A Cochrane review [Abstract] 1 included 1 study with 45 subjects examining laronidase at a dose of 0.58 mg/kg/week versus placebo in patients with mucopolysaccharidosis type I (MPS I). Urinary glycosaminoglycans (GAGs) excretion rapidly decreased in the laronidase group. By week 26 the laronidase group showed a mean reduction of 54.1% in urinary GAG excretion compared to a mean increase of 47.3% in the placebo group (P = <0.001). In the treatment group, mean reduction to levels approaching the upper limit of normal occurred by week 4 and were maintained throughout treatment.After 26 weeks of treatment patients receiving laronidase showed a mean 5.6 percentage point increase in per cent of predicted normal FVC compared with the placebo group (MD 5.60, 95% CI 1.24 to 9.96) and improvement in the 6-minute-walk test (mean improvement of 38.1 metres in the laronidase group; P = 0.039). In addition, there were improvements in hepatomegaly, sleep apnoea and hypopnoea. Laronidase antibodies were detected in nearly all patients in the treatment group with no apparent clinical effect and titres were reducing by the end of the study. Infusion-related adverse reactions occurred in both groups but all were mild and none necessitated medical intervention or infusion cessation.
Haemopoietic stem cell transplantation (HSCT) should be the gold standard for those diagnosed with severe MPS I in the first 2 to 2.5 years of life. Although, ERT with laronidase can be useful for pre-transplantation optimisation and in those with more attenuated disease. There remains uncertainty about the longer-term outcomes of this lifelong and life-limiting disease and studies looking at quality of life should be undertaken.
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