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.

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.

A Risk Score for Fluconazole Failure among Patients with Candidemia.

This study aimed to develop a prediction model to identify patients with candidemia who were at high risk of failing fluconazole treatment. Adult patients in the United States with candidemia who received fluconazole during hospitalization were selected from the Cerner Health Facts Hospital Database (04/2004 to 03/2013). Fluconazole failure was defined as switching/adding another antifungal, positive Candida culture ≥10 days after fluconazole initiation, or death during hospitalization. Patients were randomized into modeling and validation samples. Using the modeling sample, a regression analysis of least absolute shrinkage and selection operator was used to select risk predictors of fluconazole failure (demographics, Candida species, initiation of fluconazole before positive culture and after admission, and comorbidities, procedures, and treatments during the 6 months before admission and fluconazole initiation). The prediction model was evaluated using the validation sample. We found that of 987 identified patients (average age of 61 years, 51% male, 72% Caucasian), 49% failed and 51% did not fail fluconazole treatment. Of those who failed, 70% switched or added another antifungal, 21% had a second positive Candida test, and 42% died during hospitalization. Nine risk factors were included in the prediction model: days to start fluconazole after admission, Candida glabrata or Candida krusei infection, hematological malignancy, venous thromboembolism (VTE), enteral nutrition, use of nonoperative intubation/irrigation, and other antifungal use. All but VTE were associated with a higher risk of failure. The model's c-statistic was 0.65, with a Hosmer-Lemeshow test P value of 0.23. In summary, this prediction model identified patients with a high risk of fluconazole failure, illustrating the potential value and feasibility of personalizing candidemia treatment.

Poor early response to methotrexate portends inadequate long-term outcomes in patients with moderate-to-severe psoriasis: Evidence from 2 phase 3 clinical trials.

BACKGROUND: Most methotrexate-treated psoriasis patients do not achieve a long-term PASI75 (75% reduction from baseline Psoriasis Area and Severity Index score) response. Indications of nonresponse can be apparent after only 4 weeks of treatment. OBJECTIVE: To develop a prediction rule to identify patients unlikely to respond adequately to methotrexate. METHODS: Patient-level data from CHAMPION (NCT00235820, N = 110) was used to construct a prediction model for week 16 PASI75 by using patient baseline characteristics and week 4 PASI25. A prediction rule was determined on the basis of the sensitivity and specificity and validated in terms of week 16 PASI75 response in an independent validation sample from trial M10-255 (NCT00679731, N = 163). RESULTS: PASI25 achievement at week 4 (odds ratio = 8.917) was highly predictive of response with methotrexate at week 16. Patients with a predicted response probability <30% were recommended to discontinue methotrexate. The rates of week 16 PASI75 response were 65.8% and 21.1% (P < .001) for patients recommended to continue and discontinue methotrexate, respectively. LIMITATIONS: The CHAMPION trial excluded patients previously treated with biologics, and the M10-255 trial had no restrictions. CONCLUSION: A prediction rule was developed and validated to identify patients unlikely to respond adequately to methotrexate. The rule indicates that 4 weeks of methotrexate might be sufficient to predict long-term response with limited safety risk.

Real-World Outcomes of Acute Ischemic Stroke Treatment with Intravenous Recombinant Tissue Plasminogen Activator.

BACKGROUND AND PURPOSE: In clinical trials, intravenous (IV) recombinant tissue-type plasminogen activator (rt-PA) reduces the likelihood of disability if given within 3 hours of acute ischemic stroke. This study compared real-world outcomes between patients treated and patients not treated with IV rt-PA. METHODS: In this retrospective study, United States-based neurologists randomly selected eligible acute ischemic stroke patients from their charts who were and were not treated with IV rt-PA. Mortality, hospital readmission, and independence were compared between patients treated and patients not treated with IV rt-PA using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. RESULTS: A total of 1026 charts were reviewed with a median follow-up time of 15.5 months. Pretreatment stroke severity, as measured by the National Institutes of Health Stroke Scale, was comparable between cohorts (IV rt-PA =11.7; non-rt-PA = 11.3; P = .165). IV rt-PA patients experienced significantly longer survival (P = .013), delayed hospital readmission (P = .012), and shorter time to independence (P < .001) compared with patients not treated with rt-PA. After adjusting for baseline characteristics, IV rt-PA patients had significantly lower mortality (hazard ratio [95% confidence interval] = .52 [.30, .90]) and greater rates of independence (hazard ratio [95% confidence interval] = 1.42 [1.17, 1.71]) than patients not treated with rt-PA. CONCLUSIONS: This real-world study indicated that acute ischemic stroke patients treated with IV rt-PA experience long-term clinical benefits in survival and functional status.

Drug-Drug Interaction Associated with Mold-Active Triazoles among Hospitalized Patients.

The majority of hospitalized patients receiving mold-active triazoles are at risk of drug-drug interactions (DDIs). Efforts are needed to increase awareness of DDIs that pose a serious risk of adverse events. Triazoles remain the most commonly utilized antifungals. Recent developments have included the mold-active triazoles (MATs) itraconazole, voriconazole, and posaconazole, which are first-line agents for the treatment of filamentous fungal infections but have the potential for DDIs. This objective of this study was to evaluate the prevalence of triazole DDIs. Hospitalized U.S. adults with MAT use were identified in the Cerner HealthFacts database, which contained data from over 150 hospitals (2005 to 2013). The severities of DDIs with MATs were categorized, using drug labels and the drug information from the Drugdex system (Thompson Micromedex), into four groups (contraindicated, major, moderate, and minor severity). DDIs of minor severity were not counted. A DDI event was considered to have occurred if the following two conditions were met: (i) the patient used at least one drug with a classification of at least a moderate interaction with the MAT during the hospitalization and (ii) there was a period of overlap between the administration of the MAT and that of the interacting drug of at least 1 day. A total of 6,962 hospitalizations with MAT use were identified. Among them, 88% of hospitalizations with voriconazole use, 86% of hospitalizations with itraconazole use, and 93% of hospitalizations with posaconazole use included the use of a concomitant interacting drug. A total of 68% of hospitalizations with posaconazole use, 34% of hospitalizations with itraconazole use, and 20% of hospitalizations with voriconazole use included the use of at least one drug with a DDI of contraindicated severity. A total of 83% of hospitalizations with posaconazole use, 61% of hospitalizations with itraconazole use, and 82% of hospitalizations with voriconazole use included the use of at least one drug that resulted in a severe DDI. The findings of this study demonstrate that a majority of hospitalized patients receiving MAT are at risk for severe drug-drug interactions and highlight the need for antifungal stewardship.

Delay in initiation of adjuvant trastuzumab therapy leads to decreased overall survival and relapse-free survival in patients with HER2-positive non-metastatic breast cancer.

Trastuzumab reduces the risk of relapse in women with HER2-positive non-metastatic breast cancer, but little information exists on the timing of trastuzumab initiation. The study investigated the impact of delaying the initiation of adjuvant trastuzumab therapy for >6 months after the breast cancer diagnosis on time to relapse, overall survival (OS), and relapse-free survival (RFS) among patients with non-metastatic breast cancer. Adult women with non-metastatic breast cancer who initiated trastuzumab adjuvant therapy without receiving any neoadjuvant therapy were selected from the US Department of Defense health claims database from 01/2003 to 12/2012. Two study cohorts were defined based on the time from breast cancer diagnosis to trastuzumab initiation: >6 months and ≤6 months. The impact of delaying trastuzumab initiation on time to relapse, OS, and RFS was estimated using Cox regression models adjusted for potential confounders. Of 2749 women in the study sample, 79.9 % initiated adjuvant trastuzumab within ≤6 months of diagnosis and 20.1 % initiated adjuvant trastuzumab >6 months after diagnosis. After adjusting for confounders, patients who initiated trastuzumab >6 months after the breast cancer diagnosis had a higher risk of relapse, death, or relapse/death than those who initiated trastuzumab within ≤6 months of diagnosis (hazard ratios [95 % CIs]: 1.51 [1.22-1.87], 1.54 [1.12-2.12], and 1.43 [1.16-1.75]; respectively). The results of this population-based study suggest that delays of >6 months in the initiation of trastuzumab among HER2-positive non-metastatic breast cancer patients are associated with a higher risk of relapse and shorter OS and RFS.

Effect of adherence and insulin delivery system on clinical and economic outcomes among patients with type 2 diabetes initiating insulin treatment.

BACKGROUND: Adherence to insulin affects real-world health outcomes and may itself be affected by the choice of insulin delivery device (pen or vial/syringe). The choice of insulin delivery device may also have direct effects on effectiveness. OBJECTIVE: This study aimed to estimate the effects of insulin adherence and delivery device on real-world health outcomes. METHODS: This study included adults with type 2 diabetes mellitus initiating insulin, with continuous health plan insurance for 6 or more months before initiation (baseline) and 1 or more year after. Measured outcomes included glycosylated hemoglobin (Hb A1c) reduction, hospitalization rate, total health care costs, and pharmacy costs over 1 year of follow-up. Adherence (defined as having insulin fills sufficient for the entire quarter), pen or vial/syringe use, and disease-related patient characteristics were assessed in each quarter. To account for the time-varying relationship between adherence, patient characteristics, and outcomes, marginal structural generalized linear models were used to estimate the effect of adherence and device use. Mean outcomes were predicted for different combinations of adherence and device choice. RESULTS: Among the 13,428 patients (mean age 54 years; 46% women; baseline Hb A1c 9.3%), adherent pen users had greater reductions in Hb A1c (-0.35%; P = 0.045), lower hospitalization rates (-0.36; P < 0.01), and higher pharmacy costs ($2923; P < 0.01) than did nonadherent vial users, and similar total health care costs ($3906 lower; P = 0.1). Pen use and adherent vial use decreased hospitalization rate and increased pharmacy but not total costs. CONCLUSIONS: Adherence and pen use have beneficial effects on patients' real-world outcomes, with the most favorable effects attributable to adherent pen use.

Change in forced vital capacity and associated subsequent outcomes in patients with newly diagnosed idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare and serious disease characterized by progressive lung-function loss. Limited evidence has been published on the impact of lung-function loss on subsequent patient outcomes. This study examined change in forced vital capacity (FVC) across IPF patients in the 6 months after diagnosis and its association with clinical and healthcare resource utilization (HRU) outcomes in a real-world setting in the U.S. METHODS: A retrospective chart review was conducted of patients diagnosed with IPF by U.S. pulmonologists. Patient eligibility criteria included: 1) 40 years or older with a confirmed date of first IPF diagnosis with high-resolution computed tomography and/or lung biopsy between 01/2011 and 06/2013; 2) FVC results recorded at first diagnosis (±1 month) and at 6 months (±3 months) following diagnosis. Based on relative change in FVC percent predicted (FVC%), patients were categorized as stable (decline <5%), marginal decline (decline ≥5% and <10%), or significant decline (decline ≥10%). Physician-reported clinical and HRU outcomes were assessed from ~6 months post-diagnosis until the last contact date with the physician and compared between FVC% change groups. Multivariable Cox proportional-hazards models were constructed to assess risk of mortality, suspected acute exacerbation (AEx), and hospitalization post-FVC% change. Generalized estimating equations were used to account for multiple patients contributed by individual physicians. RESULTS: The sample included 490 IPF patients contributed by 168 pulmonologists. The mean (SD) age was 61 (11) years, 68% were male, and the mean (SD) baseline FVC% was 60% (26%). 250 (51%) patients were categorized as stable, 98 (20%) as marginal decline, and 142 (29%) as significant decline. The mean (SD) observation time was 583 (287) days. In both unadjusted analysis and multivariable models, significantly worse clinical outcomes and increased HRU were observed with greater lung-function decline. CONCLUSIONS: These findings suggest that nearly half of IPF patients experienced decline in FVC% within ~6 months following IPF diagnosis. Greater FVC% decline was associated with an increased risk of further IPF progression, suspected AEx, mortality, and higher rate of HRU. Management options that slow FVC decline may help improve future health outcomes in IPF.

Investigation of adverse-event-related costs for patients with metastatic breast cancer in a real-world setting.

BACKGROUND: Existing treatments for metastatic breast cancer (mBC) are often effective but can cause adverse events (AEs). This study aimed to identify AEs associated with chemotherapies commonly used in mBC treatment (phase 1) and to quantify the economic impact of these AEs (phase 2). MATERIALS AND METHODS: Patients in phase 1 had at least one claim for therapy for mBC, with at least one episode with single or multiple agents. The most common chemotherapy-related complications were identified using medical and pharmacy claims data. In phase 2, patients meeting study criteria were divided into four treatment cohorts by the line of treatment and chemotherapy received: first-line taxane-treated patients, second-line taxane-treated patients, first-line capecitabine-treated patients, and second-line capecitabine-treated patients. Average monthly AE-related health care costs per cohort were stratified by cost component. Total monthly costs per number of AEs were also calculated. RESULTS: On average, patients in phase 1 (n = 1,551) had 2 episodes of treatment, with a mean duration of 131 days. The most frequently noted complications were anemia (50.7% of mBC treatment episodes), bilirubin elevation (26.4%), and leukopenia (24.8%). In phase 2, costs related to AEs were primarily driven by incremental inpatient, outpatient, and pharmacy costs. Increases in average monthly costs ranged from $854 (9.0%) to $5,320 (69.5%), according to cohort. Overall costs increased with increasing numbers of AEs. CONCLUSION: Chemotherapy-related AEs in patients with mBC are associated with a substantial economic burden that increases with the number of AEs reported.

