Treatment Patterns and FLT3 Mutation Testing Among Patients with Acute Myeloid Leukemia in China: A Retrospective Observational Study.

Introduction: For acute myeloid leukemia (AML), prognosis is particularly poor in patients harboring FMS-like tyrosine kinase 3 (FLT3) gene mutations, though routine screening for these mutations at diagnosis has been shown to be insufficient. The understanding of the impact of FLT3 mutations on treatment decisions is limited. Methods: In this retrospective, observational study, we investigated the key epidemiological characteristics, treatment patterns and responses among adult patients with newly diagnosed (ND) AML in China, who initiated treatment from January 1, 2015, to December 31, 2019, or progressed to relapsed/refractory (R/R) AML by December 31, 2020. Results: Of the 853 ND AML patients included, 63.4% were screened for FLT3 status, and 20.1% tested positive (FLT3MUT) at initial diagnosis. Of 289 patients who progressed to R/R AML during the study period, 24.9% were screened at the diagnosis of R/R AML, and 19.4% tested positive; 20.5% of screened patients changed FLT3 status at first diagnosis of R/R AML. Initial treatment regimens or treatment responses did not seem to differ in patients with ND AML by FLT3 mutation status. In patients with R/R AML, there was an apparent difference in second-line treatment choices by FLT3 mutation status; however, the number of FLT3-mutated patients were limited to demonstrate any meaningful distinction. FLT3-mutated R/R AML was associated with shorter relapse time. Conclusion: Study findings showed that there was a lack of routine testing for FLT3 mutations at first diagnosis of R/R AML, and initial treatment decisions did not differ by FLT3 mutation status. Given the clinical burden of FLT3MUT, likelihood of FLT3 status changes, and emerging FLT3 inhibitors, further routine FLT3 screening is needed to optimize treatment of R/R AML.

Erratum: Author Correction: Surgical Treatment Patterns, Healthcare Resource Utilization, and Economic Burden in Patients with Tenosynovial Giant Cell Tumor Who Underwent Joint Surgery in the United States.

[This corrects the article DOI: 10.36469/jheor.2022.32485.].

Chronic Myeloid Leukemia: Part I-Real-World Treatment Patterns, Healthcare Resource Utilization, and Associated Costs in Later Lines of Therapy in the United States.

Background: Despite advances in tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia in chronic phase (CML-CP), a sizeable proportion of patients with CML-CP remains refractory or intolerant to these agents. Objectives: Treatment patterns, healthcare resource utilization (HRU), and costs were evaluated among patients with CML who received third or later lines of therapy (3L+), a clinical population that has not been previously well-studied, with unmet treatment needs as TKI therapy has repeatedly failed. Methods: Adult patients with CML who received 3L+ were identified in the IBM® MarketScan® Databases (January 1, 2001-June 30, 2019) and the SEER-Medicare-linked database (January 1, 2006-December 31, 2016). Treatment patterns were observed from CML diagnosis. HRU and direct healthcare costs (payer's perspective, 2019 USD) were measured in a 3L+ setting. Results: Among 296 commercially insured patients with 3L+ (median age, 58.5 years; female, 49.7%), the median duration of first-line (1L), second-line (2L), and 3L therapy was 8.5, 4.2, and 8.3 months, respectively. The annual incidence rate during 3L+ was 3.4 for inpatient days, 30.8 for days with outpatient services, and 1.2 for emergency department visits. Mean per-patient-per-month (PPPM) total healthcare costs (pharmacy + medical costs) were $18 784 in 3L+, $15 206 in 3L, and $19 546 in 4L, with inpatient costs driving most of the difference between 3L and 4L (mean [3L] = $2528 PPPM, mean [4L] = $6847 PPPM). Among 53 Medicare-insured patients with 3L+ (median age, 72.0 years; female, 39.6%), the median duration of 1L, 2L, and 3L therapy was 9.7, 5.0, and 7.0 months, respectively. During 3L+, the annual incidence rate was 10.3 for inpatient days, 61.9 for days with outpatient services, and 1.5 for emergency department visits. Mean PPPM total healthcare costs were $14 311 in 3L+, $15 100 in 3L, and $16 062 in 4L. Discussion: Patients with CML receiving 3L+ rapidly cycled through multiple lines. Costs increased from 3L to 4L; in commercially insured patients, inpatient costs were responsible for most of the cost increase between 3L and 4L, underlying these patients' continued need for care. Conclusions: These findings support the need for better treatment options in patients with CML undergoing later lines of therapy.

The Economic Burden of Eosinophilic Gastritis and Eosinophilic Enteritis in the United States.

