Healthcare Resource Utilization and Costs Among Patients With Gastroesophageal Reflux Disease, Barrett's Esophagus, and Barrett's Esophagus-Related Neoplasia in the United States.

Background: Gastroesophageal reflux disease (GERD) is a risk factor for Barrett's esophagus (BE) and BE-related neoplasia (BERN). Objectives: This study aimed to evaluate healthcare resource utilization (HRU) and costs associated with GERD, BE, and BERN in the United States. Methods: Adult patients with GERD, nondysplastic BE (NDBE), and BERN (including indefinite for dysplasia [IND], low-grade dysplasia [LGD], high-grade dysplasia [HGD] or esophageal adenocarcinoma [EAC]), were identified from a large US administrative claims database, the IBM Truven Health MarketScan® databases (Q1/2015-Q4/2019). Patients were categorized into the corresponding mutually exclusive EAC-risk/diagnosis cohorts based on the most advanced stage from GERD to EAC using diagnosis codes in medical claims. Disease-related HRU and costs (2020 USD) were calculated for each cohort. Results: Patients were categorized into the following EAC-risk/diagnosis cohorts: 3 310 385 into GERD, 172 481 into NDBE, 11 516 into IND, 4332 into LGD, 1549 into HGD, and 11 676 into EAC. Disease-related annual mean number of inpatient admissions, office visits, and emergency department visits by cohort were 0.09, 1.45, and 0.19 for GERD; 0.08, 1.55, and 0.10 for NDBE; 0.10, 1.92, and 0.13 for IND; 0.09, 2.05, and 0.10 for LGD; 0.12, 2.16, and 0.14 for HGD; and 1.43, 6.27, and 0.87 for EAC. Disease-related annual mean total healthcare costs by cohort were $6955 for GERD, $8755 for NDBE, $9675 for IND, $12 241 for LGD, $24 239 for HGD, and $146 319 for EAC. Discussion: Patients with GERD, BE, and BERN had important HRU and costs, including inpatient admissions and office visits. As patients progressed to more advanced stages, there was substantially higher disease-related resource utilization, with associated costs being 16 times higher in patients with EAC than those with NDBE. Conclusions: Findings suggest the need for early identification of high-risk individuals prior to progression to EAC to potentially improve clinical and economic outcomes in this population.

Real-world upper endoscopy utilization patterns among patients with gastroesophageal reflux disease, Barrett esophagus, and Barrett esophagus-related esophageal neoplasia in the United States.

This study fills a gap in literature by providing contemporary real-world evidence on the prevalence of patients with gastroesophageal reflux disease (GERD), Barrett esophagus (BE), and Barrett esophagus-related neoplasia (BERN) and their upper endoscopy utilization patterns in the United States. A retrospective cohort study design was used: adults with GERD, nondysplastic Barrett esophagus (NDBE), and BERN (indefinite for dysplasia [IND], low-grade dysplasia [LGD], high-grade dysplasia [HGD], or esophageal adenocarcinoma [EAC]) were identified from the MarketScan databases (January 01, 2015-December 31, 2019). For each disease stage, prevalence of adults in commercial claims by calendar year, annual number of upper endoscopies per patient and time between upper endoscopies were reported. In 2019, in commercial claims (N = 12,363,227), the annual prevalence rate of GERD was 13.7% and 0.70% for BE/BERN, among which, 87.1% had NDBE, 6.8% had IND, 2.3% had LGD, 1.0% had HGD, and 2.8% had EAC. From 2015-2019, the study included 3,310,385 patients with GERD, 172,481 with NDBE, 11,516 with IND, 4332 with LGD, 1549 with HGD, and 11,676 with EAC. Annual mean number of upper endoscopies was 0.20 per patient for GERD, 0.37 per patient for NDBE, 0.43 for IND, 0.58 for LGD, and 0.87 for HGD. Median time (months) to second upper endoscopy was 38.10 for NDBE, 36.63 for IND, 22.63 for LGD, and 11.90 for HGD. Upper endoscopy utilization increased from GERD to BE to BERN, and time between upper endoscopies decreased as the disease stage progressed from BE to BERN, with less frequent utilization in BERN than what would be expected from guideline recommendations for surveillance.

The impact of vaso-occlusive crises and disease severity on quality of life and productivity among patients with sickle cell disease in the US.

