In this video, Martha Sajatovic, MD, provides details of a study which found that the vesicular monoamine transporter 2 (VMAT2) inhibitor deutetrabenazine was effective as a treatment for tardive dyskinesia both in patients aged less than 55 years and in patients aged 55 years or older.
The study was presented in a poster at Psych Congress 2020. Dr. Sajatovic is Professor of Psychiatry and Neurology at Case Western Reserve University School of Medicine and holds the Willard Brown Chair in Neurological Outcomes at University Hospitals Cleveland Medical Center/Case Western Reserve University School of Medicine in Cleveland, Ohio.
Read the transcript:
This is the poster presentation titled “Long‑Term Safety and Efficacy of Deutetrabenazine in Younger and Older Patients With Tardive Dyskinesia.” or TD. I'm Dr. Martha Sajatovic of University Hospital's Cleveland Medical Center and Case Western Reserve University School of Medicine. I'm located in Cleveland, Ohio.
Just to provide a little background on this poster, tardive dyskinesia, or TD, is a potentially debilitating, involuntary movement disorder that results from exposure to dopamine receptor antagonists. We know that the risk for developing TD increases substantially with age.
In fact, studies have shown that TD incident rates are at least 3 to 5 times higher in elderly patients than in younger people. Deutetrabenazine is a novel vesicular monoamine transporter 2 inhibitor that is currently approved by the US FDA for the treatment of TD in adults.
The data that I'm going to be presenting here is derived from 2 pivotal, 12‑week studies, the ARM‑TD and the AIM‑TD studies, that showed treatment with deutetrabenazine provided significant improvements, as measured by a rating scale called the Abnormal Involuntary Movement Scale, or AIMS, as compared to a placebo.
The objective of this study is that it was a post‑hoc analysis that assessed the long‑term safety and efficacy of deutetrabenazine by age group. The two age groups of focus here are younger people, that was defined as less than 55 years of age, versus an older group that was defined as age 55 or older. It was an ongoing, 3‑year, single arm, open‑label extension study.
The sampling included people who completed either the ARM‑TD or AIM‑TD study. Drug dosing was dosed a little differently, as you can see here in the poster. Minor differences across study. Patients were directly enrolled in the open‑label extension study after completing a one‑week washout and a final evaluation in their parent study.
In this open‑label extension phase, patients had response‑driven dosing. They started at 12 milligrams per day of deutetrabenazine. It was titrated once per week until they achieved optimum tardive dyskinesia control, or a clinically significant maximum adverse event.
The efficacy outcomes were assessed in a variety of ways—change from baseline and AIMS score, identification of the percent of patients who had at least a 50 percent improvement in AIMS, the percent of patients who had treatment success based on 2 different rating scales, both the Patient and Clinical Global Impression Change scores, also known as the PGIC and CGIC, and change from baseline in the Modified Craniocervical Dystonia Questionnaire, the MCDQ‑24.
Safety was based on exposure‑adjusted incidence rates of adverse events. Because this was an exploratory post‑hoc analysis, the statistics were not controlled for multiplicity.
You can see our sample on the poster here, 377 patients. There were 119 in the younger group, 218 for the older group. Their baseline characteristics were very similar. Most people were receiving a dopamine receptor antagonist at baseline and had a comorbid psychotic disorder.
You can see here, in the treatment data, the mean duration of treatment and retention rates were similar between the older and younger groups, as was the drug dosing. At year 3, the mean daily dose was 39.4 milligrams per day for younger versus 39.5 for older patients.
If we look at response rate, the big picture is that patients in both groups experienced similar levels of clinical improvement based on changes in AIMS.
If we look at that 50 percent cut‑point of 50 percent change in AIMS score, the scores were numerically higher for the younger versus older groups at all time points.
The caveat here is this is a very small sample size, secondary nature of this analysis, limit our ability to conclude that is was a consistent trend that represents the larger universe of older versus younger people with TD.
The majority of patients had treatment success at years 1, 2, and 3, based on the CGIC. Importantly, the CGIC treatment success rates were similar to all time points for both younger and older patients.
We also see the MCDQ‑24 scores reflecting improvements in quality of life, for both younger and older people. With respect to tolerability, deutetrabenazine was generally well‑tolerated by both younger and older patients, really not a big difference in side effects.
Of note, however, there were 8 deaths among the older group, in contrast, compared to the younger group. However, no deaths were considered to be related to study medication. Those patients all had comorbid conditions at the time of study enrollment that are known to increase mortality risk.
In conclusion, overall, the results of this post‑hoc analysis show that the benefits of treatment with deutetrabenazine are similar in younger versus older patients with TD. Treatment was well‑tolerated in both the younger and older groups.
After 3 years, more than 60 percent of patients in both age groups had at least 50 percent improvement from their baseline AIMS score. Thank you.
Sajatovic M, Wilhelm A, Finkbeiner S. Long-term safety and efficacy of deutetrabenazine in younger and older patients with tardive dyskinesia. Poster presented at Psych Congress 2020; September 10-13, 2020; Virtual.