QUANTIFYING THE ECONOMIC BURDEN OF NEONATAL-ONSET ORNITHINETRANSCARBAMYLASEDEFICIENCY IN THE UNITED STATES
Author(s)
George B. Diaz, M.D., Ph.D.1, Bradley B. Dickerson, B.A.1, Eric B. Squinto, B.S.1, Sandra Milev, MSc2, Monique Martin, MBA, MSc, PharmD3;
1iECURE, Blue Bell, PA, USA, 2Red Nucleus, HEOR, Yardley, PA, USA, 3Red Nucleus, HEOR, London, United Kingdom
1iECURE, Blue Bell, PA, USA, 2Red Nucleus, HEOR, Yardley, PA, USA, 3Red Nucleus, HEOR, London, United Kingdom
OBJECTIVES: Ornithine transcarbamylase deficiency (OTCD) is a rare, X-linked urea cycle disorder. Neonatal-onset is the most severe phenotype, characterized by recurrent hyperammonemic crises and episodes, high mortality, and long-term neurocognitive impairment among survivors. Currently liver transplantation is the only curative option. This study aimed to estimate the economic burden of neonatal-onset OTCD from U.S. healthcare system and certain societal perspectives.
METHODS: A decision tree/Markov cohort model was developed to estimate the economic burden of neonatal-onset OTCD over a 10-year time horizon. The decision-tree component captured early disease pathways, including hyperammonemic crises (HACs) with and without coma, short-term survival, liver transplantation (LTx), graft outcomes, and development of intellectual disability. Survivors transitioned into a Markov model representing long-term health states stratified by transplant status and neurocognitive outcomes. Costs (2025 USD) included inpatient HAC management, LTx and post-transplant immunosuppression, chronic nitrogen scavenger therapy, intellectual disability-related care, caregiver burden, and end-of-life costs. Model inputs were informed by a targeted PubMed literature review (2005-2025), published data from the U.S. Urea Cycle Disorders Consortium registry, and clinical expert input.
RESULTS: Neonatal-onset OTCD is associated with substantial economic burden and high early mortality. At 10 years, the model projected that 57% of patients would be dead, 34% would be alive following liver transplantation, and 9% would be alive without transplantation. Mean per-patient total costs were estimated to reach $2.7 million at 10 years, of which $2.3 million were attributable to direct medical costs. Costs were initially driven by inpatient HAC management and liver transplantation, with longer-term costs increasingly attributable to chronic nitrogen scavenger therapy, intellectual disability-related care, and caregiving.
CONCLUSIONS: Neonatal-onset OTCD imposes a profound economic burden alongside excess early mortality, underscoring a critical unmet need for disease-modifying therapies that prevent hyperammonemic crises, reduce reliance on liver transplantation, and improve long-term survival and neurocognitive outcomes.
METHODS: A decision tree/Markov cohort model was developed to estimate the economic burden of neonatal-onset OTCD over a 10-year time horizon. The decision-tree component captured early disease pathways, including hyperammonemic crises (HACs) with and without coma, short-term survival, liver transplantation (LTx), graft outcomes, and development of intellectual disability. Survivors transitioned into a Markov model representing long-term health states stratified by transplant status and neurocognitive outcomes. Costs (2025 USD) included inpatient HAC management, LTx and post-transplant immunosuppression, chronic nitrogen scavenger therapy, intellectual disability-related care, caregiver burden, and end-of-life costs. Model inputs were informed by a targeted PubMed literature review (2005-2025), published data from the U.S. Urea Cycle Disorders Consortium registry, and clinical expert input.
RESULTS: Neonatal-onset OTCD is associated with substantial economic burden and high early mortality. At 10 years, the model projected that 57% of patients would be dead, 34% would be alive following liver transplantation, and 9% would be alive without transplantation. Mean per-patient total costs were estimated to reach $2.7 million at 10 years, of which $2.3 million were attributable to direct medical costs. Costs were initially driven by inpatient HAC management and liver transplantation, with longer-term costs increasingly attributable to chronic nitrogen scavenger therapy, intellectual disability-related care, and caregiving.
CONCLUSIONS: Neonatal-onset OTCD imposes a profound economic burden alongside excess early mortality, underscoring a critical unmet need for disease-modifying therapies that prevent hyperammonemic crises, reduce reliance on liver transplantation, and improve long-term survival and neurocognitive outcomes.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
PT14
Topic
Economic Evaluation
Topic Subcategory
Cost/Cost of Illness/Resource Use Studies
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity), SDC: Rare & Orphan Diseases