Background: There are currently ten intravenous enzyme replacement therapy (ERT) products available for the treatment of eight different lysosomal diseases (LD) in the USA. Additional ERT products are in clinical trials. The most common ERT adverse events are infusion reactions (IR). While IR are often defined as hypersensitivity or anaphylactoid reactions occurring concurrently with (i.e., during) infusion administration (CIR), there exists the potential for delayed infusion reactions (DIR), which present after completion of infusion administration. Hypothesis: Concurrent infusion reactions (CIR) are not the only infusion reactions associated with enzyme therapy. Methods: This study evaluated the occurrence of infusion reactions in 46 patients with LD who had received ERT for a minimum of 2 years. Infusion reactions were evaluated according to symptoms, time of onset, and duration of reactions. The frequency of infusion reactions with each ERT product was compared to that reported in the FDA-approved product package insert. Results and Conclusions: In this study, DIR were observed and occurred as often as CIR in the study population, despite not being characterized or reported in most ERT product package inserts. Effective methods for managing DIR and CIR differed, thus emphasizing the importance of monitoring for both types of infusion reactions in order to optimize outcomes for patients using ERT.
|Original language||English (US)|
|Title of host publication||JIMD Reports|
|Number of pages||8|
|State||Published - 2017|
Bibliographical noteFunding Information:
Acknowledgements This research was partially funded by the Lysosomal Disease Network. The Lysosomal Disease Network (U54NS065768) is a part of the National Institutes of Health (NIH) Rare Diseases Clinical Research Network (RDCRN), supported through collaboration between the NIH Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS), the National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Zahra Karimian conducted this study during a fellowship training program, the Pharmacotherapy of Inherited Metabolic Diseases Post-Doctoral PharmD Fellowship (PIMD) which received funding from an unrestricted educational grant by Genzyme-Sanofi. The authors would like to thank Dr. Barry Finzel, Dr. Tim Stratton, Dr. Li Ou, and Ms. Evelyn Redtree for their thoughtful comments, insight, and assistance in reviewing and editing this manuscript. Last but not least, the authors are grateful to the reviewers at the Journal of Inherited Metabolic Disease (JIMD) for their insightful remarks.
Dr. Jeanine Utz is the recipient of an unrestricted educational grant from Genzyme-Sanofi which helps fund the PIMD fellowship in addition to the NIH LDN grant (U54NS065768). She provides consultation for the scientific content of the annual WORLD Symposium meeting and is on the Speakers bureau for Genzyme, Shire, and Pfizer.
Dr. Chester Whitley is the Principal Investigator for the NIH Lysosomal Disease Network (LDN) grant (U54NS065768). He provides consultation for gene therapies being developed by Sangamo and the scientific content of the annual WORLD Symposium meeting.
Dr. Kyle D. Rudser is a recipient of the NCATS award (UL1TR000114) and the NIH LDN grant (U54NS065768).
Dr. Zahra Karimian is a postdoctoral research fellow in the Pharmacotherapy of Inherited Metabolic Diseases (PIMD) program, which is supported by an unrestricted educational grant from Genzyme-Sanofi in addition to the NIH LDN grant (U54NS065768).