Efficacy of different treatment strategies in patients with mucopolysaccharidosis: a systematic review and network meta-analysis of randomized controlled trials.

This systematic review of randomized controlled trials (RCT) was conducted to evaluate the efficacy of enzyme replacement therapy (ERT) for patients with mucopolysaccharidosis (MPS). We systematically searched PubMed, Embase, Web of Science, and Cochrane databases up to August 22, 2023. Study design, interventions, and outcome data were extracted. Continuous variable random-effects network meta-analysis was performed. The review included 23 studies involving 1,047 people with MPS I-VI. In MPS I, urinary glycosaminoglycan (uGAG) level was significantly reduced in patients who took 2 mg/kg/week pentosan polysulfate (-2.66, 95% confidence interval (CI)[-3.86, -1.46]) compared with those who took 1 mg/kg/week. In MPS II, compared with the placebo group, significant reduction were observed in the uGAG (-270.77, 95% CI[-406.57, -139.71]) and the cerebrospinal fluid (CSF) GAG (-1,385.29, 95% CI[-2493.33, -392.65]). In MPS IV, 6-min walking test (6MWT) (40.82, 95% CI[16.19, 64.92]) and 3-min stair climb test (3MSCT) (16.07, 95% CI[12.16, 21.62]) were significantly increased in patients who took elosulfase alfa at a dose of 4.0 mg/kg/week compared with the placebo group. In MPS VI, recombinant human arylsulfatase B (rhASB) and galsulfase (1.0 mg/kg/week) significantly reduced uGAG aggregation compared with the placebo group (-217, 95% CI[-258, -176]) and galsulfase (2.0 mg/kg/week) group (-286.5, 95% CI[-436.5, -136.5]), respectively. Moreover, most studies had high (34.8%) or unclear (43.5%) risk of bias assessments and confidence assessment were low. ERT alleviated symptoms to some extent, but current evidence was insufficient. Hence, further evidence from large-sample RCT is needed.