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Real-World Treatment Patterns and Healthcare Resource Utilization in Patients Prescribed Benztropine: A Claims Analysis From 2017-2020
- Craig Chepke, Samantha Cicero, Erika Giraldo, Michael Hull, Katharine Coyle, Jason Yeaw, Morgan Bron
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- Journal:
- CNS Spectrums / Volume 28 / Issue 2 / April 2023
- Published online by Cambridge University Press:
- 14 April 2023, pp. 249-250
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Introduction
We sought to examine real-world treatment patterns and healthcare resource utilization (HCRU) for patients receiving an antipsychotic (AP) and subsequently prescribed benztropine.
MethodsA retrospective analysis was conducted among patients with evidence of benztropine initiation using claims data from IQVIA’s New Data Warehouse from January 2017–March 2020. Patients were indexed on the date of first pharmacy claim for benztropine and had continuous enrollment in the 6 months prior (pre-index) and minimum 12 months post-index date, up to 24 months. Patients also had ≥1 pharmacy claim for an AP either pre-index or on the index date.
ResultsA total of 112,542 patients were included; 59% were female with mean age of 46 years. The most common comorbidities were bipolar disorder (BD; 28.3%), schizophrenia (SCZ; 28.3%), and depression (26.3%). Over half of the cohort (54.1%) had ≥2 comorbid conditions. Nearly 20% of patients had ≥20 medications (median 10–14) and medications with anticholinergic (AC) properties were used by 87.9%. Approximately 80% of patients had mild AC burden at baseline (using AC burden calculator). The median number of benztropine prescription fills was 5 with treatment duration <3 months in 44.3% of patients and <6 months in 61.7%. All-cause mean healthcare costs in the 12-month cohort (24-month cohort) were $11,755 ($23,128), mean costs for pharmacy were $9,229 ($18,148), and mean costs for inpatient stays were $34,669 ($41,280). Emergency room (ER) visits occurred in 47.3% and physician office visits in 78.9% of the cohort. In patients with available inpatient 12-month data (n=33,717), inpatient stays occurred in 4.0% (13.3% when extrapolated to total cohort). In patients with 24-month data (n=73,836), ER visits occurred in 61% of the cohort and inpatient stays in 6.6% (21.9% when extrapolated to the total cohort). Multivariate analyses showed baseline SCZ was associated with a significantly increased risk of ER visit of 30% and inpatient stay of 50%. Similarly, substance abuse was associated with an increased risk of ER visit of 85% and inpatient stay of about 40%. Other significant associations with ER visits included falls/accidents at baseline (148% increased risk), abnormal movement disorders (38% increased risk), and orthostatic hypotension (38% increased risk).
ConclusionsIn this real-world analysis of patients initiating benztropine, polypharmacy and AC burden were frequently observed. BD, SCZ, and depression were the most common comorbidities. Healthcare costs and HCRU were high for the entire cohort; inpatient stays contributed to high costs. Baseline SCZ, falls/accidents (ER only), and substance abuse were significantly associated with ER and inpatient admissions. The comorbidity and medication profiles of this cohort may have influenced the high healthcare costs and HCRU observed in the study.
FundingNeurocrine Biosciences, Inc.
Preclinical Pharmacology of Solriamfetol: Potential Mechanisms for Wake Promotion
- Hema Gursahani, Thierry Jolas, Maryse Martin, Sandrine Cotier, Sandrine Hughes, Wayne Macfadden, Gregory Parks, Craig Chepke
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- Journal:
- CNS Spectrums / Volume 28 / Issue 2 / April 2023
- Published online by Cambridge University Press:
- 14 April 2023, p. 222
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Introduction
Solriamfetol is a wake-promoting agent (WPA) approved for the treatment of excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea. The wake-promoting mechanism of solriamfetol may result from dopamine and norepinephrine reuptake inhibition. Preclinical pharmacology studies were conducted to further elucidate the molecular targets activated by solriamfetol and compare them to that of known WPAs and traditional stimulants.
MethodsIn vitro binding and functional studies were conducted in a panel of cell lines or membrane preparations expressing transmembrane receptors and monoamine transporters to measure the activity of solriamfetol, comparator WPAs, and traditional stimulants. Electrophysiology studies were conducted in slice preparations from mouse ventral tegmental area (VTA). Studies to measure locomotor activity and wake-promoting effects were conducted in mice.
