Abstract Details

Title Retrospective comparison clinical presentation and outcome of Natalizumab and Fingolimod-associated PML

Topic Multiple Sclerosis

Presentation(s) P7 - Poster Session 7 (8:00 AM-9:00 AM)

Poster/Presentation
Number 3-004

Objective

To compare the presentation and outcome in Fingolimod (FTY) and Natalizumab (NTZ) associated with Progressive multifocal leukoencephalopathy (PML).

Background

PML is a severe neurological disease caused by the JC virus (JCV) reactivation in immunocompromised individuals. Several multiple sclerosis treatments have been associated with the risk of developing PML. If Natalitumab-associated PML has been largely described, data on the course of Fingolimod-associated-PML are scarce.

Design/Methods

We conducted a retrospective multicenter cohort study in Japan, Germany, France, Italy, and Switzerland. All consecutive patients admitted at participating centers between 2009 and 2021 for iatrogenic PML related to Fingolimod and Natalizumab were included. Our primary outcome was the occurrence of an immune reconstitution inflammatory syndrome (IRIS) in the two groups. Exploratory variables were survival and disability (measured by Modified Ranking Scale – mRS) at 12 months. We also analyzed the clinical and radiological presentation in these two etiologies.

Results 54 patients met the inclusion criteria and 53 were included in the final analysis (10 in the Fingolimod group and 43 in the Tysabri one). PML associated with Fingolimod occurred in older patients (median (IQR25-75): 51 (41-58) vs 44 (38-47) years, p=0.023) and after a longer treatment duration (median (IQR25-75): 68 (44.5-87.42) vs 36 (23.39-49.00) months, p=0.003). Initial characteristics of PML were similar except for more frequent inflammatory signs (iPML defined as gadolinium-enhancing lesions) at onset in the Fingolimod-treated patients (60 vs 34.9 %, p=0.169). Despite these early inflammatory signs, Natalizumab-associated PML were more prone to develop IRIS (60% vs 87.2%, p= 0.07). Yet, the 12 months disability (median mRS (IQR25-75): 2 (2-3.5) vs 3 (2-4), p = 0.257) and the overall survival (10% vs 16.3%, p =1.000) were similar in the two groups.

Conclusions

Our study shows that Fingolimod-associated PML exhibits a peculiar presentation and course that should be acknowledged to recognize and treat this severe neurological complication.

Authors/Disclosures
Raphael Bernard-Valnet, MD, PhD (Centre Hospitalier Universitaire Vaudois) PRESENTER	The institution of Dr. Bernard-Valnet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Juvisé. The institution of Dr. Bernard-Valnet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Bernard-Valnet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. The institution of Dr. Bernard-Valnet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Bernard-Valnet has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. Bernard-Valnet has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. The institution of Dr. Bernard-Valnet has received research support from Novartis Foundation. The institution of Dr. Bernard-Valnet has received research support from Helmut-Horten Foundation. The institution of Dr. Bernard-Valnet has received research support from Baasch-Medicus Foundation.
	No disclosure on file
Nicola De Rossi	Nicola De Rossi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Nicola De Rossi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for novartis. Nicola De Rossi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen.
	No disclosure on file
Aude Maurousset	Aude Maurousset has received personal compensation in the range of $0-$499 for serving as a Consultant for novartis. Aude Maurousset has received personal compensation in the range of $0-$499 for serving as a Consultant for merck. Aude Maurousset has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for roche.
Markus Kraemer	Markus Kraemer has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Chugai.
	No disclosure on file
Tatsuro Misu	No disclosure on file
Jean C. Ouallet (Dept of Neurology S258)	Jean C. Ouallet has nothing to disclose.
Maud Pallix Guyot	Maud Pallix Guyot has nothing to disclose.
Ralf Gold, MD (Neurologische Universitaetsklinik)	Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen . Dr. Gold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer Vital. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Pharamaceuticals. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for SAGE Publishers. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Novartis. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Biogen. The institution of Dr. Gold has received research support from Novartis. The institution of Dr. Gold has received research support from Biogen.
	No disclosure on file
Ilya Ayzenberg (Ruhr-Universitat Bochum)	Dr. Ayzenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Ayzenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Ayzenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Aventis. Dr. Ayzenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Ayzenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Ayzenberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Ayzenberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Ayzenberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. The institution of Dr. Ayzenberg has received research support from Diamed.
Renaud A. Du Pasquier, MD, FAAN (Service of neurology, CHUV)	Dr. Du Pasquier has nothing to disclose.

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