Gaucher disease is a lysosomal storage disease for which enzyme replacement therapy has proven to be effective. A switch-over clinical trial was performed to evaluate the efficacy and safety of Abcertin(R) (ISU Abxis, Seoul, Korea) in subjects with type 1 Gaucher disease who were previously treated with imiglucerase. Five Korean patients with type 1 Gaucher disease were enrolled. Previous doses of imiglucerase ranged from 30 to 55 U/kg every other week. The same dose of Abcertin(R) was administered to all patients for 24 weeks. Primary efficacy endpoints were changes in hemoglobin levels and platelet counts, and the secondary efficacy endpoints included changes in liver and spleen volumes, serum biomarkers, skeletal status and bone mineral density (BMD). During the study period, no statistically significant changes were observed in all parameters including hemoglobin levels and platelet counts, liver and spleen volumes, skeletal status and BMD. Abcertin(R) administration was continued in three patients for another 24 weeks as an extension of the study. Hemoglobin levels and platelet counts were maintained in all three patients. In conclusion, the efficacy and safety of Abcertin(R) are similar to those of imiglucerase, and Abcertin(R) is an effective therapeutic agent for patients with type 1 Gaucher disease (Clinical Trial Registry No. NCT02053896 at www.clinicaltrials.gov).
Adolescent ; Adult ; Biosimilar Pharmaceuticals/adverse effects/pharmacokinetics/*therapeutic use ; Child ; *Enzyme Replacement Therapy/adverse effects ; Female ; Gaucher Disease/blood/*drug therapy ; Glucosylceramidase/adverse effects/pharmacokinetics/*therapeutic use ; Humans ; Male ; Recombinant Proteins/adverse effects/pharmacokinetics/*therapeutic use

OBJECTIVEGaucher disease is the most common lysosomal storage disorder. A deficiency of beta-glucocerebrosidase causes accumulation of the glucocerebroside in macrophages throughout the body. This study summarizes the effects of enzyme replacement therapy (ERT) with Imiglucerase in children with Gaucher disease.

METHODSData from 72 patients (46 were male and 26 female, age ranged from 16 months to 22 years, median 8 years and 8 months) who were treated in the hospital between May 1999 and October 2005 were collected and analyzed, 57 of the patients had type 1 Gaucher disease, 2 patients with type 2, and 13 patients with type 3. Twenty-two patients had undergone total splenectomy. Imiglucerase was given at an initial dose 60 U/kg body weight by intravenous infusion every 2 weeks. The dose was reduced to 45 U/kg when they had achieved the specified therapeutic goals after 2 years. Clinical outcome data of Imiglucerase treatment were collected using routine Gaucher clinical measures, including growth, hematology, liver and spleen 3-dimensional measurements, and skeletal assessments every 3 - 6 months.

RESULTSThree patients were lost to follow-up, 4 patients died, and 65 patients continued to receive the therapy. Hemoglobin and platelet levels of the patients with intact spleen increased most rapidly from the first 12 months of ERT (P < 0.01). Hemoglobin level of the patients who had undergone splenectomy determined at 30 months of treatment was higher than that of baseline (P < 0.01), but platelet levels were not significantly different (P > 0.05). The volumes of the liver decreased after the 6 months of ERT, decreased in average by (39 +/- 17)% at 24 months (P < 0.01). The volumes of spleen decreased after the 12 months of ERT by (59 +/- 21)% at 24 months (P < 0.01). During the first 12 month, the height and weight of the patients who were 2 - 12 years old increased (8.6 +/- 4.3) cm and (2.6 +/- 1.7) kg, respectively, and those of the patients who were 12 - 18 years old increased (5.2 +/- 3.9) cm and (4.5 +/- 3.3) kg, separately. Bone pain reported by 16 patients relieved after 3 months of treatment. But radiological evidence of bone disease did not change. The signs and symptoms of CNS involvement in patients with type 2 and type 3 disease were not improved. No serious adverse events were reported.

CONCLUSIONSERT with Imiglucerase could improve the quality of life of the patients with Gaucher disease by ameliorating the Gaucher disease-associated anemia, thrombocytopenia, organomegaly, growth retardation and bone pain.

Adolescent ; Anemia ; enzymology ; Child ; Child, Preschool ; Enzyme Replacement Therapy ; adverse effects ; methods ; Female ; Gaucher Disease ; drug therapy ; enzymology ; physiopathology ; Glucosylceramidase ; administration & dosage ; adverse effects ; deficiency ; therapeutic use ; Growth Disorders ; enzymology ; Hepatomegaly ; enzymology ; Humans ; Infant ; Male ; Recombinant Proteins ; therapeutic use ; Retrospective Studies ; Splenomegaly ; enzymology ; Thrombocytopenia ; enzymology ; Treatment Outcome ; Young Adult