Patient Characteristics, Testing and Treatment Patterns, and Outcomes in EGFR-Mutated Advanced Non-Small Cell Lung Cancer: A Multinational, Real-World Study.

INTRODUCTION: Treatment landscape for advanced/metastatic NSCLC (aNSCLC) has evolved considerably over the past few decades with the advent of targeted therapies for epidermal growth factor receptor-mutated (EGFRm+) aNSCLC treatment. This study described real-world patient and disease characteristics, treatment and practice patterns, and clinical, economic, and patient-reported outcomes (PROs) in patients with EGFRm+ aNSCLC. METHODS: Data were derived from the Adelphi NSCLC Disease Specific Programme™ (DSP™), a point-in-time survey conducted between July and December 2020. The survey included oncologists and pulmonologists, and their consulting patients (with physician-confirmed EGFRm+ aNSCLC) from nine countries: the US, Brazil, the UK, Italy, France, Spain, Germany, Japan, and Taiwan. All analyses were descriptive. RESULTS: Overall, 542 physicians reported data for 2857 patients (mean age 65.6 years), and most patients were female (56.0%), white (61.0%), and had stage IV disease at initial diagnosis (76.0%), and adenocarcinoma histology (89.0%). Most patients received EGFR-tyrosine kinase inhibitors (TKI) therapy in first- (91.0%), second- (74.0%), and third-line (67.0%). The most common tumor samples and methods for EGFR detection were EGFR-specific mutation detection tests (44.0%) and core needle biopsy (56.0%). Median time to next treatment was 14.0 (IQR 8.0-22.0) months and disease progression was the main physician-reported reason for early discontinuation. The most common physician-reported disease symptoms were cough (51.0%), fatigue (37.0%), and dyspnea (33.0%). In patients assessed for PROs, mean EQ-5D-5L index and FACT-L health utility scores were 0.71 and 83.5, respectively. On average, patients lost 10.6 h of work/week for approximately 29.2 weeks due to EGFRm+ aNSCLC. CONCLUSION: This real-world multinational data set showed that most patients with EGFRm+ aNSCLC were treated per the country relevant clinical guidelines, with progression as the main reason for early treatment discontinuation. For the included countries, these findings may offer a useful benchmark for decision makers to determine future allocation of healthcare resources for patients with EGFRm+ aNSCLC.

Sintilimab plus chemotherapy for first-line treatment of advanced or metastatic nonsquamous non-small-cell lung cancer: network meta-analysis.

Aim: This systematic literature review and network meta-analysis evaluated the efficacy and safety of sintilimab + pemetrexed + platinum versus US FDA-approved/National Comprehensive Cancer Network-recommended immune checkpoint inhibitor (ICI) combination therapies for untreated advanced/metastatic non-squamous non-small-cell lung cancer without EGFR/ALK aberrations. Methods: Bayesian network meta-analysis was the base-case analysis and included assessment of fixed and random effects, and independent and simultaneous models, adjusting for baseline risk (placebo response). Chemotherapy was the common comparator. Results: Sintilimab + pemetrexed + platinum was associated with significantly longer progression-free survival than atezolizumab + platinum + nab-paclitaxel (hazard ratio [HR]: 0.57; 95% credible interval [CrI]: 0.40-0.82) and nivolumab + ipilimumab + pemetrexed + platinum (HR: 0.66; 95% CrI: 0.48-0.92). Sintilimab + pemetrexed + platinum and pembrolizumab + pemetrexed + platinum showed comparable progression-free survival (HR: 0.96; 95% CrI: 0.71-1.30). There was no significant difference in overall survival (HR range: 0.61-0.81) or overall response rates (odds ratio [OR] range: 0.29-0.75) between sintilimab + pemetrexed + platinum and the other ICI combinations. The incidence of high-grade adverse events was higher with sintilimab + pemetrexed + platinum than with nivolumab + ipilimumab (OR: 0.46; 95% CrI: 0.33-0.64) or without chemotherapy (OR: 0.25; 95% CrI: 0.19-0.34), with no significant difference between sintilimab + pemetrexed + platinum and the other ICI combinations. Conclusion: Sintilimab + pemetrexed + platinum showed comparable efficacy and safety versus US standard-of-care first-line ICI combinations for advanced/metastatic non-squamous non-small-cell lung cancer.

Sintilimab is an immunotherapy drug that was successfully developed and tested in China to treat a kind of lung cancer that has spread, called advanced non-squamous non-small-cell lung cancer (NSCLC). The ORIENT-11 clinical study showed that adding sintilimab to two types of chemotherapy (pemetrexed and platinum) as the first treatment for people in China with advanced non-squamous NSCLC was safe and effective in reducing the risk of cancer spreading, growing or getting worse, compared with chemotherapy alone. Our study combined and analyzed the results from 11 clinical studies to look at how well sintilimab with chemotherapy may work compared with immunotherapy drugs approved in the USA. The results showed that sintilimab with chemotherapy is as effective and safe as immunotherapy drugs approved in the USA to treat people with advanced non-squamous NSCLC. These results may help doctors and payers when deciding how to treat people with this disease.

Treatment Patterns, Clinical Outcomes and Health Care Resource Utilisation in Patients with EGFR-mutated Metastatic Non-Small Cell Lung Cancer: A Real-World Study in South Korea.

