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Medical information request
Medical information request


Progressive multifocal leukoencephalopathy 

  • Cases of PML have occurred in patients with MS who received fingolimod in the post-marketing setting1
  • The overall incidence of PML under fingolimod therapy not attributed to previous natalizumab treatment is very rare and the risk remains low
  • The risk factors for developing PML in fingolimod-treated patients is not yet established
PML 1 updated
**Total exposure includes both commercial and clinical trial exposure
^Cases under fingolimod therapy not attributed to previous natalizumab treatment

Case details of 51 patients who developed PML under fingolimod

  • Mean age at the time of PML was 54 years
  • There were 40 female and 11 male patients
  • Treatment duration with fingolimod was >2 years in 49 cases
  • Based on available ALC information in 30 patients (out of 51), none exhibited sustained grade 4 lymphopenia (≤200 cells/μL)
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  • The incidence of PML appears to increase with treatment duration. However, the exact pattern of the relationship to duration of treatment is unclear due to wide 95% confidence intervals
    • Between 6 to 7 years, the estimated risk is ~0.251/1,000 patients

Incidence of PML per 1,000 patients by treatment duration#

PML Graph 1 Updated
#For each period, the number of PML cases attributed to fingolimod was divided by the corresponding exposure to estimate the incidence (hazard) within each period. Data beyond Year 7 were scarce and hence years 8,9 and 10 were pooled. 
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  • The exact shape of the relationship with age is unclear due to wide 95% confidence intervals, uncertainties around underlying assumptions, and other unknown confounding factors

Incidence of PML per 1,000 patients by age at fingolimod initiation

PML Graph 2 Updated

About PML

About PML

  • Progressive multifocal leukoencephalopathy is caused by reactivation of the JC virus, a ubiquitous human papovavirus that is typically acquired during childhood and remains latent in the kidneys and possibly other sites (eg, mononuclear cells, CNS)
  • Increasingly, PML is occurring as a complication of immunomodulatory therapy
  • Common symptoms/signs include clumsiness, hemiparesis, aphasia, dysarthria, hemianopia and cognitive impairment
  • PML is suspected in patients with unexplained progressive brain dysfunction, particularly in those with depressed cell-mediated immunity
  • CSF is analyzed for JC viral DNA using PCR; a positive result with compatible neuroimaging findings is nearly pathognomonic
  • Supportive management and management of underlying disorders are helpful in managing PML
     

Suspected or confirmed PML: Get Novartis support

Novartis support

  • Novartis can help physicians with the assessment of a suspected PML case, after the adverse event has been reported to the company via standard pharmacovigilance processes
  • Subsequently, there is access to an external expert MRI service and Novartis has constituted an external PML adjudication panel for case evaluation
  • If a second opinion on an MRI with atypical findings/suspicion of PML is requested, Novartis can support obtaining this through a MRI expert center (Medical Image Analysis Centre [MIAC]), University Hospital Basel, Switzerland. Novartis will not have access to the MRI and will only receive a report
  • In addition, Novartis can support logistics for shipment of CSF samples for testing for presence of JCV DNA (PCR) at Unilabs A/S, Denmark. In this case, both the physician and Novartis receives the report
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Last updated: December 2021. The page will be updated twice a year.

Abbreviations
CI, confidence interval; CNS, central nervous system; CSF, cerebrospinal fluid; JC, John Cunningham; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; PML, progressive multifocal leukoencephalopathy
References
1. Data on File, cutoff date 31-Aug-2021, Novartis Pharma AG.
* Indication wording varies in different countries. The current website is a global information resource. Local Prescribing Information/ Summary of Product Characteristics approved by individual country’s regulatory authority is the primary source of information for the indication of fingolimod in the individual country.