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

Area of Science:

• Pharmacovigilance
• Neuroimmunology
• Drug Safety

Background:

• Progressive multifocal leukoencephalopathy (PML) is a serious adverse drug reaction (ADR) associated with immunomodulatory biological therapies.
• The identification of PML risk has occurred at different stages in the lifecycle of various biologicals, impacting reporting dynamics.

Purpose of the Study:

• To contrast the reporting patterns of PML for natalizumab and rituximab, two biologicals with distinct timelines for risk identification.
• To evaluate the completeness and timeliness of PML adverse event reports for these two agents.

Main Methods:

• Comparative analysis of spontaneous adverse event reports for PML associated with natalizumab and rituximab.
• Examination of report completeness, timeliness, and clinical characteristics (age, gender, indication, time to event, fatality).

Main Results:

• PML reports for natalizumab were found to be more complete and received sooner after occurrence compared to rituximab.
• Significant differences in clinical characteristics of PML cases were observed, reflecting diverse contexts of use for both drugs.
• Variability in reporting patterns and heterogeneity of PML cases pose challenges for direct safety comparisons.

Conclusions:

• Spontaneous adverse event reports require cautious interpretation for quantifying and comparing drug safety profiles over time.
• Lumping uncharacterized PML reports without considering reporting patterns and case heterogeneity can lead to biased comparisons and flawed safety conclusions.