Enzyme replacement therapy for the treatment of Hunter disease: A systematic review with narrative synthesis and meta-analysis.
Por:
Wikman-Jorgensen PE, López Amorós A, Peris García J, Esteve Atienzar PJ, Cañizares Navarro R, Asensio Tomás ML, Segui J, Bonet D, Esteban-Giner MJ, Robert J and Giner-Galvañ V
Publicada:
1 sep 2020
Ahead of Print:
21 jul 2020
Resumen:
BACKGROUND: In the last 10 years enzyme replacement therapy (ERT) has become an alternative for the treatment of patients with Hunter disease (HD). Nevertheless, the information regarding efficacy and safety is scarce and mainly based on the pivotal trials. This scarcity is especially evident for adults and severe forms of HD. METHODS: A systematic review of publications in the electronic databases PUBMED, EMBASE and Cochrane Central was undertaken. Clinical trials and observational studies were included. The data about efficacy and security were retrieved and analysed with Review Manager version 5.3. RESULTS: 677 records were found, 559 remaining after the removal of duplicates. By title and abstract review, 427 were excluded. Full reading of the rest was made (122 publications) and 42 were finally included. It was not possible to perform meta-analysis of all the endpoints due to high heterogeneity in the reporting and measuring of variables in each publication. Eight clinical trials were included, 6 with high risk of bias. The quality of the other studies was low in 12%, average in 68% and good in 21%. Main findings were: a reduction in the elimination of glycosaminoglycans (GAG) in urine in all the studies (26/26), decrease in liver and spleen size (18/18), increase of 52.59 m (95% CI, 36, 42-68.76, p < .001) in the 6-min walk test (TM6M), increase in forced vital capacity (FVC) of 9.59% (95% CI 4.77-14.51, p < .001), reduction of the left ventricular mass index of 3.57% (95% CI 1.2-5.93) and reduction in mortality (OR) of 0.44 (0.27-0.71). DISCUSSION: The data suggests a clear and consistent effect of ERT in HD reducing the accumulation of GAGs in the body, demonstrated by the reduction of its urinary excretion, as well as by the reduction of its deposits (spleen, liver and heart). Likewise, there is an improvement in physical and respiratory function. In addition, a reduction in mortality has been observed. Lack of studies, small size of the samples, and methodological deficiencies are the main limitations to establish definite conclusions. CONCLUSIONS: The data suggests that ERT is effective and safe in the treatment of HD. There is a need to evaluate patient-centred outcomes and the impact on quality of life.
Filiaciones:
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Rare Diseases Unit, General Internal Medicine Department, Hospital Clínico Universitario San Juan de Alicante, San Juan de Alicante, Alicante, Spain
Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO), Spain
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General Internal Medicine Department, Hospital Universitario de Elda, Elda, Alicante, Spain
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Rare Diseases Unit, General Internal Medicine Department, Hospital Clínico Universitario San Juan de Alicante, San Juan de Alicante, Alicante, Spain
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Rare Diseases Unit, General Internal Medicine Department, Hospital Clínico Universitario San Juan de Alicante, San Juan de Alicante, Alicante, Spain
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Rare Diseases Unit, General Internal Medicine Department, Hospital Clínico Universitario San Juan de Alicante, San Juan de Alicante, Alicante, Spain
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Rare Diseases Unit, General Internal Medicine Department, Hospital Clínico Universitario San Juan de Alicante, San Juan de Alicante, Alicante, Spain
Segui J:
Rare Diseases Unit, General Internal Medicine Department, Hospital Clínico Universitario San Juan de Alicante, San Juan de Alicante, Alicante, Spain
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Rare Diseases Unit, General Internal Medicine Department, Hospital Clínico Universitario San Juan de Alicante, San Juan de Alicante, Alicante, Spain
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Rare Diseases Unit, General Internal Medicine Department, Hospital General de Alcoy, Alicante, Spain
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Rare Diseases Unit, General Internal Medicine Department, Hospital Clínico Universitario San Juan de Alicante, San Juan de Alicante, Alicante, Spain
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Rare Diseases Unit, General Internal Medicine Department, Hospital Clínico Universitario San Juan de Alicante, San Juan de Alicante, Alicante, Spain
Alianza de Investigación Traslacional de Enfermedades Raras de la Comunidad Valenciana, Generalitat Valenciana, Spain
Departamento de Medicina Clínica, Facultad de Medicina, Universidad Miguel Hernández, Elche (Alicante), Spain
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