title: Early achievement and maintenance of the therapeutic goals using velaglucerase alfa in type 1 Gaucher disease.
abstract: BACKGROUND
  Therapeutic goals have been described to monitor achievement, maintenance and continuity of therapeutic response in patients with type 1 Gaucher disease receiving enzyme replacement therapy.
  
  
  OBJECTIVE
  To benchmark the impact of velaglucerase alfa treatment against therapeutic goals for 5 key clinical parameters of type 1 Gaucher disease (anemia, thrombocytopenia, hepatomegaly, splenomegaly and skeletal pathology).
  
  
  METHODS
  In an open-label Phase I/II study, twelve adults with symptomatic type 1 Gaucher disease and intact spleens received velaglucerase alfa for 9 months (60 U/kg infusion every other week [EOW]). Eleven patients completed the study and 10 enrolled in a long-term extension. After 1 year, patients who achieved ≥ 2 hematological or organ goals began step-wise dose reduction from 60 to 45 then 30 U/kg EOW. Data for anemia, thrombocytopenia, hepatomegaly, splenomegaly and skeletal pathology at baseline and 4 years are available for 8 patients (3 male, 5 female). The proportion of patients at goal for anemia, thrombocytopenia, hepatomegaly and splenomegaly at baseline was compared with the proportion achieving each goal at 4 years. The proportion achieving the skeletal pathology goal was determined on the basis of Z-score improvement from baseline to 4 years. The proportion of patients who achieved all 5 goals at 4 years was compared with the proportion at goal for all 5 parameters at baseline.
  
  
  RESULTS
  At baseline, no patient was at goal for all clinical parameters. After 1 year of treatment, all patients maintained goals present at baseline, and all achieved ≥ 2 goals. All 8 patients began step-wise dose reduction from 60 to 30 U/kg EOW between 15 and 18 months. By year 4 of treatment, all patients met goals for all 5 clinical parameters; therefore 100% achievement was seen for each of the 5 long-term, therapeutic goals.
  
  
  CONCLUSIONS
  In this velaglucerase alfa Phase I/II and extension study, clinically meaningful achievement of each long-term, therapeutic goal was observed for each patient, despite dose reduction after 1 year. This is the first report of a cohort where all patients receiving ERT for type 1 Gaucher disease achieved all 5 of these long-term, therapeutic goals within 4 years of starting treatment and after ≥ 2years dose reduction.
authors: Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel. elstein@szmc.org.il
authors: D
authors: D
authors: Elstein
authors: G M
authors: GM
authors: Cohn
authors: N
authors: N
authors: Wang
authors: M
authors: M
authors: Djordjevic
authors: C
authors: C
authors: Brutaru
authors: A
authors: A
authors: Zimran
mesh_terms: D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy* / Q000473:pathology; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005962:Glucosylceramidase; C550184:Velaglucerase alfa, human