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.

Matching-adjusted indirect comparisons: a new tool for timely comparative effectiveness research.

OBJECTIVE: In the absence of head-to-head randomized trials, indirect comparisons of treatments across separate trials can be performed. However, these analyses may be biased by cross-trial differences in patient populations, sensitivity to modeling assumptions, and differences in the definitions of outcome measures. The objective of this study was to demonstrate how incorporating individual patient data (IPD) from trials of one treatment into indirect comparisons can address several limitations that arise in analyses based only on aggregate data. METHODS: Matching-adjusted indirect comparisons (MAICs) use IPD from trials of one treatment to match baseline summary statistics reported from trials of another treatment. After matching, by using an approach similar to propensity score weighting, treatment outcomes are compared across balanced trial populations. This method is illustrated by reviewing published MAICs in different therapeutic areas. A novel analysis in attention deficit/hyperactivity disorder further demonstrates the applicability of the method. The strengths and limitations of MAICs are discussed in comparison to those of indirect comparisons that use only published aggregate data. RESULTS: Example applications were selected to illustrate how indirect comparisons based only on aggregate data can be limited by cross-trial differences in patient populations, differences in the definitions of outcome measures, and sensitivity to modeling assumptions. The use of IPD and MAIC is shown to address these limitations in the selected examples by reducing or removing the observed cross-trial differences. An important assumption of MAIC, as in any comparison of nonrandomized treatment groups, is that there are no unobserved cross-trial differences that could confound the comparison of outcomes. CONCLUSIONS: Indirect treatment comparisons can be limited by cross-trial differences. By combining IPD with published aggregate data, MAIC can reduce observed cross-trial differences and provide decision makers with timely comparative evidence.

Comorbidity burden, healthcare resource utilization, and costs in chronic gout patients refractory to conventional urate-lowering therapy.

Patients with chronic gout refractory to conventional urate-lowering therapy have high rates of flares and incidence of tophi, which impose a significant disease and potentially economic burden. This study examined healthcare resource use and costs stratified by disease burden. Adult patients diagnosed with gout (ICD-9-CM:274.xx) and having had ≥3 flares defined by clinical surrogates within a 12-month period were selected for the case cohort from the Thomson MarketScan databases (2003/Q3-2008/Q3). Only patients who had received allopurinol treatment and a diagnosis of tophi (ICD-9-CM:274.8x) at any time before the first flare (index date) or within 12 months postindex were included and were matched in a 1:1 ratio with control gout-free subjects. The comorbidity burden, healthcare resource use, and annual healthcare costs (2008 US$) in the 12-month postindex period were compared between both cohorts using regression models adjusted for demographic characteristic and stratified for patients with ≥6 flares. A total of 679 gout patients met the inclusion criteria for the study and had a higher prevalence of comorbidities than their matched controls. Gout cohort had a significantly higher incidence of emergency room, hospitalizations, outpatient visits, and other medical services than did their matched controls (all comparisons, uncorrected P < 0.01). After adjusting for baseline characteristics, the refractory gout cohort incurred an incremental total annual healthcare cost of $10,222 where 40% of the annual medical cost was for gout-related care compared with control cohort (P < 0.01). Patients with refractory gout have a significant economic burden compared with a gout-free population.

Risks of developing psychiatric disorders in pediatric patients with psoriasis.

