Relationship Between Glucocerebrosidase Activity and Clinical Response to Enzyme Replacement Therapy in Patients With Gaucher Disease Type I
Por:
Gras-Colomer E, Martinez-Gomez MA, Climente-Marti M, Fernandez-Zarzoso M, Almela-Tejedo M, Giner-Galvan V, Marcos-Rodriguez JA, Rodriguez-Fernandez A, Torralba-Cabeza MA and Merino-Sanjuan M
Publicada:
1 jul 2018
Ahead of Print:
30 mar 2018
Resumen:
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.
Filiaciones:
:
Univ Hosp Doctor Peset Valencia, Dept Pharm, Valencia, Spain
Fdn Promot Hlth & Biomed Res Valencia FISABIO, Valencia, Spain
Department of Pharmacy, University Hospital Doctor Peset of Valencia, Valencia, Spain
Foundation for the Promotion of Health and Biomedical Research of Valencia (FISABIO), Valencia, Spain
:
Univ Hosp Doctor Peset Valencia, Dept Pharm, Valencia, Spain
Fdn Promot Hlth & Biomed Res Valencia FISABIO, Valencia, Spain
Department of Pharmacy, University Hospital Doctor Peset of Valencia, Valencia, Spain
Foundation for the Promotion of Health and Biomedical Research of Valencia (FISABIO), Valencia, Spain
:
Univ Hosp Doctor Peset Valencia, Dept Pharm, Valencia, Spain
Univ Valencia, Pharm & Pharmaceut Technol, Valencia, Spain
Department of Pharmacy, University Hospital Doctor Peset of Valencia, Valencia, Spain
Pharmacy and Pharmaceutical Technology, University of Valencia, Valencia, Spain
:
Univ Hosp Doctor Peset Valencia, Dept Hematol, Valencia, Spain
Department of Hematology, University Hospital Doctor Peset of Valencia, Valencia, Spain
:
Hosp Virgen de los Lirios Alcoi, Dept Pharm, Alcoy, Spain
Department of Pharmacy, Hospital Virgen de los Lirios of Alcoi, Alcoi, Spain
:
Hosp Virgen de los Lirios Alcoi, Dept Internal Med, Alcoy, Spain
Department of Internal Medicine, Hospital Virgen de los Lirios of Alcoi, Alcoi, Spain
Marcos-Rodriguez JA:
Univ Hosp Virgen Macarena, Dept Pharm, Seville, Spain
Department of Pharmacy, University Hospital Virgen Macarena, Seville, Spain
Rodriguez-Fernandez A:
Univ Hosp Virgen Macarena, Dept Hematol, Seville, Spain
Department of Hematology, University Hospital Virgen Macarena, Seville, Spain
Torralba-Cabeza MA:
Univ Clin Hosp Lozano Blesa Zaragoza, Deparment Internal Med, Zaragoza, Spain
Deparment of Internal Medicine, University Clinical Hospital Lozano Blesa of Zaragoza, Zaragoza, Spain
Merino-Sanjuan M:
Univ Valencia, Pharm & Pharmaceut Technol, Valencia, Spain
Univ Valencia, Mixed Unit Polytech Univ Valencia, Mol Recognit & Technol Dev Inst, Valencia, Spain
Pharmacy and Pharmaceutical Technology, University of Valencia, Valencia, Spain
Molecular Recognition and Technological Development Institute, Mixed Unit Polytechnic University of Valencia, University of Valencia, Valencia, Spain
Bronze, Green Accepted
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