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Progressive multifocal leukoencephalopathy

PML has been reported with an S1P receptor modulator and other MS therapies. Therefore, vigilance on the part of physicians and patients for signs and symptoms of infections is important while on therapy and for up to 1 month after cessation of treatment1

Clinical and postmarketing_PML_v1

Clinical trials

PML for postmarketing_V1

As of 25-September-2020, with cumulative clinical trial exposure of 7171 patient-years, no cases of PML have been reported2


 

About PML

PML background

  • PML 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)1
  • PML is increasingly occurring as a complication of immunomodulatory therapy1
  • Common symptoms/signs include clumsiness, hemiparesis, aphasia, dysarthria, hemianopia and cognitive impairment1
  • PML is suspected in patients with unexplained progressive brain dysfunction, particularly in those with depressed cell-mediated immunity1
  • CSF is analyzed for JC viral DNA using PCR; a positive result with compatible neuroimaging findings is nearly pathognomonic1
  • Supportive management and management of underlying disorders are helpful in managing PML1

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 an 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 JC DNA (PCR) at Unilabs A/S, Denmark. In this case, both the physician and Novartis receives the report
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Last updated: February 2021. The page will be updated quarterly.

Abbreviations
CNS, central nervous system; CSF, cerebrospinal fluid; JC, John Cunningham; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; PML, progressive multifocal leukoencephalopathy
Abbreviations
CNS, central nervous system; CSF, cerebrospinal fluid; JC, John Cunningham; MS, multiple sclerosis; MRI, Magnetic resonance imaging; PCR, polymerase chain reaction; PML, progressive multifocal leukoencephalopathy; S1P, sphingosine 1-phosphate receptor modulator
References
1. Greenlee JE. Progressive Multifocal Leukoencephalopathy (PML). MSD Manual Professional Version. Accessed December 23, 2020. https://www.msdmanuals.com/professional/neurologic-disorders/brain-infections/progressive-multifocal-leukoencephalopathy-pml
2. Data on File, cutoff date 6-Apr-2020, Novartis Pharma AG.
3. Data on File, PSUR 2, cutoff date 25-Sep-2020, Novartis Pharma AG.

The Pregnancy outcome Intensive Monitoring (PRIM) program is based on enhanced pharmacovigilance of the Novartis spontaneous reporting system. PRIM is an adverse event outcomes intensive monitoring program to collect information (targeted follow-up checklists) about pregnancy in patients exposed to siponimod immediately before or during pregnancy and infant outcomes 12 months after delivery.