Tetrabenazine and olanzapine in management of Huntington disease: comparative retrospective analysis of data from the worldwide observational study Enroll-HD (P2.008)

Objective: (1) To assess whether data collected during Enroll-HD visits are sufficient to study effects of tetrabenazine and olanzapine in Huntington disease (HD) and (2) to evaluate influence of these medicines on UHDRS motor scores and PBAs depression score. Background: To date, only tetrabenazine is approved for treatment of chorea in HD. However, despite of lack of evidence, a variety of other medicines, including neuroleptics, are used off-label for the same indication. Olanzapine is one of the often prescribed neuroleptics in HD. To our knowledge, no comparisons of any kind of tetrabenazine and olanzapine have been done so far — only one comparative clinical trial NEUROHD (NCT00632645) is still ongoing without any published data. Design/Methods: Of 2295 HD manifest subjects from the Enroll-HD R2 database only 17 patients on tetrabenazine and 24 on olanzapine fulfilled the criteria to be off antichoreatic medication (AM) at the first assessment (FA) and on AM at the second assessment (SA) about 1 year later. We analyzed delta for maximal chorea (dMC), maximal dystonia (dMD), and total motor (dTMS) UHDRS scores along with PBAs depression score (dDS) between SA and FA. Results: Mean size of CAG-expansion in HTT gene was 43.9 in both tetrabenazine and olanzapine groups. Mean treatment period for tetrabenazine was 221.9 d and for olanzapine — 226.8 d. For tetrabenazine: dTMS=6.4±11.0; dMC=0.9±3.7; dMD=0.5±2.7; dDS=1.9±6.4. For olanzapine: dTMS=0.87±8.2; dMC=−1.4±3.7; dMD=−0.2±2.9; dDS=−2.0±7.1. Conclusions: Our exploratory analysis demonstrates that (1) olanzapine and tetrabenazine need comprehensive head-to-head clinical comparison in regards to HD treatment; (2) there are well-known limitations of retrospective studies, including possible confounders which might impact final results of analysis. Study Supported by: Enroll-HD is a longitudinal observational study for Huntington’s disease families intended to accelerate progress towards therapeutics; it is sponsored by CHDI Foundation, a nonprofit biomedical research organization exclusively dedicated to developing therapeutics for HD. Enroll-HD would not be possible without the vital contribution of the Enroll-HD investigators, research participants and their families. Disclosure: Dr. Seliverstov has received personal compensation for activities with Teva Pharmaceuticals. Dr. Borzov has nothing to disclose. Dr. Niyazov has nothing to disclose. Dr. Belyaev has nothing to disclose. Dr. Illarioshkin has nothing to disclose.