Three cases of non-carryover fingolimod-PML

Is the risk in Japan increased?

Jin Nakahara, Laura Tomaske, Kodai Kume, Tadayuki Takata, Masaki Kamada, Kazushi Deguchi, Kenji Kufukihara, Ruth Schneider, Ralf Gold, Ilya Ayzenberg

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

ObjectiveTo report the course of 3 recent Japanese and European cases of fingolimod-associated progressive multifocal leukoencephalopathy (PML) and to analyze its risk factors and increased incidence in Japan.MethodsCase series and literature review.ResultsFingolimod-associated PML may cause both supratentorial and infratentorial lesions and a pronounced disability. Diagnosis can be challenging because PML lesions (especially infratentorial) can be initially misdiagnosed as extensive MS lesions. Immune reconstitution inflammatory syndrome (IRIS) develops a few weeks after fingolimod discontinuation and is usually mild. Age factor and therapy duration seem to be relevant because most reported patients were older than 45 years and were treated with fingolimod for more than 3 years. Combined IgG/IgM deficiency has been identified as a possible further predisposing condition in 1 case. Another patient developed an endogenous fungal skin infection, as a sign of generally compromised cellular immune response, shortly before PML. None of the reported patients had lymphocyte counts below 200/l. Two of the 3 reported and 4 of the 21 (19%) registered fingolimod-PML cases occurred in Japan (estimated risk of 0.652 per 1,000 compared with 0.083 per 1.000 worldwide).ConclusionsThe risk of PML under fingolimod is low, but there are no reliable predictors. Despite a mild IRIS phase, it causes profound disability. Patients older than 45 years, especially with known comorbid immunodeficiencies or manifestation of other opportunistic infections, should be monitored more closely. Increased surveillance and identification of further risk factors are urgently needed in Japan.

Original languageEnglish
Article numbere559
JournalNeurology: Neuroimmunology and NeuroInflammation
Volume6
Issue number3
DOIs
Publication statusPublished - 2019 May 1

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Progressive Multifocal Leukoencephalopathy
Japan
Immune Reconstitution Inflammatory Syndrome
IgG Deficiency
Mycoses
Age Factors
Opportunistic Infections
Lymphocyte Count
Diagnostic Errors
Cellular Immunity
Immunoglobulin M
Fingolimod Hydrochloride
Skin
Incidence

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Three cases of non-carryover fingolimod-PML : Is the risk in Japan increased? / Nakahara, Jin; Tomaske, Laura; Kume, Kodai; Takata, Tadayuki; Kamada, Masaki; Deguchi, Kazushi; Kufukihara, Kenji; Schneider, Ruth; Gold, Ralf; Ayzenberg, Ilya.

In: Neurology: Neuroimmunology and NeuroInflammation, Vol. 6, No. 3, e559, 01.05.2019.

Research output: Contribution to journalArticle

Nakahara, Jin ; Tomaske, Laura ; Kume, Kodai ; Takata, Tadayuki ; Kamada, Masaki ; Deguchi, Kazushi ; Kufukihara, Kenji ; Schneider, Ruth ; Gold, Ralf ; Ayzenberg, Ilya. / Three cases of non-carryover fingolimod-PML : Is the risk in Japan increased?. In: Neurology: Neuroimmunology and NeuroInflammation. 2019 ; Vol. 6, No. 3.
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