BACKGROUND: Symptoms of psoriasis can be embarrassing and distressing, and may increase risk of developing psychiatric disorders in young people. OBJECTIVE: We sought to compare incidences of psychiatric disorders between pediatric patients with psoriasis and psoriasis-free control subjects. METHODS: Patients (<18 years) with continuous health plan enrollment 6 months before and after first psoriasis diagnosis (index date) were selected (Thomson Reuters MarketScan database, 2000-2006 [Thomson Reuters, New York, NY]). Patients with psoriasis (N = 7404) were matched 1:5 on age and sex to psoriasis-free control subjects (N = 37,020). Patients were followed from index date to first diagnosis of a psychiatric disorder (ie, alcohol/drug abuse, depression, anxiety disorder, bipolar disorder, suicidal ideation, eating disorder), end of data availability, or disenrollment. Patients with psychiatric diagnoses or psychotropic medication use before the index date were excluded. Cox proportional hazard models controlling for age, sex, and comorbidities were used to estimate the effect of psoriasis on risks of developing psychiatric disorders. RESULTS: Patients with psoriasis were significantly more at risk of developing psychiatric disorders versus control subjects (5.13% vs 4.07%; P = .0001; hazard ratio = 1.25; P = .0001), especially depression (3.01% vs 2.42%; P = .0036; hazard ratio = 1.25; P = .0053) and anxiety (1.81% vs 1.35%; P = .0048; hazard ratio = 1.32; P = .0045). LIMITATIONS: Retrospective, observational studies of medical claims data are typically limited by overall quality and completeness of data and accuracy of coding for diagnoses and procedures. CONCLUSIONS: Pediatric patients with psoriasis had an increased risk of developing psychiatric disorders, including depression and anxiety, compared with psoriasis-free control subjects.

Comparative effectiveness research using matching-adjusted indirect comparison: an application to treatment with guanfacine extended release or atomoxetine in children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder.

OBJECTIVES: To illustrate a matching-adjusted indirect comparison by comparing the efficacy of guanfacine extended release (GXR) and atomoxetine (ATX) in reducing oppositional symptoms in children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder. METHODS: Individual patient data were used from a GXR trial; only published summary data were used from ATX trials. In a matching-adjusted indirect comparison, individual patients from the GXR trial were weighted such that their mean baseline characteristics matched those published for ATX trials. Placebo-arm outcomes were then compared to further assess balance between the matched populations. Changes in the Conners' Parent Rating Scale-Revised Short Form Oppositional Subscale from baseline to endpoint among GXR-treated and ATX-treated patients were then compared. RESULTS: Before matching, the GXR (n = 143) and ATX (n = 98) trial populations had significant differences in baseline characteristics and placebo-arm outcomes. After matching, baseline characteristics were well balanced across trials, and placebo-arm outcomes became nearly identical. Comparing active treatment arms across the matched populations, GXR was associated with a significantly greater reduction in mean Conners' Parent Rating Scale-Revised Short form oppositional subscale compared with ATX {-5.0 [95% confidence interval (CI): -6.6 to -3.4] vs. -2.4 [CI: -3.7 to -1.1], p = 0.01, effect size = 0.58}. CONCLUSIONS: In the absence of head-to-head randomized trials, matching-adjusted indirect comparisons can provide timely and reliable comparative evidence for decision makers and can be applied even when very few trials are available for the treatments of interest.

Treatment persistence & health care costs of adult MDD patients treated with escitalopram vs. citalopram in a medicaid population.

OBJECTIVE: Compare treatment persistence and health care costs of major depressive disorder (MDD) Medicaid patients treated with escitalopram versus citalopram. DESIGN: Retrospective analysis of Medicaid administrative claims data. METHODOLOGY: Analyzed administrative claims data from the Florida Medicaid program (07/2002-06/2006) for patients ages 18-64 years with 21 inpatient claim or 2 independent medical claims for MDD. Outcomes included discontinuation and switching rates and prescription drug, medical, and total health care costs, all-cause and related to mental disorder. Contingency table analysis and survival analysis were used to compare outcomes between treatment groups, using both unadjusted analysis and multivariate analysis adjusting for baseline characteristics. RESULTS: The study included 2,650 patients initiated on escitalopram and 630 patients initiated on citalopram. Patients treated with escitalopram were less likely to discontinue the index drug (63.7% vs. 68.9%, P=0.015) or to switch to another second-generation antidepressant (14.9% vs. 18.4%, P=0.029) over the six months post-index date. Patients treated with escitalopram had $1,014 lower total health care costs (P=0.032) and $519 lower health care costs related to mental disorder (P=0.023). More than half of the total cost difference was attributable to savings in inpatient hospitalizations related to mental disorder ($571, P=0.003) and to outpatient costs ($53, P<0.001). Escitalopram therapy was also associated with $736 lower medical costs related to mental disorder (P=0.009). CONCLUSION: In the Florida Medicaid program, compared to adult MDD patients initiated on citalopram, escitalopram patients have better treatment persistence and lower total health care costs due to any cause and due to mental disorder, mostly driven by lower hospitalization costs related to mental disorder.

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.

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.].

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.

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.