Effect of oral eliglustat on splenomegaly in patients with Gaucher disease type 1: The ENGAGE randomized clinical trial

JAMA - Journal of the American Medical Association

Volumn 313, Issue 7, 2015, Pages 695-706

  Mistry, Pramod K ^a   Lukina, Elena ^b   Turkia, Hadhami Ben ^c   Amato, Dominick ^d   Baris, Hagit ^e   Dasouki, Majed ^f   Ghosn, Marwan ^g   Mehta, Atul ^h   Packman, Seymour ⁱ   Pastores, Gregory ^j   Petakov, Milan ^k   Assouline, Sarit ^l   Balwani, Manisha ^m   Danda, Sumita ⁿ   Hadjiev, Evgueniy ^o   Ortega, Andres ^p   Shankar, Suma ^q   Solano, Maria Helena ^r   Ross, Leorah ^s   Angell, Jennifer ^s   Peterschmitt, M Judith ^s   more..

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NATIONAL RESEARCH CENTER FOR HEMATOLOGY   (Russian Federation)

^c LA RABTA HOSPITAL   (Tunisia)

^d MOUNT SINAI HOSPITAL   (Canada)

^e TEL AVIV UNIVERSITY   (Israel)

^f UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

^g SAINT JOSEPH UNIVERSITY   (Lebanon)

^h ROYAL FREE HOSPITAL   (United Kingdom)

ⁱ UNIVERSITY OF CALIFORNIA   (United States)

^j NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^k UNIVERSITY OF BELGRADE   (Serbia)

^l MCGILL UNIVERSITY   (Canada)

^m MOUNT SINAI SCHOOL OF MEDICINE   (United States)

ⁿ CHRISTIAN MEDICAL COLLEGE   (India)

^o UNIVERSITY HOSPITAL ALEXANDROVSKA   (Bulgaria)

^p Oca Hospital   (Mexico)

^q EMORY UNIVERSITY   (United States)

^r HOSPITAL DE SAN JOSÉ   (Colombia)

^s GENZYME CORPORATION   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ELIGLUSTAT; CERAMIDE GLUCOSYLTRANSFERASE; ENZYME INHIBITOR; GLUCOSYLTRANSFERASE; PYRROLIDINE DERIVATIVE;

ADULT; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; FEMALE; GAUCHER DISEASE; HUMAN; MALE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SPLENOMEGALY; SYNDROME DELINEATION; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; COMPARATIVE STUDY; COMPLICATION; DOUBLE BLIND PROCEDURE; DRUG EFFECTS; MULTICENTER STUDY; ORAL DRUG ADMINISTRATION; ORGAN SIZE; PATHOLOGY; PHASE 3 CLINICAL TRIAL; SPLEEN; YOUNG ADULT;

ADMINISTRATION, ORAL; ADULT; DOUBLE-BLIND METHOD; ENZYME INHIBITORS; FEMALE; GAUCHER DISEASE; GLUCOSYLTRANSFERASES; HUMANS; MALE; ORGAN SIZE; PYRROLIDINES; SPLEEN; SPLENOMEGALY; YOUNG ADULT;

EID: 84923186347     PISSN: 00987484     EISSN: 15383598     Source Type: Journal    
DOI: 10.1001/jama.2015.459     Document Type: Article

References (32)