INTRODUCTION: Eosinophilic gastritis and eosinophilic enteritis (EoG/EoN) are associated with a substantial clinical burden. However, limited information is available regarding the economic burden of EoG/EoN. This study was conducted to compare healthcare resource use (HRU) and costs among patients with EoG/EoN versus without EoG/EoN in the USA. METHODS: Administrative claims data from the IBM MarketScan® Commercial Claims and Encounters (CCAE) and Medicare Supplemental and Coordination of Benefits Databases (2009-2019) was used to identify two cohorts of patients. Patients without EoG/EoN were matched 3:1 to patients with EoG/EoN on sex, year of birth, and healthcare plan type. Study measures included demographic characteristics, select comorbidities, all-cause HRU, and costs. Comparisons were made over a 1-year period following EoG/EoN diagnosis for patients with EoG/EoN and an eligible date for patients without EoG/EoN. RESULTS: A total of 2219 patients with EoG/EoN and 6657 patients without EoG/EoN were analyzed. Significantly higher proportions of patients with EoG/EoN versus without EoG/EoN had comorbid conditions. Rates of all-cause HRU were significantly higher among patients with EoG/EoN versus patients without EoG/EoN (adjusted rate ratio [95% confidence interval]: inpatient visits, 6.26 [5.26, 7.46]; outpatient visits, 1.17 [1.16, 1.19]; emergency department visits, 2.11 [1.98, 2.25]; all p < 0.001). Patients with EoG/EoN incurred significantly higher costs versus patients without EoG/EoN (adjusted mean cost difference $31,180; p < 0.001). Cost differences were largely due to outpatient (adjusted mean cost difference $14,018; p < 0.001) and inpatient (adjusted mean cost difference $11,224; p < 0.001) costs. CONCLUSION: The economic burden associated with EoG/EoN is substantial, with patients with EoG/EoN having a higher rate of HRU and incurring $31,180 more than patients without EoG/EoN on average. Most of the cost difference was attributable to outpatient and inpatient costs. Cost-saving strategies to lower the burden of illness in this patient population are needed.

Discontinuation and Switchback After Non-Medical Switching from Originator Tumor Necrosis Factor Alpha (TNF) Inhibitors to Biosimilars: A Meta-Analysis of Real-World Studies from 2012 to 2018.

INTRODUCTION: To examine the prevalence rates of biosimilar discontinuation and switchback to the originator tumor necrosis factor alpha (TNF) inhibitors following non-medical switch (NMS) in patients. METHODS: Real-world studies reporting biosimilar discontinuation and switchback rates following NMS published between January 2012 and August 2018 were identified through a systematic literature review. A meta-analysis estimated the annualized discontinuation and switchback rates. A subsequent meta-analysis assessed annualized incremental discontinuation rate among studies reporting both discontinuation rates in patients who underwent an NMS (switchers) and patients who remained on originators (non-switchers). RESULTS: A total of 66 publications were identified: 31 in gastroenterology, 32 in rheumatology, and 3 in both. Half of the studies reported switchback rates; only 9 studies reported discontinuation rates for both switchers and non-switchers. Across studies, the mean/range sample size of the NMS patient population was 136/9-1641; mean/range follow-up was 10/3-24 months. Annualized biosimilar discontinuation rate was 21% (95% confidence interval [CI] 18%, 25%). Switchback rate was 14% (95% CI 10%, 17%) among all NMS patients and 62% (95% CI 44%, 80%) among discontinuers. The mean/range sample size of switchers and non-switchers was 344/89-1621 and 768/19-2870, respectively; mean/range follow-up was 11/6-18 and 12/6-8 months, respectively. Annualized incremental biosimilar discontinuation rate was 18% (95% CI 4%, 31%). CONCLUSION: Biosimilar discontinuation was found to be prevalent among patients who underwent an NMS from an originator TNF inhibitor to its biosimilar(s) in the real world. In addition, switchback to the originator TNF inhibitors was common following biosimilar discontinuation. Careful consideration is necessary when switching patients already on an originator TNF inhibitor to its biosimilar(s). Main limitations included the heterogeneity of the studies and the limited comparability of the data.

Cost-effectiveness analysis of semaglutide 2.4 mg for the treatment of adult patients with overweight and obesity in the United States.

