BACKGROUND: Clinical trials for disease modifying therapies (DMT) such as gene therapy to treat Huntington’s disease (HD) are ongoing. However, no long-term disease model has yet been developed for future DMT health economic evaluations.

OBJECTIVES: To quantify the costs and health impacts of HD natural history using an exploratory disease model.

METHODS: We developed a Markov model incorporating the five HD health states defined by Shoulson & Fahn (SF), who categorised functional decline using HD total functional score (TFC). We then estimated long-term disease progression in a 40-year-old pre-functional decline (TFC 13; UHDRS DCL<4) population and two 40-year-old motor-manifest populations: SF1 (TFC 13-11, UHDRS DCL=4) and SF2 (TFC 10-7, UHDRS DCL=4). We utilized linear extrapolations to predict long-term HD progression through the SF health states based on the TRACK-HD study population and trends observed in the ENROLL-HD study population. Longitudinal data from TRACK-HD and the ENROLL-HD database were used alongside HD burden of illness data to derive costs and quality-adjusted life-years (QALYs). For pre-functional decline patients, the prognostic index (PIN) was used to predict time to motor manifestation. Model uncertainty was assessed using deterministic and probabilistic sensitivity analyses.

RESULTS: We estimated QALYs for pre-functional decline, SF1, and SF2 patient populations of 11.77 (95% UI: 10.14-14.32), 8.29 (95% UI: 6.52 –11.31), and 5.79 (95% UI: 3.95-9.83), respectively. Pre-functional decline patients’ lifetime costs were $683,500 (UI: $250,200 - $1.1 million). SF1 patients’ estimated lifetime costs amounted to $875,000 (UI: $314,400-$1.5 million) whereas SF2 lifetime costs were $935, 277 (UI: $277,100 - $1.8M). The results were most sensitive to the linear extrapolation of HD natural history.

CONCLUSIONS: Our model attempts to demonstrate the long-term health economic outcomes of people with HD. Pending the availability of DMT clinical trial evidence, our novel model framework can be adapted for long term health economic assessments.