Assessing the use of anti-PD1 monotherapy as adjuvant therapy and determinants of treatment choice in stage III cutaneous melanoma in the US.

BACKGROUND: The objective of this study was to describe real-world adjuvant therapy (AT) use by disease substage and assess determinants of treatment choice among patients with stage III melanoma. METHODS: This non-interventional retrospective study included survey responses and data from patient records provided by US medical oncologists. Survey responses, patient demographic/clinical characteristics, treatment utilization, and reasons for treatment were reported descriptively. The association between patient and disease characteristics and AT selection was assessed using logistic and multinomial regression models, overall and stratified by AJCC8 substage (IIIA vs. IIIB/C/D) and type of AT received (anti-PD1 monotherapy, BRAF/MEK, no AT), respectively. RESULTS: In total 152 medical oncologists completed the survey and reviewed the charts of 507 patients (168 stage IIIA; 339 stages IIIB/IIIC/IIID); 405 (79.9%) patients received AT (360/405 (88.9%) received anti-PD1 therapy; 45/405 (11.1%) received BRAF/MEK therapy). Physicians reported clinical guidelines (61.2%), treatment efficacy (37.5%), and ECOG performance status (31.6%) as drivers of AT prescription. Patient-level data confirmed that improving patient outcomes (79%) was the main reason for anti-PD1 prescription; expected limited treatment benefit (37%), patient refusal (36%), and toxicity concerns (30%) were reasons for not prescribing AT. In multivariable analyses stage IIIB/IIIC/IIID disease significantly increased the probability of receiving AT (odds ratio [OR] 1.74) and anti-PD1 therapy (OR 1.82); ECOG 2/3 and Medicaid/no insurance decreased the probability of AT receipt (OR 0.37 and 0.42, respectively) and anti-PD1 therapy (OR 0.41 and 0.42, respectively) among all patients and patients with stage IIIA disease. CONCLUSION: Most patients were given AT with a vast majority treated with an anti-PD1 therapy. Physician- and patient-level evidence confirmed the impact of disease substage on AT use, with stage IIIA patients, patients without adequate insurance coverage, and worse ECOG status having a lower probability of receiving AT.

Clinical Outcomes Before and After Prucalopride Treatment: An Observational Study in Patients With Chronic Idiopathic Constipation in the United States.

INTRODUCTION: This real-world US-based claims study compared constipation-related symptoms and complications 6 months before and after prucalopride initiation in adults with chronic idiopathic constipation (CIC). METHODS: This observational, retrospective cohort analysis used the IBM MarketScan Commercial Claims and Encounters Database and the Medicare Supplemental Database (January 2015-June 2020). Prucalopride-treated patients (≥18 years old) who had ≥1 constipation-related International Classification of Diseases, Tenth Revision, Clinical Modification ( ICD-10-CM ) diagnosis code during the baseline or study period were included. The proportions of patients with constipation-related symptoms (abdominal pain, abdominal distension [gaseous], incomplete defecation, and nausea) and constipation-related complications (anal fissure and fistula, intestinal obstruction, rectal prolapse, hemorrhoids, perianal venous thrombosis, perianal/perirectal abscess, and rectal bleeding) were examined. Constipation-related symptoms and complications were identified using ICD-10-CM , ICD-10 - Procedure Coding System , or Current Procedural Terminology codes. Data were stratified by age (overall, 18-64 years, and ≥65 years). RESULTS: This study included 690 patients: The mean (SD) patient age was 48.0 (14.7) years, and 87.5% were women. The proportions of patients overall with constipation-related symptoms decreased 6 months after prucalopride initiation (abdominal pain [50.4% vs 33.3%, P < 0.001]; abdominal distension [gaseous] [23.9% vs 13.3%, P < 0.001]; and nausea [22.6% vs 17.7%, P < 0.01]; no improvements observed for incomplete defecation). Similarly, the proportions of patients overall with constipation-related complications decreased 6 months after prucalopride initiation (intestinal obstruction [4.9% vs 2.0%, P < 0.001]; hemorrhoids [10.7% vs 7.0%, P < 0.05]; and rectal bleeding [4.1% vs 1.7%, P < 0.05]). DISCUSSION: This study suggests that prucalopride may be associated with improved constipation-related symptoms and complications 6 months after treatment initiation.

Comparison of outcomes on hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) in anaemia associated with chronic kidney disease: network meta-analyses in dialysis and non-dialysis dependent populations.

Background: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are oral alternatives to current standard-of-care treatments for anaemia in chronic kidney disease (CKD). We conducted network meta-analyses to indirectly compare clinical outcomes for three HIF-PHIs in dialysis and non-dialysis populations with anaemia in CKD. Methods: The evidence base comprised phase III, randomised, controlled trials evaluating daprodustat, roxadustat, or vadadustat. Three outcomes were evaluated: efficacy [change from baseline in haemoglobin (Hgb)], cardiovascular safety [time to first major adverse cardiovascular event (MACE)] and quality of life [change from baseline in 36-Item Short Form Health Survey (SF-36) Vitality score]. Analyses were performed separately for all patients and for erythropoiesis-stimulating agent (ESA) non-users at baseline (non-dialysis population) or prevalent dialysis patients (dialysis population). Bayesian Markov Chain Monte Carlo methods with non-informative priors were used to estimate the posterior probability distribution and generate pairwise treatment comparisons. Point estimates (medians of posterior distributions) and 95% credible intervals (CrI) were calculated. Results: Seventeen trials were included. In non-dialysis patients, there were no clinically meaningful differences between the three HIF-PHIs with respect to Hgb change from baseline [all patients analysis (total n = 7907): daprodustat vs. roxadustat, 0.09 g/dL (95% CrI -0.14, 0.31); daprodustat vs. vadadustat, 0.09 g/dL (-0.04, 0.21); roxadustat vs. vadadustat, 0.00 g/dL (-0.22, 0.22)] or risk of MACE [all patients analysis (total n = 7959): daprodustat vs. roxadustat, hazard ratio (HR) 1.16 (95% CrI 0.76, 1.77); daprodustat vs. vadadustat, 0.88 (0.71, 1.09); roxadustat vs. vadadustat, 0.76 (0.50, 1.16)]. Daprodustat showed a greater increase in SF-36 Vitality compared with roxadustat [total n = 4880; treatment difference 4.70 points (95% CrI 0.08, 9.31)]. In dialysis patients, Hgb change from baseline was higher with daprodustat and roxadustat compared with vadadustat [all patients analysis (total n = 11 124): daprodustat, 0.34 g/dL (0.22, 0.45); roxadustat, 0.38 g/dL (0.27, 0.49)], while there were no clinically meaningful differences in the risk of MACE between the HIF-PHIs [all patients analysis (total n = 12 320): daprodustat vs. roxadustat, HR 0.89 (0.73, 1.08); daprodustat vs. vadadustat, HR 0.99 (0.82, 1.21); roxadustat vs. vadadustat, HR 1.12 (0.92, 1.37)]. Results were similar in analyses of ESA non-users and prevalent dialysis patients. Conclusions: In the setting of anaemia in CKD, indirect treatment comparisons suggest that daprodustat, roxadustat, and vadadustat are broadly clinically comparable in terms of efficacy and cardiovascular safety (precision was low for the latter), while daprodustat may be associated with reduction in fatigue to a greater extent than roxadustat.

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.

Safety differences across androgen receptor inhibitors in nonmetastatic castration-resistant prostate cancer.

Approval of apalutamide, enzalutamide and darolutamide has transformed the treatment landscape and guideline recommendations for patients with nonmetastatic castration-resistant prostate cancer but now raises the issue of decision-making regarding treatment selection. In this perspective, we discuss the efficacy and safety of these second-generation androgen receptor inhibitors and propose that for patients with nonmetastatic castration-resistant prostate cancer, safety considerations for these treatments are especially important. We examine these considerations in the context of patient and caregiver preferences as well as patient clinical characteristics. We further posit that consideration of treatments' safety profiles should include not only the initial direct impacts from potential treatment-emergent adverse events and drug-drug interaction events, but also the full cascade of potentially avoidable healthcare complications.

Prostate cancer is one of the most common cancers in men. Because male hormones fuel the growth of prostate cancer cells, initial treatments generally focus on reducing these hormones to very low levels. Although these treatments are usually effective in controlling the cancer in the short term, over time, patients often stop responding to them. These patients need more advanced treatments to control their prostate cancer. For patients whose cancer has not spread to other body parts ('nonmetastatic castration-resistant prostate cancer'), more advanced treatment options were unavailable until recently, but during 2018­2019, three novel therapies became available. These new therapies have raised the question of how to choose a particular therapy when deciding on a patient's treatment regimen. Here we contend that patient safety is critical when deciding among these treatments, which are all similarly effective in terms of helping patients to live longer. We review the key differences of each drug's safety profile among these treatments. We assert that treatment selection should consider patients' preferences and clinical characteristics, as the latter can influence the potential for serious harm when treatment-related complications arise. Finally, treatment selection should consider the multiple after-effects that can occur following a treatment-related safety event.

The Hospitalization-Related Costs of Adverse Events for Novel Androgen Receptor Inhibitors in Non-Metastatic Castration-Resistant Prostate Cancer: An Indirect Comparison.

INTRODUCTION: Three novel androgen receptor inhibitors are approved in the USA for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC): apalutamide, enzalutamide, and darolutamide. All three therapies have demonstrated prolonged metastasis-free survival in their respective phase III trials, with differing safety profiles. The objective of this study was to compare the mean per-patient costs of all-cause adverse events (AEs) requiring hospitalization between darolutamide versus apalutamide and enzalutamide for nmCRPC in the USA. METHODS: All-cause grade ≥ 3 AEs with corresponding any-grade AEs reported among at least 10% of patients in any arm of the ARAMIS (darolutamide), SPARTAN (apalutamide), and PROSPER (enzalutamide) trials were selected for inclusion in the primary analyses. After matching-adjusted indirect comparison, AE costs were calculated by multiplying the AE rates from the trials by their respective unit costs of hospitalization taken from the US Healthcare Cost and Utilization Project (HCUP) database. Sensitivity analyses which further included any-grade AEs reported among at least 5% of patients were also performed. RESULTS: After reweighting and adjusting for the trials' placebo arms, the mean per-patient AE costs were $1021 and $387 lower for darolutamide than for apalutamide and enzalutamide, respectively, over the trials' duration (SPARTAN and PROSPER, 43 months; ARAMIS, 48 months). For darolutamide vs. apalutamide, the largest drivers of the per-patient cost differences were fracture (adjusted difference $416), hypertension ($143), and rash ($219); for darolutamide vs. enzalutamide, they were fatigue not including asthenia ($290) and hypertension including increased blood pressure (i.e., any AE of hypertension or with elevated blood pressure not yet classified as hypertension) ($60). The results of the sensitivity analyses were consistent with the primary results. CONCLUSIONS: Patients with nmCRPC treated with darolutamide in ARAMIS incurred lower AE-related costs (USD), as determined using HCUP costing data, compared with patients treated with either apalutamide (in SPARTAN) or enzalutamide (in PROSPER).

Long-term burden of respiratory complications associated with extreme prematurity: An analysis of US Medicaid claims.