AIM: Sickle cell disease (SCD) is a lifelong blood disorder affecting approximately 100,000 individuals in the United States (US). A number of new treatments have recently become available to improve SCD clinical outcomes, but it is unclear how treatment innovations that reduce disease severity could affect patients' humanistic and economic outcomes. METHODS AND MATERIALS: To answer this question, an online survey of US adult residents with a self-reported SCD diagnosis was conducted. Humanistic outcomes based on health-related quality of life (HRQoL)) were assessed during and outside of vaso-occlusive crises (VOCs). Economic outcomes were measured by annual household income and whether the respondent received disability insurance. RESULTS: Among the 301 respondents completing the survey, average age was 34.4 years and 73.4% were female. Average HRQoL, measured using health utilities, were 0.311 (95% CI: 0.286, 0.337) during a VOC and 0.738 (0.720, 0.756) not during a VOC. The likelihood of claiming disability insurance was correlated with more frequent VOCs (0 VOCs: 12% vs. ≥4 VOCs: 47%, p = .002) and disease severity (Severity Class II: 16% vs. Severity Class III: 39%, p = .03). There was a weak relationship between VOC frequency and household income (0 VOCs: $47,488 vs. ≥4 VOCs: $34,569, p = .06) and no evidence of a relationship between disease severity class and income (Severity Class II: $42,443 vs. Severity Class III: $36,842, p = .29). CONCLUSION: In conclusion, disease severity, strongly predicted worse self-reported HRQoL, moderately predicted increased likelihood of collecting disability insurance, and weakly predicted lower household income levels.

For which diseases do broader value elements matter most? An evaluation across 20 ICER evidence reports.

BACKGROUND: U.S. value framework developers such as the Institute for Clinical and Economic Review (ICER) use cost-effectiveness analysis to value new health care technologies. Often, these value assessment frameworks use a health system perspective without fully accounting for societal and broader benefits and costs of an intervention. Although there is ongoing debate about the most appropriate methods for including broader value elements in value assessment, it remains unclear whether the inclusion of these value elements is likely to affect the quantitative estimates of treatment value. OBJECTIVE: To assess variations in the relevance of broader value elements to cost-effectiveness analysis across diseases. METHODS: Thirty-two broader value elements (e.g., caregiver burden, health equity, real option value, productivity) not traditionally included in health technology assessments were identified through a targeted literature review. Evidence reports published by ICER between July 2017 and January 2020 were evaluated to identify which broader value elements were discussed as relevant to each disease in the report text. The study examined whether there were associations among ICER's discussion of broader value elements, rare disease status, treatment cost, estimated treatment cost-effectiveness, and ICER committee voting results for contextual considerations and additional benefits/disadvantages. RESULTS: The most commonly cited broader value element category in the ICER evidence reports was household and leisure (e.g., absenteeism from normal activities and caregiver burden). More value elements were cited for inherited retinal disease (19 elements) and sickle cell disease (18 elements) than for other diseases. Cardiovascular disease and diabetes had the fewest number of value elements cited (7 elements). Rare diseases were more likely to have broader value elements cited compared with nonrare diseases (15.9 vs. 11.5, P < 0.001). Treatments with higher (i.e., less favorable) incremental cost-effectiveness ratios were more likely to have a greater number of broader value elements cited (ρ = 0.625, P < 0.001). CONCLUSIONS: The presence of broader value elements varied across diseases, with less cost-effective treatments more likely to have a higher number of relevant broader value elements. Inclusion of all relevant value elements in value assessments will more appropriately incentivize innovation and improve allocation of research funding. DISCLOSURES: This study was sponsored by Novartis Pharmaceutical Corporation. At the time of this study, Shafrin was employed by PRECISIONheor, a consultancy to the life sciences industry that received financial support from Novartis to conduct this study. Dennen, Pednekar, and Birch are employed by PRECISIONheor. Bhor was an employee of Novartis Pharmaceutical Corporation at the time this research was conducted and manuscript was developed and reports grants from Novartis, unrelated to this work. Kanter has served on scientific advisory boards and steering committees for and reports receiving consulting fees from Novartis Pharmaceutical Corporation and is a site principal investigator on studies funded by Novartis Pharmaceutical Corporation. Kantar also reports support from Sickle Cell Disease Association of America Inc. and National Heart, Lung, and Blood Institute, unrelated to this work. Neumann reports advisory boards or consulting fees from Novartis Pharmaceutical Corporation and PRECISIONheor, as well as advisory boards or consulting fees unrelated to this study from AbbVie, Amgen, Avexis, Bayer, Congressional Budget Office, Janssen, Merck, Novartis, Novo Nordisk, Precision Health Economics, Veritech, Vertex; funding from The CEA Registry Sponsors by various pharmaceutical and medical device companies; and grants from Amgen, Lundbeck, Bill and Melinda Gates Foundation, National Pharmaceutical Council, Alzheimer's Association, and the National Institutes for Health.

