Real-World Outcomes and Costs Following 6 Months of Treatment with the Long-Acting Injectable (LAI) Aripiprazole Lauroxil for the Treatment of Schizophrenia.

BACKGROUND: Continuous antipsychotic therapy is recommended as part of long-term maintenance treatment of schizophrenia, and gaps in antipsychotic treatment have been associated with increased risks of relapse and rehospitalization. Because the use of long-acting injectable (LAI) antipsychotics may reduce the likelihood of undetected medication gaps, initiating an LAI medication may affect resource utilization and costs. The LAI aripiprazole lauroxil (AL) was approved in the United States (US) in 2015 for the treatment of schizophrenia in adults. OBJECTIVE: The objective of this retrospective observational cohort study was to examine treatment patterns, resource utilization, and costs following initiation of AL for the treatment of schizophrenia in adults. METHODS: A retrospective analysis of Medicaid claims data identified a cohort of patients (N = 485) starting AL shortly after Food and Drug Administration approval in October 2015. Treatment patterns, resource utilization, and costs were compared 6 months before and after treatment initiation. Subgroup analyses were conducted based on the type of antipsychotic (LAI, oral, or none) received before initiation of AL. RESULTS: Over 6 months of follow-up, patients received an average of 4.6 injections out of a maximum of six (77%). After initiating AL, all-cause inpatient admissions decreased by 22.4%; other significant reductions were observed in mental health-related admissions and emergency room (ER) visits. All-cause inpatient costs decreased by an average of US$2836 per patient (p < 0.05) in the 6-month post-AL period, whereas outpatient pharmacy costs increased by US$4121 (p < 0.05), resulting in no significant difference in overall costs between the pre- and post-AL periods. The subgroup of patients who had been prescribed an oral antipsychotic before starting AL had significant reductions in proportion of patients with inpatient and ER visits and costs, but also reported a significant increase in pharmacy costs. CONCLUSIONS: AL was associated with a significant reduction in inpatient costs and an increase in outpatient pharmacy costs, resulting in no changes in total healthcare costs over 6 months. The adherence rate and reductions in inpatient use may indicate the potential for greater clinical stability among patients initiated on AL compared with their previous treatment.

Can a monthly exenatide extended release regimen provide a therapeutic and cost benefit?

Exenatide is used to treat type 2 diabetes mellitus. The current regimen is a 2 mg extended release (ER) weekly injection. The aim of our study was to prove the efficacy of exenatide ER if administered once-monthly. The proposed monthly dose was based on an Excel simulation using pharmacokinetic parameters extracted using Plot Digitizer® (version 2.6.8) from Cirincione et al. (2017), as well as accounting for the exenatide ER formulation characteristics, in vivo and in vitro exenatide stability. A PBPK model of exenatide molecule was developed using (Simcyp® version 19) based on data from in vitro and clinical PK studies. The model was used to confirm the Excel simulation findings of the effectiveness of exenatide ER monthly in maintaining the plasma level above the minimum effective concentration (MEC). Our simulation from Excel and Simcyp® showed that the drug plasma levels of the once monthly ER dose maintained a steady state concentration (Css ) above the MEC. The simulated Excel plasma level ranged from Cmin to Cmax of 60-130ng/L, respectively. The exenatide compound was successfully modeled and used to predict the Css of the ER monthly dose. The Simcyp® simulated Css of the ER was 117 ng/L. A monthly exenatide ER dose provides a plasma level within the therapeutic range. This new proposed dose has a significant pharmacoeconomic benefit and could well improve patient adherence.

Modulation of protein release from penta-block copolymer microspheres.

Releasing a protein according to a zero-order profile without protein denaturation during the polymeric microparticle degradation process is very challenging. The aim of the current study was to develop protein-loaded microspheres with new PLGA based penta-block copolymers for a linear sustained protein release. Lysozyme was chosen as model protein and 40 µm microspheres were prepared using the solid-in-oil-in-water solvent extraction/evaporation process. Two types of PLGA-P188-PLGA penta-block copolymers were synthetized with two PLGA-segments molecular weight (20 kDa or 40 kDa). The resulting microspheres (50P20-MS and 50P40-MS) had the same size, an encapsulation efficiency around 50-60% but different porosities. Their protein release profiles were complementary: linear but non complete for 50P40-MS, non linear but complete for 50P20-MS. Two strategies, polymer blending and microsphere mixing, were considered to match the release to the desired profile. The (1:1) microsphere mixture was successful. It induced a bi-phasic release with a moderate initial burst (around 13%) followed by a nearly complete linear release for 8 weeks. This study highlighted the potential of this penta-block polymer where the PEO block mass ratio influence clearly the Tg and consequently the microsphere structure and the release behavior at 37 °C. The (1:1) mixture was a starting point but could be finely tuned to control the protein release.

