Patients' Preferences for Adjunctive Parkinson's Disease Treatments: A Discrete-Choice Experiment.

Background: Several adjunctive medications are available to reduce OFF time between levodopa/carbidopa (LD/CD) doses for people with Parkinson's disease (PD). Objective: To explore how individuals with PD balance benefits and burdens when considering adjunctive medications. Methods: US adults (30-83 years) with self-reported PD, currently treated with LD/CD, who experienced OFF episodes were recruited through the Fox Insight study to complete a discrete-choice experiment survey. Respondents selected among experimentally designed profiles for hypothetical adjunctive PD treatments that varied in efficacy (additional ON time), potential adverse effects (troublesome dyskinesia, risk of diarrhea, risk of change in bodily fluid color), and dosing frequency or the option "No additional medicine". Data were analyzed with random-parameters logit models. Results: Respondents (N=480) would require ≥60 additional minutes of daily ON time to accept either a 40% risk of change in bodily fluid color or 10 additional minutes with troublesome dyskinesia daily. Respondents would require 40 additional minutes of daily ON time to accept a 10% risk of diarrhea and 22 additional minutes of daily ON time to switch from 1 additional pill each day to 1 pill with each LD/CD dose. On average, respondents preferred adjunctive PD medication over no additional medication. Results predicted that 59.1% of respondents would select a hypothetical treatment profile similar to opicapone, followed by no additional medication (27.5%) and a hypothetical treatment profile similar to entacapone (13.4%). Limitations: The data collected were based on responses to hypothetical choice profiles in the survey questions. The attributes and levels selected for this study were intended to reflect the characteristics of opicapone and entacapone; attributes associated with other adjunctive therapies were not evaluated. Conclusion: Patients with PD expressed interest in adjunctive treatment to increase ON time and would accept reduced ON time to avoid adverse effects.

Impact of possible tardive dyskinesia on physical wellness and social functioning: results from the real-world RE-KINECT study.

BACKGROUND: Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with antipsychotic use. Data from RE-KINECT, a real-world study of antipsychotic-treated outpatients, were analyzed to assess the effects of possible TD on patient health and social functioning. METHODS: Analyses were conducted in Cohort 1 (patients with no abnormal involuntary movements) and Cohort 2 (patients with possible TD per clinician judgment). Assessments included: EuroQoL's EQ-5D-5L utility (health); Sheehan Disability Scale (SDS) total score (social functioning); patient- and clinician-rated severity of possible TD ("none", "some", "a lot"); and patient-rated impact of possible TD ("none", "some", "a lot"). Regression models were used to analyze the following: associations between higher (worse) severity/impact scores and lower (worse) EQ-5D-5L utility (indicated by negative regression coefficients); and associations between higher (worse) severity/impact scores and higher (worse) SDS total score (indicated by positive regression coefficients). RESULTS: In Cohort 2 patients who were aware of their abnormal movements, patient-rated TD impact was highly and significantly associated with EQ-5D-5L utility (regression coefficient: - 0.023, P < 0.001) and SDS total score (1.027, P < 0.001). Patient-rated severity was also significantly associated with EQ-5D-5L utility (- 0.028, P < 0.05). Clinician-rated severity was moderately associated with both EQ-5D-5L and SDS, but these associations were not statistically significant. CONCLUSIONS: Patients were consistent in evaluating the impacts of possible TD on their lives, whether based on subjective ratings ("none", "some", "a lot") or standardized instruments (EQ-5D-5L, SDS). Clinician-rated severity of TD may not always correlate with patient perceptions of the significance of TD.

Cost-effectiveness of opicapone and entacapone in reducing OFF-time in Parkinson's disease patients treated with levodopa/carbidopa.