Patient-Reported Outcomes and Economic Burden of Adults with Sickle Cell Disease in the United States: A Systematic Review.

PURPOSE: To systematically estimate the patient-reported outcomes (PROs) and economic burden of sickle cell disease (SCD) among adults in the United States (US). PATIENTS AND METHODS: Two systematic literature reviews (SLRs), one each for the PROs and economic topics, were performed using MEDLINE and Embase to identify observational studies of adults with SCD. Included studies were published between 2007 and 2018 and evaluated health-related quality of life (HRQL), function, healthcare resource utilization (HCRU), or costs. Given the high degree of clinical and methodological heterogeneity, findings were summarized qualitatively. RESULTS: The SLRs identified 7 studies evaluating the PROs and 15 studies evaluating the economic burden meeting the pre-specified selection criteria. The PRO evidence showed the prevalence of depression and anxiety to be 21-33% and 7-36%, respectively, in adults with SCD. The mean SF-36 physical summary scores ranged from 33.6 to 59.0 and from 46.3 to 61.5 for the mental summary scores. Overall HRQL for adults with SCD was poor and significantly worse in those with opioid use. Adult SCD patients were found to have varying rates of emergency department (ED) utilization (0.3-3.5 annual ED visits), hospitalizations (0.5-27.9 per patient per year), and/or readmission (12-41%). Key factors associated with significant HCRU were age, dental infection, and SCD-related complications. SCD specialized care settings and SCD intensive management strategy were reported to significantly decrease the number of hospitalizations. CONCLUSION: This systematic evidence synthesis found that disease burden measured by PROs and economic burden of SCD on adults in the US are substantial despite the availability of approved SCD treatments during 2007-2018. The use of hydroxyurea, optimal management with opioids, and employing intensive treatment strategies may help decrease the overall burden to patients and healthcare systems. Published data on costs associated with SCD are limited and highlight the need for more economic studies to characterize the full burden of the disease.

Vaso-occlusive crises and costs of sickle cell disease in patients with commercial, Medicaid, and Medicare insurance - the perspective of private and public payers.

AIM: To characterize vaso-occlusive crises (VOCs) and describe healthcare costs among commercially-insured, Medicaid-insured, and Medicare-insured patients with sickle cell disease (SCD). MATERIALS AND METHODS: The IBM Truven Health MarketScan Commercial (2000-2018), Medicaid Analytic eXtract (2008-2014), and Medicare Research Identifiable Files (2012-2016) databases were used to identify patients with ≥2 SCD diagnoses. Study measures were evaluated during a 12-month follow-up period, stratified by annual number of VOCs (i.e. 0, 1, and ≥2). RESULTS: Among 16,092 commercially-insured patients (mean age = 36.7 years), 35.3% had 1+ VOCs. Mean annual total all-cause healthcare costs were $15,747, $27,194, and $64,555 for patients with 0, 1, and 2+ VOCs, respectively. Total all-cause healthcare costs were mainly driven by inpatient (0 VOC = 31.0%, 1 VOC = 53.1%, 2+ VOCs = 65.4%) and SCD-related costs (0 VOC = 56.4%, 1 VOC = 78.4%, 2+ VOCs = 93.9%). Among 18,287 Medicaid-insured patients (mean age = 28.5 years, fee-for-service = 50.2%), 63.9% had 1+ VOCs. Mean annual total all-cause healthcare costs were $16,750, $29,880, and $64,566 for patients with 0, 1, and 2+ VOCs, respectively. Inpatient costs (0 VOC = 37.2%, 1 VOC = 64.3%, 2+ VOCs = 72.9%) and SCD-related costs (0 VOC = 60.9%, 1 VOC = 73.8%, 2+ VOCs = 92.2%) accounted for a significant proportion of total all-cause healthcare costs. Among 15,431 Medicare-insured patients (mean age = 48.2 years), 55.1% had 1+ VOCs. Mean annual total all-cause healthcare costs were $21,877, $29,250, and $58,308 for patients with 0, 1, and ≥2 VOCs, respectively. Total all-cause healthcare costs were mainly driven by inpatient (0 VOC = 47.9%, 1 VOC = 54.9%, 2+ VOCs = 67.5%) and SCD-related costs (0 VOC = 74.9%, 1 VOC = 84.4%, 2+ VOCs = 95.3%). LIMITATIONS: VOCs managed at home were not captured. Analyses were descriptive in an observational setting; thus, no causal relationships can be inferred. CONCLUSIONS: A high proportion of patients experienced VOCs across payers. Furthermore, inpatient and SCD-related costs accounted for a significant proportion of total all-cause healthcare costs, which increased with VOC frequency.

