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

Mol Genet Metab. 2017 Jun;121(2):138-149. doi: 10.1016/j.ymgme.2017.04.004.

PMID: 28410878

Jordi Pérez-López, Montserrat Morales-Conejo, Mónica López-Rodríguez

Highlights: The aim of this study was to assess every effectiveness variable modified in Mucopolysaccharidosis Type I (MPS-I) patients who initiated laronidase at adult age.

Abstract

Background: In adults with Mucopolysaccharidosis Type I (MPS-I), the efficacy of initiating enzyme replacement therapy (ERT) is debatable. Evaluating the benefits reported by patients starting ERT with laronidase at an adult age may aid physicians in deciding whether or not ERT is clinically beneficial in these patients.

Objective: To evaluate every effectiveness variable that has been changed in MPS-I patients who started laronidase as an adult.

Methods: MEDLINE, EMBASE, CENTRAL, and LILACS were used to conduct a comprehensive search of the literature from inception to July 2016 to find randomized trials or observational studies involving ≥1 MPS-I patient with ERT initiated at adult age (18 years) and evaluating ERT efficacy. The evidence was graded using GRADE criteria after a meta-analysis of papers evaluating the same effectiveness outcome. The Chi-squared test and the I-squared statistic were used to determine heterogeneity. Case reports were not included in the meta-analysis, although their primary outcomes were assessed individually. The primary outcome was a decrease in urine glycosaminoglycans (uGAGs) levels as a percentage of patients with a reduction in uGAGs and normalization.

Results: A total of 19 clinical trials and 12 case reports were chosen. ERT reduced uGAG levels (strong evidence) and liver volume (strong evidence), enhanced the 6-minute walking test (6MWT) (moderate), and raised blood anti-ERT antibody levels (strong evidence). 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, and intrathecal therapy effectiveness were all found to be inconclusive (low or very low evidence).

Limitations: Aside from case reports, no research has been done especially in the target population (ERT≥18 years). The information came from subgroup analysis of a few studies. There was a lot of variation in the designs and clinical outcomes that were analyzed.

Conclusions: Although the putative clinical benefit associated with these changes is unknown, ERT improves uGAGs and liver volume in MPS-I patients starting therapy as adults. In the 6MWT, there was some evidence of progress. PROSPERO registration number for systematic review: 42,016,041,306.

Keywords: Adult, Enzyme replacement therapy, Laronidase, MPS-I, Mucopolysaccharidosis Type I, Systematic review