Contributions
Abstract: PB1463
Type: Publication Only
Session title: Bleeding disorders (congenital and acquired)
Background
Acid sphingomyelinase deficiency (ASMD, historically known as Neimann Pick disease types A and B) is a rare metabolic disease characterized by the accumulation of sphingomyelin in cells and tissues. ASMD is divided into subtypes A, A/B and B. Type B (also known as chronic visceral ASMD) is characterized by onset in childhood or adulthood, hepatosplenomegaly, interstitial lung disease, liver dysfunction, thrombocytopenia, and bone disease, whereas type A has onset in infancy, prominent CNS involvement, and death before age 3. ASMD is sometimes confused with Nieman Pick disease type C (NPC), which shares some clinical features but is separate and biochemically distinct. The most common causes of morbidity and mortality in ASMD type B are respiratory and liver failure. Hematologists are often instrumental in the recognition of this underdiagnosed and often life-threatening disease.
Aims
To describe overall survival (OS) in ASMD type B patients in a real-world setting using data from electronic health records (EHRs).
Methods
Patients with ≥ 2 records of of ICD-10 diagnosis codes for ASMD (E75.241 [Type B],E75.248 [Other], or E75.249 [Unknown]) were identified in Optum’s deidentified Market Clarity database between January 1, 2007 and December 31, 2019. Patients were excluded if there was any record of an ICD-10 code for NPC or ASMD type A; any evidence of neurological symptoms prior to age 40 years (typical of NPC & ASMD type A/B), or death prior to age 3 (typical of ASMD type A). Additional cohorts with varying inclusion/exclusion criteria were used for sensitivity analyses. The first ASMD diagnosis was the index date. Follow-up period was from the index date until death, end of patient record, or December 31st, 2019. OS was estimated by Kaplan-Meier time to event analyses and a standardized mortality ratio (SMR) - the ratio of the observed number of deaths in the study population divided by the number of expected deaths based on the age- and-sex-specific mortality in a general population.
Results
We identified 46 patients who met the study criteria. Median age was 35 years, 65.2% were female, and median follow-up was 2.3 years. During follow-up, the most common disease manifestations were respiratory disease (60.9%), headache (50%), cardiovascular events (28.3%) and cirrhosis (23.9%). Six patients died during follow-up. The SMR was 17.69 (95% CI: 3.54, 31.84) when compared to a 2007 general population in the database. When compared to a 2017 general population, which more closely approximates the average follow-up time of the ASMD cohort, the SMR was 57.35 (95% CI: 1.15, 113.55). These data suggest that although survival varied widely, ASMD type B patients are substantially more likely to die compared to the general population.
Conclusion
This study extends our knowledge of survival in ASMD type B patients. Although limited by the small sample size and the lack of a validated algorithm for identifying ASMD type B in an EHR database, results were consistent with known characteristics of the disease. SMRs could be considered as an alternative approach for OS in rare diseases, when sample sizes are small, and the amount of censoring is large. Our data suggest a high risk of premature death in ASMD type B. Additional studies are needed to confirm these findings and investigate factors associated with mortality in this population and explore methods for addressing limitations in time-to-event statistics in rare diseases.
Keyword(s): Hemorrhage, Liver disease, Spleen, Survival
Abstract: PB1463
Type: Publication Only
Session title: Bleeding disorders (congenital and acquired)
Background
Acid sphingomyelinase deficiency (ASMD, historically known as Neimann Pick disease types A and B) is a rare metabolic disease characterized by the accumulation of sphingomyelin in cells and tissues. ASMD is divided into subtypes A, A/B and B. Type B (also known as chronic visceral ASMD) is characterized by onset in childhood or adulthood, hepatosplenomegaly, interstitial lung disease, liver dysfunction, thrombocytopenia, and bone disease, whereas type A has onset in infancy, prominent CNS involvement, and death before age 3. ASMD is sometimes confused with Nieman Pick disease type C (NPC), which shares some clinical features but is separate and biochemically distinct. The most common causes of morbidity and mortality in ASMD type B are respiratory and liver failure. Hematologists are often instrumental in the recognition of this underdiagnosed and often life-threatening disease.
Aims
To describe overall survival (OS) in ASMD type B patients in a real-world setting using data from electronic health records (EHRs).
Methods
Patients with ≥ 2 records of of ICD-10 diagnosis codes for ASMD (E75.241 [Type B],E75.248 [Other], or E75.249 [Unknown]) were identified in Optum’s deidentified Market Clarity database between January 1, 2007 and December 31, 2019. Patients were excluded if there was any record of an ICD-10 code for NPC or ASMD type A; any evidence of neurological symptoms prior to age 40 years (typical of NPC & ASMD type A/B), or death prior to age 3 (typical of ASMD type A). Additional cohorts with varying inclusion/exclusion criteria were used for sensitivity analyses. The first ASMD diagnosis was the index date. Follow-up period was from the index date until death, end of patient record, or December 31st, 2019. OS was estimated by Kaplan-Meier time to event analyses and a standardized mortality ratio (SMR) - the ratio of the observed number of deaths in the study population divided by the number of expected deaths based on the age- and-sex-specific mortality in a general population.
Results
We identified 46 patients who met the study criteria. Median age was 35 years, 65.2% were female, and median follow-up was 2.3 years. During follow-up, the most common disease manifestations were respiratory disease (60.9%), headache (50%), cardiovascular events (28.3%) and cirrhosis (23.9%). Six patients died during follow-up. The SMR was 17.69 (95% CI: 3.54, 31.84) when compared to a 2007 general population in the database. When compared to a 2017 general population, which more closely approximates the average follow-up time of the ASMD cohort, the SMR was 57.35 (95% CI: 1.15, 113.55). These data suggest that although survival varied widely, ASMD type B patients are substantially more likely to die compared to the general population.
Conclusion
This study extends our knowledge of survival in ASMD type B patients. Although limited by the small sample size and the lack of a validated algorithm for identifying ASMD type B in an EHR database, results were consistent with known characteristics of the disease. SMRs could be considered as an alternative approach for OS in rare diseases, when sample sizes are small, and the amount of censoring is large. Our data suggest a high risk of premature death in ASMD type B. Additional studies are needed to confirm these findings and investigate factors associated with mortality in this population and explore methods for addressing limitations in time-to-event statistics in rare diseases.
Keyword(s): Hemorrhage, Liver disease, Spleen, Survival