Medical Resource Use and Costs of Treating Sickle Cell-related Vaso-occlusive Crisis Episodes: A Retrospective Claims Study.

BACKGROUND: The study investigated the economic burden of vaso-occlusive crisis (VOC) among sickle cell disease (SCD) patients, through assessment of overall utilization and costs and costs per VOC episode (regarding the number of VOC episodes and health care setting, respectively). METHODS: Using the Medicaid Analytic Extracts database, the first SCD-related diagnosis claim (index claim) between June 1, 2009-December 31, 2012 was identified among eligible adults. Patients were required to have continuous medical and pharmacy benefits for 6 months pre- and 12 months post-index. Discrete VOC claims identified within a 3-day gap were combined as a single VOC episode. Annual all-cause and SCD-related medical resources and costs were identified and stratified by number of VOC episodes during the 1-year follow-up period. Health care costs per VOC episode were also examined, stratified by care setting. RESULTS: Enrollees included 8521 eligible patients with a mean age of 32.88 years (SD=12.21). Of these, 66.5% had a Charlson Comorbidity index (CCI) score of 0 (no comorbidities) and 67.3% were female. The average total medical costs were US$34 136 (median=US$12 691) annually, and SCD accounted for 60% of the total costs (mean=US$20 206, median=US$1204). Patients with >3 episodes had the highest annual SCD-related costs (mean=US$58 950) across all settings. Health care resource utilization (HCRU) and costs increased substantially as the number of VOC episodes increased. This study was limited to observation of associations rather than causal inference, and by possible coding and identification discrepancies and the restricted generalizability of the population. CONCLUSIONS: VOC has a severe impact on medical resource use and costs among the adult SCD population. Further research among broader study populations is needed to facilitate the reduction of VOC episodes and thereby improve clinical and economic outcomes for SCD patients.

Association between Vaso-occlusive Crises and Opioid Prescriptions among Patients with Sickle Cell Disease: A Retrospective Claims-based Study.

BACKGROUND/OBJECTIVES: Among sickle cell disease (SCD) patients, vaso-occlusive crises (VOCs) are recurrent and unpredictable attacks of acute pain. These pain crises are often treated with analgesics, including opioids, which have been associated with misuse and overdose. The aim of this study was to examine the association between VOC events and opioid use and assess the association between opioid prescriptions and health care resource utilization among SCD patients. METHODS: This was a retrospective cohort study using Texas Medicaid medical and prescription claims between September 2011 and August 2016. The index date was the first SCD diagnosis. Patients (2-63 years) with at least one inpatient or two outpatient SCD diagnoses, who were continuously enrolled during 12 months postindex, were included in the study. The primary outcome was number of opioid prescriptions, while the independent variable was number of VOC events. Covariates included age, gender, nonopioid medication use, nonstudy SCD-related medication (penicillin and folic acid) use, evidence of blood transfusions, number of SCD-related complications, number of SCD-related comorbid conditions, and Charlson Comorbidity Index score. Negative binomial regression analysis was used to address study objectives. RESULTS: Of 3368 included patients, 1978 (58.7%) had at least one opioid prescription with a mean of 4.2 (SD=7.2). Overall, 2071 (61.5%) had at least one VOC event with an average of 2.9 (SD=4.4). The results from the negative binomial regression showed that for every increase in VOC events, the number of opioid prescriptions increased by 9.5% (Incidence rate ratio=1.095, 95% CI: 1.078-1.111; P ≤ 0.0001). Other significant covariates associated with higher opioid use included age (13 and older compared to 2-12) and increase in the number of nonopioid pain medications, nonstudy SCD-related medications, and SCD-related complications. CONCLUSIONS: The majority of SCD patients had at least one VOC event and were prescribed opioids during the 12-month study period. We found that each VOC event was associated with a 9.5% increase in the use of opioids. SCD guidelines recommend opioids for the treatment of VOC-related pain. Payers and providers should be aware of opioid use in this population, consider appropriate VOC prevention measures, and provide SCD patients with access to appropriate pain management.

Real-world evidence on clinical outcomes in immune thrombocytopenia treated with thrombopoietin receptor agonists.

