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

P. S. Kishnani, M. DiRocco, P. Kaplan, A. Mehta, G. M. Pastores, S. E. Smith, A. C. Puga, R. M. Lemay, N. J. Weinreb

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)164-170
Number of pages7
JournalMolecular Genetics and Metabolism
Volume96
Issue number4
DOIs
Publication statusPublished - Apr 2009

Fingerprint

Gaucher Disease
Safety
Bone
Therapeutics
Glucosylceramidase
Monitoring
Composite materials
Platelets
Bone Diseases
Liver
Physiologic Monitoring
Standard of Care
imiglucerase
Labels
Hemoglobins
Blood Platelets
Spleen
Maintenance
Bone and Bones

Keywords

  • Enzyme replacement therapy
  • Gaucher disease
  • Glucocerebrosidase
  • Glucosylceramide β-glucosidase
  • Imiglucerase
  • Infusion frequency
  • Type 1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

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. / Kishnani, P. S.; DiRocco, M.; Kaplan, P.; Mehta, A.; Pastores, G. M.; Smith, S. E.; Puga, A. C.; Lemay, R. M.; Weinreb, N. J.

In: Molecular Genetics and Metabolism, Vol. 96, No. 4, 04.2009, p. 164-170.

Research output: Contribution to journalArticle

Kishnani, P. S. ; DiRocco, M. ; Kaplan, P. ; Mehta, A. ; Pastores, G. M. ; Smith, S. E. ; Puga, A. C. ; Lemay, R. M. ; Weinreb, N. J. / 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. In: Molecular Genetics and Metabolism. 2009 ; Vol. 96, No. 4. pp. 164-170.
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