Changing Patterns of Mortality in Gaucher Disease Prior to and Following the Advent of Enzyme Replacement Therapy.

Enzyme replacement therapy (ERT) with exogenous glucosylceramide β-glucosidase (alglucerase, [Ceredase®] or imiglucerase, [Cerezyme®]) has been shown to improve anemia, thrombocytopenia, hepatosplenomegaly, bone symptoms and quality of life in patients with Gaucher disease. However, the impact of ERT on mortality has not been assessed since the inception of ERT in 1991. Data from the epoch prior to the availability of ERT were obtained from the University of Pittsburgh Gaucher Disease Registry. Data from the time period following the advent of ERT were obtained from the International Collaborative Gaucher Group (ICGG) Gaucher Registry and the Ceredase/Cerezyme pharmacovigilance database (Genzyme Corporation). Age of death was obtained for patients with reported Type 1 (non-neuronopathic) Gaucher disease. Only patients with a known cause of death were included in this analysis. Pre-ERT Era (R.E.L.) Post-ERT Era Number of patients 31 137 Treated with ERT No Yes Mean age at death (years) 53.2 55.6 Range of age at death (years) 3–85 0.2–89 Cause of death due to: n % n % • Gaucher disease 4 12.9% 1 0.7% • Leukemia 3 9.7% 7 5.1% • Lymphoma 1 3.2% 3 2.2% • Myeloma 3 9.7% 1 0.7% • Solid tumor 12 38.7% 17 12.4% • Hemorrhage 1 3.2% 14 10.2% • Thromboembolism 0 0.0% 4 2.9% • Other cardiovascular disease 2 6.5% 26 19.0% • Infectious disease 3 9.7% 6 10.9% • Other causes 2 6.5% 49 35.8% These descriptive data collected prior to the advent of ERT and following approval of ERT in 1991 raise intriguing questions about the changing pattern of mortality in Gaucher disease. Any direct comparison of these populations must be qualified by the possibility of detection bias or a cohort effect. Therefore, pending further information, it is difficult to attribute significance to the difference in mean age at death between the two populations. However, there have been shifts in the pattern of the causes of death. Most notably, deaths due to the primary manifestations of Gaucher disease and to hematologic cancers and solid tumors appear substantially less common in the post-ERT era whereas the proportion of deaths due to cardiovascular disease and other causes appears to be increasing. More accurate estimates of the patterns of mortality in Gaucher disease remain to be determined, particularly for the pre-ERT era. Additional studies of the changing patterns of mortality in Gaucher disease are ongoing.