AIMS: To assess from a US payer perspective the relative cost-effectiveness of the catechol-O-methyltransferase inhibitors opicapone and entacapone when used adjunctively to levodopa/carbidopa (LD/CD) in patients with Parkinson's disease (PD), based on the drugs' effects to reduce absolute OFF-time hours in PD patients. MATERIALS AND METHODS: A Markov model was created to estimate cost-effectiveness of adjunctive opicapone treatment compared with adjunctive entacapone treatment in a synthetic cohort of 1,000 patients with PD taking LD/CD. Clinical inputs were derived from clinical trials, published literature, and expert opinion. Cost data (in 2018 US dollars) were obtained from the Centers for Medicare & Medicaid Services, the Kaiser Family Foundation, and Analy$ource. Cost-effectiveness outcomes included incremental cost per OFF-time hours avoided, cost per life year gained, and cost per quality-adjusted life year (QALY) gained. Outcomes were projected over a 25-year lifetime horizon and discounted at 3% annually. RESULTS: Opicapone treatment was associated with an average of 1,187 fewer OFF-time hours per patient and an increase of 0.07 QALYs compared with entacapone. Total lifetime costs for opicapone were $3,100 higher than entacapone, resulting in an incremental cost-effectiveness ratio of $46,900 per QALY. One-way sensitivity analyses showed the model was most sensitive to mean OFF-time hours associated with opicapone and entacapone. Probabilistic sensitivity analysis suggested a 60-65% probability that opicapone was cost-effective relative to entacapone at any willingness-to-pay threshold ≥$5,000. LIMITATIONS: There exists a single head-to-head clinical trial comparing the effectiveness of opicapone with entacapone, thus the clinical inputs regarding relative treatment effect of the drugs to reduce OFF-time hours in PD patients receiving LD/CD were derived from that single non-inferiority trial. CONCLUSIONS: Add-on treatment with opicapone in PD patients receiving LD/CD appeared to be cost-effective compared with entacapone.

Cost-effectiveness of valbenazine compared with deutetrabenazine for the treatment of tardive dyskinesia.

AIMS: To evaluate clinical and economic outcomes associated with valbenazine compared with deutetrabenazine in patients with tardive dyskinesia (TD) using a model that accounts for multiple dimensions of patient health status. MATERIALS AND METHODS: A discretely integrated condition event model was developed to evaluate the cost-effectiveness of treatment with valbenazine and deutetrabenazine in a synthetic cohort of 1,000 patients with TD who were receiving antipsychotic medication to treat an underlying psychiatric disorder. Clinical inputs were derived from relevant clinical trials or from publicly available sources. Patients were assessed over 1 year using ≥50% improvement from baseline in Abnormal Involuntary Movement Scale (AIMS) total score as the primary definition of response. Response at 1 year using Clinical Global Impression of Change (CGIC) score ≤2 was also assessed. Health outcomes included quality-adjusted life years (QALYs), life years, proportion responding to treatment at 1 year, and number of psychiatric relapses. RESULTS: Regardless of the definition used for response, patients treated with valbenazine were more likely to have responded to treatment at 1 year, lived longer, and accrued more QALYs than patients who received deutetrabenazine. Using the AIMS response criterion, the incremental cost-effectiveness ratio was $9,951/QALY for valbenazine compared with deutetrabenazine. By comparison, using the CGIC response criterion valbenazine dominated deutetrabenazine with valbenazine-treated patients accumulating more QALYs (3.4 vs 3.3 years) and incurring lower lifetime costs ($252,311 vs $283,208) than deutetrabenazine-treated patients. LIMITATIONS: There are no head-to-head trials of valbenazine and deutetrabenazine, so probabilities of response used in the model were calculated based on an indirect treatment comparison of results from individual trials with one drug or the other, using only those metrics reported across trials. CONCLUSIONS: In patients with TD, treatment with valbenazine is highly cost-effective compared with deutetrabenazine.

Management and Outcomes for Neovascular Age-Related Macular Degeneration: Analysis of United States Electronic Health Records.

