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Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination
Published on: September 12, 2016
Interdisciplinary Risk Management in the Treatment of Multiple Sclerosis
Joachim Havla1, Clemens Warnke, Tobias Derfuss
1Institute for Clinical Neuroimmunology, Biomedical Center and Hospital, Ludwig-Maximilians Universität München, Munich; Department of Neurology, Faculty of Medicine, Heinrich Heine University Düsseldorf; Department of Neurology, University Hospital Basel; Munich Cluster for Systems Neurology (SyNergy).
Background:
Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system. There are at least 150 000 persons with MS in Germany. Recent years have seen the approval of new drugs against.
Methods:
This article is based on pertinent literature retrieved by a selective search in PubMed as well as on documentation of relevant risks and adverse effects in "red hand letters" (information bulletins from pharmaceutical companies to physicians about adverse drug effects) and elsewhere, along with data provided by the German Multiple Sclerosis Competence Network.
Results:
In recent years, there have been major advances enabling better, more individualized treatment of patients with MS. Physicians must, however, give due consideration to potentially severe or even life-threatening adverse drug effects. These can include, for example, transaminase elevation (hepatotoxicity), cardio- and nephrotoxicity, or lympho- and leukopenia with a variable risk of infection. Among patients taking natalizumab, the cumulative risk of developing progressive multifocal leukencephalopathy (PML) may be 1:100 or higher, depending on the individual risk profile. Rare cases of PML have also been seen under treatment with fingolimod and dimethyl fumarate. Moreover, any type of immunosuppressive treatment can, at least theoretically, increase the risk of malignant disease. Secondary autoimmune diseases can arise as well: approximately 35% of patients treated with alemtuzumab develop autoimmune thyroid disease within two years, and 2% of patients who take daclizumab have severe autoimmune dermatological side effects. Teriflunomide, fingolimod, natalizumab, mitoxantrone, interferon β1-a/b, and daclizumab can all damage the liver. There are also psychiatric, reproductive, and vaccineassociated risks and side effects that must be considered.
Conclusion:
Newer drugs for MS have enabled more effective treatment, but are also associated with a higher risk of side effects. Interdisciplinary risk management is needed.
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