Drug-induced progressive multifocal leukoencephalopathy: Lessons learned from contrasting natalizumab and rituximab

TY - JOUR

T1 - Drug-induced progressive multifocal leukoencephalopathy

T2 - Lessons learned from contrasting natalizumab and rituximab

AU - Vermeer, N S

AU - Straus, S M J M

AU - Mantel-Teeuwisse, A K

AU - Hidalgo-Simon, A

AU - Egberts, A C G

AU - Leufkens, H G M

AU - De Bruin, M L

N1 - © 2015 American Society for Clinical Pharmacology and Therapeutics.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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.

AB - 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.

KW - Adult

KW - Adverse Drug Reaction Reporting Systems

KW - Aged

KW - Databases, Factual

KW - Female

KW - Humans

KW - Immunologic Factors

KW - Leukoencephalopathy, Progressive Multifocal

KW - Male

KW - Middle Aged

KW - Natalizumab

KW - Rituximab

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/cpt.207

DO - 10.1002/cpt.207

M3 - Journal article

C2 - 26347128

SN - 0009-9236

VL - 98

SP - 542

EP - 550

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

IS - 5

ER -