Abstract | BACKGROUND: METHODS: Changes in blood ferritin, chitotriosidase, hemoglobin and platelets were analyzed in French GD Registry patients receiving imiglucerase/ alglucerase as ERT. We used simplified exponential pathophysiological model, with initial concentration, biomarkers amplitude of variation and rate constant of normalization during ERT. Changes in four biomarkers were analyzed separately and then all four together from initiation to discontinuation of ERT, or until the end of follow-up. Several covariates were tested, including age at ERT initiation, splenectomy, sex, genotype (N370S/N370S), and ERT dose. RESULTS: An exponential model gave a good data fit. The four biomarkers analysis showed that the rate of nomalization was the same for all biomarkers, with a half-life of 0.5 years. Predicted values of biomarkers at ERT's steady state were 40% and 10% of initial concentrations, for ferritin and chitotriosidase, respectively, and 120% and 200% for hemoglobin and platelets, respectively. We found that 3 covariates had an effect on initial concentration or on amplitude of variation in ferritin, hemoglobin and platelets: women and patients under 15 years of age had lower ferritin and hemoglobin concentrations, and patients under 15 years of age had higher platelet count. Splenectomized patients had higher ferritin concentrations and platelet count and lower amplitude of variation of hemoglobin. CONCLUSION: We report the first dynamic model of biomarker changes in GD. It enabled us to estimate that 95% of biomarker response to ERT was achieved in 2 years, but with high inter-patient variability. We also found that with the current treatment, normalization of chitotriosidase and ferritin will occur in about 65% of patients.
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Authors | Marie Vigan, Jérôme Stirnemann, Catherine Caillaud, Roseline Froissart, Anne Boutten, Bruno Fantin, Nadia Belmatoug, France Mentré |
Journal | Orphanet journal of rare diseases
(Orphanet J Rare Dis)
Vol. 9
Pg. 95
(Jun 30 2014)
ISSN: 1750-1172 [Electronic] England |
PMID | 24980507
(Publication Type: Journal Article)
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Chemical References |
- Biomarkers
- Glucosylceramidase
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Topics |
- Adolescent
- Adult
- Aged
- Biomarkers
(metabolism)
- Child
- Child, Preschool
- Female
- Gaucher Disease
(metabolism, physiopathology, therapy)
- Glucosylceramidase
(therapeutic use)
- Humans
- Infant
- Male
- Middle Aged
- Young Adult
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