(AM) Natural History of Wilson's Disease in the United States Using Optum® Electronic Health Records

Publication Number: 1037

Background: Wilson disease (WD) is a rare inherited disorder of copper metabolism; clinical presentation can vary widely. Natural history studies to date are limited and are primarily from single tertiary care institutions; no recent study has been conducted in the US.

Objectives: To describe the prevalence, clinical characteristics, treatment patterns, and disease progression of WD patients in the US coupled with validation of WD definition.

Methods: This retrospective study used the US Optum® EHR database from 1/1/2007 to 09/30/2020. The study population included patients who had at least 1 ICD diagnostic code for WD (ICD–10=E83.01 or ICD–9 code=275.1), and at least 1 of the following: ≥1 inpatient visit or ≥2 outpatient visits with WD diagnoses ≥30 days apart, a reported treatment for WD, or an ICD/CPT code for cirrhosis or liver transplantation. The first occurrence of the WD diagnostic code in the study period represents the index date. This WD definition was validated through clinician review of a subset of the sample with available clinical notes, and the positive predictive value (PPV) was calculated. WD patients’ demographics, clinical characteristics, treatment, and progression to hepatic, neurologic, and psychiatric manifestations, and death were described and calculated.

Results: A total of 4,665 WD patients were identified, with a prevalence rate of 6.6 per 100,000 person-years (95% CI: 6.4 to 6.9).,. Among the WD case population 56% were female, 78% Caucasian, and 81% non-Hispanic. The median age was 50 years (IQR: 34 to 63), and median follow-up was 3.8 years (IQR: 1.7 to 6.1). During follow-up, 17% (n = 804) of patients with WD died and the median time from index date to death was 2.1 years (IQR: 0.9 to 4.1). During follow-up, hepatic manifestations were reported in 50% of WD patients (liver cirrhosis 23%, liver failure 14%, liver transplant 7%), neurologic symptoms in 41% (gait disturbance 24%, dysphasia 24%), and psychiatric manifestations in 55% (depression 41%, psychosis 10%). Approximately 18% of WD patients were recorded to have been on treatment for WD at some point during follow-up, with 8% on chelators and 13% on zinc. After clinical review and case definition validation of 210 patients, 130 were confirmed with WD (PPV = 62%), resulting in an adjusted prevalence rate of 4.1 per 100,000 person-years (95% CI: 4.0 to 4.3).

Conclusions: No evidence of treatment for WD was reported for the vast majority of WD patients even though average follow-up was nearly 4 years, while hepatic and psychiatric manifestations occurred in an overall majority of WD patients. Future natural history studies of WD are needed to further validate these results.