Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome)

da Silva EMK, Strufaldi MWL, Andriolo RB, Silva LA

Published Online:

November 9, 2011

Hunter syndrome or mucopolysaccharidosis II is a rare genetic disease that occurs when an enzyme that the body needs is either missing or malfunctioning. The body doesn't have adequate supplies of this enzyme to break down certain complex molecules, so these molecules build up in harmful amounts in certain cells and tissues. The build-up that occurs in Hunter syndrome eventually causes permanent, progressive damage affecting appearance, mental development, organ function and physical abilities. Hunter syndrome appears in children as young as the age of two years and it nearly always occurs in males. In the past, treatment of Hunter syndrome has been limited to the relief of symptoms and complications. Enzyme replacement therapy with idursulfase aims to replace iduronate-2-sulfatase, the enzyme that is deficient or absent in people with Hunter syndrome. However, given its high cost it is essential to assess how effective and safe this treatment is. Current evidence is limited because there was only one randomised clinical trial found in the medical literature. Compared with placebo, enzyme replacement therapy with idursulfase in people with Hunter syndrome, led to some improvement in the patients' ability to walk and a reduction in the excretion of abnormal mucopolysaccharides in the urine. To date there is no evidence available in the literature showing that treatment reduces complications of the disease related to quality of life and mortality.

Abstract (click to read)

Background:

Mucopolysaccharidosis II, also known as Hunter syndrome, is a rare, X-linked disease caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase, which catalyses a step in the catabolism of glycosaminoglycans. The glycosaminoglycans accumulate within tissues affecting multiple organs and physiologic systems. The clinical manifestations include neurologic involvement, severe airways obstruction, skeletal deformities and cardiomyopathy. The disease has a variable age of onset and variable rate of progression. In those with severe disease, death usually occurs in the second decade of life, whereas those patients with less severe disease may survive into adulthood. Enzyme replacement therapy with intravenous infusions of idursulfase has emerged as a new treatment for mucopolysaccharidosis type II.

Objectives:

To evaluate the effectiveness and safety of enzyme replacement therapy with idursulfase compared to other interventions, placebo or no intervention, for treating mucopolysaccharidosis type II.

Search strategy:

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register (date of last search 01 September 2011).

We also searched EMBASE, PubMed and the Literature Latino-Americana e do Caribe em Ciências da Saúde (LILACS) (date of last search October 2009).

Selection criteria:

Randomised and quasi-randomised controlled trials of enzyme replacement therapy with idursulfase compared to no intervention, placebo or other options (e.g. behavioral strategies, transplantation).

Data collection and analysis:

Two authors independently screened the trials identified, appraised quality of papers and extracted data.

Main results:

One study (96 patients) met the inclusion criteria, although the primary outcome of this review - z score for height and weight, was not assessed in the study. Following 53 weeks of treatment, patients in the weekly idursulfase 0.5 mg/kg group demonstrated a significant improvement rate compared with placebo for the primary outcome: distance walked in six minutes on the basis of the sum of ranks of change from baseline, mean difference 37.00 (95% confidence interval 6.52 to 67.48). The every-other-week idursulfase 0.5 mg/kg group also showed an improvement, which was not significant compared with placebo, mean difference 23.00 (95% confidence interval -4.49 to 50.49). After 53 weeks, there was no statistical significance difference in per cent predicted forced vital capacity between the three groups and absolute forced vital capacity was significantly increased from baseline in the weekly dosing group compared to placebo, mean difference 0.16 (95% confidence interval CI 0.05 to 0.27). No difference was observed between the every-other-week idursulfase 0.5 mg/kg group and placebo.

In addition, liver and spleen volumes and urine glycosaminoglycan excretion were significantly reduced from baseline by both idursulfase dosing regimens. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 31.7% of patients at the end of the study and they were related to a smaller reduction in urine glycosaminoglycan levels.

Authors' conclusions:

The current evidence is limited. While the randomised clinical trial identified was considered to be of good quality, it failed to describe important outcomes. It has been demonstrated that enzyme replacement therapy with idursulfase is effective in relation to functional capacity (distance walked in six minutes and forced vital capacity), liver and spleen volumes and urine glycosaminoglycan excretion in patients with mucopolysaccharidosis type II compared with placebo. There is no available evidence in the included study and in the literature on outcomes such as improvement in growth, sleep apnoea, cardiac function, quality of life and mortality. More studies are needed to obtain more information on the long-term effectiveness and safety of enzyme replacement therapy.

This record should be cited as:

da Silva EMK, Strufaldi MWL, Andriolo RB, Silva LA. Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome). Cochrane Database of Systematic Reviews 2011, Issue 11. Art. No.: CD008185. DOI: 10.1002/14651858.CD008185.pub2

Assessed as up to date:

September 14, 2011

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Primary Review Group:

Cystic Fibrosis and Genetic Disorders Group

Health topics:

Genetic disorders > Inborn errors of metabolism > Other

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome)

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