Abstract Details

Title Assessment of Potential Risk of Progressive Multifocal Leukoencephalopathy with Fingolimod Compared with That of Natalizumab

Topic MS and Related Diseases

Presentation(s) P01 - (-)

Poster/Presentation
Number 160

Objective

Background BACKGROUND: The background risk of PML, in absence of HIV infection, is [sim]0.009/1000. There have been, as of May 2012, 242 cases of PML in patients treated with natalizumab with an overall risk of 2.1/1000, rising to 11/1000 in those with additional risk factors [>24 months treatment, JCV antibody positive (JCV+ve) and selected prior immunosuppressant use]. As fingolimod is an immunomodulatory agent, the question arises about potential risk of PML with fingolimod.

Design/Methods DESIGN/METHODS: The fingolimod safety database was explored for reports of confirmed PML. Based on the number of patients exposed and assuming 50% JCV+ve status for exposed patients, point estimates were calculated using the Exact (Clopper-Pearson) formula and compared with reported incidences with natalizumab.

Results RESULTS: As of Sep 2012, >49,000 patients (>52,000 patient-years) have been treated with fingolimod, 2630 having >24 months and over 900 patients having >5 years of exposure. To date, no case of PML related to fingolimod therapy has been observed. A single case was reported in a patient who received natalizumab for >3 years and had evidence of PML prior to starting fingolimod. Incidence of PML in patients treated for >24 months is 0/2630 for fingolimod vs. 3.98/1000 with natalizumab, and assuming 50% JCV+ve status in patients with >24-months exposure, 0/1315 vs. 5.83/1000. If fingolimod had 5-fold lower risk than natalizumab to induce PML, one would expect, with 87.7% probability, to see at least one PML case, among the 2630 fingolimod treated patients for >24 months.

Conclusions CONCLUSIONS: As of Sep 2012, the absence of PML cases associated with fingolimod yields point estimates that indicate that the potential risk with fingolimod is lower than for natalizumab.

Authors/Disclosures
Gordon S. Francis, MD, FAAN PRESENTER	No disclosure on file
Frank Dahlke, MD, PhD	Dr. Dahlke has received personal compensation for serving as an employee of Novartis.
	No disclosure on file
	No disclosure on file
	No disclosure on file

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