| Literature DB >> 34905160 |
Daniel O Claassen1, Rajeev Ayyagari2, Viviana Garcia-Horton3, Su Zhang2, Jessica Alexander4, Sam Leo5.
Abstract
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.Entities:
Keywords: Adherence patterns; Deutetrabenazine; Huntington’s disease; Tetrabenazine; Treatment discontinuation
Year: 2021 PMID: 34905160 PMCID: PMC8857359 DOI: 10.1007/s40120-021-00309-5
Source DB: PubMed Journal: Neurol Ther ISSN: 2193-6536
Fig. 1Study design. HD Huntington’s disease
Fig. 2Sample selection. HD Huntington’s disease, ICD-10-CM International Classification of Diseases, 10th Revision, Clinical Modification. There were 11 patients with both deutetrabenazine and tetrabenazine claims; 10 patients had their first tetrabenazine claim before their first deutetrabenazine claim, while 1 patient had their first deutetrabenazine claim before their first tetrabenazine claim
Patient characteristics at baseline
| Deutetrabenazine cohort ( | Tetrabenazine cohort ( | ||
|---|---|---|---|
| Demographics | |||
| Age category (years), | |||
| 18–27 | 10 (3.6%) | 9 (8.9%) | 0.1024 |
| 28–37 | 20 (7.1%) | 11 (10.9%) | |
| 38–47 | 61 (21.7%) | 22 (21.8%) | |
| 48–57 | 87 (31.0%) | 22 (21.8%) | |
| 58–65 | 103 (36.7%) | 37 (36.6%) | |
| Male, | 110 (39.1%) | 44 (43.6%) | 0.4785 |
| Health plan typea, | |||
| Medicare | 113 (40.2%) | 37 (36.6%) | < 0.001 |
| Commercial | 53 (18.9%) | 0 (0.0%) | |
| Medicaid | 50 (17.8%) | 36 (35.6%) | |
| Otherb | 19 (6.8%) | 13 (12.9%) | |
| Unspecified | 46 (16.4%) | 15 (14.9%) | |
| Index year, | |||
| 2017 | 3 (1.1%) | 12 (11.9%) | < 0.001 |
| 2018 | 160 (56.9%) | 69 (68.3%) | |
| 2019 | 118 (42.0%) | 20 (19.8%) | |
| Observed disease durationc | |||
| Patients assessed, | 254 (90.4%) | 79 (78.2%) | < 0.01 |
| Observed disease duration, mean ± SD (days) | 353.4 ± 214.3 | 257.6 ± 165.2 | < 0.001 |
| Duration of follow-up, mean ± SD | |||
| Time from index date to end of datad (days) | 229.0 ± 146.1 | 313.4 ± 156.9 | < 0.001 |
| Time from index date to last observed medical/pharmacy activity (days) | 209.9 ± 142.0 | 289.1 ± 155.7 | < 0.001 |
| CCI score, mean ± SD | 0.4 ± 0.8 | 0.4 ± 1.0 | 0.6716 |
| Selected comorbidities in the CCI, n (%) | |||
| Dementia | 23 (8.2%) | 9 (8.9%) | 0.8352 |
| Chronic pulmonary disease | 19 (6.8%) | 7 (6.9%) | 1.0000 |
| Diabetes without chronic complication | 12 (4.3%) | 7 (6.9%) | 0.2933 |
| Cerebrovascular disease | 7 (2.5%) | 2 (2.0%) | 1.0000 |
| Any malignancy, including leukemia and lymphoma, except for malignant neoplasm of skin | 7 (2.5%) | 1 (1.0%) | 0.6867 |
| Peripheral vascular disease | 4 (1.4%) | 3 (3.0%) | 0.3871 |
| Mild liver disease | 3 (1.1%) | 2 (2.0%) | 0.6110 |
| Psychiatric comorbidities, | |||
| Depressive disorders | 60 (21.4%) | 24 (23.8%) | 0.6745 |
| Anxiety disorders | 53 (18.9%) | 15 (14.9%) | 0.4486 |
| Substance-related and addictive disorders | 31 (11.0%) | 18 (17.8%) | 0.0851 |
| Bipolar and related disorders | 23 (8.2%) | 8 (7.9%) | 1.0000 |
| Trauma- and stressor-related disorders | 10 (3.6%) | 3 (3.0%) | 1.0000 |
| ADD/ADHD | 5 (1.8%) | 2 (2.0%) | 1.0000 |
| Other psychoses | 4 (1.4%) | 4 (4.0%) | 0.2159 |
| Schizoaffective disorder | 2 (0.7%) | 2 (2.0%) | 0.2858 |
| Conduct disorder | 0 (0.0%) | 2 (2.0%) | 0.0694 |
| Nonpsychiatric comorbidities, | |||
| Hypertension | 42 (14.9%) | 15 (14.9%) | 1.0000 |
| Hyperlipidemia | 42 (14.9%) | 17 (16.8%) | 0.6337 |
| Dysphagia | 42 (14.9%) | 5 (5.0%) | < 0.01 |
| Falls | 37 (13.2%) | 11 (10.9%) | 0.6044 |
| Sleep-awake disorders | 29 (10.3%) | 14 (13.9%) | 0.3599 |
| Sleep disturbance | 18 (6.4%) | 8 (7.9%) | 0.6460 |
| Osteoarthritis | 19 (6.8%) | 6 (5.9%) | 1.0000 |
| Smoking history | 19 (6.8%) | 10 (9.9%) | 0.3800 |
