Rapid Desensitization for Immediate Hypersensitivity to Galsulfase Therapy in Patients with MPS VI

Abstract

Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic, and multisystem lysosomal storage disease. Enzyme replacement therapy (ERT) with the recombinant human arylsulfatase B enzyme (galsulfase [Naglazyme]) is recommended as first-line therapy. It is generally reported as safe and well tolerated. Frequently observed mild to moderate infusion-related reactions which can be easily handled by reducing or interrupting the infusion and/or administering additional antihistamines, antipyretics, and corticosteroids are mostly mediated by non-IgE mechanisms. Here we report two children with MPS VI who experienced IgE-mediated reactions with galsulfase at the second year of the therapy. One child had anaphylaxis and the other had urticarial eruptions. They could receive ERT after successful rapid desensitization. To our knowledge, this is the second report on galsulfase allergy with IgE-mediated reaction. It is important to recognize IgE-mediated reactions since they can be lifethreatening and do not respond to the standard therapies.We recommend allergy skin tests in the evaluation of infusion-related reactions unresponsive to standard therapies, so that continuation of ERT will be feasible after successful desensitization. Abbreviations BWHBrigham and Women's Hospital ERT Enzyme replacement therapy GAG Glycosaminoglycan MPS VI Mucopolysaccharidosis type VI N-acetylgalactosamine -4-sulfatase

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

“…IARs were reported in around 35-70% MPS patients on ERT, but only 1-2% were considered severe [18,19,21,22,36,41,43,[45][46][47]114,[196][197][198][199]. Very rare serious adverse reactions, including life-threatening anaphylaxis have been reported, both in clinical studies and in postmarking experience, even after several dozen infusions of ERT [21,36,[200][201][202]. However, IARs episodes were shown to decrease progressively with time during treatment in the extension studies [36,38].…”

“…It is usually indicated in patients who have an IgE-mediated reaction appearing within a few hours after the start of infusion [204]. Effective desensitization has been reported in patients treated with laronidase, idursulfase, galsulfase and elosulfase [202,[205][206][207][208].…”