P1476: the clinical characteristics and overall survival of patients with pyruvate kinase deficiency in the uk: a real-world study

Topic: 28. Enzymopathies, membranopathies and other anemias Background: Pyruvate kinase (PK) deficiency is a rare genetic red blood cell enzyme disorder that leads to lifelong hemolytic anemia. It is associated with multiple complications, such as iron overload and gallstones and may lead to a lower life expectancy. Due to the rarity of PK deficiency and its common misdiagnosis, the understanding of its burden is limited. Aims: To evaluate the patient characteristics, burden of selected PK deficiency-related complications, and overall survival (OS) among patients with PK deficiency within primary and secondary care settings in the UK. Methods: A retrospective cohort study was conducted using data from the Clinical Practice Research Datalink (CPRD) linked to the Hospital Episode Statistics (HES) database. Patients were selected for inclusion if they had ≥1 instance of a PK deficiency diagnosis code in CPRD and were matched 1:5 with controls with no PK deficiency or congenital anemia based on birth year, sex, availability of records in the databases, registered general practitioner, and at least one medical record in the same year as the PK deficiency patient’s diagnosis. The total study period was from the earliest data availability from CPRD or HES, until 31st October 2020. Demographics and clinical characteristics (i.e., rates of iron overload, gallstones, or cholecystectomy during the study period) were summarized descriptively. OS gathered from mortality data (CPRD death dates and linked death registration data from the Office for National Statistics) was estimated using the Kaplan-Meier method and compared using the log-rank test. Results: 89 patients with PK deficiency met the inclusion criteria and were matched with 445 non-PK deficiency controls. For patients with PK deficiency and controls, respectively, mean [SD] age at index was 24.7 [21.4] and 24.5 [21.3] years, and 56% were male for both groups. Median [Q1-Q3] duration of follow-up from earliest medical record and first occurrence of a diagnosis code were 23.6 [21.3 - 23.6] years and 11.7 [6.5 - 17.5] years, respectively for patients with PK deficiency. For controls this was 23.4 [19.3 - 23.6] years from earliest medical record and 11.8 [6.8 - 17.3] years from the medical record dated in the same year as the matched PK deficiency patient’s diagnosis. From earliest medical record to end of follow-up, patients with PK deficiency had a numerically higher frequency of iron overload than matched controls (16% vs <1%). Within the same period, 26% of patients with PK deficiency had a record of gallstones and 21% had received a cholecystectomy, whilst this was 2.5% and 1.6% for matched controls, respectively. The OS rate (95% CI) at 15 years post-index for patients with PK deficiency was similar to matched controls (95% [89% - 100%] and 98% [96% - 99%], respectively), but was significantly lower at 30 years post-index (64% [44% - 95%] and 97% [94% - 99%]; p=0.001) (Figure 1). Summary/Conclusion: Findings from this study provide insight into the substantial real-world disease burden of PK deficiency in the UK. These patients had increased rates of complications such as iron overload and gallstones and had a higher 30-year mortality than matched controls. As this may consequently increase the need for disease management and healthcare resource use, clinicians should consider early intervention to help mitigate serious medical complications. Figure 1. Kaplan-Meier analysis of time from PK deficiency diagnosis record to death in patients with PK deficiency diagnosis vs time from medical record dated in the same year as the PK deficiency patient’s diagnosis in the matched non-PK deficiency comparison cohort.Keywords: Hemolytic anemia, Pyruvate kinase deficiency, Real world data, Clinical outcome