Clinical outcomes in Fabry patients switching to agalsidase beta for renal ineffectiveness of the primary Fabry therapy: a single-centre analysis

Background A treatment for classic Fabry disease (FD) should be defined effective on renal function when it maintains a decline of estimated glomerular filtration rate (eGFR) <1 ml/min/1.73 m2/year, and not effective when the eGFR loss remains ≥3 ml/min/1.73 m2/year. Therefore, considering the evidence of dose-dependent efficacy of the enzyme replacement therapy (ERT) and the data reporting the disease progression after switching form agalsidase beta to migalastat, a switch to higher doses of ERT should be considered in adult Fabry patients who have an eGFR of 45–90 ml/min/1.73 m2, with an eGFR slope ≥3 ml/min/1.73 m2/year. This study aimed to assess the effects of switching to agalsidase beta for renal ineffectiveness of the primary Fabry therapy. Methods Data retrospectively taken during the pre-switch period were compared with data prospectively collected during the post-switch period. The primary endpoint was the effect on eGFR slope. Secondary endpoints were: changes in clinical events, 24-hour proteinuria, cardiac and neurologic parameters, FD-related symptoms, lyso-Gb3 plasma concentrations, and adverse events. Results In total, 11 patients (nine males and two females) switched to agalsidase beta from 55.3 ± 31.2 months of primary therapy with agalsidase alfa (eight patients) or migalastat (three patients), were evaluated for a follow-up period of 24 months. After the switch, a significant reduction of the eGFR slope was observed (−4.61 vs −0.45 ml/min/1.73 m2/year, respectively in pre- and post-switch period; P post/pre < .005). After the switch, plasma lyso-Gb3 levels progressively reduced, and the reduction reached the significance vs baseline at T2 (P < .05). Most of FD-related symptoms ameliorated during the primary Fabry therapy and remained stable after the switch. All other parameters were stable over time. Conclusions Treatment switch from agalsidase alfa or migalastat to agalsidase beta can attenuate eGFR decline and enhance lyso-Gb3 reduction, confirming the dose-dependent effect of agalsidase beta to further slow down FD progression.