Herpes encephalitis during natalizumab treatment in multiple sclerosis

PRES Lille Nord de France, Université Catholique de Lille, Groupe Hospitalier de l'Institut Catholique de Lille, Faculté Libre de Médecine, Clinique de Neurologie, Lille, France.
Multiple Sclerosis (Impact Factor: 4.82). 11/2011; 18(6):909-11. DOI: 10.1177/1352458511428082
Source: PubMed


In this case report we describe the first non-fatal herpes simplex virus encephalitis (HSE) case with natalizumab for multiple sclerosis (MS). A 36-year-old woman, previously treated with immunomodulatory and immunosuppressive drugs for MS, developed acute encephalitis after 6 monthly natalizumab perfusions. Brain imaging demonstrated suggestive bi-temporal lesions. Herpes simplex virus type-1 DNA was detected in cerebrospinal fluid. The patient improved gradually after a 21-day course of intravenous acyclovir, but neuropsychiatric changes remained 5 months later. Our non-fatal case of HSE and other reported cases of herpes infections provide evidence of an increased risk with natalizumab and point to the need for clinicians to maintain awareness.

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    • "No increased risk of lymphoma, malignant melanoma or hypereosinophilia was reported in these studies [Abbas et al. 2011; Bujold et al. 2014; Mullen et al. 2008]. No increase in infection among patients receiving natalizumab, compared with placebo, was found [Polman et al. 2006; Rudick et al. 2006], but postmarketing studies identified a slight excess of herpes virus infections [Fine et al. 2013; Holmen et al. 2011] with rare cases of fatal herpes encephalitis [Biogen Idec, 2013; Kwiatkowski et al. 2012] and meningitis [Biogen Idec, 2013; Shenoy et al. 2011; Valenzuela et al. 2014]. "
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    ABSTRACT: Monoclonal antibody (mAb) therapies for relapsing-remitting multiple sclerosis (MS) target immune cells or other molecules involved in pathogenic pathways with extraordinary specificity. Natalizumab and alemtuzumab are the only two currently approved mAbs for the treatment of MS, having demonstrated significant reduction in clinical and magnetic resonance imaging disease activity and disability in clinical studies. Ocrelizumab and daclizumab are in the late stages of phase III trials, and several other mAbs are in the early stages of clinical evaluation. mAbs have distinct structural characteristics (e.g. chimeric, humanized, fully human) and unique targets (e.g. blocking interactions, induction of signal transduction by receptor binding, complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity) conferring different mechanisms of action in MS. Because of these differences, mAbs for MS do not constitute a single treatment class; each must be considered individually when selecting appropriate therapy. Furthermore, in reviewing the data from clinical studies of mAbs, attention should be drawn to use of different comparators (e.g. placebo or interferon β-1a) and study designs. Each mAb treatment has a unique administration schedule. In the decision to select the appropriate treatment for each individual MS patient, careful review of the benefits relative to risks of mAbs is balanced against the risk of development of MS-associated disability.
    Therapeutic Advances in Neurological Disorders 09/2015; 8(6). DOI:10.1177/1756285615605429 · 3.14 Impact Factor
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    • "HHV-6 is commonly reactivated in situations of immunosuppression and has been associated with MS.70 Several lines of evidence, including an increase in the level of HHV-6-specific antibodies in serum and an increase in HHV-6 DNA in the cerebrospinal fluid of natalizumab-treated MS patients, suggest that HHV-6 might reactivate on treatment with natalizumab.71,72 Herpes simplex and varicella zoster CNS infections have recently been reported in 20 natalizumab-treated MS patients.73,74 Finally, a single case of ocular toxoplasmosis has been reported after 11 months of treatment with natalizumab.75 "
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    ABSTRACT: Natalizumab was the first monoclonal antibody to be approved for the treatment of relapsing-remitting multiple sclerosis (RRMS) based on its short-term efficacy and overall tolerability. However, the incidence of treatment-associated progressive multifocal leukoencephalopathy (PML), an infection of the brain caused by the John Cunningham virus, jeopardized this efficacious treatment from the beginning. Eight years after licensing of natalizumab, long-term studies confirm the considerable and sustained efficacy of natalizumab, although the PML complication still threatens one of the most successful treatments available for RRMS. During these years, considerable progress has been made in identification of risk factors that allow more effective management of PML risk. In addition, long-term studies to define better when to start or stop treatment and to optimize treatment strategies after cessation of natalizumab are ongoing, and hopefully will improve management and will allow natalizumab to remain as a valuable therapeutic option for patients with highly active RRMS.
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    ABSTRACT: The treatment of relapsing remitting multiple sclerosis has witnessed major progress since the first effective disease modifying treatment, ß-interferon, became available in 1993. One of the most remarkable new treatments has been natalizumab. This review describes the evolution of this humanized anti-α4ß1 monoclonal antibody, from preclinical experimental research through proof-of-concept (phase 1/2) and pivotal (phase 3) clinical trials to the now extensive experience of its use in clinical practice. The future potential and challenges of natalizumab and oral therapies with a similar mechanism of action are also discussed.
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