New insights in efficacy of different ERT dosages in Fabry disease: Switch and switch-back studies data following agalsidase beta shortage. Update of systematic review

In 2016, a systematic review and a meta-analysis of existing data on the effects of switch from agalsidase beta to alfa in patients with Fabry disease showed that the switch was well tolerated and associated with stable disease progression. However, additional evidence that supports the need for an update of the review on the long-term effects of switching to agalsidase alfa, with a mention on the effects of reswitch to agalsidase beta, has emerged. Relevant papers were identified on PubMed, Cochrane, ISI Web, and Scopus databases from September 2015 to December 2021. Analyzed parameters were clinical events, changes in organ function or structure, disease related symptoms, lyso-globotriasolylceramide 3 (lyso-Gb3) plasma levels, presence of antidrug antibodies, and adverse effects. In total, 15 publications were evaluated, with a total of 353 subjects. The results of the review confirmed some points of the previous analysis with some new important information. After the switch from agalsidase beta to alfa, an increased number of clinical events, a significant loss of renal function, and an increase in lyso-Gb3 levels were reported; conversely, lyso-Gb3 levels decreased after the switch from agalsidase alfa to beta. The results confirm the importance of dose and recommend that patients be monitored through intensified surveillance, including lyso-Gb3 levels every 6 months.