PURPOSE: To assess anti-vascular endothelial growth factor (VEGF) management patterns and anatomic and visual acuity (VA) outcomes among patients with neovascular age-related macular degeneration (nAMD) in United States clinical practice. DESIGN: Retrospective observational cohort study. PARTICIPANTS: Patients (N = 30 106) initiating intravitreal anti-VEGF treatment for nAMD between October 2009 and November 2016. METHODS: Analysis of longitudinal electronic health records from USRetina. MAIN OUTCOME MEASURES: Number of intravitreal injections, OCT examinations, and fluorescein angiography (FA) examinations per study eye during the first 12 months; corrected VA and central retinal thickness (CRT) at 12 months; and number of ophthalmologist visits, stratified by index anti-VEGF agent. RESULTS: Over the first 12 months, patients made a mean of 8.1 (range, 1-39) ophthalmologist visits, received a mean of 6.0 (range, 1-27) anti-VEGF injections, and underwent 7.2 OCT and 5.3 FA examinations per study eye. For eyes with paired baseline and 12-month readings, mean CRT declined from 320 to 271 µm (mean change, -48 µm), and mean VA increased from 60.3 to 61.0 approximate Early Treatment Diabetic Retinopathy Study (ETDRS) letters (mean change, +0.6 letters). Twelve months after initiating index treatment with bevacizumab, ranibizumab, and aflibercept, 19.3%, 15.8%, and 15.5% of eyes, respectively, showed greater than 10-letter gain, whereas 13.2%, 14.7%, and 14.4% of eyes, respectively, showed greater than 10-letter loss. Mean change from baseline VA at 12 months increased linearly with cumulative anti-VEGF injection count: +1.79 versus -0.95 approximate ETDRS letters for eyes receiving 7 or more injections versus fewer than 7 injections. Similarly, the magnitude of the reduction from baseline CRT at 12 months tended to increase linearly with increasing number of anti-VEGF injections. Multivariate linear regression analysis, adjusted for covariates, indicated a significant association between cumulative number of anti-VEGF injections and change from baseline in VA at 12 months, with each unit increase producing an estimated gain of 0.37 approximate ETDRS letters. CONCLUSIONS: This analysis of combined morphologic and functional outcomes of anti-VEGF therapy, the largest conducted to date in nAMD, identified relatively low anti-VEGF injection frequencies, coupled with moderate anatomic and limited VA improvements, in United States clinical practice.

Assessing Health Care Burden in Glaucoma Patients with and Without Physical or Mental Comorbidities.

BACKGROUND: Glaucoma is a collection of eye diseases that damage the eye's optic nerve resulting in vision loss and blindness. Treatment for glaucoma is primarily pharmacologic; however, studies have shown patients have difficulty adhering to topical regimens. The reasons for potentially poor adherence are numerous, including influence from a myriad of either physical or mental comorbid conditions faced by many glaucoma patients. Neither adherence nor associated outcomes have been estimated in these 2 groups of glaucoma patients. OBJECTIVES: To (a) characterize glaucoma patients with and without select physical or mental comorbidities and (b) estimate differences between the 2 groups for 3 types of outcomes: health care resource use (HCRU; office-based/outpatient-based provider visits, emergency room visits, inpatient stays, home health provider days, prescription fills); health care expenditures; and health-related quality of life (HRQoL) as measured by the physical and mental component scores of the Short Form-12. METHODS: We used first-year data from each glaucoma patient's 2-year panel survey in the Medical Expenditure Panel Survey (MEPS) database, 2003-2014. Two groups were created using ICD-9-CM codes collected by MEPS to compare glaucoma patients with and without at least 1 selected physical or mental comorbid condition. Between-group comparisons in the outcomes of interest (HCRU, expenditure, HRQoL) were estimated using multivariable regression analyses while adjusting for socio-demographic and clinical characteristics at baseline. RESULTS: We identified 2,928 unique glaucoma patients during the 11 years of collected data, including 1,539 (53%) who had at least 1 physical or mental comorbid condition of interest. Comparing those with at least 1 select physical or mental comorbidity to those without (n = 1,389), unadjusted HCRU and expenditures were greater in patients with a physical or mental comorbidity (all P < 0.05). After adjustment, significant associations with increased HCRU remained for office-based provider visits and home health provider days (each P < 0.01). Average total expenditures were $12,324 in those with comorbidities and $8,590 for those without. HRQoL (unadjusted and adjusted) was lower in those with a physical or mental comorbid condition (all P < 0.05). CONCLUSIONS: Some differences in HCRU and expenditures were accounted for by differences in baseline characteristics between those with and those without 1 or more physical or mental comorbid conditions, but differences remained after adjustment. Results suggest that glaucoma patients with physical and mental comorbidities may experience greater HCRU and associated expenditures, and lower HRQoL, when compared with glaucoma patients without these comorbidities With this knowledge, future work may include estimating the effect of the number of these comorbid conditions on each of the 3 types of outcomes. DISCLOSURES: This study received funding support from Allergan. During the time this work was conducted, Serbin was a postdoctoral fellow who was supported by a training grant from Allergan to the University of Washington. Campbell is an employee of Allergan. Serbin, Devine, and Basu each have nothing to disclose. This study was presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research Meeting; May 20-24, 2017; Boston, MA.

