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Age as a risk factor for early onset of natalizumab-related progressive multifocal leukoencephalopathy
Luca Prosperini1, Cristina Scarpazza2, Luisa Imberti3
1Department of Neurology and Psychiatry, Sapienza University, Viale dell'Università 30, 00185, Rome, Italy. luca.prosperini@uniroma1.it.
Abstract:
Progressive multifocal leukoencephalopathy (PML) is a rare but potentially fatal opportunistic infection that arises almost exclusively in immunocompromised patients or in those treated with monoclonal antibodies, especially natalizumab. Here, we aimed at exploring if age at treatment start affects the time to onset of natalizumab-related PML. PubMed was searched for the terms "natalizumab and progressive multifocal leukoencephalopathy" in articles published from January 2005 to March 2017. We collected information on each identified PML case, including demographic and clinical variables at natalizumab start and at PML onset. The number of natalizumab infusions until PML onset was investigated in time-to-event analyses. We identified 238 cases who developed PML after a median number of 33 natalizumab infusions (range 6 to 103). Risk factors for an earlier onset of natalizumab-related PML were prior immunosuppressant exposure (hazard ratio [HR] = 1.43, p = 0.017) and older age at treatment start (HR = 1.02, p = 0.016). In particular, patients older than 50 years had a more than doubled-increased risk for an earlier PML onset (HR = 2.11, p = 0.006). Our findings suggest that the age at natalizumab start may represent a risk factor for an earlier PML onset, thus claiming further investigations about the interplay between immunosenescence and MS treatments.
Insights
Older age at natalizumab treatment start increases the risk of developing progressive multifocal leukoencephalopathy (PML). Patients over 50 years old face a doubled risk of earlier PML onset, highlighting age as a key factor.
Area of Science:
- Neuroimmunology
- Infectious Diseases
Background:
- Progressive multifocal leukoencephalopathy (PML) is a rare, fatal opportunistic infection.
- PML predominantly affects immunocompromised individuals and those on monoclonal antibody therapies like natalizumab.
Purpose of the Study:
- To investigate if age at the start of natalizumab treatment influences the onset time of natalizumab-related PML.
- To identify risk factors associated with earlier PML onset in patients receiving natalizumab.
Main Methods:
- A systematic literature search was conducted on PubMed for "natalizumab and progressive multifocal leukoencephalopathy" (January 2005-March 2017).
- Data from 238 identified PML cases were collected, including demographics and clinical variables.
- Time-to-event analyses were used to assess the number of natalizumab infusions until PML onset.
Main Results:
- A median of 33 natalizumab infusions preceded PML onset (range 6-103).
- Prior immunosuppressant exposure (HR=1.43, p=0.017) and older age at treatment initiation (HR=1.02, p=0.016) were risk factors for earlier PML.
- Patients over 50 years old had a >2-fold increased risk of earlier PML onset (HR=2.11, p=0.006).
Conclusions:
- Age at natalizumab treatment start is a significant risk factor for earlier PML onset.
- Further research is needed to understand the interaction between immunosenescence and natalizumab treatment in PML development.
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