Chorea in Huntington’s often goes without symptom-specific therapy
Among N. American patients in Enroll-HD, 36% given appropriate treatment
While the vast majority of Huntington’s disease patients in North America have the uncontrolled and jerky movements known as chorea at clinically relevant levels, about a third of these people are getting medications specifically for this motor symptom.
Among treated patients, about half are prescribed VMAT2 inhibitors, the only therapy class approved for Huntington’s chorea, while others are receiving off-label treatments or combination therapy.
Study findings drew on data covering people in the United States and Canada taking part in Enroll-HD (NCT01574053), the world’s largest observational study on Huntington’s.
“Our … analysis … revealed that only about one-third (or fewer than half) of patients actually received medication for their chorea,” Erin Furr Stimming, MD, the study’s first author, and a professor of neurology at the University of Texas Health Science Center at Houston, said in an emailed statement to Huntington’s Disease News. “We believe multiple factors contribute to this trend and are eager to further investigate the reasons behind these findings.”
Furr Stimming also served as the Huntington Study Group’s global principal investigator for the Phase 3 KINECT-HD (NCT04102579) trial that supported the approval of Ingrezza (valbenazine) to treat Huntington’s-related chorea.
Chorea seen as ‘significant’ disease symptom affecting life quality
The study, “Longitudinal Treatment Patterns of Chorea in North American Patients with Huntington’s Disease: Data from Enroll-HD,” was published in Neurology and Therapy. It was funded by Neurocrine Biosciences, which markets Ingrezza, and six of the study’s eight authors are employed by the company.
Huntington’s is a neurodegenerative condition marked by a range of motor, cognitive, and psychiatric disease symptoms. Its hallmark symptom is chorea, characterized by abrupt and involuntary movements.
“Chorea, while just one of many symptoms faced by individuals with Huntington’s disease, is a significant motor symptom that can negatively impact quality of life and functional independence,” Furr Stimming said.
Approved therapies for Huntington’s associated chorea — Xenazine (tetrabenazine), Austedo (deutetrabenazine), and Ingrezza in the U.S. — all work to suppress, or inhibit, VMAT2, a protein involved in communication between nerve cells in the brain.
While their mechanism isn’t fully understood, VMAT2 inhibitors are thought to help normalize the release of certain brain signaling molecules during nerve cell communication, lessening chorea.
Other medications, including certain antipsychotics, are sometimes used off label to manage chorea in Huntington’s patients, even though “the evidence base supporting their use is lacking,” the researchers wrote.
“Evidence-based and expert opinion guidelines agree that the time to initiate treatment [for chorea] is when the quality of life is impaired,” they wrote. However, Huntington’s patients are not always completely aware of their symptoms, which can make it difficult to identify the need for intervention.
96.8% of study’s 2,590 adults had chorea, 36% given symptom-specific treatment
A previous analysis of Enroll-HD data conducted by Furr Stimming and other scientists, covering data from June 2012 to October 2018, indicated that less than 30% of Huntington’s patients received chorea medications.
Furr Stimming and colleagues now retrospectively reviewed data from Enroll-HD participants in North America, spanning from June 2012 to October 2020, to further explore treatment patterns among Huntington’s patients with chorea. During this time, Austedo and Xenazine were the two approved treatments for this patient group.
Among the 2,590 adults with motor manifestations of Huntington’s who were included in the analysis, 96.8% presented with clinically significant chorea at one or more clinic visits during the study period.
As observed in previous analyses, greater chorea severity scores associated with worse overall functional capacity.
Ultimately, just over one-third of all those with chorea (36.1%) were found to be prescribed a medication specifically meant to treat this symptom.
“This observation highlights the diversity in treatment strategies for individuals with HD [Huntington’s disease] chorea and underscores the need for investigating clinical features that might cause clinicians to consider treatment,” the researchers wrote.
The most commonly prescribed first-line chorea treatment was a VMAT2 inhibitor (49.9%), followed by antipsychotics (27.7%), or other medications (18.5%). A minority of patients (3.9%) received a combination of treatments, most commonly a VMAT2 inhibitor plus an antipsychotic (40%).
About three-quarters of patients (76%) remained on their first prescribed line of therapy, while others discontinued first-line therapy (7.8%) or progressed to second-line treatment (16.1%). Second-line treatment most often involved adding another medication to the first-line agent.
Most patients on VMAT2 inhibitors, antipsychotics stayed with them
Also, 92% of the patients receiving VMAT2 inhibitors as first-line treatment — either alone or as part of combination therapy — remained on them across the entire study without gaps or discontinuation. Likewise, 84% of those given antipsychotics as first-line treatment continued to receive these medications through the study.
The researchers noted that data are still limited on the use of combination regimens for treating Huntington’s chorea, which warrants further study. The choice to use off-label treatments instead of VMAT2 inhibitors also needs to be explored.
In addition, “future investigations should focus on understanding why participants with clinically meaningful chorea are not being treated,” the team wrote, noting that focus should be placed on identifying obstacles to recognizing when chorea has become troublesome and healthcare disparities that may influence treatment access.
“Our goal is to identify any modifiable factors that could help us improve prescribing practices,” Furr Stimming said.
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