Clinical Characterization and the Caregiver Burden of Dementia in China

AbstractObjectivesThe prevalence of dementia in China is among the highest in the world, but systematic estimates of the rate of dementia subtypes and characterization of associated deficits are lacking. The primary aim of this study was to determine the clinical presentation of dementia and describe the caregiver burden in mainland China.MethodsA 3-month, open-enrollment, multicenter, cross-sectional study was conducted at 48 tier-3 hospitals. Caregivers who qualified for study entry (provided amount and duration of care information), had intimate knowledge of patient status, and accompanied enrolled patients to study sites were asked to participate in an interview about patient care and caregiver burden. Caregiver burden was assessed via the Chinese version of the validated Zarit Burden Interview.ResultsA total of 1425 caregivers completed the survey. Patients had mild to moderate dementia (mean Clinical Dementia Rating score of 1.67±0.79), and the most common dementia subtypes were Alzheimer disease (46.7%) and vascular dementia (28.7%). Among caregivers, 57% were females, 52% were patients’ spouses, and 67.3% had been caring for patients for 1 year or more. Most patients required family help and lived at home or with a family member. Caregiver awareness of dementia was limited. The mean total caregiver Zarit Burden Interview score was 26.6. Observations were similar across age, gender, education, dementia type, Clinical Dementia Rating score, and duration of care.ConclusionsChina faces multiple obstacles in preparing to care for its fast-growing dementia population. Better understanding of patients and caregivers may mitigate these challenges by improving awareness and education

Safety and Efficacy of Long‐term Deutetrabenazine Use in Children and Adolescents With Tics Associated With Tourette Syndrome: An Open‐label Extension Study

Abstract Background Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and phonic tics. Objective To assess the safety and efficacy of deutetrabenazine, a vesicular monoamine transporter 2 inhibitor, in children and adolescents with TS. Methods ARTISTS OLE (NCT03567291) was a 54‐week, global, phase 3, open‐label extension study of deutetrabenazine (6‐48 mg daily) conducted 05/28/2018–04/03/2020 with a 2‐week randomized withdrawal period. Participants (6–16 years of age) had TS and active tics causing distress or impairment. Safety (primary outcome) was assessed by treatment‐emergent adverse events (TEAEs) and clinical laboratory testing. Efficacy was measured by the Yale Global Tic Severity Scale‐Total Tic Score (YGTSS‐TTS). Results The intent‐to‐treat population (228 participants; mean age 12.0 years; 79.8% male; 86.4% white) had a median (range) duration of exposure of 28.4 (0.3‐‍52.9) weeks. Of 227 participants in the safety analysis, 161 (70.9%) reported ≥1 TEAE (exposure‐adjusted incidence rate, 2.77/patient‐year), of which 95 (41.9%) were treatment related. The most frequently reported TEAEs were headaches, somnolence, nasopharyngitis, weight increases, and anxiety. No additional safety signals were observed. Worsening of YGTSS‐TTS after the 2‐week randomized withdrawal was not statistically significant (least squares mean difference, −0.4; P = 0.78). Several exploratory measures showed sustained improvement throughout the treatment periods. Conclusions In this long‐term, open‐label trial, deutetrabenazine was well tolerated with low frequency of TEAEs. There was no significant difference in tics between treatment arms during the 2‐week randomized withdrawal period, however, descriptive statistics and comparison with baseline showed a numeric improvement in tics, quality of life, and other measures. This article is protected by copyright. All rights reserved

Safety and Efficacy of Flexible-Dose Deutetrabenazine in Children and Adolescents With Tourette Syndrome: A Randomized Clinical Trial

