Contributions
Abstract: EP1739
Type: ePoster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Teriflunomide (TER), the active metabolite of leflunomide, is prescribed by few years for relapsing remitting MS (RR) as first line therapy (Oh J, 2014). Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the central nervous system (CNS) caused by JC virus primarily seen in immunocompromised patients or associated with specific immunotherapies (Ferenczy MW,.2012). Any case of PML has been reported in patients treated with TER, but two case of leflunomide-related PML has been described. Here, we reported the first case of PML during TER treatment.
Case report: A 36-year-old woman with multiple sclerosis, taking TER since three months, on January 30, 2017 developed an acute decline in speech. She was previously treated with natalizumab (N), discontinued after 33 infusions eight months before, for JCV antibodies detection. Brain MRI showed a unilobar area suggestive for PML; cerebrospinal fluid showed JCV DNA (11 copies/ml). A dissemination of brain lesions with several new cortical and subcortical enhancing lesions was observed, making difficult the differential diagnosis between PML-immune reconstitution inflammatory syndrome and new MS relapse.
Conclusions: Up to now, there is no knowledge about the possible risk of PML related to immunosuppressant use subsequently N exposure. The acute onset of symptoms, the first unilobar PML lesion documented by brain MRI and low number of CSF JCV DNA copies, support the hypothesis that in our patient PML was in an initial phase at diagnosis time, occurring eight moths after N cessation, but few months after TER initiation. However, multiple enhancing lesions occurring without modification of clinical symptoms and without any kind of response to steroid could represent a diffuse MS relapse with exaggerated inflammatory reaction, perhaps related to the underlying not clear mechanism of the drugs. Therefore, this case highlights the debate for a more prolonged PML surveillance program, especially for patients extensively N pre-treated with high risk for PML (Schwab N, 2017) that switch to therapies with an immunosuppressant effect.
Keywords: teriflunomide, natalizumab, JC virus, Progressive Multifocal Leukoencephalopathy, safety
Disclosure:
Dr. Lorefice received speaker fee from Teva and serves on scientific advisory boards for Biogen.
Dr. Fenu received honoraria for consultancy from Novartis and for speaking from Merck Serono and Teva.
Dr. Frau serves on scientific advisory boards for Biogen, received honoraria for speaking from Merck Serono and Teva.
Dr. Coghe received speaker fee from Teva and Almirall.
Professor Cocco and Marrosu have received honoraria for consultancy or speaking from Bayer, Biogen-Idec, Novartis, Sanofi-Genzyme, Serono and Teva.
Dr. Contu, Dr. Barracciu and Dr. Gerevini have nothing to disclose.
Abstract: EP1739
Type: ePoster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Teriflunomide (TER), the active metabolite of leflunomide, is prescribed by few years for relapsing remitting MS (RR) as first line therapy (Oh J, 2014). Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the central nervous system (CNS) caused by JC virus primarily seen in immunocompromised patients or associated with specific immunotherapies (Ferenczy MW,.2012). Any case of PML has been reported in patients treated with TER, but two case of leflunomide-related PML has been described. Here, we reported the first case of PML during TER treatment.
Case report: A 36-year-old woman with multiple sclerosis, taking TER since three months, on January 30, 2017 developed an acute decline in speech. She was previously treated with natalizumab (N), discontinued after 33 infusions eight months before, for JCV antibodies detection. Brain MRI showed a unilobar area suggestive for PML; cerebrospinal fluid showed JCV DNA (11 copies/ml). A dissemination of brain lesions with several new cortical and subcortical enhancing lesions was observed, making difficult the differential diagnosis between PML-immune reconstitution inflammatory syndrome and new MS relapse.
Conclusions: Up to now, there is no knowledge about the possible risk of PML related to immunosuppressant use subsequently N exposure. The acute onset of symptoms, the first unilobar PML lesion documented by brain MRI and low number of CSF JCV DNA copies, support the hypothesis that in our patient PML was in an initial phase at diagnosis time, occurring eight moths after N cessation, but few months after TER initiation. However, multiple enhancing lesions occurring without modification of clinical symptoms and without any kind of response to steroid could represent a diffuse MS relapse with exaggerated inflammatory reaction, perhaps related to the underlying not clear mechanism of the drugs. Therefore, this case highlights the debate for a more prolonged PML surveillance program, especially for patients extensively N pre-treated with high risk for PML (Schwab N, 2017) that switch to therapies with an immunosuppressant effect.
Keywords: teriflunomide, natalizumab, JC virus, Progressive Multifocal Leukoencephalopathy, safety
Disclosure:
Dr. Lorefice received speaker fee from Teva and serves on scientific advisory boards for Biogen.
Dr. Fenu received honoraria for consultancy from Novartis and for speaking from Merck Serono and Teva.
Dr. Frau serves on scientific advisory boards for Biogen, received honoraria for speaking from Merck Serono and Teva.
Dr. Coghe received speaker fee from Teva and Almirall.
Professor Cocco and Marrosu have received honoraria for consultancy or speaking from Bayer, Biogen-Idec, Novartis, Sanofi-Genzyme, Serono and Teva.
Dr. Contu, Dr. Barracciu and Dr. Gerevini have nothing to disclose.