Enzyme replacement therapy with laronidase (Aldurazyme®) for treating mucopolysaccharidosis type I.Cochrane Database Syst Rev. 2019 06 18; 6:CD009354.CD
Mucopolysaccharidosis type I can be classified as three clinical sub-types; Hurler syndrome, Hurler-Scheie syndrome and Scheie syndrome, with the scale of severity being such that Hurler syndrome is the most severe and Scheie syndrome the least severe. It is a rare, autosomal recessive disorder caused by a deficiency of alpha-L-iduronidase. Deficiency of this enzyme results in the accumulation of glycosaminoglycans within the tissues. The clinical manifestations are facial dysmorphism, hepatosplenomegaly, upper airway obstruction, skeletal deformity and cardiomyopathy. If Hurler syndrome is left untreated, death ensues by adolescence. There are more attenuated variants termed Hurler-Scheie or Scheie syndrome, with those affected potentially not presenting until adulthood. Enzyme replacement therapy has been used for a number of years in the treatment of Hurler syndrome, although the current gold standard would be a haemopoietic stem cell transplant in those diagnosed by 2.5 years of age. This is an updated version of the original Cochrane Review published in 2013 and previously updated in 2015.
To evaluate the effectiveness and safety of treating mucopolysaccharidosis type I with laronidase enzyme replacement therapy as compared to placebo.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register, MEDLINE via OVID and Embase.Date of most recent search: 30 January 2019.
Randomised and quasi-randomised controlled studies of laronidase enzyme replacement therapy compared to placebo.
DATA COLLECTION AND ANALYSIS
Two authors independently screened the identified studies. The authors then appraised and extracted data. The quality of the evidence was assessed using GRADE.
One study (45 participants) met the inclusion criteria. This double-blind, placebo-controlled, randomised, multinational study looked at laronidase at a dose of 0.58 mg/kg/week versus placebo in people with mucopolysaccharidosis type I. All primary outcomes listed in this review were studied in this study. The laronidase group achieved statistically significant improvements in per cent predicted forced vital capacity compared to placebo, MD 5.60 (95% confidence intervals 1.24 to 9.96) (low-quality evidence) and in the six-minute-walk test (mean improvement of 38.1 metres in the laronidase group; P = 0.039, when using a prospectively planned analysis of covariance) (low-quality evidence). The levels of urinary glycoaminoglycans were also significantly reduced (low-quality evidence). In addition, there were improvements in hepatomegaly, sleep apnoea and hypopnoea. Laronidase antibodies were detected in nearly all participants in the treatment group with no apparent clinical effect and titres were reducing by the end of the study (very low-quality evidence). Infusion-related adverse reactions occurred in both groups but all were mild and none necessitated medical intervention or infusion cessation (low-quality evidence). As assessed by questionnaires,changes in a 'Disability Index' after treatment were small and did not differ between groups (low-quality evidence). There were no deaths in either group (low-quality evidence).