Twelve years of experience with miglustat in the treatment of type 1 Gaucher disease: The Spanish ZAGAL project.
We report data from a prospective, observational study (ZAGAL) evaluating miglustat 100mg three times daily orally. in treatment-naïve patients and patients with type 1 Gaucher Disease (GD1) switched from previous enzyme replacement therapy (ERT). Clinical evolution, changes in organ size, blood counts, disease biomarkers, bone marrow infiltration (S-MRI), bone mineral density by broadband ultrasound densitometry (BMD), safety and tolerability annual reports were analysed. Between May 2004 and April 2016, 63 patients received miglustat therapy; 20 (32%) untreated and 43 (68%) switched. At the time of this report 39 patients (14 [36%] treatment-naïve; 25 [64%] switch) remain on miglustat. With over 12-year follow-up, hematologic counts, liver and spleen volumes remained stable. In total, 80% of patients achieved current GD1 therapeutic goals. Plasma chitotriosidase activity and CCL-18/PARC concentration showed a trend towards a slight increase. Reductions on S-MRI (p=0.042) with an increase in BMD (p<0.01) were registered. Gastrointestinal disturbances were reported in 25/63 (40%), causing miglustat suspension in 11/63 (17.5%) cases. Thirty-eight patients (60%) experienced a fine hand tremor and two a reversible peripheral neuropathy. Overall, miglustat was effective as a long-term therapy in mild to moderate naïve and ERT stabilized patients. No unexpected safety signals were identified during 12-years follow-up.
Haematology, Miguel Servet University Hospital, Zaragoza, Spain; CIBER de Enfermedades Raras (CIBERER), Spain; Spanish Foundation for the Study and Therapy of Gaucher Disease (FEETEG), Spain; Institute of Health Research Aragon (IIS Aragón), Zaragoza, Spain. Electronic address: giraldocastellano@gmail.com.
Pilar
P
Giraldo
Haematology, Miguel Servet University Hospital, Zaragoza, Spain; CIBER de Enfermedades Raras (CIBERER), Spain; Spanish Foundation for the Study and Therapy of Gaucher Disease (FEETEG), Spain; Institute of Health Research Aragon (IIS Aragón), Zaragoza, Spain.
Marcio
M
Andrade-Campos
CIBER de Enfermedades Raras (CIBERER), Spain; Spanish Foundation for the Study and Therapy of Gaucher Disease (FEETEG), Spain.
Pilar
P
Alfonso
CIBER de Enfermedades Raras (CIBERER), Spain; Biochemistry and Molecular and Cellular Biology, Zaragoza University, Spain.
Pilar
P
Irun
Haematology, Galdakao Hospital, Usansolo, Spain.
Koldo
K
Atutxa
Haematology, Vega Baja Hospital, Alicante, Spain.
Antonio
A
Acedo
Haematology, Ntra Sra de Sonsoles Hospital, Avila, Spain.
Abelardo
A
Barez
Haematology, Virgen de la Salud Hospital, Elda, Spain.
Margarita
M
Blanes
Internal Medicine, Ronda Hospital, Ronda, Spain.
Vicente
V
Diaz-Morant
Virgen del Puerto Hospital, Plasencia, Spain.
Ma Angeles
MA
Fernández-Galán
Haematology, Punta Europa University Hospital, Cádiz, Spain.
Rafael
R
Franco
Haematology, San Vicente Hospital, Alicante, Spain.
Cristina
C
Gil-Cortes
Internal Medicine, Virgen de Los Lirios Hospital, Alcoy, Spain.
Vicente
V
Giner
Haematology, Complejo Hospitalario de Albacete, Spain.
Angela
A
Ibañez
Spanish Foundation for the Study and Therapy of Gaucher Disease (FEETEG), Spain.
Paz
P
Latre
Haematology, Complexo Hospitalario de Pontevedra, Spain.
Ines
I
Loyola
Haematology, Central de Asturias University Hospital, Oviedo, Spain.
Elisa
E
Luño
Haematology, Virgen de la Concha Hospital, Zamora, Spain.
Roberto
R
Hernández-Martin
Institute of Health Research Aragon (IIS Aragón), Zaragoza, Spain.
Blanca
B
Medrano-Engay
Haematology, Virgen de las Nieves Hospital. Granada, Spain.
José
J
Puerta
Haematology, Parc Tauli Hospital, Sabadell, Spain.
Inmaculada
I
Roig
Haematology, Doce de Octubre University Hospital, Madrid, Spain.
Javier
J
de la Serna
Haematology, Vall d'Hebron University Hospital, Barcelona, Spain.
Olga
O
Salamero
Haematology, Alcorcon Hospital, Madrid, Spain.
Lucia
L
Villalón
Institute of Health Research Aragon (IIS Aragón), Zaragoza, Spain; Biochemistry and Molecular and Cellular Biology, Zaragoza University, Spain.
Miguel
M
Pocovi
D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D005776:Gaucher Disease / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D065089:Glycoside Hydrolase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D011446:Prospective Studies; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D055815:Young Adult
D065089:Glycoside Hydrolase Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat
Efficacy; Gaucher disease type 1; Maintenance; Miglustat; Safety