title: A randomized trial comparing the efficacy and safety of imiglucerase (Cerezyme) infusions every 4 weeks versus every 2 weeks in the maintenance therapy of adult patients with Gaucher disease type 1.
abstract: Imiglucerase (Cerezyme) has been the standard of care for treatment of Gaucher disease, a lysosomal storage disorder resulting from deficiency of glucocerebrosidase, since its approval in 1994. Infusions are typically given once every 2 weeks. However, many patients have expressed a desire for less frequent infusions as a matter of convenience. This clinical study assessed the safety and efficacy of intravenous imiglucerase infused once every 4 weeks (Q4) compared to once every 2 weeks (Q2) at the same total monthly dose in adult patients with clinically stable Gaucher disease type 1 (GD1). This was a 24-month, open-label, randomized, Phase 4, dose-frequency study conducted in 25 centers worldwide. Patients receiving imiglucerase were randomized to receive their monthly dose biweekly (n=33) or every 4 weeks (n=62). Changes from baseline in hemoglobin, platelets, liver and spleen volumes, bone crisis, and bone disease comprised a predefined composite endpoint; achievement or maintenance of established Gaucher disease therapeutic goals comprised a secondary endpoint. Sixty-three percent of Q4- and 81% of Q2-treated patients met the composite endpoint at Month 24; 89% of Q4- and 100% of Q2-treated patients met the therapeutic goals-based endpoint. The frequency of related adverse events was comparable between treatment groups. This study suggests that with comprehensive monitoring, a Q4 imiglucerase infusion regimen may be a safe and effective treatment option for the majority of clinically stable adult patients with GD1 but may not be appropriate for all GD1 patients. Continued monitoring in patients treated with Q4 dosing is required to assess long-term effectiveness.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Box 103856 DUMC, 595 LaSalle St., GSRB1, 4th Floor, Durham, NC 27710, USA. kishn001@mc.duke.edu
authors.forename: P S
authors.initials: PS
authors.lastname: Kishnani
authors.forename: M
authors.initials: M
authors.lastname: DiRocco
authors.forename: P
authors.initials: P
authors.lastname: Kaplan
authors.forename: A
authors.initials: A
authors.lastname: Mehta
authors.forename: G M
authors.initials: GM
authors.lastname: Pastores
authors.forename: S E
authors.initials: SE
authors.lastname: Smith
authors.forename: A C
authors.initials: AC
authors.lastname: Puga
authors.forename: R M
authors.initials: RM
authors.lastname: Lemay
authors.forename: N J
authors.initials: NJ
authors.lastname: Weinreb
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D003710:Demography; D004334:Drug Administration Schedule; D023381:Endpoint Determination; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D006306:Health Surveys; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005962:Glucosylceramidase; C090568:imiglucerase