Efficacy and safety of intravenous laronidase for mucopolysaccharidosis type I: A systematic review and meta-analysis.

Alícia Dorneles Dornelles,André Anjos Da Silva,Taciane Alegra,Filippo Pinto E Vairo,Tiago Veiga Pereira,Ida Vanessa Doederlein Schwartz,Dora Lucia Vallejo Ardila,Osvaldo Artigalás,Andrea Dardis

doi:10.1371/journal.pone.0184065

Abstract

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease caused by deficient activity of alpha-L-iduronidase. Intravenous (IV) enzyme replacement therapy (ERT) with laronidase is currently used for treating patients with MPS I.ObjectiveTo evaluate the efficacy and safety of IV laronidase for MPS I.MethodsA systematic literature review was performed by searching the ClinicalTrials.gov, MEDLINE/PubMed, EMBASE, LILACS, and Cochrane Library databases, limited to clinical trials published until December 31, 2016. The first inclusion criterion was being a randomized controlled trial (RCT). If < five RCTs were identified, open-label and nonrandomized trials, controlled or uncontrolled (quasi-experimental), including ≥ five patients, and evaluating relevant outcomes defined a priori, would also be included. For meta-analysis, primary inferences were based on random-effects models. Assessment of article quality was performed in accordance with the GRADE criteria. The Cochrane Risk of Bias tool was used to examine the risk of bias for RCTs.ResultsThe selection phase retrieved 632 articles. During the first phase of selection, 158 had the abstract or full text read for assessment of eligibility, of which nine (two RCTs) were included for qualitative synthesis. Four papers were included in the meta-analysis, which was performed for the following outcomes: occurrence of treatment-emergent or infusion-related adverse events (65%; 95%CI 53, 76), mild in most cases; development of IgG antibodies to laronidase (88%; 95%CI 67, 100); apnea-hypopnea index (not significant—NS), urinary glycosaminoglycans (GAGs) [mean change -65.5 μg/mg creatinine (95%CI -68.8, -62.3)], liver size [mean change -31.03% (95%CI -36.1, -25.9)], left ventricular mass index (LVMI) [mean change -1.8 (95%CI -2.32, -0.25)], and distance covered in the 6-minute walk test (NS). Among the outcomes not included in meta-analysis, we found evidence for benefit of laronidase only on shoulder flexion.ConclusionsOur findings suggest that IV laronidase effectively reduces urinary GAGs excretion, hepatomegaly and LVMI, and can improve shoulder flexion in MPS I patients. Laronidase appears to be safe in the studied population.

Highlights

Mucopolysaccharidosis type I (MPS I; OMIM 252800) is an autosomal recessive lysosomal storage disease (LSD) caused by deficient activity of alpha-L-iduronidase (IDUA, EC 3.2.1.76)
During the first phase of selection, 158 had the abstract or full text read for assessment of eligibility, of which nine were included for qualitative synthesis
Four papers were included in the meta-analysis, which was performed for the following outcomes: occurrence of treatment-emergent or infusion-related

Summary

Introduction

Mucopolysaccharidosis type I (MPS I; OMIM 252800) is an autosomal recessive lysosomal storage disease (LSD) caused by deficient activity of alpha-L-iduronidase (IDUA, EC 3.2.1.76). In MPS I, these partially broken down GAGs build up within lysosomes and are excreted in urine at above-normal concentrations [1]. The worldwide incidence of this disease is estimated at approximately 1 in 100,000 newborns [1,2,3]. Cases can be divided into three broad phenotypes: Hurler syndrome, the severe form, with major intellectual impairment; Hurler– Scheie syndrome, the intermediate form, and Scheie syndrome, the attenuated form, the latter with little or no cognitive impairment. It bears noting that these subtypes are part of a continuous spectrum representing a single condition, and that clinical heterogeneity is observed even within subgroups [3]

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