Health and economic outcomes of treatment with extended-release naltrexone among pre-release prisoners with opioid use disorder (HOPPER): protocol for an evaluation of two randomized effectiveness trials.

BACKGROUND: Persons with an opioid use disorder (OUD) who were incarcerated face many challenges to remaining abstinent; concomitantly, opioid-overdose is the leading cause of death among this population, with the initial weeks following release proving especially fatal. Extended-release naltrexone (XR-NTX) is the most widely-accepted, evidence-based OUD pharmacotherapy in criminal justice settings, and ensures approximately 30 days of protection from opioid overdose. The high cost of XR-NTX serves as a barrier to uptake by many prison/jail systems; however, the cost of the medication should not be viewed in isolation. Prison/jail healthcare budgets are ultimately determined by policymakers, and the benefits/cost-offsets associated with effective OUD treatment will directly and indirectly affect their overall budgets, and society as a whole. METHODS: This protocol describes a study funded by the National Institute of Drug Abuse (NIDA) to: evaluate changes in healthcare utilization, health-related quality-of-life, and other resources associated with different strategies of XR-NTX delivery to persons with OUD being released from incarceration; and estimate the relative "value" of each strategy. Data from two ongoing, publicly-funded, randomized-controlled trials will be used to evaluate these questions. In Study A, (XR-NTX Before vs. After Reentry), participants are randomized to receive their first XR-NTX dose before release, or at a nearby program post-release. In Study B, (enhanced XR-NTX vs. XR-NTX), both arms receive XR-NTX prior to release; the enhanced arm receives mobile medical (place of residence) XR-NTX treatment post-release, and the XR-NTX arm receives referral to a community treatment program post-release. The economic data collection instruments required to evaluate outcomes of interest were incorporated into both studies from baseline. Moreover, because the same instruments are being used in both trials on comparable populations, we have the opportunity to not only assess differences in outcomes between study arms within each trial, but also to merge the data sets and test for differences across trials. DISCUSSION: Initiating XR-NTX for OUD prior to release from incarceration may improve patient health and well-being, while also producing downstream cost-offsets. This study offers the unique opportunity to assess the effectiveness and cost-effectiveness of multiple strategies, according to different stakeholder perspectives.

Economic Burden Associated With Extended-Release vs Immediate-Release Drug Formulations Among Medicare Part D and Medicaid Beneficiaries.

Importance: The United States spends more money on medications than any other country. Most extended-release drugs have not consistently shown therapeutic or adherence superiority, and switching these medications to less expensive, generic, immediate-release formulations may offer an opportunity to reduce health care spending. Objective: To evaluate Medicare Part D and Medicaid spending on extended-release drug formulations and the potential savings associated with switching to generic immediate-release formulations. Design, Setting, and Participants: This cross-sectional study used the 2012 to 2017 Medicare Part D Drug Event and Medicaid Spending and Utilization data sets to analyze 20 extended-release drugs with 37 Medicare formulations and 36 Medicaid formulations. Only cardiovascular, diabetes, neurologic, and psychiatric extended-release drugs saving at most 1 additional daily dose compared with their immediate-release counterparts were included. Extended-release drugs with therapeutic superiority were excluded. Analyses were conducted from January to December 2019. Main Outcomes and Measures: Estimated Medicare Part D and Medicaid savings from switching extended-release to immediate-release drug formulations between 2012 and 2017. Results: Of the 6252 drugs screened for eligibility from the 2017 Medicaid Drug Utilization database and the 2017 Medicare Part D database, 67 drugs with extended-release formulations that were identified in the Medicare data set (20 distinct drugs with 37 formulations [19 brand, 18 generic]) were included in the analysis. In 2017, Medicare Part D spent $2.2 billion and Medicaid spent $952 million (a combined $3.1 billion) on 20 extended-release drugs. Between 2012 and 2017, Medicare Part D and Medicaid spent $12 billion and $5.9 billion, respectively, on extended-release formulations. Switching from brand-name to generic extended-release formulations was estimated to be associated with a $247 million reduction in Medicare spending and $299 million reduction in Medicaid spending in 2017, whereas switching all brand-name and generic extended-release formulations to immediate-release formulations in both Medicare and Medicaid was estimated to reduce spending by $2.6 billion ($1.8 billion for Medicare and $836 million for Medicaid) in 2017. During the study period, the estimated spending reduction associated with switching all patients receiving extended-release formulations (brand name extended-release and generic extended-release) to generic immediate-release formulations was $13.7 billion ($8.5 billion from Medicare and $5.2 billion from Medicaid). Conclusions and Relevance: The findings suggest that switching from extended-release drug formulations to therapeutically equivalent immediate-release formulations when available represents a potential option to reduce Medicare and Medicaid spending.

