D Peaureaux, B Pignolet et al. Multiple Sclerosis Journal
Letter to the Editor
Fingolimod treatment after natalizumab-related progressive multifocal leukoencephalopathy: Three new cases Dear Editor, Maillart and colleagues1 recently reported two natalizumab-related progressive multifocal leukoencephalopathy (PML) cases where patients required MS treatment when the PML was stabilized. We would like to report three more cases treated with fingolimod (FGL) from our natalizumab (NTZ) cohort (BIONAT2).
Case 1 This patient was diagnosed with MS at the age of 32. She was first treated with interferon IM and was switched to NTZ in 2009. Expanded Disability Status Scale (EDSS) was 2.5 and retrospective analysis showed positive JC virus with gen1 ELISSA3. After 43 infusions (November 2012), she experienced progressive nystagmus, gait ataxia and fatigue. PML was suspected on MRI because of the cerebellum (pedoncular) signal. PML was confirmed4 at NIH laboratory USA with a positive JC virus DNA detection on CSF at 1500 copies. Plasma exchange (Plex) was performed, followed by steroids because of gadolinium enhanced lesions seen in December 2012. Interferon (IFN) sub-cutaneous (s.c.) was re-introduced but, five months later, she had a relapse. PML re-activation was excluded by MRI and negative JC virus detection in the CSF. FGL was started in September 2013 and she has had no new neurological signs after nine months’ follow up. Case 2 This JC positive patient was diagnosed in 1994. He was switched from IFN to NTZ in 2008 (no additional biotherapies). After 45 infusions, he experienced speech disorder and PML was diagnosed on the basis of the MRI appearance and positive JC virus DNA detection (1000 copies, NIH laboratory). After Plex, steroids (because of immune reconstitution inflammatory syndrome (IRIS) signs) and copolymer acetate, the patient was initially stable but a new relapse occurred after four months. PML re-activation was excluded (MRI and JC virus polymerase chain reaction (PCR) in the CSF). The patient was switched to
2015, Vol. 21(5) 671–672
FGL in August 2013 and is now in a stable condition with moderate speech sequelae after almost one year follow-up.
DOI: 10.1177/ 1352458514549823 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Case 3 This JC positive patient without a history of immunosuppressant drugs was diagnosed with PML in March 2012 after 50 Tysabri infusions because of seizures and rapidly progressive aphasia. JC virus was detected at 10 copies in the CSF (NIH laboratory). Copolymer acetate was re-introduced but, 12 months later, an MS relapse occurred and FGL was proposed after PML re-activation had been excluded in August 2013. She is now in a stable condition after almost one year of follow-up but needs constant help for her everyday life. FGL5 is an immunosuppressant drug that must be used with caution after PML since two PML cases have been reported under this treatment. However, the two patients had also been treated with NTZ recently. Therefore, it is likely that PML was related to NTZ. Our three patients showed common trends: after PML diagnosis they stabilized following Plex and steroids. Nevertheless MS relapses occurred, on average, nine months later. They were treated first by IFN and copolymer (BRACE), but experienced breakthrough disease features in a short period of time (five, seven and 12 months). We suggest that FGL is a credible option for BRACE breakthrough patients after NTZ-related PML. We recommend verifying that CSF is JC-virus free before introducing FGL. References 1. Maillart E, Louapre C, Lubetzki C, et al. Fingolimod to treat severe multiple sclerosis after natalizumab-associated progressive multifocal leukoencephalopathy: A valid option? Mult Scler 2014; 20: 505–509. 2. Outteryck O, Ongagna JC, Brochet B, et al.; BIONAT Network; CFSEP. A prospective observational postmarketing study of natalizumab-treated multiple sclerosis patients: Clinical, radiological and biological features and adverse events. The BIONAT cohort. Eur J Neurol 2014; 21: 40–48. 3. Olsson T, Achiron A, Alfredsson L, et al. Anti-JC virus antibody prevalence in a multinational multiple sclerosis cohort. Mult Scler 2013;19: 1533–1538.
http://msj.sagepub.com 671
Multiple Sclerosis Journal 21(5) 4. Berger JR, Aksamit AJ, Clifford DB, et al. PML diagnostic criteria: Consensus statement from the AAN Neuroinfectious Disease Section. Neurology 2013; 80: 1430–1438. 5. Cohen JA, Barkhof F, Comi G, et al.; TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362: 402–415.
Visit SAGE journals online http://msj.sagepub.com
SAGE journals
Delphine Peaureaux1, Beatrice Pignolet1,2, Damien Biotti1, Florence Bucciarelli1,2 Jana Gaina1, Cristina Bucur1, Michel Clanet1,2, Guillaume Martin-Blondel2,3 and David Brassat1,2
1Pole
des neurosciences CHU Toulouse, France UMR 1043 et Université de Toulouse; UPS; France 3Pole spécialités médicales et pathologies infectieuses, CHU Toulouse, France 2INSERM
Correspondence to: David Brassat Pole des neurosciences CHU Toulouse and INSERM UMR 1043 université de Toulouse, France [email protected]
672 http://msj.sagepub.com
Copyright of Multiple Sclerosis Journal is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Letter to the Editor
Fingolimod treatment after natalizumab-related progressive multifocal leukoencephalopathy: Three new cases Dear Editor, Maillart and colleagues1 recently reported two natalizumab-related progressive multifocal leukoencephalopathy (PML) cases where patients required MS treatment when the PML was stabilized. We would like to report three more cases treated with fingolimod (FGL) from our natalizumab (NTZ) cohort (BIONAT2).
