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Medical information request
Medical information request


Cryptococcal meningitis

To date, two cases of CM have been reported with siponimod. Cases of fatal CM and disseminated cryptococcal infections have been reported with another S1P receptor modulator1

Clinical and postmarketing_CM_v1

As of May 28, 2021, with a cumulative clinical trial exposure of 7308 patient-years, two cases of CM** have been reported with siponimod2

As of September 25, 2021, with a cumulative postmarketing exposure of 9186 patient-years, no cases of CM have been reported with siponimod3

**First case was a 62-year-old female patient with long-standing history of MS treated with siponimod for approximately 2.5 years, diagnosed with CM and completely recovered with systemic anti-fungals
Second case was a 61-year-old male patient on therapy with siponimod for 6 years and 6 months, diagnosed with CM and recovered completely with systemic antifungals.

 

About CM

CM background

  • Cryptococcosis is a pulmonary or disseminated infection acquired by inhalation of soil contaminated with the encapsulated yeast Cryptococcus neoformans or C. gattii1,4
  • After inhalation, Cryptococcus may disseminate frequently to the brain and meninges, typically manifesting as microscopic multifocal intracerebral lesions4
  • CM signs/symptoms result from cerebral edema and include nonspecific symptoms such as headache, blurred vision, confusion, depression, agitation, and other behavioral changes. Except for ocular or facial palsies, focal signs are rare until relatively late in the course4
  • CM diagnosis is suggested by symptoms of an indolent infection in immunocompetent patients and a more severe, progressive infection in immunocompromised patients and unexplained progressive brain dysfunction, particularly in those with depressed cell-mediated immunity4
    • Chest x-ray, urine collection, and lumbar puncture are frequently the initial diagnostic tests done
    • Elevated CSF protein and a mononuclear cell pleocytosis are usual in CM
    • The latex test for cryptococcal capsular antigen is positive in CSF or blood specimens or both in >90% of patients with meningitis and is generally specific
  • General recommendations for CM management4
    • Amphotericin B, flucytosine, and fluconazole are antifungal medications shown to improve survival in patients with cryptococcal infections4
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Abbreviations
CM, cryptococcal meningitis; CSF, cerebrospinal fluid; S1P, sphingosine 1-phosphate receptor modulator
References
1. Siponimod® Prescribing Information, Accessed June 29, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf.
2. Data on File, cutoff date 28-May-2021, Novartis Pharma AG.
3. Data on File, PSUR, cutoff date 25-September-2021, Novartis Pharma AG.
4. Centers for Disease Control and Prevention. CDC. Cryptococcal meningitis. Accessed February 15, 2021. https://www.cdc.gov/fungal/cdc-and-fungal/cryptococcal-meningitis.html
* 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.