Importantly, these findings were consistently observed across different patient subgroups, and were not influenced by disease severity, time of therapy initiation, or individuals’ genetic backgrounds.
The study, “Gaucher disease type 1 patients from the ICGG Gaucher Registry sustain initial clinical improvements during twenty years of imiglucerase treatment,” was published in the journal Molecular Genetics and Metabolism.
GD1 is caused by genetic mutations that result in a deficiency of the enzyme beta-glucocerebrosidase, which is needed to breakdown a fatty substance called glucocerebroside. In the absence of a functional enzyme, glucocerebroside starts to buildup inside immune cells, which then infiltrate into different tissues and organs. This, in turn, can lead to the onset of typical GD1 manifestations, including liver and spleen enlargement, bone problems, and blood anomalies.
Developed by Sanofi Genzyme, Cerezyme is an enzyme replacement therapy (ERT) approved in the U.S. in 1994 to treat children and adults with GD1. As the name suggests, ERT works in this case by providing patients with a man-made version of the beta-glucocerebrosidase enzyme they are missing.
A previous version of this therapy called Ceredase (alglucerase), which is made up of human placental tissue, was approved three years earlier for the same indication. Cerezyme, its successor, followed soon after.
In 1991, when that first therapy was approved, the International Collaborative Gaucher Group (ICGG) Gaucher Registry (NCT00358943) was created to track the clinical outcomes of people with Gaucher — regardless of the type of treatment they were receiving.
Previous analyses of the ICGG Gaucher Registry — and notably, one that examined a decade’s worth of treatment — have shown that GD1 patients treated with Ceredase or Cerezyme started seeing their symptoms ease within the first two years of such therapy. Specifically, improvements in blood parameters, liver volume, and bone health were reported up to 10 years following the start of ERT.
Now, an international group of investigators has reported the clinical outcomes of GD1 patients who were part of the registry and had completed 20 years of treatment with Cerezyme, or Ceredase followed by Cerezyme.
A total of 475 GD1 patients who had complete sets of clinical data available around the time of therapy initiation (baseline), as well as 10 and 20 years after the start of treatment, were included in the analyses.
The investigators compared 10- and 20-year clinical data to baseline information in two groups of patients: those who had undergone spleen removal surgery, called a splenectomy, and those who had not.
More than half (65%) of the patients included in the analyses did not have surgery. In both groups of patients, nearly all clinical benefits observed after a decade of treatment were maintained or enhanced after 20 years.
Regarding blood parameters, both hemoglobin levels and platelet counts rose over time since the start of treatment. These parameters — a mean of 11.4 g/dL for hemoglobin and 91.6 × 109/L for platelets — both increased in patients who did not have surgery, reaching, after 20 years of treatment, a maximum mean of 13.8 g/dL for hemoglobin and 169.1 × 109/L for platelets. Significant increases in hemoglobin and platelets also were observed over the same period of time in those who had surgery.
Regarding bone health, the percentage of patients who had no bone crises increased from 85% at baseline to 98.2% after 10 years, in the group of those who did not have surgery. In that same group, the rate was 96.5% after 20 years of treatment.
In turn, in patients who had surgery, the percentage of those who had no bone crises steadily increased over time, reaching 100% after 20 years.
In the group who did not have a splenectomy, the proportion of patients who remained free of bone pain climbed from 52.5% at baseline to 72.0% after 10 years. That percentage dropped to 58.5% after 20 years, but this decrease was not statistically significant. Increases in the proportion of pain-free patients were seen in participants who had surgery, rising from from 16.3% at baseline to 30.6% at 10 years — a change deemed not significant — to 46.9% after 20 years of ERT.
Additional analyses also indicated that the improvements associated with ERT were consistent across several patient subgroups. Moreover, the improvements were not influenced by the patients’ disease severity, their individual genetic background, or their age at treatment initiation.
“In a long-term observational setting, improvements seen during early treatment years are sustained by continuing treatment for 20 years, except for bone pain in non-splenectomized patients,” the researchers wrote. “These results are consistent when analyzed by different patient subsets, including by disease severity.”
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