ECTRIMS Online Library

Age at natalizumab start as risk cofactor for developing early onset progressive multifocal leukoencephalopathy
Author(s): ,
L Prosperini
Affiliations:
Neurology and Psychiatry, Sapienza University, Rome
,
C Scarpazza
Affiliations:
Multiple Sclerosis Centre - Spedali Civili di Brescia, Montichiari (BS)
,
L Imberti
Affiliations:
CREA, Diagnostics Dept. - Spedali Civili di Brescia, Brescia, Italy
,
N De Rossi
Affiliations:
Multiple Sclerosis Centre - Spedali Civili di Brescia, Montichiari (BS)
,
C Cordioli
Affiliations:
Multiple Sclerosis Centre - Spedali Civili di Brescia, Montichiari (BS)
,
R Capra
Affiliations:
Multiple Sclerosis Centre - Spedali Civili di Brescia, Montichiari (BS)
Italian PML Study Group
Italian PML Study Group
Affiliations:
ECTRIMS Online Library. Prosperini L. 09/16/16; 146026; P1598
Luca Prosperini
Luca Prosperini
Contributions
Abstract

Abstract: P1598

Type: LB Poster

Abstract Category: Late Breaking News

Background: Six-hundred and thirty-eight confirmed cases of natalizumab-related progressive multifocal leukoencephalopathy (PML) have been reported in patients with multiple sclerosis (MS) at March 2016. Patients are considered at risk for developing PML if they have tested positive for John Cunningham virus (JCV), and have used an immunosuppressant, either have received >24 natalizumab infusions. Higher risk patients were recommended to have brain magnetic resonance imaging (MRI) scans every 3 months. However, this risk management plan is still debated since some PML cases were diagnosed even before the 24th infusion.

Objective: To assess the potential predictors of early onset PML, defined as a PML diagnosed before 24 natalizumab infusions.

Methods: PubMed was searched for articles reporting data of individual patients who developed natalizumab-related PML. Once identified cases from literature data and removed duplicates, they were merged with data collected by the MS centre of Montichiari, the reference site for natalizumab-related PML cases in Italy. Demographic and clinical information on each identified PML case were stored into an electronic spreadsheet. Differences in demographic and clinical features were then investigated according to timing of PML diagnosis (before or after the 24th infusion).

Results: We identified 220 natalizumab-related PML cases. Early onset PML was observed in 54 (24.5%) patients who had an older age at natalizumab start than those ones diagnosed after the 24th infusion (mean: 42.6+/-9.8 versus 39.1+/-9.5, p=0.03). There were no other between-group differences. We found an indirect correlation between age at natalizumab start and number of infusion at PML diagnosis (rho=-0.21, p=0.003), that survived even after correction for country, sex, prior immunosuppressant exposure and dataset variability (rho=-0.19, p=0.008). The best possible age cut-off to discriminate early onset PML was 44 years according to ROC analysis. A multivariable regression logistic model showed a 2.4-fold increased risk for early onset PML in patients older than 44 years (p=0.02).

Conclusion: Our findings suggest that immunosenescence may influence PML risk not only with oral drugs (fingolimod and dimethylfumarate), but also in natalizumab-treated patients. Therefore, current recommendations to minimise PML risk in JCV-positive patients should be revised to encompass more frequent MRI scans as early as the 12th infusion for older ages at natalizumab start.

Disclosure: LP received consulting fees from Biogen and Novartis; speaker honoraria from Biogen, Genzyme, Novartis and Teva; travel grants from Biogen, Genzyme, Novartis and Teva; research grants from the Italian MS Society (Associazione Italiana Sclerosi Multipla) and Genzyme.

CS has nothing to disclose.

LI received consulting fees from Merck Serono and travel grants from Teva.

NDR received speaker honoraria from Biogen and Teva and travel grants from Biogen, Teva and Merk Serono.

CC received consulting fees from Novartis and Merk Serono.

RC received consulting fees from Novartis, Biogen and lecture fees and/or travel grants from Novartis, Biogen, Genzyme and Sanofi-Aventis.

Abstract: P1598

Type: LB Poster

Abstract Category: Late Breaking News

Background: Six-hundred and thirty-eight confirmed cases of natalizumab-related progressive multifocal leukoencephalopathy (PML) have been reported in patients with multiple sclerosis (MS) at March 2016. Patients are considered at risk for developing PML if they have tested positive for John Cunningham virus (JCV), and have used an immunosuppressant, either have received >24 natalizumab infusions. Higher risk patients were recommended to have brain magnetic resonance imaging (MRI) scans every 3 months. However, this risk management plan is still debated since some PML cases were diagnosed even before the 24th infusion.

Objective: To assess the potential predictors of early onset PML, defined as a PML diagnosed before 24 natalizumab infusions.

Methods: PubMed was searched for articles reporting data of individual patients who developed natalizumab-related PML. Once identified cases from literature data and removed duplicates, they were merged with data collected by the MS centre of Montichiari, the reference site for natalizumab-related PML cases in Italy. Demographic and clinical information on each identified PML case were stored into an electronic spreadsheet. Differences in demographic and clinical features were then investigated according to timing of PML diagnosis (before or after the 24th infusion).

Results: We identified 220 natalizumab-related PML cases. Early onset PML was observed in 54 (24.5%) patients who had an older age at natalizumab start than those ones diagnosed after the 24th infusion (mean: 42.6+/-9.8 versus 39.1+/-9.5, p=0.03). There were no other between-group differences. We found an indirect correlation between age at natalizumab start and number of infusion at PML diagnosis (rho=-0.21, p=0.003), that survived even after correction for country, sex, prior immunosuppressant exposure and dataset variability (rho=-0.19, p=0.008). The best possible age cut-off to discriminate early onset PML was 44 years according to ROC analysis. A multivariable regression logistic model showed a 2.4-fold increased risk for early onset PML in patients older than 44 years (p=0.02).

Conclusion: Our findings suggest that immunosenescence may influence PML risk not only with oral drugs (fingolimod and dimethylfumarate), but also in natalizumab-treated patients. Therefore, current recommendations to minimise PML risk in JCV-positive patients should be revised to encompass more frequent MRI scans as early as the 12th infusion for older ages at natalizumab start.

Disclosure: LP received consulting fees from Biogen and Novartis; speaker honoraria from Biogen, Genzyme, Novartis and Teva; travel grants from Biogen, Genzyme, Novartis and Teva; research grants from the Italian MS Society (Associazione Italiana Sclerosi Multipla) and Genzyme.

CS has nothing to disclose.

LI received consulting fees from Merck Serono and travel grants from Teva.

NDR received speaker honoraria from Biogen and Teva and travel grants from Biogen, Teva and Merk Serono.

CC received consulting fees from Novartis and Merk Serono.

RC received consulting fees from Novartis, Biogen and lecture fees and/or travel grants from Novartis, Biogen, Genzyme and Sanofi-Aventis.

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies