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Case report of treatment experience with idursulfase beta (Hunterase) in an adolescent patient with MPS II.

ABSTRACT: Mucopolysaccharidosis (MPS) II or Hunter syndrome is a chronic, progressive, multi-systemic illness associated with significant morbidity and early mortality. Available evidence in Asian populations shows that Hunter syndrome has a mean age of onset of 2 to 5 years and a life expectancy of 13 years in more severely affected individuals, with respiratory failure reported as the leading cause of death. Enzyme replacement therapy (ERT) with idursulfase (Elaprase, Shire Pharmaceuticals) and idursulfase beta (Hunterase, Green Cross Corp) are the only approved treatment for patients with MPS II. While these agents have the same amino acids, they have different glycosylation patterns because they are produced in different cell lines via different manufacturing processes. In previous studies, the beneficial effects of idursulfase beta have been confirmed in patients up to 35 years of age, without serious treatment-related safety concerns. The major drawbacks associated with ERT include the potential development of serious infusion-related anaphylactic reactions and up to 50% of treated patients develop anti-IDS antibodies. Here we report the case of a 13-year-old Malaysian patient with attenuated MPS II who developed troublesome infusion-associated reactions while receiving idursulfase treatment but tolerated and responded favorably to idursulfase beta.

SUBMITTER: Ngu LH

PROVIDER: S-EPMC5432659 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Case report of treatment experience with idursulfase beta (Hunterase) in an adolescent patient with MPS II.

Ngu Lock-Hock LH Ong Peitee Winnie W Leong Huey Yin HY Chew Hui Bein HB

Molecular genetics and metabolism reports 20170511

Mucopolysaccharidosis (MPS) II or Hunter syndrome is a chronic, progressive, multi-systemic illness associated with significant morbidity and early mortality. Available evidence in Asian populations shows that Hunter syndrome has a mean age of onset of 2 to 5 years and a life expectancy of 13 years in more severely affected individuals, with respiratory failure reported as the leading cause of death. Enzyme replacement therapy (ERT) with idursulfase (Elaprase, Shire Pharmaceuticals) and idursulf ...[more]

PMID: 28540187

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Project description:BackgroundMucopolysaccharidosis II (MPS II; Hunter syndrome) is a rare, life-limiting lysosomal storage disease caused by deficient iduronate-2-sulfatase activity. Enzyme replacement therapy (ERT) with intravenous (IV) idursulfase can stabilize or improve many somatic manifestations, but there remains a need for further analysis of long-term treatment outcomes. Using data from patients with MPS II enrolled in the Hunter Outcome Survey (HOS), mixed modeling was performed to evaluate and predict the effects of IV idursulfase treatment on selected clinical parameters for up to 8 years following treatment start. The modeling population comprised male patients followed prospectively in HOS who had received IV idursulfase for at least 5 years and who had data available for two or more time points (at least one post-ERT). Age at ERT start and time since ERT start were included as covariates.ResultsIn total, 481 patients were eligible for inclusion in at least one model. At 8 years post-ERT start, improvement from baseline was predicted for each age group (< 18 months, 18 months to < 5 years and ≥ 5 years at treatment start) in the following parameters: mean urinary glycosaminoglycan levels (percentage changes of > -75% in each group), mean left ventricular mass index (decreases of ~ 1 g/m2) and mean palpable liver size (decreases of > 2 cm). Improvements in mean 6-min walk test distance (increase of > 50 m) and stabilization in percent predicted forced vital capacity and forced expiratory volume in 1 s (decreases of ~ 4 and ~ 9 percentage points, respectively) at 8 years post-ERT start were predicted for patients aged ≥ 5 years at ERT start (these assessments are unsuitable for patients aged < 5 years). Predicted changes over time were similar across the three age groups; however, overall outcomes were most favorable in children aged < 18 months at ERT start.ConclusionsThese findings suggest that the previously reported positive effects of IV idursulfase on the somatic manifestations of MPS II are predicted to be maintained for at least 8 years following ERT initiation and highlight the value of statistical modeling to predict long-term treatment outcomes in patients with rare diseases.