Aim: Eltrombopag and romiplostim are US FDA approved for treatment of immune thrombocytopenia in patients with insufficient response to other treatments. Clinical or real-world data comparing outcomes of the two drugs are limited. Methods: This retrospective cross-sectional study sought information on bleeding-related episodes (BREs), adverse events (AEs) and other outcomes of eltrombopag or romiplostim treatment in immune thrombocytopenia. Results: Patients receiving eltrombopag experienced significantly reduced BREs, severe BREs, rescue medication use and platelet transfusions. Diarrhea and headache were significantly less frequent in patients receiving eltrombopag; other AEs occurred equally in both groups. Conclusion: There may be a potential advantage for the use of eltrombopag versus romiplostim in the practice settings studied, based on rates of BREs and AEs and rescue medication utilization.

The relationship between frequency and severity of vaso-occlusive crises and health-related quality of life and work productivity in adults with sickle cell disease.

PURPOSE: Patients with sickle cell disease (SCD) may experience sickle cell-related pain crises, also referred to as vaso-occlusive crises (VOCs), which are a substantial cause of morbidity and mortality. The study explored how VOC frequency and severity impacts health-related quality of life (HRQoL) and work productivity. METHODS: Three hundred and three adults with SCD who completed an online survey were included in the analysis. Patients answered questions regarding their experience with SCD and VOCs, and completed the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) and the Workplace Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP). Differences in ASCQ-Me and WPAI:SHP domains were assessed according to VOC frequency and severity. RESULTS: Nearly half of the patient sample (47.2%) experienced ≥ 4 VOCs in the past 12 months. The most commonly reported barriers to receiving care for SCD included discrimination by or trouble trusting healthcare professionals (39.6%, 33.3%, respectively), limited access to treatment centers (38.9%), and difficulty affording services (29.4%). Patients with more frequent VOCs reported greater impacts on emotion, social functioning, stiffness, sleep and pain, and greater absenteeism, overall productivity loss, and activity impairment than patients with less frequent VOCs (P < 0.05). Significant impacts on HRQoL and work productivity were also observed when stratifying by VOC severity (P < 0.05 for all ASCQ-Me and WPAI domains, except for presenteeism). CONCLUSIONS: Results from the survey indicated that patients with SCD who had more frequent or severe VOCs experienced deficits in multiple domains of HRQoL and work productivity. Future research should examine the longitudinal relationship between these outcomes.

Association Between Vaso-Occlusive Crises and Opioid Prescriptions Among Patients with Sickle Cell Disease: A Retrospective Claims-Based Study.

Background/Objectives: Among sickle cell disease (SCD) patients, vaso-occlusive crises (VOCs) are recurrent and unpredictable attacks of acute pain. These pain crises are often treated with analgesics, including opioids, which have been associated with misuse and overdose. The aim of this study was to examine the association between VOC events and opioid use and assess the association between opioid prescriptions and health care resource utilization among SCD patients. Methods: This was a retrospective cohort study using Texas Medicaid medical and prescription claims between September 2011 and August 2016. The index date was the first SCD diagnosis. Patients (2-63 years) with at least one inpatient or two outpatient SCD diagnoses, who were continuously enrolled during 12 months postindex, were included in the study. The primary outcome was number of opioid prescriptions, while the independent variable was number of VOC events. Covariates included age, gender, nonopioid medication use, nonstudy SCD-related medication (penicillin and folic acid) use, evidence of blood transfusions, number of SCD-related complications, number of SCD-related comorbid conditions, and Charlson Comorbidity Index score. Negative binomial regression analysis was used to address study objectives. Results: Of 3368 included patients, 1978 (58.7%) had at least one opioid prescription with a mean of 4.2 (SD=7.2). Overall, 2071 (61.5%) had at least one VOC event with an average of 2.9 (SD=4.4). The results from the negative binomial regression showed that for every increase in VOC events, the number of opioid prescriptions increased by 9.5% (Incidence rate ratio=1.095, 95% CI: 1.078-1.111; P ≤ 0.0001). Other significant covariates associated with higher opioid use included age (13 and older compared to 2-12) and increase in the number of nonopioid pain medications, nonstudy SCD-related medications, and SCD-related complications. Conclusions: The majority of SCD patients had at least one VOC event and were prescribed opioids during the 12-month study period. We found that each VOC event was associated with a 9.5% increase in the use of opioids. SCD guidelines recommend opioids for the treatment of VOC-related pain. Payers and providers should be aware of opioid use in this population, consider appropriate VOC prevention measures, and provide SCD patients with access to appropriate pain management.

Treatment patterns and economic burden of sickle-cell disease patients prescribed hydroxyurea: a retrospective claims-based study.

