David Croteau1, Charlene Flowers2, Corrinne G Kulick2, Allen Brinker2, Cindy M Kortepeter2. 1. From the Division of Pharmacovigilance I, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food & Drug Administration, Silver Spring, MD. david.croteau@fda.hhs.gov. 2. From the Division of Pharmacovigilance I, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food & Drug Administration, Silver Spring, MD.
Abstract
OBJECTIVE: To evaluate acute acalculous cholecystitis (AAC) as a potential safety risk for patients treated with alemtuzumab. METHODS: The Food and Drug Administration Adverse Event Reporting System and the medical literature were searched for cases of AAC in conjunction with alemtuzumab for all clinical indications. RESULTS: Eight spontaneously reported cases meeting the case definition of AAC in close temporal association with alemtuzumab use were identified. Based on established criteria within the Food and Drug Administration Division of Pharmacovigilance for causality assessment, 4 cases were assessed as probable while 4 were possible. All cases occurred in patients with relapsing-remitting multiple sclerosis. Seven of the 8 cases presented with AAC during or shortly after alemtuzumab treatment, thereby suggesting an acute cytokine release syndrome as a putative pathogenic mechanism. The cases identified in this review differ from the typical AAC cases described in the medical literature based on female preponderance, lack of concurrent critical illnesses, inconsistent presence of other risk factors, and resolution with conservative treatment in the majority of cases. CONCLUSIONS: AAC represents a new and potentially life-threatening adverse event associated with alemtuzumab use in relapsing-remitting multiple sclerosis. In cases seen to date, early and conservative treatment resulted in good clinical outcome, although the natural history of AAC in this population without critical illness is not well defined. Awareness of this safety risk by general and specialty neurologists is important for prompt recognition and optimal management.
OBJECTIVE: To evaluate acute acalculous cholecystitis (AAC) as a potential safety risk for patients treated with alemtuzumab. METHODS: The Food and Drug Administration Adverse Event Reporting System and the medical literature were searched for cases of AAC in conjunction with alemtuzumab for all clinical indications. RESULTS: Eight spontaneously reported cases meeting the case definition of AAC in close temporal association with alemtuzumab use were identified. Based on established criteria within the Food and Drug Administration Division of Pharmacovigilance for causality assessment, 4 cases were assessed as probable while 4 were possible. All cases occurred in patients with relapsing-remitting multiple sclerosis. Seven of the 8 cases presented with AAC during or shortly after alemtuzumab treatment, thereby suggesting an acute cytokine release syndrome as a putative pathogenic mechanism. The cases identified in this review differ from the typical AAC cases described in the medical literature based on female preponderance, lack of concurrent critical illnesses, inconsistent presence of other risk factors, and resolution with conservative treatment in the majority of cases. CONCLUSIONS: AAC represents a new and potentially life-threatening adverse event associated with alemtuzumab use in relapsing-remitting multiple sclerosis. In cases seen to date, early and conservative treatment resulted in good clinical outcome, although the natural history of AAC in this population without critical illness is not well defined. Awareness of this safety risk by general and specialty neurologists is important for prompt recognition and optimal management.
Authors: Rosa C Lucchetta; Fernanda S Tonin; Helena H L Borba; Letícia P Leonart; Vinicius L Ferreira; Aline F Bonetti; Bruno S Riveros; Jefferson Becker; Roberto Pontarolo; Fernando Fernandez-Llimós; Astrid Wiens Journal: CNS Drugs Date: 2018-09 Impact factor: 5.749
Authors: E Mattone; M Sofia; E Schembari; V Palumbo; R Bonaccorso; V Randazzo; G La Greca; C Iacobello; D Russello; S Latteri Journal: Ann Med Surg (Lond) Date: 2020-08-31
Authors: Alasdair J Coles; Douglas L Arnold; Ann D Bass; Aaron L Boster; D Alastair S Compston; Óscar Fernández; Eva Kubala Havrdová; Kunio Nakamura; Anthony Traboulsee; Tjalf Ziemssen; Alan Jacobs; David H Margolin; Xiaobi Huang; Nadia Daizadeh; Madalina C Chirieac; Krzysztof W Selmaj Journal: Ther Adv Neurol Disord Date: 2021-04-23 Impact factor: 6.570