Zahra Karimian1,2,3, Chester B Whitley4,5,6, Kyle D Rudser7, Jeanine R Jarnes Utz4,5. 1. Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA. karimian@umn.edu. 2. Advanced Therapies Program, University of Minnesota (UMMC) and Fairview Hospitals, Minneapolis, MN, USA. karimian@umn.edu. 3. Gene Therapy Center, MMC 391, 420 Delaware St. SE, Minneapolis, MN, 55455-0341, USA. karimian@umn.edu. 4. Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA. 5. Advanced Therapies Program, University of Minnesota (UMMC) and Fairview Hospitals, Minneapolis, MN, USA. 6. Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, MN, USA. 7. Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
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.
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.
Authors: Priya S Kishnani; Patricia I Dickson; Laurie Muldowney; Jessica J Lee; Amy Rosenberg; Rekha Abichandani; Jeffrey A Bluestone; Barbara K Burton; Maureen Dewey; Alexandra Freitas; Derek Gavin; Donna Griebel; Melissa Hogan; Stephen Holland; Pranoot Tanpaiboon; Laurence A Turka; Jeanine J Utz; Yow-Ming Wang; Chester B Whitley; Zoheb B Kazi; Anne R Pariser Journal: Mol Genet Metab Date: 2015-11-10 Impact factor: 4.797