Review question
We reviewed the evidence about the effect and safety of enzyme replacement therapy with idursulfase compared to other interventions, placebo ('dummy treatment') or no intervention, for treating people with mucopolysaccharidosis type II. This is an update of a previously published version of this review.
Background
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.
Search date
The evidence is current to: 23 November 2015.
Study characteristics
The review included one study with 96 males with Hunter syndrome aged between 4.9 and 30.9 years of age. The trial compared idursulfase 0.5 mg/kg given either weekly or every-other week, or weekly infusions of placebo (a substance which contains no medication) and people were selected for one treatment or the other randomly. The study lasted 53 weeks.
Key results
Current evidence is limited given there was only one randomised clinical trial found in the medical literature. As compared with placebo, enzyme replacement therapy with idursulfase in people with Hunter syndrome, led to some improvement in the individuals' 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.
Quality of the evidence
This trial was considered to be of overall good quality.
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 people 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.
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 individuals 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. This is an update of a previously published version of this review.
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.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register (date of last search 23 November 2015).
We also searched Embase, PubMed and the Literature Latino-Americana e do Caribe em Ciências da Saúde (LILACS) (date of last search 28 November 2015).
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).
Two authors independently screened the trials identified, appraised quality of papers and extracted data.
One study (96 male participants) met the inclusion criteria, although the primary outcome of this review - z score for height and weight, was not assessed in the study. This trial was considered to be of overall good quality. Following 53 weeks of treatment, participants 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 participants at the end of the study and they were related to a smaller reduction in urine glycosaminoglycan levels.