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VANCOUVER— Research has revealed that deutetrabenazine (DTB) outperforms placebo for the treatment of tardive dyskinesia (TD), as it was safe, well tolerated, and improved quality of life.
In addition, patients were more likely to perceive treatment success with the drug compared with placebo.
The findings of the 3 studies, 2 of which examined results of the ARM-TD (ClinicalTrials.gov Identifier: NCT02195700) and AIM-TD (ClinicalTrials.gov Identifier: NCT02291861) trials and one of AIM-TD alone, were presented at the 2017 International Congress of Parkinson’s Disease and Movement Disorders.
The first analysis,1 which was an open-label, single-arm extension study, included patients who completed the ARM-TD and AIM-TD trials. The 304 enrolled patients were divided into 2 groups: those who received DTB (n=202) and those who received placebo (n=102). Overall, the study consisted of a 6-week titration period and a long-term maintenance phase of up to 104 weeks. All patients restarted/started DTB 12 mg/d and doses were titrated up to a maximum total daily dosage of 48 mg/d, according to dyskinesia control and tolerability.
By the cutoff date of June 30, 2016, patients demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores (-5.1 points) and Clinical Global Impression of Change (72% were “much improved” or “very much improved”).
The researchers reported comparable exposure-adjusted incidence rates (EAIRs) of adverse events (incidence/patient-years) between groups (DTB, 2.04 vs placebo, 1.74). Also similar between groups were the most common adverse events, according to EAIR, including anxiety, somnolence, depression, headache, diarrhea, and nasopharyngitis.
The results also indicated that between prior treatment groups, neuropsychiatric adverse event rates were low and comparable, and that more than 90% were mild to moderate in severity.
“DTB was generally safe and well tolerated for up to 54 weeks in patients with TD, with low rates of neuropsychiatric [adverse events],” the researchers concluded.
In a separate analysis of the ARM-TD and AIM-TD trials,2 the same group of researchers sought to determine patients’ impressions of treatment benefit with DTB. They enrolled 259 patients with an AIMS score ≥6, of whom 161 had a psychotic disorder.
Among patients with a disorder, 12-week results suggested that 41% in the DTB group compared with 32% in the placebo group were “much improved” or “very much improved” (P =.379).
In subgroup analysis of patients with a mood disorder (n = 97), 47% of those who received DTB vs 26% of those who received placebo were “much improved” or “very much improved” (P =.003). Further, patients with a mood disorder were nearly 3 times as likely to report treatment success with DTB than placebo (odds ratio, 2.8).
“These results corroborate clinicians’ perception of improvement in TD symptoms, as assessed by the Clinical Global Impression of Change, and add to the overall knowledge of DTB’s efficacy,” the researchers concluded.
A third study,3 also performed by the same group of researchers but in which only the AIM-TD trial was analyzed, included 298 patients with moderate to severe TD. Patients were randomly assigned 1:1:1:1 to receive 1 of 3 DTB dosages (12 mg/d, 24 mg/d, or 36 mg/d) or placebo.
At 12 weeks, the researchers reported a clinically meaningful least-squares mean treatment difference for those receiving DTB 36 mg/d (-4.4; P =.123) and 24 mg/d (-3.5; P =.242) when compared with placebo. No improvements were observed with 12 mg/d vs placebo.
Moreover, 4 of 5 modified Craniocervical Dystonia Questionnaire (mCDQ-24) subdomains assessed were improved with DTB 36 mg/d vs placebo at 12 weeks: activities of daily living (-11.8 vs -6.8); pain (-15.5 vs -6.1); social (-10.5 vs -3.6); and stigma (-13.3 vs -9.9).
Additionally, when compared with placebo, DTB 24 mg/d improved the pain (-15.2 vs -6.1) and stigma (-17.8 vs -9.9) subdomains.
No improvement in emotional well-being was reported in the study.
“These results suggest that [DTB] may be a valuable and effective treatment option to potentially decrease the burden of TD,” the researchers wrote, “while allowing patients to maintain uninterrupted treatment of their underlying psychiatric disorder.”
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- Anderson K, Stamler D, Davis M, et al. Long-term safety of deutetrabenazine for the treatment of tardive dyskinesia: results from an open-label, long-term study. Presented at: International Congress of Parkinson’s Disease and Movement Disorders. June 4-8, 2017; Vancouver, BC, Canada. Abstract 402.
- Fernandez H, Stamler D, Davis M, et al. Evaluation of patient-reported outcomes in tardive dyskinesia patients with underlying psychotic and mood disorders in the ARM-TD and AIM-TD trials. Presented at: International Congress of Parkinson’s Disease and Movement Disorders. June 4-8, 2017; Vancouver, BC, Canada. Abstract 407.
- Factor S, Anderson K, Stamler D, et al. Effect of deutetrabenazine on quality of life in patients with tardive dyskinesia in AIM-TD, a 12-week double-blind, placebo-controlled study. Presented at: International Congress of Parkinson’s Disease and Movement Disorders. June 4-8, 2017; Vancouver, BC, Canada. Abstract 403.