Successful switch from enzyme replacement therapy to miglustat in an adult patient with type 1 Gaucher disease: a case report.
BACKGROUND
Gaucher disease is one of the most common lipid-storage disorders, affecting approximately 1 in 75,000 births. Enzyme replacement therapy with recombinant glucocerebrosidase is currently considered the first-line treatment choice for patients with symptomatic Gaucher disease type 1. Oral substrate reduction therapy is generally considered a second-line treatment option for adult patients with mild to moderate Gaucher disease type 1 who are unable or unwilling to receive lifelong intravenous enzyme infusions. The efficacy and safety of the oral substrate reduction therapy miglustat (Zavesca®) in patients with Gaucher disease type 1 have been established in both short-term clinical trials and long-term, open-label extension studies. Published data indicate that miglustat can be used as maintenance therapy in patients with stable Gaucher disease type 1 switched from previous enzyme replacement therapy.


METHODS
We report a case of a 44-year-old Caucasian man with Gaucher disease type 1 who was initially treated with enzyme replacement therapy but, owing to repeated cutaneous allergic reactions, had to be switched to miglustat after several attempts with enzyme replacement therapy. Despite many attempts, desensitization treatment did not result in improved toleration of imiglucerase infusions, and the patient became unwilling to continue with any intravenous enzyme replacement therapy. He subsequently agreed to switch to oral substrate reduction therapy with miglustat 100 mg twice daily titrated up to 100 mg three times daily over a short period. Long-term miglustat treatment maintained both hemoglobin and platelet levels within acceptable ranges over 8 years. The patient's spleen volume decreased, his plasma chitotriosidase levels stayed at reduced levels, and his bone mineral density findings have remained stable throughout follow-up. The patient's quality of life has remained satisfactory. Miglustat showed good gastrointestinal tolerability in this patient, and no adverse events have been reported.


CONCLUSIONS
Oral miglustat therapy proved to be a valid alternative treatment to intravenous enzyme replacement therapy for long-term maintenance in this patient with Gaucher disease type 1, who showed persistent allergic intolerance to imiglucerase infusions. This report exemplifies the type of patient with Gaucher disease type 1 who can benefit from switching from enzyme replacement therapy to substrate reduction therapy.
Regional Reference Center for Rare Diseases, Clinical Division of Hematology and Transplantation, PO Ferrarotto Hospital, Azienda Ospedaliera-Universitaria Policlinico-Vittorio Emanuele, Via Citelli, 6-95100, Catania, Italy. gaegiuffrida@gmail.com.
Gaetano
G
Giuffrida
Regional Reference Center for Rare Diseases, Clinical Division of Hematology and Transplantation, PO Ferrarotto Hospital, Azienda Ospedaliera-Universitaria Policlinico-Vittorio Emanuele, Via Citelli, 6-95100, Catania, Italy.
Rita
R
Lombardo
Regional Reference Center for Rare Diseases, Clinical Division of Hematology and Transplantation, PO Ferrarotto Hospital, Azienda Ospedaliera-Universitaria Policlinico-Vittorio Emanuele, Via Citelli, 6-95100, Catania, Italy.
Ernesto
E
Di Francesco
Regional Reference Center for Rare Diseases, Clinical Division of Hematology and Transplantation, PO Ferrarotto Hospital, Azienda Ospedaliera-Universitaria Policlinico-Vittorio Emanuele, Via Citelli, 6-95100, Catania, Italy.
Laura
L
Parrinello
Regional Reference Center for Rare Diseases, Clinical Division of Hematology and Transplantation, PO Ferrarotto Hospital, Azienda Ospedaliera-Universitaria Policlinico-Vittorio Emanuele, Via Citelli, 6-95100, Catania, Italy.
Francesco
F
Di Raimondo
Department of Clinical Medicine and Pediatrics, Pediatric Clinic, Gaspare Rodolico Azienda Ospedaliera-Universitaria Policlinico-Vittorio Emanuele, Catania, Italy.
Agata
A
Fiumara
D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D004334:Drug Administration Schedule; D003875:Drug Eruptions; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D056947:Enzyme Replacement Therapy / Q000009:adverse effects*; D005776:Gaucher Disease / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D011788:Quality of Life; D013154:Spleen / Q000187:drug effects / Q000473:pathology*; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat
Enzyme replacement therapy; Gaucher disease; Miglustat; Substrate reduction therapy