Indirect treatment comparison of valbenazine and deutetrabenazine efficacy and safety in tardive dyskinesia.

Aim: Utilize the Bucher indirect treatment comparison (ITC) method to compare valbenazine and deutetrabenazine efficacy using clinical trial data. Methods: Outcomes included mean change from baseline in Abnormal Involuntary Movement Scale (AIMS) total score, AIMS response (≥50% improvement), clinical global impression of change response (score ≤2) and safety outcomes. Data were pooled by trial and dose; outcomes were analyzed at multiple time points. Results: ITC of AIMS score improvement significantly favored valbenazine 80 mg/day at 6 weeks versus deutetrabenazine 36 mg/day at 8 weeks, while valbenazine 40 mg/day was statistically similar to all doses of deutetrabenazine at all time points. No significant differences between drugs were found in AIMS and clinical global impression of change responses and safety outcomes. Conclusion: In this ITC of pooled trial data, valbenazine was generally favorable over deutetrabenazine, although dose titration and equivalency should be considered when interpreting results.

Clopidogrel-Proton Pump Inhibitor Drug-Drug Interaction and Risk of Adverse Clinical Outcomes Among PCI-Treated ACS Patients: A Meta-analysis.

BACKGROUND: Uncertainty regarding clopidogrel effectiveness attenuation because of a drug-drug interaction with proton pump inhibitors (PPI) has led to conflicting guidelines on concomitant therapy. In particular, the effect of this interaction in patients who undergo a percutaneous coronary intervention (PCI), a population known to have increased risk of adverse cardiovascular events, has not been systematically evaluated. OBJECTIVE: To synthesize the evidence of the effect of clopidogrel-PPI drug interaction on adverse cardiovascular outcomes in a PCI patient population. METHODS: We conducted a systematic literature review for studies reporting clinical outcomes in patients who underwent a PCI and were initiated on clopidogrel with or without a PPI. Studies were included in the analysis if they reported at least 1 of the clinical outcomes of interest (major adverse cardiovascular event [MACE], cardiovascular death, all-cause death, myocardial infarction, stroke, stent thrombosis, and bleed events). We excluded studies that were not exclusive to PCI patients or had no PCI subgroup analysis and/or did not report at least a 6-month follow-up. Statistical and clinical heterogeneity were evaluated and HRs and 95% CIs for adverse clinical events were pooled using the DerSimonian and Laird random-effects meta-analysis method. RESULTS: We identified 12 studies comprising 50,277 PCI patients that met our inclusion and exclusion criteria. Our analysis included retrospective analyses of randomized controlled trials (2), health registries (3), claims databases (2), and institutional records (5); no prospective studies of PCI patients were identified. On average, patients were in their mid-60s, male, and had an array of comorbidities, including hyperlipidemia, diabetes, hypertension, and smoking history. Concomitant therapy following PCI resulted in statistically significant increases in composite MACE (HR = 1.28; 95% CI = 1.24-1.32), myocardial infarction (HR = 1.51; 95% CI = 1.40-1.62), and stroke (HR = 1.46; 95% CI = 1.15-1.86). However, concomitant therapy had no statistically significant effect on stent thrombosis, mortality measured by all-cause or cardiovascular death, or major bleeding before or after the grouping of studies that reported a major or minor bleed outcome. Only 1 study reported on gastrointestinal bleed, and pooled analysis could not be conducted. Statistical testing suggested heterogeneity among studies, but subgroup analysis did not reveal a clear source. CONCLUSIONS: Based on the results from this meta-analysis of retrospective analyses of randomized controlled trials and observational studies, concomitant clopidogrel-PPI therapy following PCI appears to be significantly associated with adverse cardiovascular events. Further research on the effect of individual PPIs is needed. DISCLOSURES: Serbin, Guzauskas, and Veenstra were supported by the NIH Common Fund and NIA (1U01AG047109-01, Veenstra, PI) via the Personalized Medicine Economics Research (PriMER) project. The authors do not report any conflicting interests. All authors contributed to the study concept and design. Serbin took the lead in data collection; data interpretation was performed primarily by Serbin, with assistance from the other authors. The manuscript was written primarily by Serbin, along with Guzauskas, and revised by Guzauskas and Veenstra, with assistance from Serbin.