Review question
How effective and safe is enzyme replacement therapy (ERT) with galsulfase (a manufactured version of the enzyme arylsulphatase B) for treating mucopolysaccharidosis type VI (MPS VI) compared to other treatments, no treatment or treatment with a placebo?
Background
Mucopolysaccharidosis type VI (MPS 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.
Before ERT was available, it was only possible to treat the symptoms of MPS VI and not the underlying condition. Treatment with ERT allows the missing enzyme to be replaced to try to reduce the effects of the disease and prevent it getting worse.
Search date
The evidence is current to: 09 June 2021.
Study characteristics
The review includes one study with 39 people with MPS 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 extension period of an additional 24 weeks where everyone was given ERT and they knew it).
Key results
The evidence for this treatment is limited because we only found and assessed the results of one small study. Given the very low certainty of the evidence, we are unsure whether galsulfase improves motor function (i.e. the ability to walk and climb stairs) in people with MPS VI. We found that treatment with galsulfase may lower levels of the chemicals associated with MPS VI (glycosaminoglycan levels) in urine tests. These results were seen in a short study and may reflect only short-term effects. There were no differences between treatment with galsulfase and placebo in relation to adverse effects.
More research is needed to study the long-term effects on heart and lung function, quality of life and survival.
Certainty of the evidence
The methods and the study design were not clearly described and the impact of this on possible bias is unclear. The certainty of the evidence has been graded as low to very low.
The results of this review are based only on one small study (a 24-week randomised phase of the study and prior to the open-label extension). We are uncertain whether galsulfase is more effective than placebo, for treating people with MPS VI, in relation to the 12-minute walk test or the three-minute stair climb, as the certainty of the evidence has been assessed as very low. We found that galsulfase may reduce urinary glycosaminoglycans levels. We are also uncertain whether there are any differences between treatment groups in relation to 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 ERT with galsulfase.
Mucopolysaccharidosis type VI (MPS 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 (ERT) with galsulfase is considered a new approach for treating MPS VI.
To evaluate the effectiveness and safety of treating MPS VI by ERT with galsulfase compared to other interventions, placebo or no intervention.
Eletronic searches were performed on the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register. Date of the latest search: 09 June 2021.
Further searches of the following databases were also performed: CENTRAL, MEDLINE, LILACS, the Journal of Inherited Metabolic Disease, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. Date of the latest search: 20 August 2021.
Randomized and quasi-randomized controlled clinical studies of ERT with galsulfase compared to other interventions or placebo.
Two authors independently screened the studies, assessed the risk of bias, extracted data and assessed the certainty of the the evidence using the GRADE criteria.
One study was included involving 39 participants who received either ERT with galsulfase (recombinant human arylsulphatase B) or placebo. This small study was considered overall to have an unclear risk of bias in relation to the design and implementation of the study, since the authors did not report how both the allocation generation and concealment were performed.
Given the very low certainty of the evidence, we are uncertain whether at 24 weeks there was a difference between groups in relation to the 12-minute walk test, mean difference (MD) of 92.00 meters (95% confidence interval (CI) 11.00 to 172.00), or the three-minute stair climb, MD 5.70 (95% CI -0.10 to 11.50).
In relation to respiratory tests, we are uncertain whether galsulfase makes any difference as compared to placebo in forced vital capacity in litres (FVC (L) (absolute change in baseline), given the very low certainty of the evidence. Cardiac function was not reported in the included study. We found that galsulfase, as compared to placebo, may decrease urinary glycosaminoglycan levels at 24 weeks, MD -227.00 (95% CI -264.00 to -190.00) (low-certainty evidence).
We are uncertain whether there are differences between the galsulfase and placebo groups in relation to adverse events (very low-certainty evidence)
.
In general, the dose of galsulfase was well tolerated and there were no differences between groups. 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.