Case 1 This patient was diagnosed with MS at the age of 32. She was first treated with interferon IM and was switched to NTZ in 2009. Expanded Disability Status Scale (EDSS) was 2.5 and retrospective analysis showed positive JC virus with gen1 ELISSA3. After 43 infusions (November 2012), she experienced progressive nystagmus, gait ataxia and fatigue. PML was suspected on MRI because of the cerebellum (pedoncular) signal. PML was confirmed4 at NIH laboratory USA with a positive JC virus DNA detection on CSF at 1500 copies. Plasma exchange (Plex) was performed, followed by steroids because of gadolinium enhanced lesions seen in December 2012. Interferon (IFN) sub-cutaneous (s.c.) was re-introduced but, five months later, she had a relapse. PML re-activation was excluded by MRI and negative JC virus detection in the CSF. FGL was started in September 2013 and she has had no new neurological signs after nine months’ follow up. Case 2 This JC positive patient was diagnosed in 1994. He was switched from IFN to NTZ in 2008 (no additional biotherapies). After 45 infusions, he experienced speech disorder and PML was diagnosed on the basis of the MRI appearance and positive JC virus DNA detection (1000 copies, NIH laboratory). After Plex, steroids (because of immune reconstitution inflammatory syndrome (IRIS) signs) and copolymer acetate, the patient was initially stable but a new relapse occurred after four months. PML re-activation was excluded (MRI and JC virus polymerase chain reaction (PCR) in the CSF). The patient was switched to
2015, Vol. 21(5) 671–672
FGL in August 2013 and is now in a stable condition with moderate speech sequelae after almost one year follow-up.
DOI: 10.1177/ 1352458514549823 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Case 3 This JC positive patient without a history of immunosuppressant drugs was diagnosed with PML in March 2012 after 50 Tysabri infusions because of seizures and rapidly progressive aphasia. JC virus was detected at 10 copies in the CSF (NIH laboratory). Copolymer acetate was re-introduced but, 12 months later, an MS relapse occurred and FGL was proposed after PML re-activation had been excluded in August 2013. She is now in a stable condition after almost one year of follow-up but needs constant help for her everyday life. FGL5 is an immunosuppressant drug that must be used with caution after PML since two PML cases have been reported under this treatment. However, the two patients had also been treated with NTZ recently. Therefore, it is likely that PML was related to NTZ. Our three patients showed common trends: after PML diagnosis they stabilized following Plex and steroids. Nevertheless MS relapses occurred, on average, nine months later. They were treated first by IFN and copolymer (BRACE), but experienced breakthrough disease features in a short period of time (five, seven and 12 months). We suggest that FGL is a credible option for BRACE breakthrough patients after NTZ-related PML. We recommend verifying that CSF is JC-virus free before introducing FGL. References 1. Maillart E, Louapre C, Lubetzki C, et al. Fingolimod to treat severe multiple sclerosis after natalizumab-associated progressive multifocal leukoencephalopathy: A valid option? Mult Scler 2014; 20: 505–509. 2. Outteryck O, Ongagna JC, Brochet B, et al.; BIONAT Network; CFSEP. A prospective observational postmarketing study of natalizumab-treated multiple sclerosis patients: Clinical, radiological and biological features and adverse events. The BIONAT cohort. Eur J Neurol 2014; 21: 40–48. 3. Olsson T, Achiron A, Alfredsson L, et al. Anti-JC virus antibody prevalence in a multinational multiple sclerosis cohort. Mult Scler 2013;19: 1533–1538.
http://msj.sagepub.com 671
Multiple Sclerosis Journal 21(5) 4. Berger JR, Aksamit AJ, Clifford DB, et al. PML diagnostic criteria: Consensus statement from the AAN Neuroinfectious Disease Section. Neurology 2013; 80: 1430–1438. 5. Cohen JA, Barkhof F, Comi G, et al.; TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362: 402–415.
Visit SAGE journals online http://msj.sagepub.com
SAGE journals
Delphine Peaureaux1, Beatrice Pignolet1,2, Damien Biotti1, Florence Bucciarelli1,2 Jana Gaina1, Cristina Bucur1, Michel Clanet1,2, Guillaume Martin-Blondel2,3 and David Brassat1,2
1Pole
des neurosciences CHU Toulouse, France UMR 1043 et Université de Toulouse; UPS; France 3Pole spécialités médicales et pathologies infectieuses, CHU Toulouse, France 2INSERM
Correspondence to: David Brassat Pole des neurosciences CHU Toulouse and INSERM UMR 1043 université de Toulouse, France [email protected]
672 http://msj.sagepub.com
Copyright of Multiple Sclerosis Journal is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
