Background Hunter syndrome or type II mucopolysaccharidosis (MPS II) is a lysosomal storage disease caused by iduronate-2-sulfatase (I2S) deficiency, an enzyme involved in the metabolism of glycoaminoglycans. It is a rare recessive hereditary disorder linked to chromosome X that mainly affects children. The current therapeutic approach to MPS II is based on multidisciplinary intervention. Idursulfase (Elaprase®) is a recombinant form of the I2S human enzyme, approved by the European Medicines Agency (EMEA) in January 2007 for the long term treatment of patients with MPS II. Objectives To assess the efficacy, safety and efficiency of idursulfase versus any other treatment alternatives, including placebo, in patients with MPS II. Methodology A systematic search of the scientific evidence up until March 2009 has been conducted in the primary biomedical databases. Clinical trials that assess the efficacy and safety of idursulfase versus any other treatment alternatives, including placebo, in patients affected by MPS II, have been selected. The internal validity of the studies included was assessed by two independent reviewers in accord with the criteria proposed by the Scottish Intercollegiate Guidelines Network (SIGN). Results The primary efficacy and safety data of idursulfase have been derived from a phase II/III double blind randomised clinical trial (pivotal study) that compares two idursulfase dosages (0.5 mg/kg every week or 0.5 mg/kg every two weeks) with placebo over the course of one year in 96 patients with MPS II; and from a phase I/II non-comparative support clinical trial. The results of the pivotal study suggest an improvement of the combined primary variable (six-minute walk test-forced vital capacity; 6MWT-FVC) in patients treated with idursulfase. Patients who received a weekly dosage experienced a modest, yet statistically significant, improvement in the mean distance walked without help at six minutes, versus placebo (36.7 m more at twelve months). A significant reduction in GAG excretion in urine, liver volume and spleen volume was observed, in addition to an increase in the absolute value of FVC in patients treated with idursulfase, but not in the other variables analysed. The most frequent adverse events were fever, headaches, coughing, pharyngitis, upper respiratory infections, nasal congestion, nausea and vomiting, abdominal pain and diarrhoea. In most cases these side effects were mild or moderate. The adverse reactions associated with perfusion are the most frequent adverse events possibly related with the administration of idursulfase. Two deaths have been reported in the pivotal study (one in the placebo group and one in the weekly dosage group). Nearly half of all patients treated with idursulfase have developed IgG antibodies against the drug. The only data available on the cost-effectiveness of idursulfase in patients with MPS II stem from a secondary source. According to this source, the incremental cost-effectiveness ratio of idursulfase when compared to base treatment is 564.69 pounds per quality-adjusted life year. Conclusions Idursulfase has demonstrated short term efficacy in patients with non-advanced forms of MPS II when compared to placebo. However, the clinical relevance of these results is unknown. No evidence has been published on the benefits of idursulfase in terms of quality of life.
Hunter syndrome; Mucopolysaccharidosis type II; Idursulfase
Comitè d'Avaluació de Medicaments d'Utilització Hospitalària (CAMUH). Idursulfasa (Elaprase®) per al tractament de la mucopolisacaridosi II. Barcelona: Agència d’Avaluació de Tecnologia i Recerca Mèdiques; 2010.
Use this identifier for quote and/or link this documenthttps://hdl.handle.net/11351/842
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