Transformation in pretreatment manifestations of Gaucher disease type 1 during two decades of alglucerase/imiglucerase enzyme replacement therapy in the International Collaborative Gaucher Group (ICGG) Gaucher Registry

Abstract

This study tests the hypothesis that the prevalence of severe clinical manifestations in Gaucher disease type 1 (GD1) patients at the time of treatment initiation has changed since alglucerase/imiglucerase enzyme replacement therapy (ERT) was approved in the United States (US) in 1991. US alglucerase/imiglucerase‐treated GD1 patients from the International Collaborative Gaucher Group Gaucher Registry clinicaltrials.gov NCT00358943 were stratified by age at ERT initiation (<18, 18 to <50, ≥50 years), era of ERT initiation (1991‐1995, 1996‐2000, 2001‐2005, 2006‐2009), and splenectomy status pre‐ERT. Prevalence of splenectomy decreased dramatically across the eras among all age groups. Bone manifestations were more prevalent in splenectomized patients than non‐splenectomized patients in all age groups. Prevalence of bone manifestations differed across eras in certain age groups: non‐splenectomized patients had a lower prevalence of ischemic bone events (pediatric patients) and bone crisis (pediatric patients and adults 18 to <50 years) in later eras; splenectomized adult (18 to <50 years) patients had a lower prevalence of ischemic bone events and bone crisis in later eras. Over two decades after the introduction of ERT, the prevalence of splenectomy and associated skeletal complications has declined dramatically. Concomitantly, the interval between diagnosis and initiation of ERT has decreased, most strikingly in pediatric patients who have the most severe disease. Together, these findings suggest that since the introduction of alglucerase/imiglucerase ERT, optimal standard of care has become established in the US to prevent destructive complications of GD1.

Identification of risk features for complication in Gaucher’s disease patients: a machine learning analysis of the Spanish registry of Gaucher disease

“…Two observations, already accepted in Gaucher research, were also confirmed in this machine-learning study: first, the fact that spleen-removal patients have a higher risk of presenting more serious and extensive bone disease; second, our observation that almost all patients with new bone crisis – despite having received long-term ERT – had previous bone lesions, which remind us that the most feared complication in GD1 are not solved merely by starting ERT. These two facts confirm previous reports and provide validity of our analysis [ 42 , 45 – 47 ]. In addition, genotypes different from homozygous NM_000175.…”

Identification of risk features for complication in Gaucher’s Disease patients: A Machine Learning analysis of the Spanish Registry of Gaucher Disease.

“…Two observations, already accepted in Gaucher research, were also con rmed in this machine-learning study: rst, the fact that spleen-removal patients have a higher risk of presenting more serious and extensive bone disease; second, our observation that almost all patients with new bone crisis -despite having received long-term ERT -had previous bone lesions, which remind us that the most feared complication in GD1 are not solved merely by starting ERT. These two facts con rm previous reports and provide validity of our analysis (39,(42)(43)(44). In addition, genotypes different from homozygous NM_000175.4:c.1226A > G are signi cantly correlated with bone disease (p = 0.05).…”

Are Glucosylceramide-Related Sphingolipids Involved in the Increased Risk for Cancer in Gaucher Disease Patients? Review and Hypotheses

“…Life expectancy in type 1 GD can be normal. Specific treatment of GD is currently based on enzyme replacement therapy, which consists of intravenous infusions of recombinant human GCase every two weeks, or substrate reduction therapy through the oral administration of an inhibitor of GlcCer synthase [20][21][22].…”