The clinical and economic impact of three-monthly long-acting formulation of paliperidone palmitate versus the one-monthly formulation in the treatment of schizophrenia in France: A cost-utility study.

OBJECTIVES: Schizophrenia entails a considerable humanistic and economic burden. Improved treatment continuity to antipsychotic therapy is paramount to reduce the risk of relapse. The novel three-monthly paliperidone palmitate treatment (PP3M) offers the longest dosing interval currently available in France. This study assesses its cost-effectiveness, versus the currently available one-monthly long-acting treatment (PP1M) in French schizophrenic patients. METHODS: A Markov model with monthly cycles was developed and adapted. It encompassed [a] administration of PP3M or PP1M in first-line, [b] a period where the patient does not receive any active treatment, and [c] a follow-up treatment line consisting of a treatment mix reflecting French clinical practice. Relapse rates in first-line were based on a pivotal non-inferiority head-to-head trial, and treatment discontinuation rates were based on French real-world data. Accounting for differences in drug exposure, time-dependent monthly relapse rates were applied following discontinuation to first line. The impact of a less frequent injection schedule for PP3M in QoL was accounted for through the application of a utility differential. The collective perspective was adopted throughout a 5-year time horizon. Four percent discount rates were applied on costs and outcomes. RESULTS: PP3M was dominant when compared to PP1M, featuring an incremental QALY of 0.123 and a cost saving effect (-669€) resulting from reduced therapy costs (drug acquisition, administration and monitoring) and relapse-related costs. Sensitivity analysis supported the robustness of the results. CONCLUSION: With slightly better QALY outcomes and a cost-saving effect when compared to PP1M, introducing PP3M is an improvement to the current treatment in France.

Modeling the potential impact of abuse-deterrent opioids on medical resource utilization.

Objectives: To extend a previously published manuscript on a model for estimating potential avoided medical events and cost savings in the US associated with the introduction of extended-release abuse-deterrent opioids and incorporate new methods of evaluating abuse deterrence using human abuse potential studies. Methods: A model was developed to estimate reductions in abuse-related events and annual savings in the US. Model inputs included: opioid abuse prevalence, abuse-deterrent opioid cost and effectiveness at deterring abuse, and opioid abuse-related events and costs. Direct (medical and drug) and indirect (work loss) cost savings (2017 US$) and abuse-related events were estimated assuming the replacement of the entire extended-release opioid market (brand and generic) by brand abuse-deterrent opioids. Results: Replacing the extended-release opioid market with abuse-deterrent opioids is estimated to lower annual abuse-related medical events by ∼13-31% (e.g. 78,000-186,000 emergency department visits) and lower annual medical costs by ∼$640 M-$1,538 M, depending on the abuse-deterrent technology (physical/chemical barrier or agonist/antagonist). Replacement of extended-release oxycodone with extended-release abuse-deterrent oxycodone is associated with the largest amount of cost savings and highest number of avoided medical events, followed by replacing extended-release morphine with an extended-release abuse-deterrent opioid. Replacement of transdermal fentanyl is associated with the smallest amount of cost savings and lowest number of avoided medical events. Conclusion: Agonist/antagonist abuse-deterrent opioid technology is associated with higher annual medical cost savings and more avoided events than physical/chemical barrier technology. Total net savings are dependent upon the abuse-deterrent opioid price relative to non-abuse-deterrent opioids.

Modeling operational quality metrics and costs of long-acting antibiotics for acute bacterial skin and skin structure infection treatment in the emergency department.

Aims: To model implementation of a new treatment pathway leveraging long-acting antibiotics (LAs) for treatment of acute bacterial skin and skin structure infections (ABSSSIs) in a hospital emergency department (ED) with an observation unit, and to quantify health resource utilization and economic outcomes versus standard care (intravenous vancomycin). Materials and methods: Discrete-event simulation was used to model implementation of the LA treatment pathway in the ED versus standard care from the US Medicare perspective. Model inputs were derived from published sources to simulate a real-world hospital ED with an observation unit. Outcomes included key ED metrics such as patient throughput rate and length of stay (LOS) and cost (estimated through reimbursed amounts in 2017 USD). Results: Implementation of an LA pathway in the ED improved ABSSSI patient throughput rate by 350% (+5.8 dispositions/ED and observation unit day) and reduced LOS by 68% (-7.2 h/patient). These improvements in patient outcomes are driven by the reduced infusion time required for LA antibiotics and are greater for dalbavancin than oritavancin owing to the shorter infusion duration (30 min vs. 3 h). Limitations: External validity of the model was not assessed. The model was limited to care received in EDs; therefore, certain clinical variables outside the ED were not captured for this analysis. Conclusions: LA pathway implementation for ABSSSI treatment in the ED supported improved efficiency, which may translate to economic value. As EDs continue to focus on improving key metrics such as throughput rate and LOS, LA pathway implementation should be considered as a potential approach for abbreviated ABSSSI treatment in the ED.

