High clinical burden of classical homocystinuria in the United States: a retrospective analysis.

Background: Classical homocystinuria (HCU) is a rare genetic metabolic disorder resulting in elevated homocysteine and methionine levels. The clinical characteristics and associated complications of HCU are well documented. However, there is limited published research on the clinical burden of patients with HCU, especially stratified by total homocysteine (tHcy) levels. This study aimed to describe the overall clinical burden of patients with HCU in the United States and key clinical events by tHcy levels using administrative claims data.

Methods: This non-interventional retrospective cohort analysis from January 01, 2016, through September 30, 2021, used Optum's de-identified Market Clarity Data. Patients who had 1 or more International Classification of Diseases, Tenth Revision code for homocystinuria (E72.11) or the signs, disease, and symptoms term homocystinuria in the natural language processing dataset were included. To obtain a study population most likely to have HCU, stratifications by tHcy levels, clinical characteristics, and phenotypic expressions were applied to refine the cohort. Included patients were then stratified by highest tHcy level. Clinical burden was measured by category of HCU-related events. Descriptive statistics were reported.

Results: Six hundred thirty-three patients met the inclusion criteria, and 601 patients had a tHcy level: < 50 µM (n = 278), 50 to < 100 µM (n = 212), and ≥ 100 µM (n = 111). Among the 601 patients with a tHcy level, almost one-half (n = 297, 49.4%) had at least one thrombotic/thromboembolic, skeletal, ocular, or neurological event and 14.1% (n = 85) had multiple events. Thrombotic/thromboembolic events (n = 186, 30.9%) were the most common type of events, followed by skeletal (n = 100, 16.6%), ocular (n = 63, 10.5%), and neurological events (n = 50, 8.3%). During follow-up, 5.7% (n = 34) of the patients died. All events assessed were more prevalent in the 50 to < 100 µM group and ≥ 100 µM group compared with those in the < 50 µM group.

Conclusions: As has been believed, patients with tHcy ≥ 100 µM carried a substantial clinical burden, but the burden is also very high in those whose levels were ≥ 50 µM. Thrombotic/thromboembolic events were more common than skeletal, ocular, or neurological events. Meaningfully lowered tHcy levels may help to reduce significant clinical events.