Longitudinal Treatment Patterns for Chorea in Patients with Huntington Disease: Data from Enroll-HD
Erin Furr-Stimming1, Daniel Claassen2, Ginny Sen3, Mallory Farrar3, Ericha Franey3, Chuck Yonan3, Dietrich Haubenberger3
1The University of Texas Health Science Center at Houston, 2Vanderbilt University Medical Center, 3Neurocrine Biosciences, Inc.
Objective:

To determine longitudinal treatment patterns for chorea in individuals with Huntington disease (HD) using Enroll-HD Periodic Dataset 5.0.

Background:

Enroll-HD is a worldwide, prospective, observational study of individuals with (or at-risk for) HD. Previous analyses of Enroll-HD data suggest that chorea may be undertreated despite the availability of FDA-approved medications such as the vesicular monoamine transporter 2 [VMAT2] inhibitors and off-label medications such as antipsychotics and benzodiazepines.

Design/Methods:
Data were collected from Jun-2012 to Oct-2020 for North American patients (≥18 years) with Unified Huntington’s Disease Rating Scale (UHDRS) Diagnostic Confidence Level 4 at each study visit. Presence of chorea was defined as UHDRS Total Maximal Chorea ≥2. Medications intended for chorea (as indicated in the Enroll-HD Database) were categorized as follows: VMAT2 alone, antipsychotics alone, medications other than VMAT2 inhibitors or antipsychotics (Other), and 2+ different medications from previous 3 categories (Combination). 
Results:
Chorea was documented in 96.8% (2507/2590) of eligible patients and 96.5% (6678/6920) of visits. Medications for chorea were prescribed to 36.1% (906/2507) of patients with chorea, with first-line treatments as follows: VMAT2 inhibitors (49.9%), antipsychotics (27.5%), other medications (18.7%), and combination treatments (4.0%). Average treatment duration ranged from 28.8 (VMAT2) to 41.2 (antipsychotics) months. Of the 906 treated patients, 688 (75.9%) continued their first-line medication; 147 (16.2%) changed treatment, often to a combination therapy (e.g., VMAT2 inhibitor plus antipsychotic, with/without other medication [n=43]); and 71 (7.8%) discontinued treatment for >90 days (mean 1-2 years). 29.4% (64/218) of patients switched/discontinued their second-line therapy.
Conclusions:

In this analysis of a natural history database, 36.1% of patients with chorea received medication intended for chorea. Patients generally continued their first-line treatment, but those who switched often received a combination therapy. Continued research is needed to better understand optimal treatment patterns for chorea in patients with HD.