BACKGROUND: Infants born extremely premature (EP) (<28 weeks gestational age) are at high risk of complications, particularly bronchopulmonary dysplasia (BPD), which can develop into chronic lung disease (CLD). METHODS: The burden of respiratory complications in EP infants up to 2 years corrected age (CA) was evaluated using real-world data from the US Medicaid program. Data recorded between 1997 and 2018 on EP infants without major congenital malformations were collected from Medicaid records of six states. EP infants were divided into three cohorts: BPD, CLD, and without BPD or CLD. The incidence of respiratory conditions, respiratory medication use, and healthcare resource utilization were compared between the BPD cohort and CLD cohort versus the cohort without BPD or CLD, using unadjusted and adjusted generalized linear models. RESULTS: A total of 4462 EP infants were identified (17.4% of all premature infants in the database). Of these, BPD and CLD were diagnosed in 61.9% and 72.1%, respectively, and 14.5% were diagnosed with neither BPD nor CLD. Compared with infants without BPD or CLD, infants with BPD or CLD had more complications and a longer length of birth hospitalization stay. Respiratory distress syndrome was the most frequently reported complication (94.6%, 92.5%, and 82.3% of EP infants in the BPD, CLD, and without BPD or CLD cohorts, respectively). After the birth hospitalization, respiratory conditions, respiratory medication use, and incidence rates of rehospitalizations, emergency room visits, and outpatient visits were higher for infants with BPD or CLD. Rehospitalization occurred in 50.5%, 51.6%, and 27.3% of EP infants with BPD, CLD, or without BPD or CLD, respectively; most hospitalizations occurred for respiratory-related reasons. CONCLUSION: In this analysis of a large population of EP infants up to 2 years CA, respiratory conditions were prevalent after the birth hospitalization and were associated with high rates of medication and healthcare resource utilization.

Real-world effectiveness after initiating fremanezumab treatment in US patients with episodic and chronic migraine or difficult-to-treat migraine.

BACKGROUND: Fremanezumab, a fully humanized monoclonal antibody (mAb; IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for the preventive treatment of migraine in adults. The efficacy and safety of fremanezumab for migraine prevention have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world effectiveness data are needed to complement clinical trial data. This study assessed the effectiveness of fremanezumab across different subgroups of adult patients with episodic migraine (EM), chronic migraine (CM), or difficult-to-treat (DTT) migraine in real-world clinical settings. METHODS: This retrospective, panel-based online chart review used electronic case report forms. Patient inclusion criteria were a physician diagnosis of EM or CM; age ≥ 18 years at the time of first fremanezumab initiation; ≥ 1 dose of fremanezumab treatment; ≥ 1 follow-up visit since first initiation; and ≥ 2 measurements of monthly migraine days (MMD; with 1 within a month before or at first initiation and ≥ 1 after first initiation). Changes in MMD and monthly headache days were assessed during the follow-up period. These endpoints were evaluated in subgroups of patients by migraine type (EM/CM) and in subgroups with DTT migraine (diagnosis of medication overuse [MO], major depressive disorder [MDD], generalized anxiety disorder [GAD], or prior exposure to a different CGRP pathway-targeted mAb [CGRP mAb]). RESULTS: Data were collected from 421 clinicians and 1003 patients. Mean (percent) reductions from baseline in MMD at Month 6 were - 7.7 (77.0%) in EM patients, - 10.1 (68.7%) in CM patients, - 10.8 (80.6%) in the MO subgroup, - 9.9 (68.3%) in the MDD subgroup, - 9.5 (66.4%) in the GAD subgroup, and - 9.0 (68.7%) in the prior CGRP mAb exposure subgroup. Improvements in MDD or GAD severity were reported by 45.5% and 45.8% of patients with comorbid MDD or GAD, respectively. CONCLUSIONS: In this real-world study, fremanezumab demonstrated effectiveness for migraine regardless of migraine type or the presence of factors contributing to DTT migraine (MO, GAD, MDD, or prior exposure to a different CGRP mAb).

Real-world effectiveness of fremanezumab in migraine patients initiating treatment in the United States: results from a retrospective chart study.