BACKGROUND: The rising prevalence and associated public health burden of obesity has led to advancements in pharmaceuticals for weight management. Semaglutide 2.4 mg, an anti-obesity medication (AOM) recently approved by the US Food and Drug Administration, has demonstrated clinically relevant weight loss in its phase 3 clinical trials. Economic evaluation comparing semaglutide 2.4 mg with other available weight management therapies is essential to inform payers for decision-making. OBJECTIVES: To assess the cost-effectiveness of semaglutide 2.4 mg in the treatment of adult patients with obesity (ie, body mass index [BMI] ≥ 30) and adult patients who are overweight (ie, BMI 27-29.9) with 1 or more weight-related comorbidities from a US third-party payer perspective. METHODS: A cohort Markov model was constructed to compare semaglutide 2.4 mg with the following comparators: no treatment, diet and exercise (D&E), and 3 branded AOMs (liraglutide 3 mg, phentermine-topiramate, and naltrexone-bupropion). All AOMs, including semaglutide 2.4 mg, were assumed to be taken in conjunction with D&E. Changes in BMI, blood pressure, cholesterol level, experience of acute and chronic obesity-related complications, costs, and quality-adjusted life years (QALYs) were simulated over 30 years based on pivotal trials of the AOMs and other relevant literature. Drug and health care prices reflect 2021 standardized values. Cost-effectiveness was examined with a willingness-to-pay (WTP) threshold of $150,000 per QALY gained. Sensitivity analyses were conducted to test the robustness of the cost-effectiveness results to plausible variation in model inputs. RESULTS: In the base-case analysis, treatment with semaglutide 2.4 mg was estimated to improve QALYs by 0.138 to 0.925 and incur higher costs by $3,254 to $25,086 over the 30-year time horizon vs comparators. Semaglutide 2.4 mg is cost-effective against all comparators at the prespecified WTP threshold, with the incremental cost per QALY gained ranging from $23,556 to $144,296 per QALY gained. In the sensitivity analysis, extended maximum treatment duration, types of subsequent treatment following therapy discontinuation, and weight-rebound rates were identified as key drivers for model results. The estimated probability of semaglutide 2.4 mg being cost-effective compared with comparators ranged from 67% to 100% when varying model parameters and assumptions. CONCLUSIONS: As a long-term weight management therapy, semaglutide 2.4 mg was estimated to be cost-effective compared with no treatment, D&E alone, and all other branded AOM comparators under a WTP threshold of $150,000 per QALY gained over a 30-year time horizon. DISCLOSURES: Financial support for this research was provided by Novo Nordisk Inc. The study sponsor was involved in several aspects of the research, including the study design, the interpretation of data, the writing of the manuscript, and the decision to submit the manuscript for publication. Dr Kim and Ms Ramasamy are employees of Novo Nordisk Inc. Ms Kumar and Dr Burudpakdee were employees of Novo Nordisk Inc at the time this study was conducted. Dr Sullivan received research support from Novo Nordisk Inc for this study. Drs Wang, Song, Wu, Ms Xie, and Ms Sun are employees of Analysis Group, Inc, who received consultancy fees from Novo Nordisk Inc in connection with this study.

Surgical Treatment Patterns, Healthcare Resource Utilization, and Economic Burden in Patients with Tenosynovial Giant Cell Tumor Who Underwent Joint Surgery in the United States.

Background: Tenosynovial giant cell tumors (TGCT) are rare and locally aggressive neoplasms in synovium, bursae, and tendon sheaths, which cause pain, joint dysfunction, and damage to the affected joints. Objective: To evaluate the surgical patterns and economic burden among patients with TGCT who underwent joint surgery in the United States. Methods: Patients newly diagnosed with TGCT, aged 18-64 years, who underwent joint surgery post-TGCT diagnosis were identified from the OptumHealth Care Solutions, Inc database (Q1/1999-Q1/2017). Patients were required to be continuously enrolled for ≥1 year before and ≥3 years after the first TGCT diagnosis (index date). Surgical patterns were assessed post-index. Healthcare resource utilization and associated healthcare costs, and indirect costs related to work loss in year 1, year 2, and year 3 post-index, were compared with those at baseline. Results: Of 835 eligible TGCT patients, 462 (55%) patients who had ≥1 joint surgery post-index were included. During a median follow-up of 5.7 years, 78% of patients underwent their first joint surgery in year 1 and 41% had ≥1 repeat surgery. Magnetic resonance imaging utilization was highest during baseline (46%) and declined afterward (28%, 17%, and 19% in years 1, 2, and 3, respectively). Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), and physical therapy, occupational therapy, and rehabilitation services, were commonly used during baseline (45%, 40%, and 30%, respectively). More patients used opioids in year 1 vs baseline (78% vs 45%; P<0.0001), while its utilization return to baseline levels in year 2 (41%) and year 3 (42%). A similar pattern was observed for NSAIDs and physical/occupational therapy/rehabilitation services. Healthcare resource utilization and associated healthcare costs surged in year 1 and returned to baseline or lower in years 2 and 3. A similar pattern was observed for indirect costs associated with work loss. Discussion: The high proportion of patients undergoing repeat surgeries and prevalent use of opioids, NSAIDs, and physical/occupational therapy/rehabilitation services suggests an unmet medical need after surgical treatment. Conclusions: Surgical resection alone might be inadequate to control TGCT. New treatment options may complement surgery and alleviate the clinical and economic burden experienced by patients with TGCT who had received prior surgery.