Cost-effectiveness of gastro-resistant risedronate tablets for the treatment of postmenopausal women with osteoporosis in France.

The use of gastro-resistant risedronate, a convenient dosing regimen for oral bisphosphonate therapy, seems a cost-effective strategy compared with weekly alendronate, generic risedronate, and no treatment for the treatment of postmenopausal women with osteoporosis in France. INTRODUCTION: Gastro-resistant (GR) risedronate tablets are associated with improved persistence compared to common oral bisphosphonates but are slightly more expensive. This study assessed its cost-effectiveness compared to weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France. METHODS: A previously validated Markov microsimulation model was used to estimate the lifetime costs (expressed in €2017) per quality-adjusted life-years (QALY) of GR risedronate compared with weekly alendronate, generic risedronate, and no treatment. Pooled efficacy data for bisphosphonates derived from a previous meta-analysis were used for all treatment options, and persistence data (up to 3 years) were obtained from a large Australian longitudinal study. Evaluation was done for high-risk women 60-80 years of age, with a bone mineral density (BMD) T-score ≤ - 2.5 and/or prevalent vertebral fractures. RESULTS: In all of the simulated populations, GR risedronate was cost-effective compared to alendronate, generic risedronate, and no treatment at a threshold of €60,000 per QALY gained. In women with a BMD T-score ≤ - 2.5 and prevalent vertebral fractures, the cost per QALY gained of GR risedronate compared to alendronate, generic risedronate, and no treatment falls below €20,000 per QALY gained. In women aged 75 years and older, GR risedronate was even shown to be dominant (more QALYs, less costs) compared to alendronate, generic risedronate, and no treatment. CONCLUSION: This study provides the first economic results about GR risedronate, suggesting that it represents a cost-effective strategy compared with weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France.

Comparison of cost and outcomes in patients receiving thoracic epidural versus liposomal bupivacaine for video-assisted thoracoscopic pulmonary resection.

BACKGROUND: Thoracic Epidural has long been the most recommended treatment for postoperative pain management in general thoracic surgery. This study compares liposomal bupivacaine (LB) as an alternative method for pain control and compares it to the standard. METHODS: LB was compared to thoracic epidural bupivacaine hydrochloride (TE BH) in 387 patients who underwent video-assisted thoracoscopic pulmonary resection (VATS-R) at our institution. Patients received either continuous TE BH or intraoperative LB at a predetermined dose. A total of 237 patients received TE BH from April 2010 to March 2014 and 143 patients received LB from April 2014 to March 2016. After propensity matching, 95 patients in each group had similar demographics and clinical characteristics including gender, age, race, American Society of Anesthesia (ASA) classification, Zubrod scores, and FEV1 and DLCO percent predicted measurements. Outcome measures included hospital costs, length of stay (LOS), adverse events, postoperative opioid medication use, and pain scores. RESULTS: Compared to the TE BH group, the LB group had significantly lower pain scores (average visual analogue scale the day of surgery: 3.9 versus 4.5, p < 0.05), decreased postoperative opioid medication (morphine equivalent dose during the first 3 days: 344.5 versus 269.5, p < 0.05), and lower total and direct hospital costs ($2906 and $1865 respectively, p < 0.05). Although a shorter LOS in the LB group was not statistically significant (4.3 versus 5.1 days, p = 0.156), more patients in the LB group were discharged directly home than the control group (44.2% versus 28.4%, p < 0.05). There was no difference noted in overall adverse events including 30-day readmissions between the two groups. CONCLUSION: LB is a viable alternative for pain management in patients undergoing VATS-R. With recent scrutiny on healthcare costs and the opioid epidemic, these results are encouraging and should be further investigated.

Cost-Effectiveness of Buprenorphine-Naloxone Versus Extended-Release Naltrexone to Prevent Opioid Relapse.