BACKGROUND: This study aimed to evaluate sickle-cell disease (SCD) treatment patterns and economic burden among patients prescribed hydroxyurea (HU) in the US, through claims data. METHODS: SCD patients with pharmacy claims for HU were selected from the Medicaid Analytic Extracts (MAX) from January 1, 2009 - December 31, 2013. The first HU prescription during the identification period was defined as the index date and patients were required to have had continuous medical and pharmacy benefits for ≥6 months baseline and 12 months follow-up periods. Patient demographics, clinical characteristics, treatment patterns, health care utilization, and costs were examined, and variables were analyzed descriptively. RESULTS: A total of 3999 SCD patients prescribed HU were included; the mean age was 19.24 years, most patients were African American (73.3%), and the mean Charlson comorbidity index (CCI) score was 0.6. Asthma (20.3%), acute chest syndrome (15.6%), and infectious and parasitic diseases (20%) were the most prevalent comorbidities. During the 12-month follow-up period, 58.9% (N = 2357) of patients discontinued HU medication. The mean medication possession ratio (MPR) was 0.52, and 22.3% of patients had MPR ≥80%. The average length of stay (LOS) for SCD-related hospitalization was 13.35 days; 64% of patients had ≥1 SCD-related hospitalization. The mean annual total SCD-related costs per patient were $27,779, mostly inpatient costs ($20,128). CONCLUSIONS: Overall, the study showed the patients had significant unmet needs manifest as poor medication adherence, high treatment discontinuation rates, and high economic burden.

Sickle cell disease complications: Prevalence and resource utilization.

OBJECTIVES: This study evaluated the prevalence rate of vaso-occlusive crisis (VOC) episodes, rates of uncomplicated and complicated VOC episodes, and the primary reasons for emergency room (ER) visits and inpatient admissions for sickle cell disease (SCD) patients. METHODS: The Medicaid Analytic extracts database was used to identify adult SCD patients using claims from 01JUL2009-31DEC2012. The date of the first observed SCD claim was designated as the index date. Patients were required to have continuous medical and pharmacy benefits for ≥6 months baseline and ≥12 months follow-up period. Patient demographics, baseline clinical characteristics, the rate of uncomplicated and complicated VOC (VOC with concomitant SCD complications) episodes, and reasons for ER visits and inpatient stays were analyzed descriptively. RESULTS: A total of 8,521 patients were included in the analysis, with a median age of 30 years. The average follow-up period was 2.7 years. The rate of VOC episodes anytime in the follow-up was 3.31 in person-years. During the first-year follow-up period, an average of 2.79 VOC episodes were identified per SCD patients, with 1.06 VOC episodes treated in inpatient setting and 0.90 VOC episodes in ER without admission. A total of 76,154 VOC episodes were identified during the entire follow-up period for the overall SCD patients. Most of the VOC episodes (70.3% [n = 53,523]) were uncomplicated episodes, and 29.7% were complicated episodes. Using primary diagnosis claims only, the most frequent complications during the VOC episode were infectious diseases (25.9%), fever (21.8%), and pulmonary disorders (16.2%). Among ER and hospitalizations related to VOC or SCD complication, ~85.0% had VOCs as the primary reason for admission; 15.0% had SCD complications as the primary reason. CONCLUSION: In summary, SCD and its related comorbidities and complications result in high acute health care utilization. In addition, VOC remains the primary reason for SCD patients' ER visits and inpatient admissions.

Evaluation of Vaso-occlusive Crises in United States Sickle Cell Disease Patients: A Retrospective Claims-based Study.

Sickle cell disease (SCD) is a life-threatening vascular disease that burdens affected persons physically. SCD-related vaso-occlusive crises (VOCs) are one of the primary causes of morbidity and mortality. Our objective was to examine the epidemiology of pain crises and the relationship between pain crises and major acute complications among SCD patients. Using the Medicaid Analytic Extracts from 2009-2013, patients with SCD were selected and the first clinical claim indicating SCD during the identification period was defined as the index date. Patients were required to have continuous Medicaid enrollment for ≥6 months pre- and 12 months post-index period. Clinical outcomes included mortality, inpatient pain crises, and complications. Cox regressions were applied to examine the relationship between pain crises and deaths or acute complications, respectively. A total of 20 909 patients were included with a mean age of 17.9 years. The rate of VOC events in 100 person-years was 142.20 for adults and 53.91 for pediatric patients. Patients with VOCs were associated with a higher risk for death (hazard ratio=1.56; 95% confidence interval: [1.19-2.05]) or acute complications including acute chest syndrome, stroke, pulmonary embolism, splenic sequestration, and pulmonary hypertension. SCD patients have a substantial burden of disease-related complications. This study suggests that inpatient vaso-occlusive crisis is a key risk factor for acute complications.

