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
; 121(2): 138-149, 2017 06.
Article
em En
| MEDLINE
| ID: mdl-28410878
ABSTRACT
BACKGROUND:
The 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.OBJECTIVE:
To assess every effectiveness variable modified in MPS-I patients who initiated laronidase at adult age.METHODS:
A 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 (≥18years) 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.RESULTS:
Nineteen 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.LIMITATIONS:
Excluding case reports, there was no study conducted specifically in the target population (ERT ≥18years). Data were from subgroup analyses of selected studies. There was a great heterogeneity between designs and clinical outcomes evaluated.CONCLUSIONS:
ERT 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.Palavras-chave
Texto completo:
1
Eixos temáticos:
Pesquisa_clinica
Base de dados:
MEDLINE
Assunto principal:
Mucopolissacaridose I
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Terapia de Reposição de Enzimas
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Iduronidase
Tipo de estudo:
Clinical_trials
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Observational_studies
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Prognostic_studies
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Systematic_reviews
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article