Tourette syndrome is a neurodevelopmental disorder characterized by childhood onset of motor and phonic tics; treatments for tics are associated with safety concerns. Deutetrabenazine is a selective vesicular monoamine transporter 2 inhibitor approved for the treatment of chorea associated with Huntington disease and tardive dyskinesia in adults. To examine whether deutetrabenazine is effective and safe for the treatment of Tourette syndrome in children and adolescents. This phase 2/3, randomized, double-masked, placebo-controlled, parallel-group, dose-titration study included children and adolescents (aged 6-16 years) with Tourette syndrome with active tics causing distress or impairment (ie, Yale Global Tic Severity Scale-Total Tic Score [YGTSS-TTS] ≥20). The trial was conducted over 12 weeks, with 1 week of follow-up from February 2018 to November 2019 at 36 centers in the United States, Canada, Denmark, Russia, Serbia, and Spain. Data analysis was conducted from January 31 to April 22, 2020. Patients were randomized (1:1) to receive deutetrabenazine or placebo, titrated during 7 weeks to an optimal level, followed by a 5-week maintenance period. The maximum total daily deutetrabenazine dose was 48 mg/d. The primary efficacy end point was change from baseline to week 12 in YGTSS-TTS. Key secondary end points included changes in Tourette Syndrome-Clinical Global Impression, Tourette Syndrome-Patient Global Impression of Impact, and Child and Adolescent Gilles de la Tourette Syndrome-Quality of Life Activities of Daily Living subscale score. Safety was assessed based on treatment-emergent adverse events, vital signs, questionnaires, and laboratory parameters. A total of 119 participants were randomized to deutetrabenazine (59 participants; mean [SD] age, 11.5 [2.5] years; 53 [90%] boys; 49 [83%] White; 3 [5%] Black) and placebo (60 participants; mean [SD] age, 11.5 [2.6] years; 51 [85%] boys; 53 [88%] White; 3 [5%] Black). At week 12, the difference in YGTSS-TTS score was not significant between deutetrabenazine and placebo (least squares mean difference, -0.7; 95% CI, -4.1 to 2.8; P = .69; Cohen d, -0.07). There were no nominally significant differences between groups for key secondary end points. Treatment-emergent adverse events were reported for 38 patients (66%) and 33 patients (56%) receiving deutetrabenazine and placebo, respectively, and were generally mild or moderate. In this study of deutetrabenazine in children and adolescents with Tourette syndrome, the primary efficacy end point was not met. No new safety signals were identified. These results may be informative for future studies of treatments for tics in Tourette syndrome. ClinicalTrials.gov Identifier: NCT03452943

Efficacy and Safety of Fixed-Dose Deutetrabenazine in Children and Adolescents for Tics Associated With Tourette Syndrome: A Randomized Clinical Trial

Tourette syndrome is a neurodevelopmental disorder characterized by childhood onset of motor and phonic tics, often accompanied by behavioral and psychiatric comorbidities. Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor approved in the US for the treatment of chorea associated with Huntington disease and tardive dyskinesia. To report results of the ARTISTS 2 (Alternatives for Reducing Tics in Tourette Syndrome 2) study examining deutetrabenazine for treatment of Tourette syndrome. This phase 3, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study was conducted over 8 weeks with a 1-week follow-up (June 21, 2018, to December 9, 2019). Children and adolescents aged 6 to 16 years with a diagnosis of Tourette syndrome and active tics causing distress or impairment were enrolled in the study. Children were recruited from 52 sites in 10 countries. Data were analyzed from February 4 to April 22, 2020. Participants were randomized (1:1:1) to low-dose deutetrabenazine (up to 36 mg/d), high-dose deutetrabenazine (up to 48 mg/d), or a matching placebo, which were titrated over 4 weeks to the target dose followed by a 4-week maintenance period. The primary efficacy end point was change from baseline to week 8 in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) for high-dose deutetrabenazine. Key secondary end points included changes in YGTSS-TTS for low-dose deutetrabenazine, Tourette Syndrome Clinical Global Impression score, Tourette Syndrome Patient Global Impression of Impact score, and Child and Adolescent Gilles de la Tourette Syndrome-Quality of Life Activities of Daily Living subscale score. Safety assessments included incidence of treatment-emergent adverse events, laboratory parameters, vital signs, and questionnaires. The study included 158 children and adolescents (mean [SD] age, 11.7 [2.6] years). A total of 119 participants (75%) were boys; 7 (4%), Asian; 1 (1%), Black; 32 (20%), Hispanic; 4 (3%), Native American; 135 (85%), White; 2 (1%), multiracial; 9 (6%), other race; and 1 (0.6%), of unknown ethnic origin. Fifty-two participants were randomized to the high-dose deutetrabenazine group, 54 to the low-dose deutetrabenazine group, and 52 to the placebo group. Baseline characteristics for participants were similar between groups. Of the total 158 participants, 64 (41%) were aged 6 to 11 years, and 94 (59%) were aged 12 to 16 years at baseline. Mean time since Tourette syndrome diagnosis was 3.3 (2.8) years, and mean baseline YGTSS-TTS was 33.8 (6.6) points. At week 8, the difference in YGTSS-TTS was not significant between the high-dose deutetrabenazine and placebo groups (least-squares mean difference, -0.8 points; 95% CI, -3.9 to 2.3 points; P = .60; Cohen d, -0.11). There were no nominally significant differences between groups for key secondary end points. Treatment-emergent adverse events were reported for 34 participants (65%) treated with high-dose deutetrabenazine, 24 (44%) treated with low-dose deutetrabenazine, and 25 (49%) treated with placebo and were generally mild or moderate. In this fixed-dose randomized clinical trial of deutetrabenazine in children and adolescents with Tourette syndrome, the primary efficacy end point was not met. No new safety signals were identified. ClinicalTrials.gov Identifier: NCT03571256