Progressive Multifocal Leukoencephalopathy in a Multiple Sclerosis Patient Diagnosed after Switching from Natalizumab to Fingolimod

Abstract

Background. Natalizumab- (NTZ-) associated progressive multifocal leukoencephalopathy (PML) is a severe and often disabling infectious central nervous system disease that can become evident in multiple sclerosis (MS) patients after NTZ discontinuation. Recently, novel diagnostic biomarkers for the assessment of PML risk in NTZ treated MS patients such as the anti-JC virus antibody index have been reported, and the clinical relevance of milky-way lesions detectable by MRI has been discussed. Case Presentation and Conclusion. We report a MS patient in whom PML was highly suspected solely based on MRI findings after switching from NTZ to fingolimod despite repeatedly negative (ultrasensitive) polymerase chain reaction (PCR) testing for JC virus DNA in cerebrospinal fluid. The PML diagnosis was histopathologically confirmed by brain biopsy. The occurrence of an immune reconstitution inflammatory syndrome (IRIS) during fingolimod therapy, elevated measures of JCV antibody indices, and the relevance of milky-way-like lesions detectable by (7 T) MRI are discussed.

Neurological safety of fingolimod: An updated review

“…To our knowledge, four cases of PML‐IRIS during FTY treatment have been reported so far, and all were linked to prior NTZ therapy 82, 83, 84, 85. Killestein et al reported a 52‐year‐old RRMS male patient switched to FTY from NTZ as a result of a positive JCV antibody test 82.…”

Managing Multiple Sclerosis: Treatment Initiation, Modification, and Sequencing

“…- 144 The latest evidence suggests that no washout period is recommended 113 . However, since both drugs carry a risk of PML, it would be important to perform an “exit MRI” and CSF for JCV PCR before initiating fingolimod as there have been many cases of “carry-over” PML from natalizumab-treated patients initiated on fingolimod 145 146 …”

Shortening the washout to 4 weeks when switching from natalizumab to fingolimod and risk of disease reactivation in multiple sclerosis

“…Fingolimod's main effect in MS is mediated by retention of lymphocytes in lymphnodes (Mehling et al, 2011;Matloubian et al, 2004;Mandala et al, 2002). Although 19 cases of PML have been reported to date on official quarterly updates (Calic et al, 2015;Killestein et al, 2014;Peaureaux et al, 2015;Sinnecker et al, 2016), the risk of developing PML under fingolimod is regarded as low (0.069/1000) (Berger et al, 2018;Berger, 2017). An analysis of data from the MSBase Registry (Jokubaitis et al, 2014) indicated that rebound disease activity is not to be expected after switching from natalizumab to fingolimod.…”