Predictors of persistence and adherence to deutetrabenazine among patients with Huntington disease or tardive dyskinesia.

Introduction: Deutetrabenazine is approved for treatment of Huntington disease (HD)-related chorea and tardive dyskinesia (TD) in adults. Factors associated with deutetrabenazine persistence and adherence are not well understood. Methods: Claims data from the Symphony Health Solutions Integrated Dataverse (2017-2019) were analyzed to identify real-world predictors of deutetrabenazine persistence and adherence in adults with HD or TD in the United States. Predictive models for persistence and adherence that considered patient demographics, payer type, comorbidities, treatment history, and health care resource use were developed. Results: In HD, use of anticonvulsants (HR = 2.00 [95% CI = 1.03, 3.85]; P < .05), lipid-lowering agents (2.22 [1.03, 4.76]; P < .05), and Medicaid versus Medicare insurance (2.27 [1.03, 5.00]; P < .05) predicted persistence, whereas only comorbid anxiety disorders predicted discontinuation (0.46 [0.23, 0.93]; P < .05). Of these patients, 62.5% were adherent at 6 months. Use of ≤2 treatments for chronic diseases (OR = 0.18 [95% CI = 0.04, 0.81]; P < .05) and Medicaid versus Medicare insurance (0.27 [0.09, 0.75]; P < .05) was associated with lower odds of adherence. In TD, use of lipid-lowering agents (HR = 4.76 [95% CI = 1.02, 20.00]; P < .05) predicted persistence, while comorbid schizoaffective disorder and/or schizophrenia (0.16 [0.14, 0.69]; P < .05) and sleep-wake disorders (0.18 [0.04, 0.82]; P < .05) predicted discontinuation. Of these patients, 46.7% were adherent at 6 months. Comorbid schizoaffective disorder and/or schizophrenia was associated with lower odds of adherence (OR = 0.26 [0.07, 0.91]; P < .05). Discussion: Identifying factors predictive of discontinuation and/or nonadherence to deutetrabenazine may facilitate the development of personalized support programs that seek to improve outcomes in patients with HD or TD.

Impact of tardive dyskinesia on patients and caregivers: a survey of caregivers in the United States.

BACKGROUND: Tardive dyskinesia (TD) has a multidimensional impact on patients with TD and, as importantly, their caregivers. An online survey was developed and administered to assess patient and caregiver burden of TD. Survey participants were unpaid caregivers for patients with diagnoses of TD and schizophrenia, bipolar disorder, and/or major depressive disorder. Overall, 162 caregivers rated the 7-day impact of TD on the physical, psychological, and social functioning of patients and the impact of TD on these domains in their own lives and in their professional lives. RESULTS: Across physical, psychological, and social domains, most caregivers (82.7%) reported that TD had severe impact on the cared-for patients, and 23.5% reported severe impact of TD in their own lives. Caregivers experienced 46.4% activity impairment, and caregivers who were employed (n = 136) experienced 49.5% overall work impairment because of TD-related caregiving. CONCLUSIONS: These results suggest that TD imposes substantial burden for both caregivers and patients.

Impact of Tardive Dyskinesia on Physical, Psychological, Social, and Professional Domains of Patient Lives: A Survey of Patients in the United States.

Objective: To assess the physical, psychological, social, and professional impact of tardive dyskinesia (TD) on patients in the United States.Methods: An online survey (April 2020-June 2021) to assess patient burden of TD was developed using targeted literature review and interviews with clinicians, patients, and caregivers. Survey participants (aged ≥ 18 years) with current diagnoses of TD and schizophrenia, bipolar disorder, or major depressive disorder rated the 7-day impact of TD on their physical, psychological, and social functioning via Likert scales (scored from 1 [least impact] to 5 [most impact]). Impact scores were calculated and summarized descriptively overall by self-reported disease severity and underlying disease. Participants also completed the Work Productivity and Activity Impairment Questionnaire and reported the impact of TD on their underlying psychiatric condition.Results: Overall, 269 patients (mean [SD] age = 40.6 years [9.9]; 74.7% employed) responded to the survey. Mean (SD) impact scores of 3.1 (0.9), 3.5 (1.0), and 3.2 (1.1) were reported in the physical, psychological, and social domains, respectively, and scores increased with reported TD symptom severity. Patients with underlying schizophrenia reported the highest burden for all domains. Patients reported 66.2% activity impairment because of TD. Employed patients (n = 193) indicated 29.1% absenteeism, 68.4% presenteeism, and 73.5% overall work impairment. Over one-third of patients reported skipping/reducing (48.4%) or stopping (39.3%) their antipsychotic medication and stopping visits to clinicians treating their underlying condition (35.7%) because of TD.Conclusion: TD imposes a substantial burden on patients' physical, psychological, social, and professional lives and impacts management of their underlying condition.

