Real-World Effectiveness and Safety of Deutetrabenazine in Combination with Antipsychotic Drugs in Patients With Chorea Associated With Huntington Disease
Daniel Claassen1, Hela Romdhani2, Rajeev Ayyagari2, Debbie Goldschmidt2, Sarah Moroz3, Adreanna Hernandez1, Nayla Chaijale4, Sam Leo5
1Vanderbilt University Medical Center, 2Analysis Group, Inc., 3East Tennessee State University, 4Teva Branded Pharmaceutical Products R&D, Inc., Global Medical Affairs, 5Teva Branded Pharmaceutical Products R&D, Inc., Global Health Economics and Outcomes Research
Objective:

To describe the effectiveness and safety of vesicular monoamine transporter 2 inhibitor deutetrabenazine (DTBZ) combined with antipsychotic agents (APs) in patients with Huntington disease (HD)-related chorea in a real-world setting.

Background:
DTBZ effectiveness and safety for HD-related chorea have been well documented in clinical trials; however, patients receiving APs were not included. Safety and effectiveness data for DTBZ+AP are needed to inform real-world practice. 
Design/Methods:

Data were collected from charts of patients with HD-associated chorea who received DTBZ+AP at Vanderbilt University Medical Center from April 3, 2017, until data collection (May-November 2021). Effectiveness was assessed by Total Maximal Chorea (TMC) scores over time. Safety was assessed via adverse drug reactions (ADRs) based on a predefined list of known DTBZ ADRs.

Results:

Among 57 patients treated with DTBZ+AP, 13 started APs first and had TMC scores available within 1 month before and any time after DTBZ addition, and 8 had TMC scores available within 1 month before AP initiation. After initiating APs and before adding DTBZ, TMC scores improved for 2/8 (25%) patients and worsened for 6 (75%). After adding DTBZ, TMC scores further improved for 8/13 (62%) patients, did not change for 1 (8%), and worsened for 4 (31%). In patients with history of tetrabenazine use, TMC scores improved after adding DTBZ for 4/8 (50%), versus 4/5 (80%) patients without history. Among all 57 patients treated with DTBZ+AP, 25 (44%) patients had ≥1 new/continuing ADR, with agitation, akathisia (both n=7; 12%), and somnolence (n=4; 7%) being most frequent; 2 (4%) patients discontinued DTBZ because of ADRs/tolerability issues while receiving combination treatment.

Conclusions:
In this retrospective chart review, adding DTBZ to APs improved motor signs and had a favorable benefit-risk profile. However, prospective, controlled trials investigating the efficacy and safety of DTBZ+AP in patients with HD-related chorea are needed. 
10.1212/WNL.0000000000201971