Drug-induced progressive multifocal leukoencephalopathy: Lessons learned from contrasting natalizumab and rituximab.
Progressive multifocal leukoencephalopathy (PML) has been identified as a serious adverse drug reaction (ADR) of several immunomodulatory biologicals. 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.
Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.|Medicines Evaluation Board, Utrecht, The Netherlands.
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NS
Vermeer
Medicines Evaluation Board, Utrecht, The Netherlands.|Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands.
S M J M
SM
Straus
Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.
A K
AK
Mantel-Teeuwisse
European Medicines Agency, London, United Kingdom.
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A
Hidalgo-Simon
Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.|Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
A C G
AC
Egberts
Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.|Medicines Evaluation Board, Utrecht, The Netherlands.
H G M
HG
Leufkens
Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.|Medicines Evaluation Board, Utrecht, The Netherlands.
M L
ML
De Bruin
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000639:trends*; D000368:Aged; D016208:Databases, Factual / Q000639:trends; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D000069442:Natalizumab / Q000009:adverse effects*; D000069283:Rituximab / Q000009:adverse effects*
D007155:Immunologic Factors; D000069442:Natalizumab; D000069283:Rituximab