BACKGROUND: The efficacy and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP) and is approved for the preventive treatment of migraine in adults, have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world data can further support those clinical trial data and demonstrate the full clinical benefits of fremanezumab. This chart review assessed the effectiveness of fremanezumab for improving clinical outcomes in adult patients with migraine treated according to real-world clinical practice. METHODS: This retrospective, panel-based, online physician chart review study used electronic case report forms with US physicians. Patient inclusion criteria were a physician diagnosis of migraine, fremanezumab treatment initiation at ≥ 18 years of age after US Food and Drug Administration approval, ≥ 1 dose of fremanezumab treatment, and ≥ 2 assessments of monthly migraine days (MMD; 1 within 30 days before treatment initiation and ≥ 1 after initiation). Changes from baseline in MMD, monthly headache days (MHD), and Migraine Disability Assessment (MIDAS) and 6-item Headache Impact Test (HIT-6) scores were assessed over 6 months. These endpoints were evaluated in the overall population and subgroups divided by dosing schedule and number of prior migraine preventive treatment failures. RESULTS: This study included data from 421 clinicians and 1003 patients. Mean age at fremanezumab initiation was 39.7 years, and most patients were female (75.8%). In the overall population, mean baseline MMD and MHD were 12.7 and 14.0, respectively. Mean (percent) reductions from baseline in MMD and MHD, respectively, were - 4.6 (36.2%) and - 4.7 (33.6%) at Month 1, - 6.7 (52.8%) and - 6.8 (48.6%) at Month 3, and - 9.2 (72.4%) and - 9.8 (70.0%) at Month 6. Mean (percent) reductions from baseline in MIDAS and HIT-6 scores also increased over the 6-month study period, from - 6.2 (21.6%) and - 8.4 (14.0%) at Month 1 to - 18.1 (63.1%) and - 16.2 (27.0%) at Month 6, respectively. Improvements in these outcomes over 6 months were observed across all evaluated subgroups. CONCLUSIONS: This real-world study demonstrated effectiveness of fremanezumab treatment for up to 6 months, irrespective of dosing regimen or number of prior migraine preventive treatment failures, reflecting ongoing, clinically meaningful improvements in patient outcomes.

Indirect Treatment Comparison of Larotrectinib versus Entrectinib in Treating Patients with TRK Gene Fusion Cancers.

Information regarding the comparative efficacy of first-generation receptor tyrosine kinase inhibitors is limited. This matching-adjusted indirect comparison (MAIC) evaluated differences in efficacy and safety across larotrectinib and entrectinib trials. Data from clinical trials for larotrectinib (LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431)) and entrectinib (ALKA-372-001 (EudraCT 2012-000148-88), STARTRK-1 (NCT02097810), and STARTRK-2 (NCT02568267)) were used. Adults (≥18 years) across trials were matched on available baseline characteristics. Outcomes evaluated included overall response rate (ORR), complete response (CR) rate, duration of response (DoR), overall survival (OS), progression-free survival (PFS), any serious treatment-related adverse events of grade ≥ 3 (TRAEs), and TRAEs leading to treatment discontinuation. The MAIC included 74 patients from entrectinib trials and 117 and 147 patients for the larotrectinib efficacy and safety populations, respectively. Post-matching, larotrectinib was associated with a significantly longer median duration of OS than entrectinib (p < 0.05) and a numerically longer median PFS (p = 0.07). ORR was similar for both agents (p = 0.63). The CR rate was higher (p < 0.05) and the DoR was longer for larotrectinib (p < 0.05). Safety outcomes were comparable and low for both treatments. Results were consistent in sensitivity analyses. These findings suggest favorable efficacy for larotrectinib and comparable safety profiles versus entrectinib in treating tropomyosin receptor kinase fusion cancer.

Health-care resource use and costs associated with diabetic and idiopathic gastroparesis: A claims analysis of the first 3 years following the diagnosis of gastroparesis.

BACKGROUND: Due to limited treatment options, many patients with diabetic gastroparesis (DG) or idiopathic gastroparesis (IG) experience inadequate symptom control resulting in increased health-care resource utilization (HRU) and associated costs. We compared all-cause HRU and health-care costs over the 3 years after patients' first gastroparesis diagnosis with that of matched controls without gastroparesis. METHODS: Newly diagnosed adults with DG or IG were identified in Optum's de-identified Clinformatics® Data Mart Database (Q1-2007 to Q1-2019). Patients with DG/IG were matched 1:1 to controls using a mixed approach of exact matching and propensity score matching. The index date was the first gastroparesis diagnosis for cases or randomly selected for controls. All-cause HRU and direct health-care costs per person-year (PPY) were compared between DG/IG cases and controls in Years 1-3 post-index. KEY RESULTS: Demographics and comorbidities were balanced between patients with gastroparesis (n = 18,015 [DG]; n = 14,305 [IG]) and controls. In each of the Years 1-3 post-index, patients with DG or IG had significantly higher annual HRU and costs versus controls (mean total cost differences PPY: DG Year 1 $34,885, Year 2 $28,071, Year 3 $25,606; IG Year 1 $23,176, Year 2 $16,627, Year 3 $14,396) (all p < 0.05). Across all 3 years, DG/IG cohorts had approximately twice the costs of controls. HRU and costs were highest in Year 1 post-index for both DG and IG. CONCLUSIONS & INFERENCES: The economic burden of gastroparesis remains high several years after diagnosis, emphasizing the need for chronic treatment to effectively manage symptoms and consequently reduce the burden of this disorder.

