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Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination
Published on: September 12, 2016
New disease-modifying therapies and new challenges for MS
Vijayshree Yadav1, Dennis Bourdette
1Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, L226, Portland, OR 97239, USA. yadavv@ohsu.edu
Current Neurology and Neuroscience Reports
|July 5, 2012
Summary
Second-generation multiple sclerosis (MS) therapies like natalizumab and fingolimod offer improved efficacy but pose increased safety risks, including progressive multifocal leukoencephalopathy (PML) and cardiac events. Risk stratification is now possible for natalizumab-induced PML.
Area of Science:
- Neurology
- Immunology
- Pharmacology
Background:
- Second-generation therapies for relapsing multiple sclerosis (MS), including natalizumab and fingolimod, represent advancements over first-generation treatments like interferon beta and glatiramer acetate.
- While demonstrating greater efficacy, these newer therapies are associated with significant safety concerns not typically seen with earlier treatments.
Purpose of the Study:
- To evaluate the efficacy and safety profiles of second-generation MS therapies, specifically natalizumab and fingolimod.
- To highlight the challenges and risks associated with these advanced treatments, including progressive multifocal leukoencephalopathy (PML) and cardiac adverse events.
- To introduce risk stratification methods for natalizumab-induced PML.
Main Methods:
- Comparative analysis of clinical trial data for natalizumab and fingolimod against first-generation MS therapies.
- Review of safety data, focusing on adverse events such as progressive multifocal leukoencephalopathy (PML), asystole, sudden death, and serious herpes infections.
- Development and application of risk stratification criteria for natalizumab-associated PML, considering JC virus antibodies, immunosuppressant history, and treatment duration.
Main Results:
- Natalalizumab and fingolimod show higher efficacy than interferon beta and glatiramer acetate for relapsing MS.
- Natalizumab treatment carries a significant risk of progressive multifocal leukoencephalopathy (PML), caused by the JC virus.
- Fingolimod is associated with risks of asystole, sudden death, serious herpes infections, and paradoxical MS activation.
Conclusions:
- Risk stratification for natalizumab-induced PML is now feasible based on JC virus antibody status, prior immunosuppressant use, and treatment duration.
- Further research is required to fully understand and mitigate the serious side effects of fingolimod, ensuring its safe clinical application.
- The introduction of second-generation MS therapies necessitates careful patient selection and monitoring due to their complex risk-benefit profiles.
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