Relationship between Glucocerebrosidase Activity and clinical response to Enzyme Replacement Therapy in patients with Gaucher Disease type I.

The quantification of enzyme activity in the patient treated with enzyme replacement therapy (ERT) has been suggested as a tool for dosage individualization, so we conducted a study to evaluate the relationship between glucocerebrosidase activity and clinical response in patients with Gaucher disease type I (GD1) to ERT. The study included patients diagnosed with GD1, who were being treated with ERT, and healthy individuals. Markers based on glucocerebrosidase activity measurement in patients' leucocytes were studied: enzyme activity at 15 min. post-infusion (Act(75)) reflects the amount of enzyme that is distributed in the body post-ERT infusion, and accumulated glucocerebrosidase activity during ERT infusion (Act(75-0)) indicates the total drug exposure during infusion. The clinical response was evaluated based on criteria established by Pastores et al. and Gaucher Severity Score Index. Statistical analysis included ROC analysis and area under the curve test. Act(75) and Act(75-0) were found to be moderate predictive markers of an optimal clinical response (area under the ROC of Act(75) was 0.733 and Act(75-0) was 0.817). Act(75-0) showed statistical significance in its discriminative capacity (p < 0.05) for obtaining an optimal response to ERT. The cut-off point was 58% (RR = 1.800; 95% CI: 1.003-3.229; p < 0.05). Moreover, Act(75) showed a significant and inverse correlation with the Gaucher Severity Score Index, and Act(75) and Act(75-0) presented a significant correlation with residual enzyme activity at diagnosis. Markers based on glucocerebrosidase activity have a good correlation with clinical response to ERT. Therefore, it could provide supporting clinical data for dose management in GD1 patients.