Background: Not enough evidence exists to compare buprenorphine-naloxone with extended-release naltrexone for treating opioid use disorder. Objective: To evaluate the cost-effectiveness of buprenorphine-naloxone versus extended-release naltrexone. Design: Cost-effectiveness analysis alongside a previously reported randomized clinical trial of 570 adults in 8 U.S. inpatient or residential treatment programs. Data Sources: Study instruments. Target Population: Adults with opioid use disorder. Time Horizon: 24-week intervention with an additional 12 weeks of observation. Perspective: Health care sector and societal. Interventions: Buprenorphine-naloxone and extended-release naltrexone. Outcome Measures: Incremental costs combined with incremental quality-adjusted life-years (QALYs) and incremental time abstinent from opioids. Results of Base-Case Analysis: Use of the health care sector perspective and a willingness-to-pay threshold of $100 000 per QALY showed buprenorphine-naloxone to be preferable to extended-release naltrexone in 97% of bootstrap replications at 24 weeks and in 85% at 36 weeks. Similar results were obtained with incremental time abstinent from opioids as an outcome and with use of the societal perspective. Results of Sensitivity Analysis: The base-case results were sensitive to the cost of the 2 treatments and the success of randomized treatment initiation. Limitation: Relatively short follow-up for a chronic condition, substantial missing data, no information on patient out-of-pocket and social service costs. Conclusion: Buprenorphine-naloxone is preferred to extended-release naltrexone as first-line treatment when both options are clinically appropriate and patients require detoxification before initiating extended-release naltrexone. Primary Funding Source: National Institute on Drug Abuse, National Institutes of Health.

Treatment Patterns, Healthcare Resource Utilization and Costs Among Schizophrenia Patients Treated with Long-Acting Injectable Versus Oral Antipsychotics.

INTRODUCTION: Long-acting injectable (LAI) antipsychotic use may reduce healthcare resource utilization compared with oral antipsychotic use by improving adherence and reducing dosing frequency. Our goal was to examine treatment patterns, healthcare utilization, and costs among recently diagnosed schizophrenia patients receiving oral versus LAI antipsychotics. METHODS: The MarketScan Multi-state Medicaid database was used to identify schizophrenia patients aged ≥ 18 years who received an LAI or oral antipsychotic between January 1, 2011 and December 31, 2014. Primary outcomes included treatment patterns such as adherence (measured as proportion of days covered-PDC), persistence, discontinuation, switching, and healthcare resource utilization and costs. Propensity score matching (PSM) was used to control for differences in baseline characteristics between the cohorts. Outcomes were assessed over a 12-month post-index period and compared between treatment cohorts. RESULTS: After PSM, 2302 patients were included in each of the LAI and oral antipsychotics cohorts. There were no differences in PDC or therapy switching between the two cohorts. Compared with the oral cohort, patients receiving LAIs had lower discontinuation rates (46.1 vs. 61.6%, p < 0.001), fewer inpatient admissions (0.5 vs. 0.9, p < 0.001), hospital days (3.9 vs. 6.5, p < 0.001), and ER visits (2.4 vs. 2.9, p = 0.007), and a higher number of prescription fills (29.5 vs. 25.3, p < 0.001). Patients prescribed LAIs had lower monthly inpatient ($US4007 vs. 8769, p < 0.001) and ER visits costs ($682 vs. 891, p < 0.001) but higher monthly medication costs ($10,713 vs. $655, p < 0.001) compared with the oral cohort over the 12-month post-index period. Overall, both cohorts had similar total medical costs (LAI vs. oral: $24,988 vs. 23,887, p = 0.354) during the follow-up period. CONCLUSION: Patients receiving LAIs were more likely to remain on medication compared with the oral group, which may account for reduced inpatient admissions. Hospitalization cost reductions offset the higher costs of LAI medications, resulting in no increase in total healthcare costs relative to oral antipsychotic use. FUNDING: Alkermes Inc.

Qualitative Consumer Research on Acceptance of Long-Acting Pre-Exposure Prophylaxis Products Among Men Having Sex with Men and Medical Practitioners in the United States.

Pre-exposure prophylaxis (PrEP) with oral Truvada® prevents HIV infection. However, the adherence to pill taking required for efficacy has sparked interest in developing new antiretroviral delivery systems that decrease such demands. Long-acting formulations, such as injections and implants, represent promising options that require less frequent adherence. It is important, however, that development of these new modalities be driven by understanding of the value seen in them by target users to maximize their uptake. To identify the key product features that impact user acceptance, we used a three-phase marketing research approach. In this study, we describe the results of the first-phase, qualitative focus group research performed in Chicago and San Francisco that explored subjective perceptions of oral versus alternative PrEP modalities among men having sex with men (MSM) and medical practitioners caring for MSM. Data revealed that potential value in long-acting PrEP lies more in simplifying the lives of users rather than in making them more confident in their adherence. The results provide an important guidance for designing and promoting these future long-acting products to enhance their contribution to increasing the current limited uptake of PrEP that will better stem the HIV epidemic.

First Opioid Prescription and Subsequent High-Risk Opioid Use: a National Study of Privately Insured and Medicare Advantage Adults.

