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Four cases of natalizumab-related PML: a less severe course in extended interval dosing?
Cristina Scarpazza1,2, Nicola De Rossi3, Giulietta Tabiadon4
1Regional Multiple Sclerosis Center, ASST - Spedali Civili di Brescia, Via Ciotti 154, 25018, Montichiari, Brescia, Italy. cristina.scarpazza@gmail.com.
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.
Insights
Extended interval dosing (EID) of natalizumab (NTZ) may reduce progressive multifocal leukoencephalopathy (PML) risk. Strict monitoring of high-risk patients ensures an indolent course for NTZ-PML cases.
Area of Science:
- Neurology
- Immunology
- Virology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a serious adverse event associated with natalizumab (NTZ) therapy.
- Extended interval dosing (EID) of NTZ is being explored to mitigate PML risk while preserving therapeutic benefits.
Observation:
- This paper details four cases of natalizumab-associated PML within the Italian PML cohort, all treated with EID.
- Patients received at least 38 NTZ infusions, had a John Cunningham virus (JCv) index >1.5, and no prior immunosuppressant use.
Findings:
- Two patients were asymptomatic at PML onset; two experienced mild motor or speech impairment.
- All patients had undetectable JCv viral load, except one with 37 JCv copies/ml.
- MRI revealed unilobar lesions with delayed contrast enhancement, indicating immune reconstitution, and all cases showed favorable clinical outcomes (ΔEDSS up to 1).
Implications:
- While PML incidence may be lower with EID, vigilant monitoring of high-risk individuals is crucial.
- These cases demonstrate an indolent PML course in EID patients, marked by a prolonged pre-symptomatic phase, mild symptoms, low JCv load, and minimal disability.
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