Reactivation of herpesvirus under fingolimod: A case of severe herpes simplex encephalitis

Pfender, Nikolai; Jelčić, Ilijas; Linnebank, Michael; Schwarz, Urs; Martin, Roland

doi:10.1212/wnl.0000000000001659

Cited by 49 publications

(33 citation statements)

References 6 publications

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“…Interestingly, FTY720 also leads to a subtle defect in immunocompetence regarding control of viral infection . Only two herpes viruses that reside in cells of the nervous system, that is, varicella zoster virus and herpes simplex virus 1 (HSV1), are affected by FTY720 treatment . More frequent reactivation of these two viruses from the latent state and, in a few cases, severe generalized varicella zoster virus infection and HSV1 encephalitis even with fatal outcome have occurred .…”

Section: Treatments Of Msmentioning

confidence: 99%

“…Only two herpes viruses that reside in cells of the nervous system, that is, varicella zoster virus and herpes simplex virus 1 (HSV1), are affected by FTY720 treatment . More frequent reactivation of these two viruses from the latent state and, in a few cases, severe generalized varicella zoster virus infection and HSV1 encephalitis even with fatal outcome have occurred . PML has been observed as well under FTY720 treatment, but only in very few cases compared with NTZ .…”

Section: Treatments Of Msmentioning

confidence: 99%

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Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

et al. 2016

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Multiple sclerosis (MS) is the most common inflammatory disorder of the central nervous system (CNS) in young adults. When MS is not treated, it leads to irreversible and severe disability. The etiology of MS and its pathogenesis are not fully understood. The recent discovery that MS-associated genetic variants code for molecules related to the function of specific immune cell subsets is consistent with the concept of MS as a prototypic, Tcell-mediated autoimmune disease targeting the CNS. While the therapeutic efficacy of the currently available immunomodulatory therapies further strengthen this concept, differences observed in responses to MS treatment as well as additional clinical and imagingobservations have also shown that the autoimmune pathogenesis underlying MS is much more complex than previously thought. There is therefore an unmet need for continued detailed phenotypic and functional analysis of disease-relevant adaptive immune cells and tissues directly derived from MS patients to unravel the immune etiology of MS in its entire complexity. In this review, we will discuss the currently available MS treatment options and approved drugs, including how they have contributed to the understanding of the immune pathology of this autoimmune disease.Keywords: Autoantibodies r Autoimmune pathogenesis r Autoimmunity r Autoreactive B cells r Autoreactive T cells r Experimental autoimmune encephalomyelitis r Multiple sclerosis r Treatment Introduction-MS as an autoimmune diseaseMS is considered a prototypic organ-specific autoimmune disease targeting the CNS with inflammatory lesions, demyelination, axonal/neuronal damage, and metabolic changes [1,2]. Relapsing-remitting and secondary progressive MS (RRMS, SPMS) are the two most frequent forms of MS, which often affect young adults between 20 and 40 years of age, and women three times more often than men [3]. Typical clinical signs include temporary loss of vision, sensory and motor problems, but also fatigue, neurocognitive changes, and impairment of bladder, bowel, and Correspondence: Britta Engelhardt ; Roland Martin e-mail: bengel@tki.unibe.ch; roland.martin@usz.ch sexual functions. During the relapsing-remitting phase neurological deficits, which occur in bouts and may last from days to a few weeks, usually disappear again, but after several years, disability gradually builds up. Depending on the individual course this secondary progressive disease with continuously increasing disability may never set in, but often starts after 15-20 years of RRMS. In a small percentage of patients such a progressive course is seen from the beginning, which is referred to as primary progressive MS (PPMS) and seen in females and males with equal frequency [3].Evidence for an autoimmune pathogenesis of MS was shown in its animal model, experimental autoimmune encephalomyelitis (EAE) (summarized in [4,5] Treatments of MSAs already noted above, the various treatments of MS deserve particular mentioning not only because they have changed clinical practice and can be considered ...