Real-World Management of Hyperkalemia in the Emergency Department: An Electronic Medical Record Analysis.

INTRODUCTION: Hyperkalemia is often managed in the emergency department (ED) and it is important to understand how ED management and post-discharge outcomes vary by hyperkalemia severity. This study was conducted to characterize ED management and post-discharge outcomes across hyperkalemia severities. METHODS: Adults with an ED visit with hyperkalemia (at least one serum potassium lab measure above 5.0 mEq/L) were selected from US electronic medical record data (2012-2018). Patient characteristics, potassium levels, treatments, and monitoring prior to and during the ED visit were compared by hyperkalemia severity (mild [> 5.0-5.5 mEq/L], moderate [> 5.5-6.0], severe [> 6.0]) using unadjusted analyses. Death, immediate inpatient admission, 30-day hyperkalemia recurrence, and 30-day inpatient admission were also assessed by severity. RESULTS: Of 6222 patients included, 4432 (71.2%) had mild hyperkalemia, 1085 (17.4%) had moderate, and 705 (11.3%) had severe hyperkalemia. Chronic kidney disease (39.9-50.1%) and heart failure (21.6-24.3%) were common. In the ED, electrocardiograms (mild, 56.5%; moderate, 69.6%; severe, 81.0%) and patients with at least two potassium laboratory values increased with severity (15.0%; 40.4%; 75.5%). Among patients with at least two potassium laboratory values, over half of patients (60.4%) had potassium levels ≤ 5.0 mEq/L prior to discharge. Use of potassium-binding treatments (sodium polystyrene sulfonate: mild = 4.1%; moderate = 17.1%; severe = 27.4%), temporizing agents (5.6%; 15.5%; 31.6%), or dialysis (0.4%; 0.8%; 3.0%) increased with severity; treatment at discharge was not common. Death (1.1%; 3.7%; 10.6%), immediate admission to inpatient care (5.8%; 8.7%; 12.7%), 30-day hyperkalemia recurrence (2.9%; 19.0%; 32.5%), 30-day inpatient admission with hyperkalemia (6.5%; 7.9%; 9.3%) also increased with severity. CONCLUSION: Patients with moderate and severe hyperkalemia experienced elevated risk of hyperkalemia recurrence and hyperkalemia-related inpatient readmission following discharge from the ED from a descriptive analysis. Future research to assess strategies to reduce hyperkalemia recurrence and inpatient admission in this patient population would be beneficial.

Real-World Data for Healthcare Research in China: Call for Actions.

OBJECTIVES: This study aimed to provide an overview of major data sources in China that can be potentially used for epidemiology, health economics, and outcomes research; compare them with similar data sources in other countries; and discuss future directions of healthcare data development in China. METHODS: The study was conducted in 2 phases. First, various data sources were identified through a targeted literature review and recommendations by experts. Second, an in-depth assessment was conducted to evaluate the strengths and limitations of administrative claims and electronic health record data, which were further compared with similar data sources in developed countries. RESULTS: Secondary databases, including administrative claims and electronic health records, are the major types of real-world data in China. There are substantial variations in available data elements even within the same type of databases. Compared with similar databases in developed countries, the secondary databases in China have some general limitations such as variations in data quality, unclear data usage mechanism, and lack of longitudinal follow-up data. In contrast, the large sample size and the potential to collect additional data based on research needs present opportunities to further improve real-world data in China. CONCLUSIONS: Although healthcare data have expanded substantially in China, high-quality real-world evidence that can be used to facilitate decision making remains limited in China. To support the generation of real-world evidence, 2 fundamental issues in existing databases need to be addressed-data access/sharing and data quality.

Hemophilia Gene Therapy Value Assessment: Methodological Challenges and Recommendations.

