Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat
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Author
Kamath, Ravi S.
Lukina, Elena
Watman, Nora
Dragosky, Marta
Pastores, Gregory M.
Arreguin, Elsa Avila
Rosenbaum, Hanna
Zimran, Ari
Aguzzi, Rasha
Puga, Ana Cristina
Norfleet, Andrea M.
Peterschmitt, M. Judith
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1007/s00256-014-1891-9Metadata
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Kamath, R. S., E. Lukina, N. Watman, M. Dragosky, G. M. Pastores, E. A. Arreguin, H. Rosenbaum, et al. 2014. “Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat.” Skeletal Radiology 43 (10): 1353-1360. doi:10.1007/s00256-014-1891-9. http://dx.doi.org/10.1007/s00256-014-1891-9.Abstract
Objective: Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective monitoring of bone mineral density (BMD), fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial (NCT00358150). Materials and methods Institutional review board approval and patient informed consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth twice daily; 19 patients completed 4 years of treatment. All were skeletally mature (age range, 18–55 years). DXA and MRI assessments were conducted at baseline and annually thereafter. X-rays were obtained annually until month 24, and then every other year. Results: Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean (SD) of 9.9 % (14.2 %) from baseline to year 4; corresponding T-scores increased significantly (p = 0.01) from a mean (SD) of −1.6 (1.1) to −0.9 (1.3). Mean femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56 %) patients had decreased Gaucher cell infiltration compared to baseline; one patient with early improvement had transient worsening at year 4. There were no lumbar spine or femoral fractures and no reported bone crises during the study. At baseline, 8/19 (42 %) patients had focal bone lesions, which remained stable, and 7/19 (37 %) patients had bone infarctions, which improved in one patient by year 2. At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved. Conclusions: Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141971/pdf/Terms of Use
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