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.

An Experimental Study to Assess the Professional and Social Consequences of Tardive Dyskinesia.

OBJECTIVE: Antipsychotic medications may cause tardive dyskinesia (TD), an often-irreversible movement disorder characterized by involuntary movements that are typically stereotypic, choreiform, or dystonic and may impair quality of life. This study evaluated others' perceptions of abnormal TD movements in professional and social situations. METHODS: This was an experimental, randomized, blinded, digital survey in a general population sample. Participants were randomized 1:1 into a test or control group to view a video of a professional actor simulating TD movements or no TD movements prior to completing surveys on employment, dating, and friendship domains. Assessments for mild-to-moderate and moderate-to-severe TD movements were conducted separately. Authenticity of abnormal movements and Abnormal Involuntary Movement Scale (AIMS) scores were evaluated by physician experts. RESULTS: Surveys were completed by 2,400 participants each for mild-to-moderate and moderate-to-severe TD. In all domains, participants responded significantly less favorably to persons with TD movements (both mild-to-moderate and moderate-to-severe) than those without TD movements. Fewer participants in the test versus control group for mild-to-moderate and moderate-to-severe TD, respectively, considered the candidate as a potential employee (29.2% and 22.7% fewer), found him/her attractive (20.5% and 18.7% fewer), and were interested in becoming friends with him/her (12.3% and 16.5% fewer). CONCLUSION: Professional actors simulating TD movements were perceived more negatively than those without TD movements in employment, dating, and friendship domains. To our knowledge, this is the first randomized study to quantify professional and social stigma associated with TD movements that may reduce opportunities for gainful employment, marital status, and an effective support system.

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.

Burden of Comorbidities and Healthcare Resource Utilization Among Medicaid-Enrolled Extremely Premature Infants.

Background: The effect of gestational age (GA) on comorbidity prevalence, healthcare resource utilization (HCRU), and all-cause costs is significant for extremely premature (EP) infants in the United States. Objectives: To characterize real-world patient characteristics, prevalence of comorbidities, rates of HCRU, and direct healthcare charges and societal costs among premature infants in US Medicaid programs, with respect to GA and the presence of respiratory comorbidities. Methods: Using International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification codes, diagnosis and medical claims data from 6 state Medicaid databases (1997-2018) of infants born at less than 37 weeks of GA (wGA) were collected retrospectively. Data from the index date (birth) up to 2 years corrected age or death, stratified by GA (EP, ≤28 wGA; very premature [VP], >28 to <32 wGA; and moderate to late premature [M-LP], ≥32 to <37 wGA), were compared using unadjusted and adjusted generalized linear models. Results: Among 25 573 premature infants (46.1% female; 4462 [17.4%] EP; 2904 [11.4%] VP; 18 207 [71.2%] M-LP), comorbidity prevalence, HCRU, and all-cause costs increased with decreasing GA and were highest for EP. Total healthcare charges, excluding index hospitalization and all-cause societal costs (US dollars), were 2 to 3 times higher for EP than for M-LP (EP $74 436 vs M-LP $27 541 and EP $28 504 vs M-LP $15 892, respectively). Conclusions: Complications of preterm birth, including prevalence of comorbidities, HCRU, and costs, increased with decreasing GA and were highest among EP infants during the first 2 years in this US analysis.

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.