Gene therapy for hemophilia is designed to produce health gains for patients over many years. Rewarding that value creation on the basis of a one-time treatment implies a large upfront cost. This cost can only be justified by long-term health benefits and being cost-effective compared with conventional treatments. Yet, uncertainties about the long-term benefits make it challenging to assess clinical and economic value of gene therapies at launch. We identify and discuss key methodological challenges in assessing the value of gene therapy for hemophilia, including the immaturity of evidence on the durability of benefits, lack of definition and valuation of cure for chronic diseases, absence of randomized controlled trials, limitations of traditional quality of life measures in hemophilia, approach for qualifying cost-savings compared with current treatments, and choice of perspective. The Institute for Clinical and Economic Review has developed a framework for assessing single or short-term therapies (ICER-SST) and has applied it in hemophilia. After reviewing this framework and its application, we recommend the following when assessing the value of hemophilia gene therapies: (1) leveraging expert clinical opinion to justify assumptions on the durability of benefits; (2) using external synthetic controls and lead-in, self-controlled trials to assess comparative effectiveness; (3) addressing limitations of traditional quality of life measures through the use of modified utility collection approaches; (4) adjusting cost offsets from gene therapies with caution; (5) considering outcome-based contracting to address uncertainties about prices and long-term outcomes; and (6) presenting societal and healthcare system perspectives in parallel.

Prevalence of Metabolic Acidosis Among Patients with Chronic Kidney Disease and Hyperkalemia.

INTRODUCTION: Although hyperkalemia and metabolic acidosis often co-occur in patients with chronic kidney disease (CKD), the prevalence of metabolic acidosis among patients with CKD and hyperkalemia is understudied. Therefore, we used medical record data from the Research Action for Health Network to estimate this prevalence. METHODS: Adult patients with CKD stage 3-5, ≥ 1 outpatient potassium value > 5.0 mEq/l, and ≥ 1 outpatient bicarbonate value available were identified. Patients with end stage kidney disease (ESKD) in the prior year were excluded. The prevalence of metabolic acidosis in each calendar year from 2014 to 2017 among patients with CKD and hyperkalemia was estimated using two definitions of hyperkalemia (potassium > 5.0 mEq/l and > 5.5 mEq/l) and metabolic acidosis (bicarbonate < 18 mEq/l and < 22 mEq/l). RESULTS: In the 2017 patient cohort and among patients with CKD and hyperkalemia, patients with metabolic acidosis were younger (69 versus 74 years), more likely to have advanced CKD (35% versus 13%), and use oral sodium bicarbonate (21% versus 4%) than patients without metabolic acidosis. The prevalence of metabolic acidosis (< 22 mEq/l) ranged from 25 to 29% when hyperkalemia was defined by potassium > 5.0 mEq/l and ranged from 33 to 39% when hyperkalemia was defined by potassium > 5.5 mEq/l. CONCLUSION: Results demonstrated that prevalence estimates of metabolic acidosis varied based on the definition of hyperkalemia and metabolic acidosis utilized.

Real-World Treatment Profiles, Clinical Outcomes, and Healthcare Resource Utilization of Patients with Migraine Prescribed Erenumab: A Multicenter Chart-Review Study of US Headache Centers.

INTRODUCTION: Erenumab, a first-in-class monoclonal antibody targeting the calcitonin gene-related peptide pathway, was approved by the US Food and Drug Administration in 2018 for the prevention of migraine in adults. There is limited data available on its impact in real-world settings. The study aim was to characterize the real-world treatment profiles, clinical outcomes, and healthcare resource utilization of patients prescribed erenumab from select major US headache centers. METHODS: A retrospective chart review of patients with migraine treated with erenumab for at least 3 months across five major headache centers was conducted. Data was collected from patient charts between April 2019 and April 2020 and included patient and clinical characteristics, migraine medication use, and outpatient visits. The date of the first prescription fill of erenumab was defined as the index date. The baseline period comprised the 3 months prior to the index date and the study period comprised the at least 3 months on erenumab treatment. RESULTS: Data from a total of 1034 patients with chronic migraine with a mean of 9.3 months of erenumab treatment were analyzed. Patients were on average 48 years old, 86% were female, and 79% were white. Patients had a mean of 5 preventive treatment failures prior to erenumab initiation. Patients used a mean of 2 preventive treatments (excluding erenumab) and 2 acute treatments during baseline and study periods. Among patients with effectiveness data, 45% of patients had improvement in physician-reported migraine severity and 35% experienced at least 50% reduction in mean headache/migraine days per month. The average number of monthly outpatient visits was 0.43 and 0.30 before and after erenumab initiation, respectively. CONCLUSION: In this predominantly refractory chronic migraine population treated in select headache centers, patients had fewer headache/migraine days per month and outpatient visits after initiating erenumab. However, patients largely continued to be managed via a polypharmacy approach after erenumab initiation.

