149 Deutetrabenazine for the Treatment of Tardive Dyskinesia: Results From an Open-Label, Long-Term Study

Abstract

IntroductionTardive dyskinesia (TD) is an involuntary movement disorder resulting from exposure to dopamine-receptor antagonists. In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo, and was generally well tolerated.ObjectiveTo evaluate the efficacy and safety of long-term deutetrabenazine therapy in patients with TD.MethodsPatients with TD who completed the ARM-TD or AIM-TD studies were eligible to enter this open-label, single-arm, long-term safety study after they completed the 1-week washout period and final evaluation in the blinded portion of the trial. Efficacy endpoints included the change in AIMS score from baseline, and treatment success (defined as “much improved” or “very much improved”) on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC). This analysis reports results up to Week 54.Results304 patients enrolled in the extension study. At Week 54, the mean (standard error) change in AIMS score was –5.1 (0.52). After 6 weeks of deutetrabenazine treatment, the proportion of patients who achieved treatment success was 58% per the CGIC and 53% per the PGIC, and by Week 54 was 72% per the CGIC and 59% per the PGIC, thus demonstrating maintenance or enhancement of benefit over time. Deutetrabenazine was well tolerated for up to 54 weeks, and compared with the ARM-TD and AIM-TD studies, no new safety signals were detected.Conclusions54 weeks of deutetrabenazine treatment was generally efficacious, safe, and well tolerated in patients with TD.Presented at: The American Psychiatric Association 2017 Annual Meeting; May 20–24, 2017; San Diego, California, USA.Funding AcknowledgementsThis study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.

Treatment of tardive dyskinesia with VMAT-2 inhibitors: a systematic review and meta-analysis of randomized controlled trials

“… 56 In the AIM-TD trial, suicidality was reported in the 24 and 36 mg/day arms (2.7% the highest), 57 but without any difference from placebo. Also, in the long-term, OLE study, deutetrabenazine showed 42 , 58 , 59 similar adjusted incidences of AEs, compared with both the acute-phase trials and the placebo. Moreover, >90% of psychiatric AEs were mild to moderate.…”

“…Conversely, in the ITT population, deutetrabenazine did not differ significantly from placebo regarding the Patient Global Impression of Change (PGIC) defined responder rate (12 mg/day: p =0.37, 24 mg/day: p =0.13, 36 mg/day: p =0.30) or mCDQ-24 scores (12 mg/day: p =0.66, 24 mg/day: p =0.24, 36 mg/day: p =0.12). 57 In the OLE study 58 , 59 (59 weeks, ongoing, n=304 from the ARM-TD and AIM-TD studies), all efficacy measures (continuous scores or responder rates) continued to improve from week 6 to week 54. No head to head comparison with other VMAT-2 inhibitors has been performed.…”

Deutetrabenazine for tardive dyskinesia: A systematic review of the efficacy and safety profile for this newly approved novel medication-What is the number needed to treat, number needed to harm and likelihood to be helped or harmed?

“…EMBASE provided a total of 115 records and upon elimination of duplicates, additional relevant abstracts regarding deutetrabenazine for the treatment of TD from congress presentations were identified . The corresponding posters from congress presentations were made available by the manufacturer, together with additional posters not routinely abstracted in EMBASE such as from presentations at the annual meetings of the American Psychiatric Association and the US Psychiatric and Mental Health Congress . An additional document from a corporate presentation by Auspex Pharmaceuticals was also accessed .…”

“…Additional efficacy data have been presented from an open‐label long‐term study . Patients who completed the 12‐week short‐term studies were included.…”

“…[17][18][19][20][21][22][23][24][25][26][27][28][29] The corresponding posters from congress presentations were made available by the manufacturer, together with additional posters not routinely abstracted in EMBASE such as from presentations at the annual meetings of the American Psychiatric Association and the US Psychiatric and Mental Health Congress. [30][31][32] An additional document from a corporate presentation by Auspex Pharmaceuticals was also accessed. 33 The FDA Drug Approval Package for deutetrabenazine for the treatment of chorea associated with Huntington's disease was another source of information, particularly regarding pharmacokinetic and pharmacodynamic data.…”