journal-article","created":{"date-parts":[[2015,9,8]],"date-time":"2015-09-08T06:02:56Z","timestamp":1441692176000},"page":"542-550","source":"Crossref","is-referenced-by-count":19,"title":["Drug\u2010induced progressive multifocal leukoencephalopathy: Lessons learned from contrasting natalizumab and rituximab"],"prefix":"10.1111","volume":"98","author":[{"given":"NS","family":"Vermeer","sequence":"first","affiliation":[{"name":"Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht University Utrecht The Netherlands"},{"name":"Medicines Evaluation Board Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SMJM","family":"Straus","sequence":"additional","affiliation":[{"name":"Medicines Evaluation Board Utrecht The Netherlands"},{"name":"Medical Informatics Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"AK","family":"Mantel\u2010Teeuwisse","sequence":"additional","affiliation":[{"name":"Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht University Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Hidalgo\u2010Simon","sequence":"additional","affiliation":[{"name":"European Medicines Agency London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ACG","family":"Egberts","sequence":"additional","affiliation":[{"name":"Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht University Utrecht The Netherlands"},{"name":"Department of Clinical Pharmacy University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"HGM","family":"Leufkens","sequence":"additional","affiliation":[{"name":"Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht University Utrecht The Netherlands"},{"name":"Medicines Evaluation Board Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ML","family":"De Bruin","sequence":"additional","affiliation":[{"name":"Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht University Utrecht The Netherlands"},{"name":"Medicines Evaluation Board Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,9,8]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70040-5"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0733-8619(18)31105-8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/81.1.93"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24966"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/595299"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70028-4"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-186999"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051847"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051782"},{"key":"e_1_2_10_10_1","unstructured":"Public Health Advisory \u2013 Suspended Marketing of Tysabri (natalizumab). 28 February 2005. <http:\/\/www.fda.gov\/Drugs\/DrugSafety\/PostmarketDrugSafetyInformationforPatientsandProviders\/ucm051761.htm> Accessed 30 October2014."},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051586"},{"key":"e_1_2_10_12_1","unstructured":"US Food and Drug Administration news release.FDA approves resumed marketing of tysabri under a special distribution program. 5 June 2006. <http:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/2006\/ucm108662.htm>. 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