BACKGROUND: National guidelines make recommendations regarding the initial opioid prescriptions, but most of the supporting evidence is from the initial episode of care, not the first prescription. OBJECTIVE: To examine associations between features of the first opioid prescription and high-risk opioid use in the 18 months following the first prescription. DESIGN: Retrospective cohort study using data from a large commercial insurance claims database for 2011-2014 to identify individuals with no recent use of opioids and follow them for 18 months after the first opioid prescription. PARTICIPANTS: Privately insured patients aged 18-64 and Medicare Advantage patients aged 65 or older who filled a first opioid prescription between 07/01/2011 and 06/30/2013. MAIN OUTCOMES AND MEASURES: High-risk opioid use was measured by having (1) opioid prescriptions overlapping for 7 days or more, (2) opioid and benzodiazepine prescriptions overlapping for 7 days or more, (3) three or more prescribers of opioids, and (4) a daily dosage exceeding 120 morphine milligram equivalents, in each of the six quarters following the first prescription. KEY RESULTS: All three features of the first prescription were strongly associated with high-risk use. For example, among privately insured patients, receiving a long- (vs. short-) acting first opioid was associated with a 16.9-percentage-point increase (95% CI, 14.3-19.5), a daily MME of 50 or more (vs. less than 30) was associated with a 12.5-percentage-point increase (95% CI, 12.1-12.9), and a supply exceeding 7 days (vs. 3 or fewer days) was associated with a 4.8-percentage-point increase (95% CI, 4.5-5.2), in the probability of having a daily dosage of 120 MMEs or more in the long term, compared to a sample mean of 4.2%. Results for the Medicare Advantage patients were similar. CONCLUSIONS: Long-acting formulation, high daily dosage, and longer duration of the first opioid prescription were each associated with increased high-risk use of opioids in the long term.

Projecting the Potential Effect of Using Paliperidone Palmitate Once-Monthly and Once-Every-3-Months Long-Acting Injections Among Medicaid Beneficiaries with Schizophrenia.

BACKGROUND: Once-monthly and once-every-3-months long-acting injectable (LAI) formulations of paliperidone palmitate (PP1M and PP3M, respectively) are available for the treatment of patients with schizophrenia. However, information on the comparative effectiveness and costs of using these LAIs versus oral antipsychotics (OAs) is not available. The population effectiveness of using these treatments is also not known. OBJECTIVE: To project the effect of using PP1M and PP3M LAIs on psychiatric (Psych) and all-cause (AC) hospitalization rates over 18 months in patients with schizophrenia receiving Medicaid and treated with OAs. METHODS: A decision model, informed by data from 3 randomized controlled trials (PRIDE [NCT01157351], 3001 [NCT00111189], and 3012 [NCT01529515]), was developed to compare 3 strategies: (a) initiating OA and switching only to OA; (b) initiating with PP1M and continuing PP1M if the patient was stable at 6 months (or switching to OA if unstable; PP1M→PP1M); and (c) initiating with PP1M and switching to PP3M if the patient was stable at 6 months (or switching to OA if unstable; PP1M→PP3M). PRIDE data were used to inform the first 6-month outcomes; 3001 and 3012 data were used to inform outcomes in stable patients over the following 12 months. The primary outcome for this decision model study was Psych hospitalizations. AC hospitalizations and time to discontinuation were also assessed. Outcomes from each arm and time portions within an arm were reweighted to reflect the distribution of patient characteristics found in the real-world Medicaid sample with PRIDE trial inclusion/exclusion criteria applied. Several validation exercises were carried out to ensure that the reweighted results could reproduce observed outcomes in the Medicaid sample. RESULTS: Our final target real-world sample size was N=4,609. We found that in the Medicaid sample, compared with initiating treatments with OA, the PP1M→PP1M strategy was projected to produce a per patient decrease of 0.27 (95% CI = -0.43-0.97) and 0.28 (95% CI = -0.28-0.84) in Psych- and AC-related hospitalizations, respectively. Similarly, the PP1M→PP3M strategy was projected to produce a per patient decrease of 0.31 (95% CI = -0.27-0.87) in both Psych- and AC-related hospitalizations over OA. Validation exercises ensured that the reweighting methodology used could replicate observed outcomes in the Medicaid sample. These incremental reductions in hospitalization rates are worth about $3.4-$3.8 billion over an 18-month period in patients with schizophrenia receiving Medicaid. CONCLUSIONS: Our results suggest that using PP1M and PP3M treatment strategies for patients with schizophrenia receiving Medicaid could result in reduced hospitalizations. This finding, along with improvement to patients' health, should be considered when assessing the value of these LAIs. DISCLOSURES: This study was supported by Janssen Scientific Affairs and by unrestricted funds from a consortium of 12 biomedical life sciences companies to the University of Washington. Janssen Scientific Affairs was responsible for the design and conduct of the study; the collection, management, analysis, and interpretation of data; the preparation, review, and approval of the manuscript; and the decision to submit the manuscript for publication. Basu received financial support from Janssen Pharmaceuticals, and his time on this project was also partly covered through unrestricted gift funds from the consortium of biomedical life sciences companies. Benson and Alphs are employees of Janssen Scientific Affairs and are stockholders of Johnson & Johnson. Opinions expressed here do not necessarily reflect those of the University of Washington. This study was presented as a poster at the AMCP Managed Care & Specialty Pharmacy 2017 Annual Meeting; March 27-30, 2017; Denver, CO.

