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Cryptococcal Meningitis Reported With Fingolimod Treatment: Case Series
Maurizio Del Poeta1, Brian J Ward1, Benjamin Greenberg1
1From the Department of Microbiology and Immunology (M.D.P.), Stony Brook University; Division of Infectious Diseases (M.D.P.), School of Medicine, Stony Brook University; Veterans Affairs Medical Center (M.D.P.), Northport, NY; Infectious Diseases Division (B.J.W.), Research Institute of the McGill University Health Centre, Montreal, QC, Canada; University of Texas Southwestern Medical Center (B.G.), Department of Neurology, Dallas, TX; Department of Neurology (B.H.), Klinikum Rechts der Isar, Technical University of Munich; Munich Cluster for Systems Neurology (SyNergy) (B.H.), Germany; UCSF Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Novartis Healthcare Pvt. Ltd. (S.K., J.M.), Hyderabad, India; Novartis Pharmaceuticals Corporation (R.S.), East Hanover, NJ; Novartis Pharma AG (A.K., A.M., T.H.), Basel, Switzerland; and Department of Neurology (J.R.B.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Background And Objectives:
To describe the characteristics of patients with MS reporting cryptococcal meningitis (CM) while treated with fingolimod.
Methods:
The Novartis safety database was searched for cases with CM between January 26, 2006, and February 28, 2020. The reporting rate of CM was estimated based on the case reports received and exposure to fingolimod in the postmarketing setting during the relevant period.
Results:
A total of 60 case reports of CM were identified, mostly from the United States. The median age was 48 years, and 51.8% were women. Most of the patients had recovered or were recovering at the time of final report. A fatal outcome occurred in 13 cases. During the study period, the rate of CM in patients with MS receiving fingolimod was estimated to be 8 per 100,000 patient-years (95% CI: 6.0; 10.0). The incidence of CM seemed to increase with duration of treatment; however, this relationship remains uncertain due to wide CIs and missing data.
Discussion:
The causal relationship between fingolimod treatment and CM is not yet fully understood. The CM mortality rate in fingolimod-treated patients is similar to that reported in HIV-negative patients. Vigilance for signs and symptoms of CM in patients receiving fingolimod, particularly the new onset of headaches and altered mental status, is essential. Early diagnosis and treatment are critical to reducing CM-associated mortality.
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