From 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.
Neurol Neuroimmunol Neuroinflamm. 2022 Mar 22;9(3). doi: 10.1212/NXI.0000000000001156. Print 2022 May.
To describe the characteristics of patients with MS reporting cryptococcal meningitis (CM) while treated with fingolimod.
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.
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.
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.
描述接受芬戈莫德治疗的多发性硬化症（MS）患者并发隐球菌性脑膜炎（CM）的特征。
检索诺华安全数据库，以获取 2006 年 1 月 26 日至 2020 年 2 月 28 日期间发生的 CM 病例。根据相关时期上市后接受芬戈莫德治疗的病例报告和暴露情况，估计 CM 的报告率。
共确定了 60 例 CM 病例报告，主要来自美国。中位年龄为 48 岁，51.8%为女性。大多数患者在最终报告时已康复或正在康复。13 例患者死亡。在研究期间，接受芬戈莫德治疗的 MS 患者中 CM 的发生率估计为每 100,000 患者年 8 例（95%CI：6.0；10.0）。尽管由于置信区间较宽且数据缺失，CM 的发生率似乎随治疗时间的延长而增加，但这种关系仍不确定。
芬戈莫德治疗与 CM 之间的因果关系尚未完全阐明。接受芬戈莫德治疗的患者的 CM 死亡率与报告的 HIV 阴性患者相似。接受芬戈莫德治疗的患者必须密切注意 CM 的症状和体征，尤其是新发头痛和精神状态改变。早期诊断和治疗对于降低 CM 相关死亡率至关重要。