Cost Effectiveness Analysis of Tisagenlecleucel for the Treatment of Adult Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma in Japan.

There are limited treatment options and substantial unmet needs for adult patients with relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL) in Japan. In 2019, tisagenlecleucel, a CD19-directed chimeric antigen receptor T cell therapy, was approved for r/r DLBCL in Japan. The efficacy and safety of tisagenlecleucel were demonstrated in the pivotal phase II single-arm JULIET trial. The objective of the current study was to assess the cost-effectiveness of tisagenlecleucel treatment strategy versus current standard of care (salvage chemotherapy treatment strategy) for the treatment of patients with r/r DLBCL in Japan. A three-state partitioned survival model was constructed from a Japanese public healthcare payer's perspective, with the following three health states: progression-free survival, progressive/relapsed disease, and death. Because the tisagenlecleucel arm included patients who did or did not receive the infusion, a decision-tree structure was used to partition patients based on their infusion status. Treatment efficacy and costs were based on tisagenlecleucel-infused patients for those who received the infusion; for non-infused patients, they were based on standard salvage chemotherapy. The efficacy inputs for tisagenlecleucel-infused patients and salvage chemotherapy were based on observed data in the JULIET trial and the international SCHOLAR-1 meta-analysis, respectively, before year 3. Afterward, all patients were assumed to have no further progression and to incur the mortality risk of long-term DLBCL survivors. The base case analysis explored a lifetime horizon (44 years), with costs and effectiveness discounted 2.0% annually, and it used a monthly model cycle. Direct costs were considered in the base case, composed of pretreatment costs, treatment costs, adverse events management costs, follow-up costs before progression, subsequent SCT costs, post-progression costs, and terminal care costs. Total incremental costs, life years (LYs), and quality-adjusted life years (QALYs) were compared for tisagenlecleucel versus salvage chemotherapy. The incremental cost-effectiveness ratio (ICER) was estimated as the costs per QALY gained, and a threshold of ¥7.5 million was used to assess whether tisagenlecleucel is cost effective. Deterministic and probabilistic sensitivity analyses were performed. The total LYs (discounted) for tisagenlecleucel and salvage chemotherapy were 7.24 and 4.35 years, respectively; the corresponding QALYs were 5.42 and 2.57 years, respectively. The discounted incremental LYs and QALYs comparing tisagenlecleucel to salvage chemotherapy were estimated as 2.89 and 2.85 years, respectively. Over a lifetime horizon, the model estimated that tisagenlecleucel had a total incremental cost of ¥15,590,335 (discounted) versus salvage chemotherapy. Tisagenlecleucel was associated with an ICER of ¥5,476,496 per QALY gained compared to salvage chemotherapy. Extensive sensitivity analyses supported the base-case findings. Tisagenlecleucel is a cost-effective treatment strategy for r/r DLBCL compared to salvage chemotherapy treatment strategy from a Japanese public healthcare payer's perspective.

Health care resource utilization and cost burden of hemophilia B in the United States.

Hemophilia B is a rare congenital blood disorder characterized by factor IX deficiency. Clinical profiles of hemophilia B range from mild to severe forms of the disease. The objective of this study was to characterize the economic burden associated with differing clinical profiles of hemophilia B from a US health system perspective. Using the IBM MarketScan database (June 2011-February 2019), a claims-based algorithm was developed to identify 4 distinct profiles (mild, moderate, moderate-severe, and severe) in adult males with hemophilia B based on the frequency of hemorrhage events and factor IX replacement claims. Mean annual health care resource use (HRU) and costs were statistically compared between patients with hemophilia B (N = 454) and 1:1 demographic-matched controls (N = 454), both overall and with stratification by clinical profile. Compared with matched controls, patients with hemophilia B had a significantly higher comorbidity burden (Charlson Comorbidity Index, mean ± standard deviation [SD]: 0.9 ± 1.7 vs 0.3 ± 0.9, P < .001). Across all clinical profiles, patients with hemophilia B had significantly higher HRU vs matched controls (mean ± SD: 0.3 ± 0.6 vs 0.1 ± 0.3 inpatient admissions; 0.6 ± 1.2 vs 0.2 ± 0.6 emergency department visits; 17.7 ± 22.9 vs 8.0 ± 11.0 outpatient visits; all P < .001). Annual total health care costs per patient among patients with hemophilia B were more than 25-fold higher vs matched controls (mean ± SD: $201 635 ± $411 530 vs $7879 ± $29 040, respectively, P < .001). Annual total health care costs per patient increased with increasing severity (mean ± SD: mild, $80 811 ± $284 313; moderate, $137 455 ± $222 021; moderate-severe, $251 619 ± $576 886; severe, $632 088 ± $501 270). The findings of this study highlight the substantial burden of illness associated with hemophilia B.

