Natalizumab-associated PML: Challenges with incidence, resulting risk, and risk stratification
Nicholas Schwab1, Tilman Schneider-Hohendorf2, Nico Melzer2
1From the Department of Neurology (N.S., T.S.-H., N.M., H.W.), University of Münster, Germany; and University of Alabama School of Public Health (G.C.), Birmingham. nicholas.schwab@ukmuenster.de.
Neurology
|February 24, 2017
Summary
Current methods for assessing progressive multifocal leukoencephalopathy (PML) risk in natalizumab patients may be outdated. Cumulative risk and treatment duration are crucial for accurate stratification to prevent this severe neurological complication.
Area of Science:
- Neurology
- Immunology
- Pharmacovigilance
Background:
- Progressive multifocal leukoencephalopathy (PML) is a severe risk associated with natalizumab therapy, impacting treatment success.
- Existing risk stratification methods for natalizumab-associated PML may be inaccurate and underestimate patient risk, particularly for those with prior immunosuppression.
Purpose of the Study:
- To update developments in risk stratification for natalizumab-associated PML.
- To discuss current approaches for depicting and calculating PML incidence and risk.
- To highlight the limitations of current risk factors and propose improved stratification strategies.
Main Methods:
- Review and analysis of current PML incidence and risk calculation methodologies.
- Evaluation of risk stratification based on treatment duration epochs and JC virus (JCV) serostatus.
- Assessment of the impact of anti-JCV seroconversion and patient treatment duration on PML risk specificity.
Main Results:
- Current PML incidence and risk calculations may be outdated, potentially underestimating risk in patients with prior immunosuppression.
- Risk stratification by treatment duration epochs can be misleading, as it does not accurately reflect cumulative risk over extended treatment periods.
- JC virus (JCV) serostatus has limited specificity for PML prediction, further reduced by anti-JCV seroconversion during natalizumab treatment.
Conclusions:
- Clinicians must consider the cumulative risk for each patient when stratifying for natalizumab-associated PML.
- Current risk stratification models, including treatment duration and JCV serostatus, require refinement for accurate PML risk assessment.
- More accurate methods are needed to address the ongoing challenge of PML in patients receiving natalizumab therapy.
