. 2023 Sep 1;10:1220637. doi: 10.3389/fmed.2023.1220637

Table 6.

Recommendations for α-Gal A measurement and lyso-Gb₃, in patients with Fabry disease.

α-Gal A measurements in patients receiving migalastat	Lyso-Gb₃ measurements
No consensus was reached regarding a threshold percentage increase in α-Gal A activity from baseline or normal levels that would indicate biological activity of migalastat *(statements 1G and 1H; no consensus [0.5 and 0.1, respectively]); therefore, the utility of α-Gal A as a pharmacodynamic treatment response biomarker for migalastat remains unclear.* α-Gal A activity in leukocytes should be measured before migalastat initiation and during routine follow-up to inform assessment of the biological activity of migalastat (statement 1F; moderate consensus [0.6]). In female patients receiving migalastat, α-Gal A activity should not be used to make decisions about whether to continue migalastat treatment (statement 1B; strong consensus [1.1]). Migalastat should be continued in female patients showing stabilization or improvement in Fabry-related symptoms and/or organ involvement, regardless of the change in α-Gal A activity (statement 1A; strong consensus [1.2]). In male patients receiving migalastat, α-Gal A activity should be measured as part of routine follow-up (statement 1C; moderate consensus [1.0]). Migalastat should be continued in male patients showing stabilization or improvement in Fabry-related symptoms, regardless of the change in α-Gal A activity (statement 1D; moderate consensus [1.0]). Migalastat should be continued in both male and female patients with stable or improved organ function, regardless of any change in α-Gal A activity (statement 1E; moderate consensus [0.8]).	No consensus was reached regarding the reliability of lyso-Gb₃ as a pharmacodynamic biomarker for monitoring treatment response in patients with Fabry disease receiving migalastat *(statement 2N; no consensus [0.3]). This should be considered when evaluating all other lyso-Gb₃-related recommendations. Lyso-Gb₃ analysis should be performed in all patients at diagnosis (statement 2A; strong consensus [1.5]), and every 6 months–1 year in patients receiving either ERT (statement 2J; moderate consensus [0.8]) or migalastat (statement 2G; moderate consensus [1.0]). In both male and female treatment-naïve patients, a decrease in lyso-Gb₃ from BL within ≤12 months after migalastat initiation indicates biological activity of migalastat (statements 2H and 2K; moderate consensus [1.0 and 0.8, respectively]). In ERT-experienced male (statement 2E; strong consensus [1.1]) or female (statement 2I; moderate consensus [0.9]) patients switched to migalastat, stable or declining lyso-Gb₃ levels after 12 months of migalastat treatment relative to during ERT treatment indicate biological activity of migalastat and support a clinical decision to continue treatment. Migalastat treatment should be continued in any patient showing a symptomatic response and/or stable or improved organ function, if lyso-Gb₃ is stable or declining (statements 2F and 2D; strong consensus [1.1 and 1.3, respectively]). Following any increase in lyso-Gb₃ from BL, where there has been no change in treatment, patients should be asked about their adherence to migalastat (statement 2B; strong consensus [1.5]). Treatment adherence with migalastat should be discussed in a systematic way, reviewing the patient’s current dosing and posology (statement 2C; strong consensus [1.5]*).

α-Gal A measurements in patients receiving migalastat

Lyso-Gb₃ measurements

No consensus was reached regarding a threshold percentage increase in α-Gal A activity from baseline or normal levels that would indicate biological activity of migalastat (statements 1G and 1H; no consensus [0.5 and 0.1, respectively]); therefore, the utility of α-Gal A as a pharmacodynamic treatment response biomarker for migalastat remains unclear.

α-Gal A activity in leukocytes should be measured before migalastat initiation and during routine follow-up to inform assessment of the biological activity of migalastat (statement 1F; moderate consensus [0.6]).
In female patients receiving migalastat, α-Gal A activity should not be used to make decisions about whether to continue migalastat treatment (statement 1B; strong consensus [1.1]). Migalastat should be continued in female patients showing stabilization or improvement in Fabry-related symptoms and/or organ involvement, regardless of the change in α-Gal A activity (statement 1A; strong consensus [1.2]).
In male patients receiving migalastat, α-Gal A activity should be measured as part of routine follow-up (statement 1C; moderate consensus [1.0]). Migalastat should be continued in male patients showing stabilization or improvement in Fabry-related symptoms, regardless of the change in α-Gal A activity (statement 1D; moderate consensus [1.0]).
Migalastat should be continued in both male and female patients with stable or improved organ function, regardless of any change in α-Gal A activity (statement 1E; moderate consensus [0.8]).

No consensus was reached regarding the reliability of lyso-Gb₃ as a pharmacodynamic biomarker for monitoring treatment response in patients with Fabry disease receiving migalastat (statement 2N; no consensus [0.3]). This should be considered when evaluating all other lyso-Gb₃-related recommendations.

Lyso-Gb₃ analysis should be performed in all patients at diagnosis (statement 2A; strong consensus [1.5]), and every 6 months–1 year in patients receiving either ERT (statement 2J; moderate consensus [0.8]) or migalastat (statement 2G; moderate consensus [1.0]).
In both male and female treatment-naïve patients, a decrease in lyso-Gb₃ from BL within ≤12 months after migalastat initiation indicates biological activity of migalastat (statements 2H and 2K; moderate consensus [1.0 and 0.8, respectively]).
In ERT-experienced male (statement 2E; strong consensus [1.1]) or female (statement 2I; moderate consensus [0.9]) patients switched to migalastat, stable or declining lyso-Gb₃ levels after 12 months of migalastat treatment relative to during ERT treatment indicate biological activity of migalastat and support a clinical decision to continue treatment.
Migalastat treatment should be continued in any patient showing a symptomatic response and/or stable or improved organ function, if lyso-Gb₃ is stable or declining (statements 2F and 2D; strong consensus [1.1 and 1.3, respectively]).
Following any increase in lyso-Gb₃ from BL, where there has been no change in treatment, patients should be asked about their adherence to migalastat (statement 2B; strong consensus [1.5]). Treatment adherence with migalastat should be discussed in a systematic way, reviewing the patient’s current dosing and posology (statement 2C; strong consensus [1.5]).

Food and caffeine should not be consumed at least 2 h prior to and 2 h after taking migalastat to give a minimum 4 h fast (38, 39).

α-Gal A, α-galactosidase A; BL, baseline; ERT, enzyme replacement therapy; and lyso-Gb₃, globotriaosylsphingosine.