ResultsIn vitro functional studies showed agonist activity of solriamfetol at human, mouse, and rat TAAR1 receptors. hTAAR1 EC50 values (10–16 μM) were within the clinically observed therapeutic solriamfetol plasma concentration range and overlapped with the observed DAT/NET inhibitory potencies of solriamfetol in vitro. TAAR1 agonist activity was unique to solriamfetol; neither the WPA modafinil nor the DAT/NET inhibitor bupropion had TAAR1 agonist activity. Solriamfetol (1–10 μM) dose-dependently inhibited the firing frequency of dopaminergic VTA neurons in mouse brain slices, similar to known TAAR1 agonists; however, these effects were inhibited by a D2 antagonist, suggesting a DAT-mediated effect. Unlike traditional stimulants, solriamfetol did not increase locomotor activity in naive mice, but inhibited the increase in locomotor activity in DAT knockout mice.
ConclusionsPreclinical studies have identified agonist activity at the TAAR1 receptor and, possibly, lower potency agonist activity at 5-HT1A receptors as potential pharmacological targets for solriamfetol, in addition to its activity as a DAT/NET inhibitor. Given the current understanding of TAAR1 agonists as modulators of monoamine transmission with potential wake-promoting effects in multiple preclinical species, agonist activity at the hTAAR1 receptor may represent an additional pharmacological target underlying the wake-promoting effects for solriamfetol, in addition to its DNRI activity.
FundingAxsome Therapeutics, Jazz Pharmaceuticals
123 Long-Term Outcomes with Valbenazine 40 mg/day in Adults With Tardive Dyskinesia
- Craig Chepke, Stephen R. Marder, Cynthia L. Comella, Carlos Singer, Khodayar Farahmand, Leslie Lundt
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- Journal:
- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, pp. 279-280
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Study Objective:
Tardive dyskinesia (TD), a persistent and potentially disabling movement disorder, is associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Valbenazine (VBZ) is a novel and highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of TD in adults. Using data from two long-term phase 3 studies (KINECT 3 [K3], NCT02274558; KINECT 4 [K4], NCT02405091) and a rollover study (1506, NCT02736955), the long-term outcomes of once-daily VBZ on TD were examined in participants who received 40mg or had a dose reduction from 80 to 40mg.
Methods:The effects of VBZ 40mg (as well as VBZ 80mg) were evaluated in the following studies: the pivotal K3 study (6 weeks double-blind, placebo controlled), the extension phase of K3 (42 additional weeks of VBZ, 4 week discontinuation), and the open-label K4 study (48 weeks of VBZ, 4 week discontinuation). Completers from K3 extension and K4 were invited to participate in 1506 (up to 72 additional weeks of VBZ or until commercial availability of VBZ). Few participants reached Week 60 (n=4) or Week 72 (n=0) in the 1506 study before termination. Analyses focused on VBZ 40mg in two populations: pooled K3/K4 (participants who received VBZ 40mg throughout K3 or K4 or who had a dose reduction [80/40mg] during K3 or K4); and 1506 (participants who received VBZ 40mg from beginning of K3 or K4 to last visit in 1506 or who had a dose reduction [80/40mg] at any time). Outcomes for the K3/K4 population included mean change from baseline (CFB) in Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1-7) and AIMS response (≥50% total score improvement from baseline) at Week 48 of K3 or K4. Outcomes for the 1506 population included a Clinical Global Impression of Severity-Tardive Dyskinesia (CGIS-TD) score ≤2 (“normal, not at all ill” or “borderline ill”).
Results:In the K3/K4 population, AIMS CFB to Week 48 indicated mean TD improvements in participants who received 40mg continuously (40mg, -5.7 [n=54]) and in those who had a dose reduction to 40mg (80/40mg, -6.2 [n=13]). In addition, a majority of these participants had an AIMS response after 48 weeks of treatment (40mg, 53.7%; 80/40mg, 53.8%). In the 1506 population, the percentage of participants who had a CGIS-TD score ≤2 (rating of “normal, not at all ill” or “borderline ill”) at Week 12 was 63.6% (7/11) in the 40mg group and 30.8% (4/13) in the 80/40mg group. Data from Weeks 24 to 60 of 1506 were limited by the small sample sizes (<10 participants each in 40mg or 80/40mg group at each of these visits).
Conclusions:Based on these analyses and results from published studies, VBZ 40mg may be an effective long-term option for some TD patients. Dose reductions from 80 to 40mg, if necessary, did not appear to compromise long-term benefit.
Funding Acknowledgements:This study was sponsored by Neurocrine Biosciences, Inc.