Director, Global Medical Epidemiology Pfizer, Inc. New York, United States
Background: Gaucher disease (GD) is a systemic metabolic disorder caused by the deficiency of the enzyme glucocerebrosidase, resulting in lysosomal accumulation of glucosylceramide and enlargement of the spleen and liver, anemia, thrombocytopenia, bone destruction, and lung involvement. Of the three variants, GD Type 1 (GD1) accounts for 95% of GD cases, with prevalence of 1 in 40,000 in the United States (US). There is limited data and unclear definition of sub-optimal responders to standard of care (SOC) treatments, Enzyme Replacement Therapy (ERT)/Substrate Replacement Therapy (SRT) in GD1 patients.
Objectives: To utilize a RWD source to identify and characterize sub-optimal responders to SOC treatments in a population of GD1 patients
Methods: GD1 patients were identified using Electronic Medical Records (EMR) data from the TriNetX Dataworks USA network, with over 90.8 million patients treated in outpatient and inpatient settings of 54 Health Care Organizations (HCOs). Patients were included if they had at least 1 inpatient or 2 outpatient ICD-10 codes for GD (at least 30 days apart) between October 2015 and August 2022, were 18 to 70 years of age at the time of GD diagnosis, and ≥ 6 months follow-up since the first GD diagnosis in the database. Patients were further classified into optimal and sub-optimal response cohorts if they had at least one ERT/SRT prescription and one year of continuous treatment (i.e., without a gap in treatment of greater than 5 months). Treatment response was defined using GD treatment guidelines (hemoglobin and platelet levels, presence or absence of hepatomegaly, splenomegaly). Descriptive statistics were used to summarize the findings.
Results: A total of 261 GD1 patients were identified and included in the analysis. Majority of patients were female (59%) and younger than 47 years, of which 113 patients were treated with ERT or SRT (43.3%). Over 70% were ever-treated with an ERT and 47% were ever-treated with an SRT. Among the treated cohort, 21/113 patients were treated continuously for ≥1 year (Optimal: 62.5%, Sub-optimal: 37.5%) and 13/113 patients were treated continuously for ≥2 years (Optimal: 54.5%, Sub-optimal: 45.5%). Similar findings in proportion of sub-optimal responders were observed in sensitivity analyses among patients with continuous follow-up and gaps in treatment. Sub-optimal responders with one-year continuous treatment were mostly male (66.7%), younger than 65 years, white (100%), and with top comorbidities of lipid metabolism (100%) and joint disorders (50%).
Conclusions: Based on application of the proposed definition of sub-optimal responders in a structured EMR dataset, the findings suggest that 38-46% of GD1 patients with up to two years of continuous treatment were sub-optimal responders to SOC treatments.
