Efficacy of laronidase therapy in patients with mucopolysaccharidosis type I who initiated enzyme replacement therapy in adult age. A systematic review and meta-analysis

- The efficacy of starting ERT in adults with MPS-I is controversial.
- ERT in adulthood decreased uGAG levels and liver volum with high evidence.
- ERT in adulthood improved 6MWT with moderate evidence.
- Further research should be specifically conducted in adult subgroups.

BackgroundThe efficacy of starting enzyme replacement therapy (ERT) in adults with Muchopolysaccharidosis Type I (MPS-I) is controversial. Evaluating the benefits reported by patients initiating ERT with laronidase at adult age might help physicians decide whether the use of ERT in these patients is worthwhile from a clinical point of view.ObjectiveTo assess every effectiveness variable modified in MPS-I patients who initiated laronidase at adult age.MethodsA systematic search of the literature, from inception to July 2016, was conducted using MEDLINE, EMBASE, CENTRAL and LILACS to identify randomized trials or observational studies including ≥ 1 MPS-I patients with ERT initiated in adult age (≥ 18 years) and evaluating ERT efficacy. A meta-analysis of studies evaluating the same effectiveness outcome was performed and the evidence was rated according to GRADE criteria. Heterogeneity was assessed by the Chi-squared test and the I-squared statistic. Case reports were excluded from meta-analysis but their main outcomes were separately evaluated. The decrease in urine glycosaminoglycans (uGAGs) levels as patient percentage with reduction in uGAGs and with normalization was the primary outcome.ResultsNineteen clinical studies and 12 case reports were selected. ERT decreased uGAG levels (high evidence) and liver volume (high), improved 6-min walking test (6MWT) (moderate) and increased blood anti-ERT antibody levels (high). There was no conclusive results (low or very low evidence) regarding improvement/stabilization of respiratory function, change in shoulder flexion, cardiac improvement/stabilization, improvement in symptoms of nocturnal hypoventilation and sleep apnea, improvement in quality of life, visual acuity, otolaryngologic function, bone mineral density or effectiveness of intrathecal therapy.LimitationsExcluding case reports, there was no study conducted specifically in the target population (ERT ≥ 18 years). Data were from subgroup analyses of selected studies. There was a great heterogeneity between designs and clinical outcomes evaluated.ConclusionsERT improves uGAGs and liver volume in MPS-I patients initiating therapy as adults, although the putative clinical benefit associated to these improvements is unclear. Moderate evidence was shown for improvement in 6MWT.Systematic review registration number (PROSPERO): 42,016,041,306