Barbara K Burton1, David A H Whiteman. 1. Dept. of Pediatrics, Northwestern University Feinberg School of Medicine, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614, USA. bburton@childrensmemorial.org
Abstract
OBJECTIVE: To evaluate the occurrence of infusion-related reactions (IRRs) in patients with mucopolysaccharidosis type II (MPS II) receiving idursulfase enrolled in the observational database HOS - the Hunter Outcome Survey. STUDY DESIGN: Information in HOS regarding the frequency, timing and severity of reported IRRs during the first year of treatment with idursulfase was analyzed, and formation of antibodies to idursulfase was characterized. The analysis was restricted to patients who started treatment with idursulfase at or after enrolment in HOS and for whom at least 1 year of follow-up data was available (n=104; data collected on or before 16 October 2009). RESULTS: A total of 65 IRRs were reported in 33 (31.7%) patients in the first year of enzyme replacement therapy (ERT). Six of these patients experienced more than three events. Nearly all of the initial IRRs occurred during the first 3months of ERT; five patients (4.8% of the total patient population) experienced their first IRR after 3months of treatment. Only two patients (1.9% of the total patient population) experienced their first IRR after more than 6 months of ERT. Most of the IRRs were of mild-to-moderate severity. After initially stopping the infusion, IRRs were generally readily managed by slowing the infusion and/or use of antihistamines or antipyretics. No patient in this analysis discontinued ERT because of an IRR event. IgG antibodies to idursulfase were detected in 32/63 patients (50.8%) for whom samples were taken; no patient developed IgE to idursulfase. Serum antibody levels were measured within 24h of an IRR for 10 IRRs in 7 patients; 7/9 samples contained IgG to idursulfase, 2 of which had neutralizing activity. CONCLUSIONS: IRRs in patients receiving idursulfase can typically be readily managed without interruption of treatment. Initial IRRs usually occur in the first 3 months of treatment, but in rare instances may occur after more than 6 months of therapy. Physicians using ERT to treat patients with MPS II, either in the clinic or at home, should therefore be familiar with the timing, nature and recommended management of IRRs.
OBJECTIVE: To evaluate the occurrence of infusion-related reactions (IRRs) in patients with mucopolysaccharidosis type II (MPS II) receiving idursulfase enrolled in the observational database HOS - the Hunter Outcome Survey. STUDY DESIGN: Information in HOS regarding the frequency, timing and severity of reported IRRs during the first year of treatment with idursulfase was analyzed, and formation of antibodies to idursulfase was characterized. The analysis was restricted to patients who started treatment with idursulfase at or after enrolment in HOS and for whom at least 1 year of follow-up data was available (n=104; data collected on or before 16 October 2009). RESULTS: A total of 65 IRRs were reported in 33 (31.7%) patients in the first year of enzyme replacement therapy (ERT). Six of these patients experienced more than three events. Nearly all of the initial IRRs occurred during the first 3months of ERT; five patients (4.8% of the total patient population) experienced their first IRR after 3months of treatment. Only two patients (1.9% of the total patient population) experienced their first IRR after more than 6 months of ERT. Most of the IRRs were of mild-to-moderate severity. After initially stopping the infusion, IRRs were generally readily managed by slowing the infusion and/or use of antihistamines or antipyretics. No patient in this analysis discontinued ERT because of an IRR event. IgG antibodies to idursulfase were detected in 32/63 patients (50.8%) for whom samples were taken; no patient developed IgE to idursulfase. Serum antibody levels were measured within 24h of an IRR for 10 IRRs in 7 patients; 7/9 samples contained IgG to idursulfase, 2 of which had neutralizing activity. CONCLUSIONS: IRRs in patients receiving idursulfase can typically be readily managed without interruption of treatment. Initial IRRs usually occur in the first 3 months of treatment, but in rare instances may occur after more than 6 months of therapy. Physicians using ERT to treat patients with MPS II, either in the clinic or at home, should therefore be familiar with the timing, nature and recommended management of IRRs.
Authors: Christina Lampe; Andrea Atherton; Barbara K Burton; Maria Descartes; Roberto Giugliani; Dafne D G Horovitz; Sandra O Kyosen; Tatiana S P C Magalhães; Ana Maria Martins; Nancy J Mendelsohn; Joseph Muenzer; Laurie D Smith Journal: JIMD Rep Date: 2014-02-11
Authors: Arian Pano; Ann J Barbier; Bonnie Bielefeld; David A H Whiteman; David A Amato Journal: Orphanet J Rare Dis Date: 2015-04-24 Impact factor: 4.123