High Healthcare Utilization in Adolescents with Sickle Cell Disease Prior to Transition to Adult Care: A Retrospective Study.

BACKGROUND: The transition from pediatric to adult care in the US is often difficult for individuals with sickle cell disease (SCD). Young adults (18 to 25 years of age) have higher acute care utilization and an increased risk of poor outcomes. The current study was designed to provide greater insights into patients (16 to 18 years of age) with SCD prior to their transition to adult care. OBJECTIVES: To describe current treatment patterns, pain crises prevalence, SCD-related complications, and healthcare resource utilization (HCRU) in 16-to-18-year-old patients with SCD. METHODS: From 1/1/2015-6/30/2017 using MarketScan Databases, patients were included if they were 16 to 18 years old at the index date, had ≥1 inpatient or 2 outpatient SCD diagnosis claims during the identification period, and were continuously enrolled in the database for at least one year prior (baseline) and post index date. Outcomes included medications, disease management interventions, Charlson Comorbidity Index (CCI), vaso-occlusive (VOC) crises requiring healthcare visits, HCRU, and SCD complications. RESULTS: 1,186 patients were included; most (64.3%) were female. The mean CCI was 1.3 (SD: 0.7). In the overall cohort, patients experienced an average of 3.9 (SD: 4.2) VOCs and most patients (61.1%, n=725) had chronic complications during the one-year follow-up. Pulmonary disease (31.1%, n=369) was the most frequent complication; blood transfusions (mean: 8.4 [SD:7.0]) and iron-chelating therapies (mean: 8.6 [SD:10]) were the most common interventions and medications, respectively. In the 16 to 18 year old group, patients with SCD had 2.0 (SD = 2.3) hospital admissions, 3.4 (SD = 4.0) ER visits, and 5.0 (SD = 4.2) office visits. CONCLUSIONS: Prior to transition to adult care, adolescents with SCD already have significant a cute and chronic disease-related complications, possibly contributing to frequent healthcare visits. Increased attention to this age group, including improvements in disease modifying therapy, are needed prior to transition to adult care systems to improve outcomes.

Cost-consequence model comparing eltrombopag versus romiplostim for adult patients with chronic immune thrombocytopenia.

BACKGROUND: Thrombopoietin-receptor agonists eltrombopag (EPAG) and romiplostim (ROMI) are treatment options for adults with chronic immune thrombocytopenia (cITP) who have had an insufficient response to corticosteroids or immunoglobulins. METHODS: A cost-consequence model was developed to evaluate the costs relative to treatment success of EPAG, ROMI, and watch and rescue (W&R) in previously treated patients. The primary endpoint assessed was severe bleeding, derived from all identified phase III registered clinical trials. Health outcomes were compared via indirect treatment comparison. Costs incorporated in the model included drug and administration, routine care, rescue medications, bleeding-related adverse events, other adverse events, and mortality costs. A trial (26-week) time horizon was used, as certain endpoints used in the model were bound to within-trial results. RESULTS: In the intent-to-treat (ITT) population, the overall estimated cost per patient for EPAG was US$66,560 compared to US$91,039 for ROMI and US$30,099 for W&R. Compared to the ITT population, the difference in cost between EPAG and ROMI was slightly greater in splenectomized patients (US$65,998 for EPAG compared to US$91,485 for ROMI) and slightly less in non-splenectomized patients (US$67,151 for EPAG compared to US$91,455 for ROMI), though the overall trend remained the same. When assessing cost per severe bleeding event avoided in the ITT population, EPAG dominated (less expensive, more effective) ROMI. Sensitivity analyses confirmed these results. CONCLUSION: EPAG was preferred over ROMI in the treatment of cITP, largely driven by the reduction in severe bleeding events associated with its use.