Project description:BackgroundMucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by iduronate-2-sulfatase gene (IDS) deficiency and downstream glycosaminoglycan accumulation. Two-thirds of patients present with neuronopathic disease and evaluating cognitive function in these patients is challenging owing to limitations of currently available tests. During the clinical development of intrathecal idursulfase (idursulfase-IT), regulatory authorities requested qualitative data to further understand the neurocognitive changes observed by the investigators through the clinical trials.ResultsThis qualitative study consisted of semi-structured interviews with all nine of the principal investigators who participated in the idursulfase-IT phase 2/3 (NCT02055118) and extension (NCT02412787) trials. These investigators enrolled the 56 patients with neuronopathic MPS II who qualified for the extension phase of the trial. The investigators were asked to rate the disease status of their patients. Of the 56 patients, 49 (88%) were rated as having disease that was improved/improving, stabilized or slowing progression compared with the expected outcomes with no treatment. Three patients were rated as worsening, while the remaining four patients were considered to have slowing progression or worsening disease. Similar results were demonstrated for patients aged from 3 to under 6 years at baseline, with 33 of 39 patients (85%) rated as having disease that was improved/improving, stabilized or slowing progression. Of the seven patients rated with slowing progression/worsening or worsening disease, five of them had an IDS variant other than missense, while two had a missense class variant. All the assigned improved/improving ratings were in patients receiving idursulfase-IT from the start of the phase 2/3 trial. Moreover, patients under 3 years of age at baseline were all rated as either improved/improving or stabilized disease. In a blinded review of patient profiles, investigators were requested to assign a disease status rating to 18 patients with large IDS deletions; 67% of these patients were rated as improved/improving or stabilized disease.ConclusionsThis qualitative analysis provides a snapshot of clinicians' considerations when evaluating treatment in patients with neuronopathic MPS II, compared with the expected decline in cognitive function in the absence of treatment. The results highlight the importance of robust assessment tools in treatment evaluation.

Project description:BackgroundIdursulfase and laronidase are drugs used to treat Hunter syndrome (mucopolysaccharidosis type 2) and Scheie syndrome (mucopolysaccharidosis type 1 S), respectively. These are rare lysosomal storage disorders, leading to accumulation of glycosaminoglycans within lysosomes. Failure of early recognition of the disease and/or delay in starting the appropriate treatment result in severe clinical impairment and death. For almost 20 years, enzyme replacement therapy with recombinant proteins has represented the first line therapeutic option. However, administration of idursulfase and laronidase is associated with infusion-related hypersensitivity reactions, in approx. 20% of patients. In these patients, rapid desensitization by intravenous administration protocols has been used in order to avoid treatment discontinuation. This approach proved effective and safe. However, long-term tolerance could not be achieved. Thus, we decided to combine rapid desensitization with allergen immunotherapy-like desensitization.ResultsTwo patients with Hunter syndrome and one patient with Scheie syndrome developed severe allergy to idursulfase and laronidase, respectively, preventing them from continuing the otherwise indispensable therapy. In all three patients, the possible IgE-mediated nature of the reactions suffered was suggested by positive skin tests with the two enzymes, respectively. By devising 12-step, 3-dilution rapid desensitization protocols, we resumed the enzyme replacement therapy. However, the prolonged time required for administration (a not negligible pitfall, since therapy should be given weekly for life) and the persistent occurrence of reactions (mild but still requiring anti-allergic medication at full dosage) led us to combine rapid desensitization with a compact 11-step, 24-day allergen immunotherapy-like desensitization protocol. Thus, idursulfase and laronidase were injected subcutaneously, with a 500-fold increase from step 1 to step 11 for idursulfase and a 222-fold increase for laronidase. This strategy led to restoration of long-term tolerance, allowing weekly intravenous therapy administration under standard conditions, according to the manufacturer instructions, in the absence of side effects and with only precautionary low-dose premedication.ConclusionRapid desensitization is a suitable and safe option in the case of idursulfase and laronidase allergy. Combination with subcutaneous allergen immunotherapy-like desensitization afforded restoration of enzyme replacement therapy given by the normal administration schedule, by inducing sustained tolerance.

Dataset Information

Case report of treatment experience with idursulfase beta (Hunterase) in an adolescent patient with MPS II.

Publications

Case report of treatment experience with idursulfase beta (Hunterase) in an adolescent patient with MPS II.

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