Enzyme replacement therapy in mucopolysaccharidosis type II with alternative dosing 1mg/kg idursulfase in every other week infusions

Enzyme replacement therapy for mucopolysaccharidosis II (MPS II) with Idursulfase (Elaprase R ) has proven effective in reducing urinary glycosaminoglycan (uGAG) levels, liver and spleen volumes and in increasing walking distance. During phase II/III studies, 0.5mg/kg every other week (EOW) showed effectiveness in combined outcomes (6-minute walk test - 6MWT, pulmonary function and uGAG reduction), although some were not significantly effective when individually analyzed. A weekly 1.5mg/kg dose was tested in 4 patients for 48weeks and proven safe (Muenzer et al, 2007). Double dose EOW infusions was considered an acceptable treatment option in MPS I in a dose study (Giugliani et al, 2009) and proven safe and effective in 20 patients (Horovitz et al., 2016). Such data might suggest that double dose Idursulfase every other week infusions for MPS II might also be effective. A dose of 1mg/kg EOW substituted the recommended weekly dose in seven MPS II patients in three different centers in Brazil. Patients had to be under enzyme replacement therapy with Idursulfase for at least one year without adverse events. Before switching to EOW thorough clinical examination, 4 week uGAG collection, and additional evaluations (echocardiogram, endurance tests, pulmonary function studies, abdominal ultrasound and quality of life questionnaires) were performed whenever possible. Upon completion of 48 weeks under EOW intravenous infusions of 1mg/kg of ERT evaluations were repeated. Six patients completed 48 weeks on EOW one patient died from acute complications of cardiac surgery after 4 months under the protocol. No infusion-associated adverse events were observed. uGAG evaluated regularly showed stable excretion, similar to when receiving the weekly dose. Patients were well and families very satisfied with the new dosing regimen repeated evaluations after one year on EOW therapy showed no difference when compared to the previous dose. Most patients chose to continue with the EOW regimen after the protocol.