title: Recommendations for the use of eliglustat in the treatment of adults with Gaucher disease type 1 in the United States.
abstract: In Gaucher disease, deficient activity of acid β-glucosidase results in accumulation of its substrates, glucosylceramide and glucosylsphingosine, within the lysosomes of cells primarily in the spleen, liver, bone marrow, and occasionally the lung. The multisystem disease is predominantly characterized by hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. Enzyme replacement therapy with recombinant human acid β-glucosidase has been the first-line therapy for Gaucher disease type 1 for more than two decades. Eliglustat, a novel oral substrate reduction therapy, was recently approved in the United States and the European Union as a first-line treatment for adults with Gaucher disease type 1. Eliglustat inhibits glucosylceramide synthase, thereby decreasing production of the substrate glucosylceramide and reducing its accumulation. Although existing recommendations for the care of patients with Gaucher disease remain in effect, unique characteristics of eliglustat require additional investigation and monitoring. A panel of physicians with expertise in Gaucher disease and experience with eliglustat in the clinical trials provide guidance regarding the use of eliglustat, including considerations before starting therapy and monitoring of patients on eliglustat therapy.
authors.affiliation: Department of Genetics and Genomic Sciences, One Gustave L. Levy Place, Box 1497, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: manisha.balwani@mssm.edu.
authors.forename: Manisha
authors.initials: M
authors.lastname: Balwani
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Human Genetics, 3333 Burnet Avenue, MLC 4006, Cincinnati, OH 45229, USA. Electronic address: thomas.burrow@cchmc.org.
authors.forename: Thomas Andrew
authors.initials: TA
authors.lastname: Burrow
authors.affiliation: Department of Pediatrics, Northwestern University Feinberg School of Medicine, Division of Genetics, Birth Defects and Metabolism, Ann and Robert H. Lurie Children's Hospital of Chicago, 225 East Chicago Avenue, Chicago, IL 60611, USA. Electronic address: jcharrow@northwestern.edu.
authors.forename: Joel
authors.initials: J
authors.lastname: Charrow
authors.affiliation: Lysosomal Disorders Unit, O&O Alpan, LLC, 11212 Waples Mill Road, Fairfax, VA 22030, USA. Electronic address: ogokeralpan@oandoalpan.com.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Goker-Alpan
authors.affiliation: Lysosomal Center, Division of Genetics, Children's Hospital of Philadelphia, Civic Center Blvd, Philadelphia, PA 19104, USA. Electronic address: kaplan@email.chop.edu.
authors.forename: Paige
authors.initials: P
authors.lastname: Kaplan
authors.affiliation: Duke University School of Medicine, Department of Pediatrics, DUMC 103856, 595 Lasalle Street, GSRB 1, 4th Floor, Room 4010, Durham, NC 27710, USA. Electronic address: kishn001@mc.duke.edu.
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
authors.affiliation: Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address: pramod.mistry@yale.edu.
authors.forename: Pramod
authors.initials: P
authors.lastname: Mistry
authors.affiliation: Massachusetts General Hospital, Electrophysiology Lab/Arrhythmia Service, 55 Fruit Street, Boston, MA 02114-2696, USA. Electronic address: jruskin@mgh.harvard.edu.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Ruskin
authors.affiliation: University Research Foundation for Lysosomal Storage Diseases, Inc., 7367 Wexford Terrace, Boca Raton, FL 33433, USA. Electronic address: boneal@winning.com.
authors.forename: Neal
authors.initials: N
authors.lastname: Weinreb
mesh_terms: D000818:Animals; D019468:Disease Management; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D056947:Enzyme Replacement Therapy; D005776:Gaucher Disease / Q000188:drug therapy*; D006801:Humans; D010349:Patient Compliance; D011759:Pyrrolidines / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States
chemical_list: D004791:Enzyme Inhibitors; D011759:Pyrrolidines; C522917:eliglustat
keywords: Eliglustat; Enzyme replacement therapy; Gaucher disease type 1; Substrate reduction therapy