ILUVIEN® technology in the treatment of center-involving diabetic macular edema: a review of the literature.

Diabetic macular edema (DME) is one of the major causes of blindness, caused primarily by hyperglycemia and results from multiple pathological processes mostly secondary to increased levels of VEGF and other inflammatory cytokines. DME management includes control of systemic risk factors together with laser photocoagulation, frequent intraocular injections of anti-VEGF agents and steroids implants. Recent adoption of novel alternative drug delivery options has led to the development of sustained release ocular implants with longer duration of action with less injection frequency. This article will review the pharmacology and clinical data in terms of efficacy, safety and benefits of the sustained release steroid implants in treatment of DME with special emphasis on the fluocinolone acetonide ILUVIEN® implant.

Opioid Medications in Expensive Formulations Are Sold at a Lower Price than Immediate-Release Morphine in Countries throughout the World: Third Phase of Opioid Price Watch Cross-Sectional Study.

BACKGROUND: International Association for Hospice and Palliative Care implemented Opioid Price Watch (OPW) to monitor availability, dispensing prices and affordability of opioids. We found that opioids with complex delivery mechanisms [fentanyl transdermal (TD) patches, sustained-release (SR) morphine, and SR oxycodone] had lower dispensing prices than immediate-release (IR) morphine formulations. OBJECTIVE: Identify the extent that SR and TD formulations are dispensed at lower prices than generic IR morphine and the possible reasons to explain this observation. DESIGN: Using OPW data for 30-day treatment Defined Daily Dosages, we identified where SR and TD formulations are dispensed at lower prices than IR morphine. Then we analyzed national lists of essential medicines (EML) in middle- and low-income countries to answer two questions: (1) Do they have opioids included? If yes, (2) Which ones? We then sought information on selection, budget allocation, and procurement for EML. OPW participants confirmed/verified the EML information. RESULTS: Eighteen countries reported higher dispensing prices for IR morphine (oral and/or injectable) than TD or SR formulation. Injectable morphine was highest in seven and lowest in two (range: $74-$742). SR morphine was the least expensive, while TD fentanyl was second. Median dispensing price for IR oral morphine was higher than SR morphine. The EML for 10 countries include opioids in TD and/or SR formulations. CONCLUSIONS: Opioids in expensive formulations are being favored over IR morphine both at the dispensing level and in their inclusion in national EML. Governments must take decisions based on efficacy, safety, and cost-effectiveness of medications.

The effect of financial incentives on patients' motivation for treatment: results of "Money for Medication," a randomised controlled trial.

BACKGROUND: Offering financial incentives is an effective intervention for improving adherence in patients taking antipsychotic depot medication. We assessed whether patients' motivation for treatment might be reduced after receiving financial rewards. METHODS: This study was part of Money for Medication, a multicentre, open-label, randomised controlled trial, which demonstrated the positive effects of financial incentives on antipsychotic depot compliance. Three mental healthcare institutions in Dutch secondary psychiatric care services participated. Eligible patients were aged 18-65 years, had been diagnosed with schizophrenia or another psychotic disorder, had been prescribed antipsychotic depot medication or had an indication to start using depot medication, and were participating in outpatient treatment. For 12 months, patients were randomly assigned either to treatment as usual (control group) or to treatment as usual plus a financial reward for each depot of medication received (€30 per month if fully compliant; intervention group). They were followed up for 6 months, during which time no monetary rewards were offered for taking antipsychotic medication. To assess treatment motivation after 0, 12 and 18 months, interviews were conducted using a supplement to the Health of the Nation Outcome Scales (HoNOS) and the Treatment Entry Questionnaire (TEQ). RESULTS: Patients were randomly assigned to the intervention (n = 84) or the control group (n = 85). After 12 months, HoNOS motivation scores were available for 131 patients (78%). Ninety-one percent of the patients had no or mild motivational problems for overall treatment; over time, there were no significant differences between the intervention and control groups. TEQ data was available for a subgroup of patients (n = 61), and showed no significant differences over time between the intervention and control groups for external motivation (ß = 0.37 95% CI: -2.49 - 3.23, p = 0.799); introjected motivation (ß = - 2.39 95% CI: -6.22 - 1.44, p = 0.222); and identified motivation (ß = - 0.91 95% CI: -4.42 - 2.61, p = 0.613). After the 6-month follow-up period, results for the HoNOS and TEQ scores remained comparable. CONCLUSIONS: Offering financial incentives for taking antipsychotic depot medication does not reduce patients' motivation for treatment. TRIAL REGISTRATION: Netherlands Trial registration, number NTR2350 .