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Section: Treatments Of Msmentioning

confidence: 99%

Section: Treatments Of Msmentioning

confidence: 99%

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

et al. 2016

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“…5,7 To the authors' knowledge, no available direct randomized clinical trials have been conducted on comparing fingolimod with other oral therapies, glatiramer acetate, and natalizumab. 8 New complications in the post-marketing phase have been observed: progressive multifocal leukoencephalopathy )PML(, 9 cases of severe herpes simplex virus encephalitis 10 and varicella zoster encephalitis in an immunized patient, 11 cases of tumefactive MS under fingolimod treatment, 12 and other rare complications. 3 Although the clinical efficacy and safety of fingolimod have been established in pivotal clinical trials, concerns remain about its emerging complications in subsequent trials and the differences in its effectiveness and safety in different ethnic populations.…”

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confidence: 99%

Clinical effectiveness and safety of fingolimod in relapsing remitting multiple sclerosis in Western Iran

Ouspid

Razazian

Moghadasi

et al. 2018

NSJ

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To investigate the clinical effectiveness and safety of fingolimod in the western Iranian population. Methods: This study was performed as a prospective observational study between March 2014 and October 2015. Sixty patients with relapsing remitting multiple sclerosis)RRMS(who were referred to the MS clinic of Imam Reza Hospital, which is affiliated with Kermanshah University of Medical Sciences, Iran, were treated with 0.5 mg oral fingolimod capsules once daily for 12 months. The outcomes were clinical and included the annualized relapse rate, expanded disability status scale)EDSS(change, proportion of relapse-free patient, and side effects. Results: An 85% reduction in the annualized relapse rate compared with the baseline)from 1.8±1.35 to 0.27±0.58, p=0.001(was observed, and 76.66% of patients were free from relapse after the 12-month intervention. In addition, a significant reduction of EDSS was measured from 3.32 at baseline to 2.97)p=0.001(. The overall adverse events in our study were similar to those in previous studies. Conclusion: The present study confirms the effectiveness of fingolimod as a second-line therapy in western Iranian RRMS patients. Fingolimod side effects were generally mild and tolerable.

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“…The patient was previously on natalizumab and had positive varicella zoster titers; developed reactivation within six months of fingolimod 0.5 mg. Recently, a case of herpes simplex encephalitis in a patient on fingolimod was reported [19]. These cases highlight the relative increased risk of herpes infections in patients on fingolimod.…”

Section: Fingolimod (Fty720 Gilenya® Novartis Pharmaceuticals Ag)mentioning

confidence: 99%

Sphingosine 1-Phosphate Receptor Modulators in Multiple Sclerosis

2015

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Sphingosine 1-phosphate (S1P) receptor modulators possess a unique mechanism of action as disease modifying therapy for multiple sclerosis (MS). Subtype 1 S1P receptors are expressed on the surfaces of lymphocytes and are important in regulating egression from lymph nodes. The S1P receptor modulators indirectly antagonize the receptor’s function and sequester lymphocytes in lymph nodes. Fingolimod was the first S1P agent approved in the United States in 2010 for relapsing MS after two phase 3 trials (FREEDOMS and TRANSFORMS) demonstrated potent efficacy, and good safety and tolerability. Post-marketing experience as well as a third phase 3 trial (FREEDOMS II) also showed favorable results. More selective S1P receptor agents: ponesimod (ACT128800), siponimod (BAF312), ozanimod (RPC1063), ceralifimod (ONO-4641), GSK2018682, and MT-1303 are still in relatively early stages of development, but phase 1 and 2 trials showed promising efficacy and safety. However, these observations have yet to be reproduced in phase 3 clinical trials.

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Reactivation of herpesvirus under fingolimod: A case of severe herpes simplex encephalitis

Cited by 49 publications

References 6 publications

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

Clinical effectiveness and safety of fingolimod in relapsing remitting multiple sclerosis in Western Iran

Sphingosine 1-Phosphate Receptor Modulators in Multiple Sclerosis

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