Defining Utility Values for Chorea Health States in Patients with Huntington's Disease.

INTRODUCTION: Chorea is characterized by sudden, involuntary movements that interfere with quality of life (QOL). Utility values measure preferences for different health states and reflect societal perceived disease severity. To date, no studies have reported utility values specifically for Huntington's disease (HD) chorea. We estimated impact on QOL of HD chorea severity using utility values from the general population. METHODS: Participants were enrolled using computer-assisted telephone interviews. Participants read vignettes describing four health states for varying levels of chorea severity, with the same underlying HD severity. Time trade-off (TTO) methods were used to estimate utility values, which range from -1 (worse than death) to +1 (perfect health) and represent the number of years in an imperfect health state an individual is willing to give up to live in full health. TTO utilities were augmented with visual analog scale (VAS) participant responses. The primary outcome was HD chorea utility estimated by TTO. RESULTS: Mean ± SD TTO-derived utility values were 0.07 ± 0.52, 0.26 ± 0.50, 0.48 ± 0.47, and 0.64 ± 0.41 for severe, moderate/severe, moderate/mild, and mild chorea severity, respectively. Differences between each health state and its adjacent less severe health state were statistically significant (all P < 0.0001). Respondents were willing to give up 3.6, 5.2, 7.4, and 9.3 years during a 10-year life span to avoid living with mild, mild/moderate, moderate/severe, and severe chorea, respectively. VAS and TTO results were consistent. CONCLUSIONS: Significant decreases in utility values were seen as HD chorea severity increased. These data can be leveraged for cost-effectiveness modeling to better understand the value of treatments for chorea.

Defining utility values for patients with tardive dyskinesia.

OBJECTIVE: To measure health state preferences and estimate utility values for tardive dyskinesia (TD) from the perspective of the US general population, accounting for factors affecting quality of life (QOL). METHODS: Participants from the general population were recruited and asked to watch and assess videos of professional actors simulating nine health states, including psychiatric disorders with/without TD and moderate-to-severe TD without any underlying disease. Time tradeoff (TTO) methods were used to elicit utility values, which ranged from -1 (worse than death) to +1 (perfect health) and represented individual preferences for avoiding specific health states associated with TD. Lower TTO utility values indicated individuals' willingness to give up more years of life to avoid living in each health state. RESULTS: Based on TTO responses (n = 157), mean ± standard deviation utility for TD alone was 0.59 ± 0.38. Mean utilities for schizophrenia with negative symptoms (without TD: 0.43; with TD: 0.29) and positive symptoms (without TD: 0.44; with TD: 0.30) were generally lower than those for bipolar disorder (without TD: 0.59; with TD: 0.46) and major depressive disorder (without TD: 0.60; with TD: 0.44). According to utility decrements associated with TD (0.13-0.16), respondents were willing to give up 1.3 to 1.6 years during a 10-year lifespan to avoid living with TD. CONCLUSIONS: Utility decrements for TD in this study were slightly larger than previously reported values, potentially due to incorporation of QOL and social consequences in TD health state descriptions. An important limitation of this analysis is that participants' willingness to trade future years of healthy life may not indicate actual willingness to accept the life decrement. These findings can be leveraged to improve cost-effectiveness analyses used to assess the value of treatments for TD.

Real-World Adherence to Tetrabenazine or Deutetrabenazine Among Patients With Huntington's Disease: A Retrospective Database Analysis.

