Contributions
Abstract: P762
Type: Poster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Fingolimod (FTY) has been approved as a first-line disease-modifying drug for relapsing multiple sclerosis (MS) in Japan since 2011. As of 01/2017, FTY has been prescribed to 5,400 Japanese MS patients, which constitutes approximately 3% of FTY prescription worldwide (184,000). By the end of year 2016, nine FTY-associated progressive multifocal leukoencephalopathy (PML) cases had been reported in natalizumab (NAT)-naïve MS, with two of them (22%) from Japan.
Case presentation: Here we report the third FTY-associated PML case in NAT-naïve Japanese. The patient is 47-year-old male diagnosed with MS in 2002. He was treated with interferon β from 2002 to 2013, before switching to FTY in 2013, when his EDSS was 6.0. During the course, he was exposed to a single 1000mg infusion of cyclophosphamide, which was terminated due to the lack of efficacy. He had never been tested for serum anti-JC virus (JCV) antibodies. His blood lymphocyte counts maintained over 200/µl for most of the time. His biannual MRI in 11/2016 revealed a new punctate T2 lesion in left middle cerebellar peduncle and an enlarging T2 lesion in cerebral white matter near the angular gyrus, both of which lacked contrast-enhancement (CE). He remained clinically stable (EDSS=6.5) and continued FTY (for total of 44 months) until late 12/2016, when he exhibited word-finding difficulties with cognitive impairment akin to Gerstmann syndrome. FTY was discontinued immediately and the patient was admitted to hospital for further evaluations. While waiting for the JCV test result in cerebrospinal fluid (CSF), progressive hemiparesis and seizures in his right leg and ataxia in his left arm were noted concomitantly with the development of CE in the T2 lesions. PML was diagnosed upon confirmation of JCV in his CSF (25 and 423 copies/ml in 12/2016 and 01/2017, respectively). He was treated with mirtazapine, levetiracetam for seizures, repeated courses of intravenous methylprednisolone therapy with oral taper for immune reconstitution inflammatory syndrome (IRIS). JCV became negative in CSF and the patient is to be discharged in 06/2017. Sequelae of PML-IRIS were worsened disability (EDSS=7.5) and moderate cognitive impairment.
Conclusion: This is the tenth confirmed case of FTY-associated PML in natalizumab-naïve MS patients. Three of which (30%), including this case, were reported from Japan, raising a possibility that Japanese MS patients are at a greater risk of developing PML under FTY treatment.
Disclosure:
Jin Nakahara: received honoraria from Biogen, Mitsubishi Tanabe, Novartis, and Takeda; served as a paid scientific advisor to Biogen, Novartis, and Takeda.
Kenji Kufukihara: nothing to disclose.
Mariko Tanikawa: nothing to disclose.
Kazuo Nakamichi: nothing to disclose.
Yoshiharu Miura: nothing to disclose.
Hirokazu Fujiwara: nothing to disclose.
Masahiro Jinzaki: received research funds from GE Healthcare.
Takahito Yoshizaki: nothing to disclose.
Shigeaki Suzuki: nothing to disclose.
Shinichi Takahashi: nothing to disclose.
Norihiro Suzuki: nothing to disclose.
Abstract: P762
Type: Poster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Fingolimod (FTY) has been approved as a first-line disease-modifying drug for relapsing multiple sclerosis (MS) in Japan since 2011. As of 01/2017, FTY has been prescribed to 5,400 Japanese MS patients, which constitutes approximately 3% of FTY prescription worldwide (184,000). By the end of year 2016, nine FTY-associated progressive multifocal leukoencephalopathy (PML) cases had been reported in natalizumab (NAT)-naïve MS, with two of them (22%) from Japan.
Case presentation: Here we report the third FTY-associated PML case in NAT-naïve Japanese. The patient is 47-year-old male diagnosed with MS in 2002. He was treated with interferon β from 2002 to 2013, before switching to FTY in 2013, when his EDSS was 6.0. During the course, he was exposed to a single 1000mg infusion of cyclophosphamide, which was terminated due to the lack of efficacy. He had never been tested for serum anti-JC virus (JCV) antibodies. His blood lymphocyte counts maintained over 200/µl for most of the time. His biannual MRI in 11/2016 revealed a new punctate T2 lesion in left middle cerebellar peduncle and an enlarging T2 lesion in cerebral white matter near the angular gyrus, both of which lacked contrast-enhancement (CE). He remained clinically stable (EDSS=6.5) and continued FTY (for total of 44 months) until late 12/2016, when he exhibited word-finding difficulties with cognitive impairment akin to Gerstmann syndrome. FTY was discontinued immediately and the patient was admitted to hospital for further evaluations. While waiting for the JCV test result in cerebrospinal fluid (CSF), progressive hemiparesis and seizures in his right leg and ataxia in his left arm were noted concomitantly with the development of CE in the T2 lesions. PML was diagnosed upon confirmation of JCV in his CSF (25 and 423 copies/ml in 12/2016 and 01/2017, respectively). He was treated with mirtazapine, levetiracetam for seizures, repeated courses of intravenous methylprednisolone therapy with oral taper for immune reconstitution inflammatory syndrome (IRIS). JCV became negative in CSF and the patient is to be discharged in 06/2017. Sequelae of PML-IRIS were worsened disability (EDSS=7.5) and moderate cognitive impairment.
Conclusion: This is the tenth confirmed case of FTY-associated PML in natalizumab-naïve MS patients. Three of which (30%), including this case, were reported from Japan, raising a possibility that Japanese MS patients are at a greater risk of developing PML under FTY treatment.
Disclosure:
Jin Nakahara: received honoraria from Biogen, Mitsubishi Tanabe, Novartis, and Takeda; served as a paid scientific advisor to Biogen, Novartis, and Takeda.
Kenji Kufukihara: nothing to disclose.
Mariko Tanikawa: nothing to disclose.
Kazuo Nakamichi: nothing to disclose.
Yoshiharu Miura: nothing to disclose.
Hirokazu Fujiwara: nothing to disclose.
Masahiro Jinzaki: received research funds from GE Healthcare.
Takahito Yoshizaki: nothing to disclose.
Shigeaki Suzuki: nothing to disclose.
Shinichi Takahashi: nothing to disclose.
Norihiro Suzuki: nothing to disclose.