Relationship Between Glucocerebrosidase Activity and Clinical Response to Enzyme Replacement Therapy in Patients With Gaucher Disease Type I

Autor:	Alicia Rodríguez-Fernández, María-Amparo Martínez-Gómez, Mónica Climente-Martí, Matilde Merino-Sanjuán, Vicente Giner-Galvañ, Mercedes Almela-Tejedo, Miguel-Ángel Torralba-Cabeza, Jose-Antonio Marcos-Rodríguez, Elena Gras-Colomer, Miguel Fernandez-Zarzoso
Rok vydání:	2018
Předmět:	Adult Male congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Disease Toxicology Severity of Illness Index Gastroenterology 03 medical and health sciences Glucocerebrosidase activity 0302 clinical medicine Statistical significance Internal medicine Leukocytes Humans Medicine Enzyme Replacement Therapy In patient Prospective Studies 030212 general & internal medicine Inverse correlation Aged Enzyme Assays Pharmacology Gaucher Disease Dose-Response Relationship Drug biology business.industry Area under the curve nutritional and metabolic diseases General Medicine Enzyme replacement therapy Middle Aged Enzyme assay Treatment Outcome 030220 oncology & carcinogenesis biology.protein Glucosylceramidase Female business Biomarkers Follow-Up Studies
Zdroj:	Basic & Clinical Pharmacology & Toxicology. 123:65-71
ISSN:	1742-7835
DOI:	10.1111/bcpt.12977
Popis:	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 (Act75 ) reflects the amount of enzyme that is distributed in the body post-ERT infusion, and accumulated glucocerebrosidase activity during ERT infusion (Act75-0 ) 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. Act75 and Act75-0 were found to be moderate predictive markers of an optimal clinical response (area under the ROC of Act75 was 0.733 and Act75-0 was 0.817). Act75-0 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, Act75 showed a significant and inverse correlation with the Gaucher Severity Score Index, and Act75 and Act75-0 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.
Databáze:	OpenAIRE
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