Abstract
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.
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References
Aldurazyme® [package insert] (2002) BioMarin, San Rafael, CA. Downloadable full U.S. prescribing information is available at: https://www.genzyme.com/Products/Product-Information.aspx (Retrieved from 4-21-2016). Accessed 14 Sept 2015
Cerezyme® [package insert] (2014) Genzyme, Cambridge, MA. Downloadable full U.S. prescribing information is available at: https://www.genzyme.com/Products/Product-Information.aspx (Retrieved from 4-21-2016). Accessed 14 Sept 2015
Elaprase® [package insert] (2014) BioMarin, San Rafael, CA. Downloadable full U.S. prescribing information is available at: http://elaprase.com/ (Retrieved from 4-21-2016). Accessed 14 Sept 2015
Elelyso® [package insert] (2012) Pfizer, New York, NY. Downloadable full U.S. prescribing information is available at: http://www.elelyso.com/ (Retrieved from 4-21-2016). Accessed 14 Sept 2015
Fabrazyme® [package insert] (2003) Genzyme, Cambridge, MA. Downloadable full U.S. prescribing information is available at: https://www.genzyme.com/Products/Product-Information.aspx (Retrieved from 4-21-2016). Accessed 14 Sept 2015
Haller C, Agarwal S, Kakkis E (2016) A novel approach to characterization and categorization of infusion reactions associated with ERT using adverse physiology related groups. Mol Genet Metab 117(2):S54
Kanuma™ [package insert] (2015) BioMarin, San Rafael, CA. Downloadable full U.S. prescribing information is available at: http://www.kanuma.com/ (Retrieved from 4-21-2016). Accessed 14 Sept 2015
Kim KH, Decker C, Burton BK (2008) Successful management of difficult infusion-associated reactions in a young patient with mucopolysaccharidosis type VI receiving recombinant human arylsulfatase B (galsulfase [Naglazyme]). Pediatrics 121(3):e714–e717
Kishnani PS, Dickson PI, Muldowney L et al (2016) Immune response to enzyme replacement therapies in lysosomal storage diseases and the role of immune tolerance induction. Mol Genet Metab 117(2):66–83
Lumizyme® [package insert] (2014) Genzyme, Cambridge, MA. Downloadable full U.S. prescribing information is available at: https://www.genzyme.com/Products/Product-Information.aspx (Retrieved from 4-21-2016). Accessed 14 Sept 2015
Miebach E (2009) Management of infusion-related reactions to enzyme replacement therapy in a cohort of patients with mucopolysaccharidosis disorders. Int J Clin Pharmacol Ther 47(Suppl 1):S100–S106
Naglazyme® [package insert] (2013) BioMarin, San Rafael, CA. Downloadable full U.S. prescribing information is available at: http://www.naglazyme.com/#indication_read (Retrieved from 4-21-2016). Accessed 14 Sept 2015
Nicholls K, Bleasel K, Becker G (2012) Severe infusion reactions to Fabry enzyme replacement therapy: rechallenge after tracheostomy. JIMD Rep 5:109–112
Online Mendelian Inheritance in Man (OMIM) (2016). http://www.omim.org/ (Retrieved from 4-20-2016)
R Core Team (2014) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. http://www.R-project.org/ (Retrieved from January 2016)
University of Minnesota Medical Center (UMMC) Advanced Therapies Clinic (2016) Protocol for the management of infusion reactions to ERT in lysosomal diseases: treatment and prevention strategies. Accessed Jan 2016
Utz JR, Doyen C, Whitley CB (2008) Delayed infusion reactions to enzyme replacement therapy. Mol Genet Metab 93:S40
Vimizim® [package insert] (2013) BioMarin, San Rafael, CA. Downloadable full U.S. prescribing information is available at: http://www.vimizim.com/ (Retrieved from 4-21-2016). Accessed 14 Sept 2015
VPRIV® [package insert] (2010) Shire, Lexington, MA. Downloadable full U.S. prescribing information is available at: http://www.vpriv.com/general/important-safety-info.php#forhcps (Retrieved from 4-21-2016). Accessed 14 Sept 2015
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.
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Communicated by: William Ross Wilcox, MD, PhD
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One Sentence Synopsis of Article
Although not reported in most product package inserts, delayed infusion reactions to enzyme replacement therapy must be recognized, and their successful prevention and treatment require distinction from concurrent infusion reactions.
Contributions of Individual Authors
Dr. Jeanine R. Utz is the Principal Investigator and Director of the Pharmacotherapy of Inherited Metabolic Diseases (PIMD) fellowship program. She provides ongoing clinical care for the patients in the study. Dr. Utz conceived, designed, and conducted the study, orchestrated funding, coordinated efforts of collaborators, and participated in the interpretation of data. She is the guarantor for this article, accepts full responsibility for the work and the conduct of this study, and provided final approval of the version to publish.
Dr. Chester B. Whitley is the Co-Investigator for this study, Director of the Advanced Therapies Program and Gene Therapy Center. He provides continuous medical care for the patients in the study, has made significant contributions to formulating the hypothesis and study design, and offered critical revisions of the article.
Dr. Kyle D. Rudser is a senior biostatistician at the Clinical and Translational Science Institute. He offered statistical expertise in the study design, data monitoring, and analyses for this project, conducted the statistical analysis and interpretation of the results, and wrote relevant portions of the paper.
Dr. Zahra Karimian is a postdoctoral research associate and fellow in the PIMD program. Contributed substantially to the project through acquisition, reporting, analysis, and interpretation of the data, and wrote major portions of the paper.
All authors are responsible for the validity of the entire work and manuscript submitted for publication.
Funding and Conflict of Interest
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).
The contents of this article have not been influenced by the financial resources disclosed above and the authors declare that they have no conflict of interest.
Compliance with Ethics Guidelines
This study was conducted under University of Minnesota Institutional Review Board (IRB) approval. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in this study. Patients were made aware that participation in the study was voluntary, that they had the right to withdraw from the study at any time, and would continue to have access to unrestricted health care despite withdrawal.
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Karimian, Z., Whitley, C.B., Rudser, K.D., Utz, J.R.J. (2016). Delayed Infusion Reactions to Enzyme Replacement Therapies. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 34. JIMD Reports, vol 34. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_8
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DOI: https://doi.org/10.1007/8904_2016_8
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