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Medical information request
Medical information request

 

 

Progressive multifocal leukoencephalopathy

To date, one case of confirmed PML attributed to natalizumab treatment has been reported in a patient exposed to siponimod in the post-marketing setting. PML has been reported with another 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

PML Updated

As of May 28, 2021, with a cumulative clinical trial exposure of 7308 patient-years, no cases of PML have been reported with siponimod2

As of January, 2022, with a cumulative postmarketing exposure of 12962 patient-years, one case of PML** attributed to prior natalizumab treatment have been reported with siponimod3

** A 53 year-old female MS patient with suspected symptom and signs (MRI lesions) of PML was switched from natalizumab to siponimod after having been treated for around 5 years. Therapy with siponimod was stopped after diagnostic confirmation of PML (JCV PCR: 522 copies at CSF, and gadolinium enhancing lesions in the subcortical white matter of the left precentral gyrus), approximately 5 weeks after siponimod treatment initiation.  As per the latest available information (mid-Feb 2022), the patient’s PML symptoms improved, and she was discharged from the hospital. The independent adjudication panel assessed the event of PML as attributable to natalizumab and unrelated to siponimod treatment. 

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

References
1. Greenlee JE. Progressive Multifocal Leukoencephalopathy (PML). MSD Manual Professional Version. Accessed June 29, 2021. https://www.msdmanuals.com/professional/neurologic-disorders/brain-infections/progressive-multifocal-leukoencephalopathy-pml
2. Data on File, cutoff date 28-May-2021, Novartis Pharma AG.
3. Data on File, Novartis Safety database, cutoff date February 24-2022, Novartis Pharma AG.
* Indication varies in different countries. 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 siponimod in the individual country.

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.