All Title Author
Keywords Abstract

Achievement of Therapeutic Goals with Low-Dose Imiglucerase in Gaucher Disease: A Single-Center Experience

DOI: 10.1155/2013/151506

Full-Text   Cite this paper   Add to My Lib


Gaucher disease, a lysosomal storage disorder, is a multisystem disorder with variable and unpredictable onset and severity. Disease-specific enzyme replacement therapy (ERT) has been shown to reverse or ameliorate disease-specific hepatosplenomegaly and anemia and thrombocytopenia. ERT also impacts bone manifestations, including bone crises, bone pain, and appearance of new osteonecrosis, and improves bone mineral density to varying degrees. The objective of this study was to assess achievement of predefined therapeutic goals based on international registry outcomes for Israeli patients with Gaucher disease receiving imiglucerase for four consecutive years on a low-dose regimen followed in a single center. All data were taken from patient files. The therapeutic goals were taken from standards published in the literature for disease-specific clinical parameters. Among 164 patients at baseline, values for spleen and liver volumes, hemoglobin and platelet counts, and Z-scores for lumbar spine and femoral were significantly different from the goal. After four years ERT, there was a significant improvement ( ) in each of the therapeutic goal parameters from baseline. 15.2% of these patients achieved all hematology-visceral goals. In children, there was achievement of linear growth and puberty. This survey highlights the good overall response in symptomatic patients receiving low-dose ERT with imiglucerase in Israel. 1. Introduction Gaucher disease, a prevalent lysosomal storage disorder, is a multisystem disorder with variable and unpredictable onset and severity especially in the common nonneuronopathic form [1]. Patients with nonneuronopathic (type 1) Gaucher disease may suffer from varying degrees of splenomegaly, hepatomegaly, thrombocytopenia, bleeding tendencies, anemia, hypermetabolism, skeletal pathology, growth retardation in children, and/or pulmonary disease; invariably, health-related quality of life is affected. Age of onset may be in any decade of life, and there are no apparent triggers to onset; yet there are also periods of quiescence even in patients with severe manifestations such as debilitating and irreversible skeletal complications. Disease characteristics, including genotype, provide only a statistical estimation of the expected trajectory of the signs and symptoms of the disease for any particular patient. Disease-specific enzyme replacement therapy (ERT) with mannose-terminated glucocerebrosidase (alglucerase, Ceredase, Genzyme Corporation, Cambridge, MA, USA) was introduced in 1991 [2]. Subsequently, a recombinant enzyme


[1]  A. Zimran and D. Elstein, “Lipid storage diseases,” in Williams Hematology, M. A. Lichtman, T. Kipps, U. Seligsohn, K. Kaushansky, and J. T. Prchal, Eds., pp. 1065–1071, McGraw-Hill, New York, NY, USA, 8th edition, 2010.
[2]  N. W. Barton, R. O. Brady, J. M. Dambrosia et al., “Replacement therapy for inherited enzyme deficiency: macrophage-targeted glucocerebrosidase for Gaucher's disease,” The New England Journal of Medicine, vol. 324, no. 21, pp. 1464–1470, 1991.
[3]  G. A. Grabowski, N. W. Barton, G. Pastores et al., “Enzyme therapy in type 1 Gaucher disease: comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources,” Annals of Internal Medicine, vol. 122, no. 1, pp. 33–39, 1995.
[4]  A. Zimran, D. Elstein, E. Levy-Lahad et al., “Replacement therapy with imiglucerase for type 1 Gaucher's disease,” The Lancet, vol. 345, no. 8963, pp. 1479–1480, 1995.
[5]  N. J. Weinreb, J. Charrow, H. C. Andersson et al., “Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher registry,” The American Journal of Medicine, vol. 113, no. 2, pp. 112–119, 2002.
[6]  N. J. Weinreb, “Advances in Gaucher disease: therapeutic goals and evaluation and monitoring guidelines,” Seminars in Hematology, vol. 41, no. 4, supplement 5, pp. 1–3, 2004.
[7]  G. M. Pastores, N. J. Weinreb, H. Aerts et al., “Therapeutic goals in the treatment of Gaucher disease,” Seminars in Hematology, vol. 41, no. 5, supplement 5, pp. 4–14, 2004.
[8]  N. Weinreb, J. Taylor, T. Cox, J. Yee, and S. vom Dahl, “A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase,” The American Journal of Hematology, vol. 83, no. 12, pp. 890–895, 2008.
[9]  D. Elstein, A. Abrahamov, I. Hadas-Halpern, A. Meyer, and A. Zimran, “Low-dose low-frequency imiglucerase as a starting regimen of enzyme replacement therapy for patients with type I Gaucher disease,” Quarterly Journal of Medicine, vol. 91, no. 7, pp. 483–488, 1998.
[10]  D. Elstein, I. Hadas-Halpern, Y. Azuri, A. Abrahamov, Y. Bar-Ziv, and A. Zimran, “Accuracy of ultrasonography in assessing spleen and liver size in patients with Gaucher disease: comparison to computed tomographic measurements,” Journal of Ultrasound in Medicine, vol. 16, no. 3, pp. 209–211, 1997.
[11]  G. A. Grabowski, K. Kacena, J. A. Cole et al., “Dose-response relationships for enzyme replacement therapy with imiglucerase/alglucerase in patients with Gaucher disease type 1,” Genetics in Medicine, vol. 11, no. 2, pp. 92–100, 2009.
[12]  E. Sidransky, G. M. Pastores, and M. Mori, “Dosing enzyme replacement therapy for Gaucher disease: older, but are we wiser?” Genetics in Medicine, vol. 11, no. 2, pp. 90–91, 2009.
[13]  H. Andersson, P. Kaplan, K. Kacena, and J. Yee, “Eight-year clinical outcomes of long-term enzyme replacement therapy for 884 children with Gaucher disease type 1,” Pediatrics, vol. 122, no. 6, pp. 1182–1190, 2008.
[14]  A. Khan, T. Hangartner, N. J. Weinreb, J. S. Taylor, and P. K. Mistry, “Risk factors for fractures and avascular osteonecrosis in type 1 Gaucher disease—a study from the international collaborative Gaucher group (ICGG) Gaucher registry,” Journal of Bone and Mineral Research, vol. 27, no. 8, pp. 1839–1848, 2012.
[15]  P. Stein, A. Malhotra, A. Haims, G. M. Pastores, and P. K. Mistry, “Focal splenic lesions in type I Gaucher disease are associated with poor platelet and splenic response to macrophage-targeted enzyme replacement therapy,” Journal of Inherited Metabolic Disease, vol. 33, no. 6, pp. 769–774, 2010.


comments powered by Disqus