Potential trade-offs in treatment of premanifest Huntington's disease.

The potential long-term consequences of treatments delaying manifestations of neurodegenerative diseases have not been explored. Using Huntington disease (HD) data and Markov chain Monte Carlo methods, we simulated the effects of therapies with equivalent effects on time to onset of HD and survival with HD. Our results suggest substantial potential trade-offs in effects of these therapies; significant delays in time to onset of HD were accompanied by significant prolongations of survival after onset of HD. Under a variety of assumptions, treatments delaying onset of HD result in some patients likely to have a greater increase in survival with manifest HD compared to delays in time to onset of HD. Our results suggest that future work in HD should be sensitive to the potential existence of such trade-offs and that understanding the preferences of HD patients and the broader HD community will be increasingly important. Future research, trial design, and treatment strategies in HD and other mid-life-onset neurodegenerative disorders should consider the possibility of trade-offs in long-term consequences of disease-modifying treatments.