Cost-Effectiveness Analysis of Tisagenlecleucel for the Treatment of Pediatric and Young Adult Patients with Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia in Japan.

Until recently, treatment options were relatively limited for children and young adults with relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL). Tisagenlecleucel is a chimeric antigen receptor T cell (CAR-T) immunotherapy with promising efficacy and manageable safety that was approved in Japan in 2019 for the treatment of CD19-positive r/r B cell ALL (B-ALL). However, there is no publication assessing the cost-effectiveness of CAR-T in Japan. The objective of this study was to assess the cost-effectiveness of a tisagenlecleucel treatment strategy compared to a blinatumomab treatment strategy and a clofarabine combination treatment strategy (i.e., clofarabine + cyclophosphamide + etoposide) in Japan for pediatric and young adult patients up to 25 years of age with r/r B-ALL. A partitioned survival model with a lifetime horizon and monthly cycle was constructed from a Japanese public healthcare payer's perspective. Patients were distributed across the following partitioned health states: event-free survival (EFS), progressive disease, and death, which were informed by the EFS and overall survival (OS) data of respective clinical trials before year 5. For the tisagenlecleucel arm, a decision-tree structure was used to partition patients based on the infusion status; those who discontinued prior to receiving infusion were assigned efficacy and cost inputs of blinatumomab and those who received infusion were assigned efficacy and costs inputs based on tisagenlecleucel-infused patients. As trial data for blinatumomab and clofarabine ended before year 5, matching-adjusted indirect comparisons were used to extrapolate OS between the end of trial observation and up to year 5. All surviving patients followed the mortality risk of long-term ALL survivors without additional risk of disease relapse after year 5, regardless of initial treatment strategies. The model accounted for pretreatment costs, treatment costs, adverse event costs, follow-up costs, subsequent allogeneic hematopoietic stem cell transplantation costs, and terminal care costs. Incremental cost-effectiveness ratios (ICERs) per life-years (LYs) gained and ICERs per quality-adjusted life-years (QALYs) gained were evaluated using a 2% discount rate, and a threshold of ¥7.5 million was used to assess cost-effectiveness. Deterministic and probabilistic sensitivity analyses were performed. The total LYs (discounted) for tisagenlecleucel, blinatumomab, and clofarabine combination treatment strategies were 13.3, 4.0, and 2.7 years, respectively; the corresponding QALYs were 11.6, 3.1, and 2.1 years, respectively. The ICERs per QALY gained for tisagenlecleucel were ¥2,035,071 versus blinatumomab and ¥2,644,702 versus clofarabine combination therapy. Extensive sensitivity analyses supported the findings. Tisagenlecleucel is a cost-effective treatment strategy for pediatric and young adult patients with r/r B-ALL from a Japanese public healthcare payer's perspective.

The Economic Burden of Tenosynovial Giant Cell Tumors Among Employed Workforce in the United States.

OBJECTIVE: To assess the economic burden of tenosynovial giant cell tumor (TGCT) among US employed workforce. METHODS: Patients with TGCT medical claims (N = 1395) and matched controls (1:10) without TGCT claims (N = 13,950) were identified from the OptumHealth Care Solutions, Inc. database (January 1, 1999 to March 31, 2017). Adjusted regression models were used to compare healthcare resource utilization, time lost from work, and associated costs between cohorts. RESULTS: In patients with TGCT, the rates of inpatient admissions, emergency room visits, outpatient visits, and work loss days were 2.8, 1.5, 2.2, and 2.6 times those of matched controls, respectively (all P < 0.001). Total annual all-cause healthcare costs and work loss-related costs were $9368 and $2708 higher for TGCT patients than for matched controls, respectively (all P < 0.001). CONCLUSIONS: TGCT was associated with a significant healthcare and work loss burden on US employers.

Treatment patterns and outcomes in patients with myelodysplastic syndromes treated with hypomethylating agents: a SEER-Medicare analysis.

