Enzyme replacement therapy with galsulfase for mucopolysaccharidosis type VI

Review question
We reviewed the evidence about the effectiveness and safety of treating mucopolysaccharidosis type VI by enzyme replacement therapy with galsulfase (a manufactured version of the enzyme arylsulphatase B) compared to other interventions, no intervention or placebo.

Background
Mucopolysaccharidosis type VI is a rare genetic disorder where there is a lack of the enzyme arylsulphatase B. It is a progressive and life-limiting condition with a range of symptoms, which may include coarse facial features, reduced joint mobility, short stature and problems with the eyes, lungs and heart.

Prior to enzyme replacement therapy, only symptoms could be treated and not the underlying condition. Treatment with enzyme replacement therapy has allowed the missing enzyme to be replaced with the aim to reduce the effects of the disease and prevent it progressing.

Search date
The evidence is current to: 05 February 2016.

Study characteristics
The review includes one study with 39 people with mucopolysaccharidosis type VI aged between five and 20 years old. The study compared galsulfase to placebo (a substance which contains no medication) and people were selected for one treatment or the other randomly. The study lasted for 24 weeks (with an open-label extension period of an additional 24 weeks).

Key results
Given that there is only one small study included, the evidence for this treatment is limited. The included study showed that motor function improved in people who had received galsulfase, especially in their ability to walk. There was also an improvement in the results of urine tests, which showed lower levels of the chemicals associated with MPS VI (glycosaminoglycan levels). These results were seen in a short study and may reflect only short-term effects. There were no significant differences between treatment with galsulfase and placebo in relation to adverse effects.

More research is required to study the long-term effects on heart and lung function, quality of life and survival.

Quality of the evidence
The methods of the study design were not clearly described and the impact of this on possible bias is unclear.

Authors' conclusions: 

The results of one small study (based on 24-week randomised phase of the study and prior to the open-label extension) demonstrated that galsulfase is more effective than placebo in people with MPS VI, with significant improvements in the 12-minute walk test and a reduction in urinary glycosaminoglycans.

There were no significant changes in cardiac or pulmonary functions, liver or spleen volume, overnight apnea-hypopnea, height and weight, quality of life and adverse effects.

Further studies are needed to obtain more information on the long-term effectiveness and safety of enzyme replacement therapy with galsulfase.

Read the full abstract...
Background: 

Mucopolysaccharidosis type VI or Maroteaux-Lamy syndrome is a rare genetic disorder caused by the deficiency of arylsulphatase B. The resultant accumulation of dermatan sulphate causes lysosomal damage.

The clinical symptoms are related to skeletal dysplasia (i.e. short stature and degenerative joint disease). Other manifestations include cardiac disease, impaired pulmonary function, ophthalmological complications, hepatosplenomegaly, sinusitis, otitis, hearing loss and sleep apnea. Intellectual impairment is generally absent. Clinical manifestation is typically by two or three years of age; however, slowly progressive cases may not present until adulthood.

Enzyme replacement therapy with galsulfase is considered a new approach for treating mucopolysaccharidosis type VI.

Objectives: 

To evaluate the effectiveness and safety of treating mucopolysaccharidosis VI by enzyme replacement therapy with galsulfase compared to other interventions, placebo or no intervention.

Search strategy: 

Eletronic searches were performed on the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register, in CENTRAL, MEDLINE, LILACS, the Journal of Inherited Metabolic Disease and ClinicalTrials.gov.

Date of the last search of the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register: 05 February 2016.

Selection criteria: 

Randomized and quasi-randomized controlled clinical studies of enzyme replacement therapy with galsulfase compared to other interventions or placebo.

Data collection and analysis: 

Two authors independently screened the studies, assessed the risk of bias and extracted data.

Main results: 

One study was included involving 39 participants who received either enzyme replacement therapy with galsulfase (recombinant human arylsulphatase B) or placebo. This small study was considered to be of overall unclear quality, since the authors did not report how both the allocation generation and concealment were performed.

The key finding at 24 weeks in the 12-minute walk test was a statistically significant mean difference of 92.00 meters between the two groups in favour of the galsulfase group (95% confidence interval 11.00 to 172.00). While week 24 results for the three-minute stair climb demonstrated some improvement in the treatment group as compared to the placebo group, this was not significant, mean difference 5.70 (95% confidence interval -0.10 to 11.50).

A significant decrease in the urinary glycosaminoglycan levels was observed in favour of the galsulfase group at 24 weeks, mean difference -227.00 (95% confidence interval -264.00 to -190.00).

In general, the dose of galsulfase was well tolerated and there were no significant differences in relation to adverse events. These events include drug-related adverse events, serious and severe adverse events, those during infusion, drug-related adverse events during infusion, and deaths. More infusion-related reactions were observed in the galsulfase group and were managed with interruption or slowing of infusion rate or administration of antihistamines or corticosteroids drugs. No deaths occurred during the study.

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