Adherence, persistence, and inpatient utilization among adult schizophrenia patients using once-monthly versus twice-monthly long-acting atypical antipsychotics.

AIMS: This study compared healthcare resource utilization (HRU), healthcare costs, adherence, and persistence among adult patients with schizophrenia using once-monthly (OM) vs twice-monthly (TM) atypical long-acting injectable (LAI) antipsychotic (AP) therapy. MATERIALS AND METHODS: A longitudinal retrospective cohort study was conducted using Medicaid claims data from six states. Patients initiated on aripiprazole or paliperidone palmitate were assigned to the OM cohort; risperidone-treated patients were assigned to the TM cohort. HRU and healthcare costs were assessed during the first 12 months following stabilization on the medication. Adherence was measured using the proportion of days covered (PDC) during the first year of follow-up. Persistence to the index medication was measured during the first 2 years following the index date. Comparison between the cohorts was achieved using multivariable generalized linear models, adjusting for demographic and clinical characteristics. RESULTS: Patients in the OM LAI cohort had lower inpatient HRU and medical costs when compared with patients in the TM cohort. Higher medical costs in the TM LAI cohort offset the higher pharmacy costs in the OM LAI cohort. Mean PDC during the first 12 months of follow-up was higher in the OM cohort than in the TM cohort (0.56 vs 0.50, p < .01). Median persistence was longer in the OM cohort than in the TM cohort (7.5 months vs 5.5 months), as was the hazard of discontinuing the index medication (hazard ratio = 0.83, p = .01). Kaplan-Meier rates of persistence at 1 year were higher for OM patients than for TM patients (37.6% vs 29.6%, p < .01). LIMITATIONS: This was a Medicaid sample with few aripiprazole LAI patients (5.4% of OM cohort). Medication use was inferred from pharmacy claims. CONCLUSIONS: Among Medicaid patients in these six states, OM AP treatment was associated with lower HRU, better adherence and persistence, and similar total costs compared to patients on TM treatment.

"Impact of drug-reimbursement policies on prescribing: A case-study of a newly marketed long-acting injectable antipsychotic among relapsed schizophrenia patients".

OBJECTIVE: To quantify and explain variation in use of long-acting injectable antipsychotics (LAIs) in the United States, and understand the relationship between patient characteristics, drug reimbursement policies, and LAI prescribing after relapse. METHODS: A cohort of recently relapsed patients with schizophrenia ages 18 to 64, were identified immediately after discharge from a related inpatient hospitalization, partial hospitalization, or emergency room visit, drawn from 2004 to 2006 Medicaid claims, and followed for 90 days until LAI initiation. Data on state-level Medicaid prior authorization (PA) policies for LAIs were collected. Sequential longitudinal Poisson regression models were developed to understand the relationship between patient and PA policy variables and LAI prescribing, including prior adherence to oral antipsychotics, demographics, clinical variables, and presence of PA policy for LAI. RESULTS: Among 36 282 patients, 3.1% received risperidone LAI, and 3.8% received a first-generation (FGA) LAI with wide variation across states. Prior adherence ranged from 29% to 89% but was marginally associated with initiation and did not explain variation for LAI prescribing. FGA initiation was associated with geography and race/ethnicity but not PA policy. For risperidone LAI initiation, demographics and clinical factors explained, respectively, 5.0% and 3.0% of the variation; PA policy had a large negative association with initiation (RR = 0.41; 95%CI 0.20-0.87) and explained 8.4% of the variation. CONCLUSIONS: PA policies may represent a major treatment barrier for risperidone LAI among relapsed patients. Non-adherence plays a little role in predicting which patients receive LAIs. Policy makers and health insurers will need to consider these findings when guiding the use of LAIs. KEY POINTS Among a nationwide cohort of relapsed schizophrenia patients enrolled in US Medicaid, 3.1% received Risperdal Consta, a long-acting injectable antipsychotic (LAI), and 3.8% initiated a first-generation first-generation LAI within 90 days after discharge. During 2004 to 2006, there was marked variation in 90 day post-relapse initiation of Risperdal-Consta-a newly marketed medication during this period-and also marked variation in 90 day post-relapse initiation of any first-generation LAI, which appeared to be associated with race/ethnicity and geography. Prior authorization policies were associated with substantially lower initiation of Risperdal Consta in this cohort of relapsed patients even after accounting for clinical indication (non-adherence), relapse history, demographics, adjunctive medication, and mental health service use.