| Abnormal weight loss | 14 (5.0%) | 4 (4.0%) | 0.7905 |
| Dystonia | 10 (3.6%) | 10 (9.9%) | < 0.05 |
| Tardive dyskinesia | 5 (1.8%) | 6 (5.9%) | 0.0745 |
| Tachycardia | 2 (0.7%) | 4 (4.0%) | < 0.05 |
| Treatment history, | |||
| Antidepressants | 185 (65.8%) | 61 (60.4%) | 0.3348 |
| Anticonvulsants | 113 (40.2%) | 37 (36.6%) | 0.5543 |
| Anti-anxiety medications | 64 (22.8%) | 26 (25.7%) | 0.5851 |
| Lipid-lowering agents | 53 (18.9%) | 25 (24.8%) | 0.2492 |
| Anticholinergics | 44 (15.7%) | 9 (8.9%) | 0.0966 |
| Antihypertensives | 39 (13.9%) | 11 (10.9%) | 0.4960 |
| Cognition-enhancing medication | 23 (8.2%) | 8 (7.9%) | 1.0000 |
| Anti-diabetic drugs | 15 (5.3%) | 8 (7.9%) | 0.3384 |
| Sedatives and hypnotics | 14 (5.0%) | 7 (6.9%) | 0.4524 |
| Stimulants/ADHD medications | 14 (5.0%) | 5 (5.0%) | 1.0000 |
| First-generation or second-generation antipsychotics | 105 (37.4%) | 38 (37.6%) | 1.0000 |
| First-generation antipsychotics | 23 (8.2%) | 8 (7.9%) | 1.0000 |
| Haloperidol | 22 (7.8%) | 5 (5.0%) | 0.4967 |
| Second-generation antipsychotics | 85 (30.2%) | 35 (34.7%) | 0.4537 |
| Risperidone | 29 (10.3%) | 15 (14.9%) | 0.2747 |
| Quetiapine | 29 (10.3%) | 11 (10.9%) | 0.8514 |
| Olanzapine | 19 (6.8%) | 8 (7.9%) | 0.6572 |
| All-cause HCRU, | |||
| Any inpatient visit | 24 (8.5%) | 10 (9.9%) | 0.6859 |
| Any outpatient visite | 250 (89.0%) | 81 (80.2%) | < 0.05 |
| Any emergency visit | 49 (17.4%) | 24 (23.8%) | 0.1846 |
| Any other visit | 110 (39.1%) | 53 (52.5%) | < 0.05 |
| Any unknown visit | 3 (1.1%) | 0 (0.0%) | 0.5689 |
All demographics, CCI, and psychiatric comorbidities with prevalence higher than 2% in any cohort; any non-psychiatric comorbidities and treatments with prevalence higher than 5% in any cohort; and all HCRU were presented in this table
ADHD attention-deficit/hyperactivity disorder; CCI Charlson comorbidity index, ICD-10-CM International Classification of Diseases; 10th Revision, Clinical Modification, HD Huntington’s disease, HCRU health-care resource utilization, SD standard deviation
aHealth plan type is associated with a patient’s index claim
bOther health plan types include cash, employer group, third-party administrator, processors and workers’ compensation
cObserved disease duration (time between first diagnosis and index date) was assessed among patients who were diagnosed with HD before their index date
dEnd of data, May 31, 2019
eOutpatient visits include medical office, hospital outpatient, and clinic visits. Other visits include home health, hospital outpatient pharmacy, intermediate care facility, laboratory, long-term care facility, and other facilities
Fig. 3Adherence as measured by PDC. PDC proportion of days covered. Mean PDC values are denoted by ×, with a range of 6–100% for the deutetrabenazine cohort and 3.9–99.4% for the tetrabenazine cohort. Horizontal lines within each box denote the median values and the limits of the box represent the interquartile range (Q1–Q3)
Fig. 4Kaplan–Meier curve for time to discontinuation of deutetrabenazine and tetrabenazine
| The vesicular monoamine transporter 2 (VMAT2) inhibitors tetrabenazine and deutetrabenazine are approved by the US Food and Drug Administration to treat chorea associated with Huntington’s disease (HD). |
| Real-world adherence data for VMAT2 inhibitors to treat HD chorea are limited. |
| This analysis of a large database of United States claims showed that significantly higher proportions of patients in the deutetrabenazine versus the tetrabenazine cohort were adherent to treatment, as measured by the proportion of days covered. |
| In addition, discontinuation rates were lower among patients in the deutetrabenazine compared with the tetrabenazine cohort. |