Cost-consequence model comparing eltrombopag and romiplostim in pediatric patients with chronic immune thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is an auto-immune disorder characterized by enhanced platelet destruction and, subsequently, the potential for increased bleeding. Thrombopoietin receptor (TPO-R) agonists have recently emerged as promising therapies for ITP patients who are refractory to other treatments. While eltrombopag (EPAG) is the only TPO-R agonist US Food and Drug Administration approved for use in pediatric patients, romiplostin (ROMI) has been used in Phase III clinical studies. METHODS: A cost-consequence model (CCM) was developed to evaluate the costs of EPAG, ROMI, and watch-and-rescue (W&R) in relation to their respective treatment outcomes in previously-treated pediatric chronic ITP (cITP) over a 26-week time horizon. The costs of drugs, administration, routine care, rescue medications, adverse events, and mortality were included. Data on platelet count response rate, bleeding events, and adverse events were derived from all relevant identified Phase III-registered clinical trials, health outcomes were compared via indirect treatment comparison. RESULTS: The overall estimated cost of EPAG per patient was US$66,550, compared to US$101,056 for ROMI and US$32,720 for W&R. EPAG's lower cost compared to ROMI was largely due to lower drug costs (US$62,202 vs US$84,396), administration costs (US$0 vs US$1,955), and significantly lower costs due to severe bleeding (US$354 vs US$10,191). When assessing cost per severe bleeding event avoided, EPAG was dominant over ROMI (less expensive and more effective). EPAG was again dominant over ROMI when assessing the cost per responder and per bleeding event (any grade). Sensitivity analysis was consistent with the base case findings. CONCLUSION: EPAG was the preferred TPO-R agonist to treat cITP when indirectly compared to ROMI, largely driven by its favorable severe bleeding outcomes and lower drug and administration costs.

A decision framework for treating chronic immune thrombocytopenia with thrombopoietin receptor agonists.

Aim: Eltrombopag and romiplostim are comparable second-line therapies in chronic immune thrombocytopenia. Treatment decisions are made in different contexts. A framework was created to outline decision pathways for physicians and payers. Materials & methods: The costs of drugs, administration, routine care, bleeding, other adverse events and mortality were included in the year-long calculation of total costs from a US private payer perspective. Treatment parameters and outcome data were obtained from relevant clinical trials. Results: The total cost per year, per patient of eltrombopag was US$51,000 versus US$76,000 for romiplostim. Drug costs and costs associated with bleeding-related events were the main drivers of cost difference. Conclusion: This framework facilitates decision-making in the management of chronic immune thrombocytopenia with eltrombopag and romiplostim.

Systematic literature review and assessment of patient-reported outcome instruments in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a chronic condition associated with high mortality and morbidity. It is characterized by acute clinical symptoms such as painful vaso-occlusive crises, which can impair health-related quality of life (HRQL). This study was conducted to identify validated patient-reported outcome (PRO) instruments for use in future trials of potential treatments for SCD. METHODS: A systematic literature review (SLR) was performed using MEDLINE and EMBASE to identify United States (US)-based studies published in English between 1997 and 2017 that reported on validated PRO instruments used in randomized controlled trials and real-world settings. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the quality of PRO instruments. RESULTS: The SLR included 21 studies assessing the psychometric properties of 24 PRO instruments. Fifteen of those instruments were developed and validated for adults and 10 for children (one instrument was used in both children and young adults aged up to 21 years). Only five of the 15 adult instruments and three of the 10 pediatric instruments were developed specifically for SCD. For most instruments, there were few or no data on validation conducted in SCD development cohorts. Of the 24 PRO instruments identified, 16 had strong internal reliability (Cronbach's α ≥0.80). There was often insufficient information to assess the content validity, construct validity, responsiveness, or test-retest reliability of the instruments identified for both child and adult populations. No validated PRO instruments measuring caregiver burden in SCD were identified. CONCLUSIONS: The evidence on the psychometric properties of PRO instruments was limited. However, the results of this SLR provide key information on such tools to help inform the design of future clinical trials for patients with SCD in the US.

Treatment patterns and medication adherence among patients diagnosed with multiple myeloma and treated with panobinostat.

AIM: To examine real-world treatment patterns in multiple myeloma (MM) patients treated with panobinostat. MATERIALS & METHODS: Using a US claims database, MM patients treated with panobinostat during 02/01/2015-01/31/2017 were evaluated. Lines of therapy, combination regimens, dosing and duration were measured. RESULTS: Ninety-five patients were included (mean age: 61.4 years). Patients were heavily pretreated, with 88.4% exposed to both a proteasome inhibitor and an immunomodulatory agent. A panobinostat containing regimen was started in the fourth or more (86%) lines of therapy within a median of 3.77 years from initial treatment. The most common treatment combination was bortezomib/dexamethasone/panobinostat (31.6%) with 69.5% receiving the recommended dose (20 mg). Mean duration was 98.8 days. CONCLUSION: Patients received the recommended dose, most commonly with bortezomib and dexamethasone. Panobinostat was used in heavily pretreated patients within 4 years post-diagnosis, reflecting an advanced MM population.