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Risk estimates of progressive multifocal leukoencephalopathy related to fingolimod
Author(s): ,
D. Ontaneda
Affiliations:
Mellen Center, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, United States
,
A. Moore
Affiliations:
Novartis, Basle, Switzerland
,
R. Bakshi
Affiliations:
Novartis, Basle, Switzerland
,
A. Zajicheck
Affiliations:
Quantitative Health Sciences
,
M. Kattan
Affiliations:
Quantitative Health Sciences
R. Fox
Affiliations:
Mellen Center, Cleveland Clinic, Cleveland, OH, United States
ECTRIMS Online Library. Ontaneda D. Oct 12, 2018; 228153
Daniel Ontaneda
Daniel Ontaneda
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Abstract
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Abstract: P1775

Type: Poster Sessions

Abstract Category: N/A

Background and objective: Progressive multifocal leukoencephalopathy (PML) is a serious and potentially fatal side effect of multiple sclerosis (MS) disease modifying agents. PML is a rare complication of fingolimod but precise estimates and risk stratification tools are not available. The primary objective of this investigation was to estimate the global risk of PML in MS patients taking fingolimod and assess the impact of age and treatment duration.
Methods: A simulation model was created using an estimate of the worldwide population starting and stopping fingolimod, and those developing PML from available literature sources, assuming a static risk of PML. A clock was run from August 1, 2010 to August 31, 2017 where the total number of patients entering matched the estimated global population taking fingolimod. The occurrence of PML was simulated to match the 15 cases of fingolimod-related PML reported at that time. In a separate analytical approach, the number of PML cases attributed to fingolimod was compared with the estimated number of commercial patients at risk overall by treatment duration and age at start of treatment.
Results: In the simulation, the parameter search was able to achieve the extrapolated real-world experience of 15 cases over the time period. The mean, median, and IQR of the number of PML cases in simulations were 15.52, 15, and 4.3, respectively (95% confidence interval for the mean was 7.5-24.4) and the overall risk of PML was 1 in 33,315 patient-years. Analytical methods estimated an overall incidence rate of 1 in 30,216 (18,320, 53,988) patient-years. The incidence of PML appeared to increase with treatment duration and age at start of treatment. The estimated incidence of PML in different categories of treatment-duration (0-7 years) ranged between 0 and 1 in 5,747 patients .For quintiles of treatment start age the incidence ranged between 0 and 1 in 7,575 patients. For both features, the precision of the incidence estimates is low due to few case numbers. The small number of cases did not allow the identification of critical treatment-duration or age-group thresholds.
Conclusions: PML associated with fingolimod is very rare. Although the estimated risk appears to increase with cumulative exposure and increased age at start of treatment, the precise pattern of this relationship remains unclear and the modeled risk of PML remains low even for those starting treatment at an older age or with longer treatment duration.
Disclosure: Daniel Ontaneda has recieved research support from NIH, PCORI, NMSS, R2E Foundation, Novarits, Genzyme, Genenetech and Consulting fees from Biogen Idec, Genzyme, Roche/Genentech.
Alan Moore, Rajesh Bakshi are full time employees of Novartis.
Alexander Zajichek has no disclosures.
Michael Kattan is a consultant for Novartis
Robert Fox has received personal consulting fees from Actelion, Biogen , EMD Serono, Genentech, Novartis, and Teva, has served on advisory committees for Actelion, Biogen, Novartis, and received clinical trial contract and research grant funding from Biogen and Novartis.

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