Cristina Scarpazza1,2, Nicola De Rossi3, Giulietta Tabiadon4, Maria Vittoria Turrini3, Simonetta Gerevini5, Ruggero Capra6. 1. Regional Multiple Sclerosis Center, ASST - Spedali Civili di Brescia, Via Ciotti 154, 25018, Montichiari, Brescia, Italy. cristina.scarpazza@gmail.com. 2. Department of General Psychology, University of Padova, Padova, Italy. cristina.scarpazza@gmail.com. 3. Regional Multiple Sclerosis Center, ASST - Spedali Civili di Brescia, Via Ciotti 154, 25018, Montichiari, Brescia, Italy. 4. Department of Neurology, Regional General Hospital, Bolzano, Italy. 5. Department of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milan, Italy. 6. Regional Multiple Sclerosis Center, ASST - Spedali Civili di Brescia, Via Ciotti 154, 25018, Montichiari, Brescia, Italy. ruggero.capra@gmail.com.
Abstract
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a severe adverse event of natalizumab (NTZ). The administration of NTZ with extended interval dosing (EID) has been proposed as a strategy to potentially reduce the incidence of PML while maintaining its therapeutic efficacy. METHODS: In the current paper, we describe 4 cases of NTZ-PML in EID included in the Italian PML cohort. RESULTS: The patients developed PML after at least 38 NTZ infusions. Their John Cunningham virus (JCv) index was > 1.5, and patients had not previously used immunosuppressant. Two patients were asymptomatic at PML onset, while two had mild motor impairment of the right hand and anomia, respectively. All of them had undetectable viral load but one (37 JCv copies/ml). In all patients, MRI revealed unilobar lesions with deferred contrast enhancement suggestive of immune reconstitution. The clinical course ended with a favorable clinical outcome (ΔEDSS up to 1). CONCLUSIONS: Although PML in EID seems to occur less frequently than in conventional dosing regimen, strict monitoring of high-risk patients contributed to the indolent course observed in the four described cases, characterized by a prolonged pre-symptomatic phase, paucisymptomatic onset, low JCv load, less severe functional impairment during immune reconstitution, and a mild disability burden.
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a severe adverse event of natalizumab (NTZ). The administration of NTZ with extended interval dosing (EID) has been proposed as a strategy to potentially reduce the incidence of PML while maintaining its therapeutic efficacy. METHODS: In the current paper, we describe 4 cases of NTZ-PML in EID included in the Italian PML cohort. RESULTS: The patients developed PML after at least 38 NTZ infusions. Their John Cunningham virus (JCv) index was > 1.5, and patients had not previously used immunosuppressant. Two patients were asymptomatic at PML onset, while two had mild motor impairment of the right hand and anomia, respectively. All of them had undetectable viral load but one (37 JCv copies/ml). In all patients, MRI revealed unilobar lesions with deferred contrast enhancement suggestive of immune reconstitution. The clinical course ended with a favorable clinical outcome (ΔEDSS up to 1). CONCLUSIONS: Although PML in EID seems to occur less frequently than in conventional dosing regimen, strict monitoring of high-risk patients contributed to the indolent course observed in the four described cases, characterized by a prolonged pre-symptomatic phase, paucisymptomatic onset, low JCv load, less severe functional impairment during immune reconstitution, and a mild disability burden.
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