1. Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat.
- Author
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Kamath RS, Lukina E, Watman N, Dragosky M, Pastores GM, Arreguin EA, Rosenbaum H, Zimran A, Aguzzi R, Puga AC, Norfleet AM, Peterschmitt MJ, and Rosenthal DI
- Subjects
- Absorptiometry, Photon methods, Administration, Oral, Adolescent, Adult, Bone Demineralization, Pathologic diagnosis, Bone Demineralization, Pathologic etiology, Enzyme Inhibitors administration & dosage, Female, Femur diagnostic imaging, Femur drug effects, Femur pathology, Follow-Up Studies, Fractures, Bone etiology, Fractures, Bone prevention & control, Gaucher Disease complications, Humans, Lumbar Vertebrae diagnostic imaging, Lumbar Vertebrae drug effects, Lumbar Vertebrae pathology, Magnetic Resonance Imaging methods, Male, Middle Aged, Prospective Studies, Pyrrolidines administration & dosage, Young Adult, Bone Demineralization, Pathologic drug therapy, Bone Density drug effects, Enzyme Inhibitors therapeutic use, Gaucher Disease drug therapy, Pyrrolidines therapeutic use
- 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.
- Published
- 2014
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