A Systematic Review and Meta-analyses of Longitudinal Studies on Drug Treatments for Gaucher Disease

Abstract

Objective: Gaucher disease (GD) is a rare disorder linked to the absence/deficiency of glucocerebrosidase. GD can be treated by enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). The aim of this systematic review (SR) is to assess the effectiveness of drugs used for GD treatment. Data Sources: Searches were conducted in PubMed and Scopus, in April 2021. The search strategies encompassed the name of the disease and of the drug treatments. Manual search was also conducted. Study Selection and Data Extraction: Observational and interventional longitudinal studies evaluating ERT and SRT for GD were included. Single mean meta-analyses were conducted for each drug using R. Data Synthesis: The initial search retrieved 2246 articles after duplicates were removed. Following screening and eligibility assessment, 68 reports were included. The studies evaluated imiglucerase, velaglucerase alfa, taliglucerase alfa, miglustat, and eliglustat. The results showed that ERT is effective as a treatment in both naïve and experienced patients. Miglustat did not significantly improve blood outcomes in naïve patients and resulted in a decrease in the platelet levels of experienced patients. Eliglustat was mainly assessed for experienced patients and resulted in stable outcome values. Relevance to Patient Care and Clinical Practice: This extensive SR confirms the effectiveness of GD treatments in short- and long-term follow-ups. Conclusions: The results were favorable for all ERTs and for eliglustat. Based on the assessed evidence, miglustat did not achieved expressive results. However, all evidence should be interpreted considering its limitations and does not replace well-conducted randomized trials.

Mucopolysaccharidoses and the blood–brain barrier

“…Although significant progress has been made on these approaches, clinically approved therapies for MPSs were currently limited to HSCT and ERTs (Table 1 ) [ 24 ]. However, two SRT agents are approved for treating type I Gaucher’s disease, another type of LSDs, while treating the CNS symptoms remains an issue [ 25 – 27 ].…”

A retrospective and prospective observational study of MRI changes in bone in patients with type 1 Gaucher disease treated with velaglucerase alfa: the EIROS study.

“…ERT is widely used as the rst-line treatment and two intravenously administered ERTs have received marketing authorization in the EU, imiglucerase (Cerezyme®) [5] and velaglucerase alfa (VPRIV®) [6]. Both substances have been shown to be safe and effective, leading to improvements in the hematologic and visceral manifestations of GD [7][8][9][10][11][12].…”

A Real-World Investigation of MRI Changes in Bone in Patients with Type 1 Gaucher Disease Treated with Velaglucerase Alfa: The EIROS Study

“…ERT is widely used as the first-line treatment and two intravenously administered ERTs have received marketing authorization in the EU, imiglucerase (Cerezyme ® ) [4] and velaglucerase alfa (VPRIV ® ) [5]. Both substances have been shown to be safe and effective, leading to improvements in the hematologic and visceral manifestations of GD [6][7][8][9][10][11]. Although ERT cannot reverse pre-existing permanent bone damage, data from clinical trials have indicated that long-term ERT is associated with a reduction in bone crises and bone pain, an improvement in bone mineral density, and a decrease in bone marrow infiltration based on bone marrow burden (BMB) scores [11][12][13][14][15][16].…”