1. Chen M, Wang J. Gaucher disease: review of the literature. Arch Pathol LabMed. 2008;132(5):851-853.
2. Grabowski G, Kolodny E, Weinreb N, et al. Gaucher disease: phenotypic and genetic variation. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis ES, Ballabio A, eds. The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill; 2011.
3. Barton NW, Brady RO, Dambrosia JM, et al. Replacement therapy for inherited enzyme deficiency-macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med. 1991;324(21):1464-1470.
4. Andersson HC, Charrow J, Kaplan P, et al; International Collaborative Gaucher Group US Regional Coordinators. Individualization of long-term enzyme replacement therapy for Gaucher disease. Genet Med. 2005;7(2):105-110.
5. Mistry PK, Liu J, Yang M, et al. Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage. Proc Natl Acad Sci U S A. 2010;107(45):19473-19478.
6. Cox TM. Eliglustat tartrate, an orally active glucocerebroside synthase inhibitor for the potential treatment of Gaucher disease and other lysosomal storage diseases. Curr Opin Investig Drugs. 2010;11(10):1169-1181.
7. Zavesca [package insert]. South San Francisco, CA: Actelion Pharmaceuticals US Inc; 2008.
8. Cox T, Lachmann R, Hollak C, et al. Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet. 2000;355(9214): 1481-1485.
9. Hollak CE, Hughes D, van Schaik IN, Schwierin B, Bembi B. Miglustat (Zavesca) in type 1 Gaucher disease: 5-year results of a post-authorisation safety surveillance programme. Pharmacoepidemiol Drug Saf. 2009;18(9):770-777.
10. Lukina E, Watman N, Arreguin EA, et al. A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood. 2010;116(6):893-899.
11. Kamath RS, Lukina E, Watman N, et al. Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat. Skeletal Radiol. 2014;43(10):1353-1360.
12. Lukina E, Watman N, Dragosky M, et al. Eliglustat, an investigational oral therapy for Gaucher disease type 1: phase 2 trial results after 4 years of treatment. Blood Cells Mol Dis. 2014;53(4): 274-276.
13. Pastores GM, Weinreb NJ, Aerts H, et al. Therapeutic goals in the treatment of Gaucher disease. Semin Hematol. 2004;41(4)(suppl 5):4-14.
14. Aerts JM, van Breemen MJ, Bussink AP, et al. Biomarkers for lysosomal storage disorders: identification and application as exemplified by chitotriosidase in Gaucher disease. Acta Paediatr Suppl. 2008;97(457):7-14.
15. de Fost M, Hollak CE, Groener JE, et al. Superior effects of high-dose enzyme replacement therapy in type 1 Gaucher disease on bone marrow involvement and chitotriosidase levels: a 2-center retrospective analysis. Blood. 2006;108(3):830-835.
16. Giraldo P, Cenarro A, Alfonso P, et al. Chitotriosidase genotype and plasma activity in patients type 1 Gaucher's disease and their relatives (carriers and non carriers). Haematologica. 2001;86 (9):977-984.
17. Dworkin RH, Turk DC, Wyrwich KW, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9(2):105-121.
18. Mathias SD, Crosby RD, Qian Y, Jiang Q, Dansey R, Chung K. Estimatingminimally important differences for the worst pain rating of the Brief Pain Inventory-Short Form. J Support Oncol. 2011;9 (2):72-78.
19. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore. 1994;23(2):129-138.
20. Goligher EC, Pouchot J, Brant R, et al. Minimal clinically important difference for 7 measures of fatigue in patients with systemic lupus erythematosus. J Rheumatol. 2008;35(4):635-642.
21. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The Fatigue Severity Scale: application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46(10):1121-1123.
22. Rogers WH, Wittink H, Wagner A, Cynn D, Carr DB. Assessing individual outcomes during outpatient multidisciplinary chronic pain treatment by means of an augmented SF-36. Pain Med. 2000; 1(1):44-54.
23. Maas M, Hangartner T, Mariani G, et al. Recommendations for the assessment and monitoring of skeletal manifestations in children with Gaucher disease. Skeletal Radiol. 2008;37(3): 185-188.
24. Robertson PL, Maas M, Goldblatt J. Semiquantitative assessment of skeletal response to enzyme replacement therapy for Gaucher's disease using the bone marrow burden score. AJR Am J Roentgenol. 2007;188(6):1521-1528.
25. Weinreb NJ, Cappellini MD, Cox TM, et al. A validated disease severity scoring system for adults with type 1 Gaucher disease. Genet Med. 2010;12(1):44-51.
26. Peterschmitt MJ, Burke A, Blankstein L, et al. Safety, tolerability, and pharmacokinetics of eliglustat tartrate (Genz-112638) after single doses, multiple doses, and food in healthy volunteers. J Clin Pharmacol. 2011;51(5):695-705.
27. Grabowski GA, Petsko GA, Kolodny EH. Gaucher disease. In: Valle D, Beaudet AL, Vogelstein B, et al, eds. OMMBID: The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 2013. http://ommbid.mhmedical.com/content.aspx ?bookid=474&Sectionid=45374148. Accessed January 22, 2015.
28. McEachern KA, Fung J, Komarnitsky S, et al. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease. Mol Genet Metab. 2007;91(3): 259-267.
29. Wennekes T, Meijer AJ, Groen AK, et al. Dual-action lipophilic iminosugar improves glycemic control in obese rodents by reduction of visceral glycosphingolipids and buffering of carbohydrate assimilation. J Med Chem. 2010;53 (2):689-698.
30. Kuter DJ, Mehta A, Hollak CE, et al. Miglustat therapy in type 1 Gaucher disease: clinical and safety outcomes in a multicenter retrospective cohort study. Blood Cells Mol Dis. 2013;51(2):116-124.
31. Cox TM, Amato D, Hollak CE, et al;Miglustat Maintenance Study Group. Evaluation ofmiglustat as maintenance therapy after enzyme therapy in adults with stable type 1 Gaucher disease: a prospective, open-label non-inferiority study. Orphanet J Rare Dis. 2012;7(1):102.
32. Lukina E, Watman N, Arreguin EA, et al. Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study. Blood. 2010;116(20):4095-4098.