Open AccessEfficacy and safety of intravenous laronidase for mucopolysaccharidosis type I: A systematic review and meta-analysis
Author(s) -
Alícia Dorneles Dornelles,
Osvaldo Alfonso Pinto Artigalás,
André Anjos da Silva,
Dora Lucía Vallejo Ardila,
Taciane Alegra,
Tiago Pereira,
Filippo Pinto e Vairo,
Ida Vanessa Döederlein Schwartz
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0184065
Subject(s) - medicine , mucopolysaccharidosis type i , meta analysis , randomized controlled trial , cochrane library , medline , adverse effect , systematic review , enzyme replacement therapy , disease , political science , law
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. Objective To evaluate the efficacy and safety of IV laronidase for MPS I. Methods A 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. Results The 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. Conclusions Our 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.