INTRODUCTION: Chorea, a common clinical manifestation of Huntington's disease (HD), involves sudden, involuntary movements that interfere with daily functioning and contribute to the morbidity of HD. Tetrabenazine and deutetrabenazine are FDA-approved to treat chorea associated with HD. Compared to tetrabenazine, deutetrabenazine has a unique pharmacokinetic profile leading to more consistent systemic exposure, less frequent dosing, and a potentially more favorable safety/tolerability profile. Real-world adherence data for these medications are limited. Here, we evaluate real-world adherence patterns with the vesicular monoamine transporter 2 inhibitors, tetrabenazine and deutetrabenazine, among patients diagnosed with HD. METHODS: Insurance claims data from the Symphony Health Solutions Integrated Dataverse (05/2017-05/2019) were retrospectively analyzed for patients diagnosed with HD (ICD-10-CM code G10). Patients were categorized into cohorts based on treatment. Outcomes included adherence, which was measured by proportion of days covered (PDC), adherence rate (PDC > 80%), and discontinuation rates during the 6-month follow-up period (after a 30-day dose stabilization period). RESULTS: Patient demographic characteristics between the deutetrabenazine (N = 281) and tetrabenazine (N = 101) cohorts were comparable at baseline. Mean ± SD PDC was significantly higher in the deutetrabenazine versus tetrabenazine cohort (78.5% ± 26.7% vs. 69.3% ± 31.4%; P < 0.01). Similarly, a higher adherence rate was observed in the deutetrabenazine versus tetrabenazine cohort, though the difference was not statistically significant (64.1% vs. 55.4%; P = 0.1518). Discontinuation rates were significantly lower in the deutetrabenazine versus tetrabenazine cohort during the 6-month follow-up period (1 month, 3.5% vs. 9.2%; 3 months, 14.7% vs. 23.3%; 6 months, 25.4% vs. 37.2%; P < 0.05). CONCLUSIONS: Results from this real-world analysis indicate that patients treated with deutetrabenazine are more adherent to treatment and have lower discontinuation rates compared with patients in the tetrabenazine cohort. However, a potential limitation is overestimated adherence, as claims for prescription fills may not capture actual use. Additional research is warranted to explore the differences in adherence patterns between treatments, which may inform treatment decision-making.

The Impact of Antipsychotic Dose Reduction on Clinical Outcomes and Health Care Resource Use Among Medicare Patients with Schizophrenia.

BACKGROUND: Antipsychotic medications are used to treat schizophrenia and may be associated with adverse effects, including tardive dyskinesia (TD), following prolonged use or upon changes in dosing regimen. OBJECTIVE: This retrospective analysis evaluated the burden of antipsychotic dose reduction in Medicare patients with schizophrenia. METHODS: This matched cohort study used Medicare claims data (2006-2017) analyzed for patients with schizophrenia and two or more claims for antipsychotics, with one or more antipsychotic monotherapy period ≥ 90 days. Cohorts were defined for patients with antipsychotic dose reductions ≥ 10% and stable doses. A separate analysis was conducted using patients with dose reductions ≥ 30%. Outcomes included all-cause emergency room (ER) visits, all-cause inpatient visits, schizophrenia relapse, other psychiatric relapse, and TD diagnosis. Covariates included age, disease duration, comorbidities, and medication use. RESULTS: The analysis included 276,030 patients with ≥ 10% dose reductions and 211,575 patients with ≥ 30% dose reductions. Patient characteristics were balanced between cohorts. Patients with ≥ 10% or ≥ 30% dose reductions had a shorter time to ER visit, inpatient visit, schizophrenia relapse, other psychiatric relapse, and TD diagnosis versus those receiving stable doses (all p < 0.001). Significance was maintained when unmatched baseline characteristics were adjusted. CONCLUSIONS: Patients with antipsychotic dose reductions may be at risk for increased ER visits, increased hospitalizations, and significant unfavorable mental health-related clinical outcomes, suggesting that dose reduction may increase overall health care burden in some patients with schizophrenia. This work highlights the need for alternative strategies in the management of patients with TD.