To describe real-world treatment patterns and outcomes among adult patients with myelodysplastic syndromes (MDS) treated with hypomethylating agents (HMA), patients were identified in the SEER-Medicare database (01/2006-12/2016); 3,046 patients with MDS treated with HMA were included. An algorithm was developed to categorize patients into MDS risk groups: the majority of patients were classified as Higher-risk (70.9%), 8.0% as Intermediate-risk, and 21.1% as Unknown-risk. Overall, 77.4% of patients initiated azacitidine and 22.6% decitabine; they received an average of 5.1 index-HMA cycles, of which 90.9% were complete with a median cycle duration of 28 days. Median survival was 11.6, 18.4, and 19.1 months for the Higher-risk, Intermediate-risk, and Unknown-risk groups, respectively. Median time-to-AML transformation was 19.3 months for the Higher-risk group and 50.4 months for the Intermediate-risk group (not reached for Unknown-risk). Data highlight the unmet medical needs of patients with MDS treated with HMA, particularly for the Higher-risk MDS group.

Healthcare resource utilization and costs in patients with myelodysplastic syndromes treated with hypomethylating agents: a SEER-Medicare analysis.

AIMS: To describe healthcare resource utilization (HRU) and costs in patients with myelodysplastic syndromes (MDS) treated with hypomethylating agents (HMA) based on HMA-treatment response. MATERIALS AND METHODS: SEER-Medicare data (January 2006-December 2016) were used to identify adults diagnosed with MDS (SEER: January 2009-December 2015) initiated on HMA (index date). HMA-treatment success (indicators: ≥7 HMA cycles, stem cell transplantation, and transfusion independence) or failure (indicators: acute myeloid leukemia [AML], AML-like treatment, and death) was determined using a claim-based algorithm. HRU and costs were assessed from the index date to 1-year post-index, overall and stratified by HMA-treatment success or failure. Among patients with HMA-treatment failure, HRU and costs were also assessed from failure to 1-year post-failure. RESULTS: The study included 3,046 patients (mean age: 77.4 years; females: 36.8%). Rates of HMA-treatment success and failure were 44.4% and 76.2%, respectively (20.6% had HMA-treatment success then failure). Overall, patients had 15.2 inpatient admissions per-100-patients-per-month (median follow-up: 5.9 months). Patients with HMA-treatment success had 7.5 inpatient admissions per-100-patients-per-month (median follow-up: 12.0 months), while those with HMA-treatment failure had 20.4 and 35.3 admissions per-100-patients-per-month pre- and post-HMA-treatment failure, respectively (median follow-up: 4.3 and 1.8 months, pre- and post-HMA-treatment failure, respectively). Mean total healthcare costs were $12,494 per-patient-per-month overall, $8,069 per-patient-per-month among patients with HMA-treatment success, and $13,809 and $19,242 per-patient-per-month pre- and post-HMA-treatment failure, respectively. Outpatient costs (68.3%) were the main contributor of total healthcare costs overall, while inpatient costs (80.3%) were the main cost driver post-HMA-treatment failure. LIMITATIONS: Without available laboratory test results, clinical indicators observed in claims were used to assess HMA-treatment response. CONCLUSIONS: Over 75% of patients with MDS failed HMA-treatment within 6 months of initiation and were observed with more inpatient admissions than those with HMA-treatment success, translating into substantially higher healthcare costs. HMA-treatment failure results in an important economic burden in MDS patients.

An overview of patients with haemophilia A in China: Epidemiology, disease severity and treatment strategies.

INTRODUCTION: Haemophilia A (HA) is a rare X chromosome-linked bleeding disorder resulting in missing or defective clotting factor VIII (FVIII) and causes large disease burden. AIM: As a member of World Federation of Hemophilia, China seeks to understand the current epidemiology, disease profile and treatment landscape of patients with HA through the Hemophilia Treatment Center Collaboration Network of China (HTCCNC). METHODS: The HTCCNC enabled data collection on patients with HA from 166 member hospitals (2007-2019) across China. The distribution of patients across 31 divisions was summarized using a heat map. Patient demographics, disease severity and clinical and treatment information were summarized using descriptive statistics. RESULTS: HTCCNC identified 17,779 patients with HA during 2007-2019. Patients were predominantly male (99.99%), and 28.3% had a known family history of haemophilia. Among patients with lab-measured disease severity (N = 13,116), 6,519 had severe HA (49.7%), 4,788 had moderate HA (36.5%), and 1,809 had mild HA (13.8%). Among patients with information on the delays, delays in diagnosis and in treatment initiation were observed in 1,437 (28.8%) and 1,750 (39.2%) patients, respectively. On average, those patients had an 8.4 years gap between the first bleed and HA diagnosis and a delay of 8.6 years from the first bleed to treatment initiation. Additionally, 44.33% of patients relied solely on episodic treatments, and 16.2% received any prophylaxis treatments. CONCLUSIONS: Using data from the largest haemophilia registry in China, this study indicated that delayed diagnosis and treatment, together with low utilization of prophylaxis, are key challenges for patients with HA.