Efficacy of Idursulfase therapy in patients with Mucopolysaccharidosis type II who initiated enzyme replacement therapy in adult age. A systematic review of the literature.

ABSTRACT

BACKGROUND: Enzyme replacement therapy (ERT) has been shown to decrease urine glycosaminoglycans (uGAGs) and liver and spleen volumes, and to improve clinical symptoms in mucopolysaccharidosis type II (MPS-II) patients. METHODS: A systematic search of the literature, from inception to August 2017, was conducted to identify randomized trials or observational studies including ≥1 MPS-II patients with ERT initiated in adult age (≥16 years) and evaluating ERT efficacy. Evidence was rated according to GRADE criteria. Common efficacy outcomes of the clinical studies were analyzed. Case reports were separately evaluated. RESULTS: One randomized clinical trial, 4 observational studies and 5 case reports were selected. ERT decreased uGAG levels and liver and spleen size with moderate evidence level and led to anti-ERT antibody and IRRS development in a significant proportion of patients with moderate evidence level. There were no conclusive results for beneficial effects on 6MWT, respiratory, cardiac and neurological function, joint mobility, sleep disorders of respiratory origin, and quality of life. LIMITATIONS: Excluding one observational study, all others were not conducted specifically in the target population (ERT ≥16 years). Data were from subgroup analyses of selected studies. There was a great heterogeneity between study designs and clinical outcomes evaluated. CONCLUSIONS: ERT improves uGAGs and liver/spleen volume with a moderate evidence level in MPS-II patients initiating therapy as adults, although the putative associated clinical benefit is unclear.