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 modulator1,2

As of March 31, 2023, with a cumulative clinical trial exposure of 8,722 patient-years, two cases of CM** have been reported with siponimod3
As of March 25, 2024, with a cumulative postmarketing exposure of 50,657 patient-years, no cases of CM have been reported with siponimod4
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. gattii5
- After inhalation, Cryptococcus may disseminate frequently to the brain and meninges, typically manifesting as microscopic multifocal intracerebral lesions5
- 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 course5
- 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 immunity5
- 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 management5
- Amphotericin B, flucytosine, and fluconazole are antifungal medications shown to improve survival in patients with cryptococcal infections5