BACKGROUND: Despite the dynamic treatment landscape for EGFR mutant-positive metastatic non-small cell lung cancer (EGFRm+ mNSCLC), most of the earlier studies have focused on US or Western populations. OBJECTIVE: The objective of this study was to explore real-world treatment patterns and outcomes of South Korean patients with EGFRm+ mNSCLC. METHODS: Retrospective chart review of adult patients with EGFRm+ mNSCLC who received systemic treatment between January-2019 and June-2019. RESULTS: A total of 162 patients were included from 21 hospitals, with a median follow-up of 15.6 months. Median age was 65.0 years, 22% had central nervous system metastasis, and 57% and 38% had exon 19 deletion and exon 21 L858R, respectively. Among 144 patients (89%) who received first-line EGFR-tyrosine kinase inhibitor, afatinib was most the common (44%), followed by gefitinib (28%) and erlotinib (13%). First-line chemotherapy was more common when an EGFR-mutation was detected after versus before first-line treatment initiation (31% vs 5%). Discontinuation of first-line treatment was mostly due to disease-progression (81%) and toxicity (7%). Among 58 (78%) patients who received second-line treatment, osimertinib was the most common (40%). Most (60%) patients reported ≥1 Grade ≥3 adverse event during first-line treatment. Following initiation of first-line treatment, physician visits and chest X-rays were the most frequent healthcare utilisation events. Rates of emergency-room visits and hospitalization were 12% and 16%, respectively, with a mean length-of-stay of 10.4 days. At 12 months, overall survival rate was 95%, and numerically worse for patients with exon 21 versus 19 mutations. CONCLUSIONS: Characteristics and clinical outcomes of Korean patients with EGFRm+ mNSCLC in real-world practice were comparable to those observed in clinical trials. As osimertinib was not reimbursed for first-line treatment before study completion, further investigation is warranted to explore evolving treatment practice.

TP53 Co-Mutation Status Association with Clinical Outcomes in Patients with EGFR-Mutant Non-Small Cell Lung Cancer.

TP53 co-mutations have shown association with poor prognosis in various solid tumors. For EGFR-mutated advanced non-small cell lung cancer (aNSCLC), conflicting results exist regarding its impact on survival. Clinical outcomes and genomic data were obtained retrospectively from the real-world (rw) de-identified clinicogenomic database. Patients who initiated therapy for EGFR-mutated aNSCLC between January 2014 and December 2020 were identified. Clinical outcomes were evaluated by TP53-mutational status. In 356 eligible EGFR-mutated aNSCLC patients (median age 68 years), 210 (59.0%) had TP53 co-mutation and 146 (41.0%) had TP53 wild-type tumor. Unadjusted analysis showed significantly shorter survival in patients with TP53 co-mutation versus TP53 wild-type (rw progression-free survival [rwPFS]: HR = 1.4, 95% CI 1.1-1.9, p = 0.0196; overall survival [OS]: HR = 1.6, 95% CI 1.1-2.2, p = 0.0088). Multivariable analysis confirmed independent association between TP53 co-mutation and worse rwPFS (HR = 1.4, 95% CI 1.0-0.9, p = 0.0280) and OS (HR = 1.4, 95% CI 1.0-2.0, p = 0.0345). Directionally consistent findings were observed for response rates, and subgroups by EGFR-activating mutation and first-line (1 L) therapy, with more pronounced negative effect in 1 L EGFR-TKI subgroup. TP53 co-mutations negatively affected survival in patients with EGFR-mutated aNSCLC receiving standard 1 L therapy in real-world practice.

Generalizability of ORIENT-11 trial results to a US standard-of-care cohort with advanced non-small-cell lung cancer.

Aim: This retrospective study estimated efficacy and safety of sintilimab + pemetrexed + platinum (SPP) versus placebo + pemetrexed + platinum (PPP) in untreated locally advanced/metastatic, nonsquamous non-small-cell lung cancer (NSCLC), after adjusting each ORIENT-11 trial patient's contribution to ORIENT-11 data based on characteristics of a target US population. Materials & methods: The target US population (n = 557) was selected from a real-world deidentified advanced NSCLC database based on key ORIENT-11 eligibility criteria. Inverse probability weights for ORIENT-11 patients (n = 397) relative to US patients were calculated. Efficacy and safety of SPP versus PPP were adjusted by inverse probability weights. Results: After adjustment, progression-free survival remained superior for SPP. Other efficacy and safety outcomes were consistent. Conclusion: These results provide evidence on how the effects observed with SPP in ORIENT-11 could translate to a US population with untreated locally advanced/metastatic nonsquamous NSCLC.

Sintilimab is an immunotherapy drug that was successfully developed and tested in China for untreated locally advanced/metastatic nonsquamous non-small-cell lung cancer. To assess if results from the Chinese ORIENT-11 trial are applicable to the US population, this study used US real-world patient data to adjust the ORIENT-11 trial analysis. After adjustment, progression-free survival benefit observed in ORIENT-11 with the addition of sintilimab to standard chemotherapy remained superior, and other efficacy and safety end points were consistent. This finding may help inform clinical decisions about the applicability of ORIENT-11 trial results to US patients with untreated locally advanced/metastatic nonsquamous NSCLC. In addition, this study offers another way real-world evidence can be applied to help complement clinical trial evidence and optimize treatment decisions.

Data Integration to Improve Real-world Health Outcomes Research for Non-Small Cell Lung Cancer in the United States: Descriptive and Qualitative Exploration.

BACKGROUND: The integration of data from disparate sources could help alleviate data insufficiency in real-world studies and compensate for the inadequacies of single data sources and short-duration, small sample size studies while improving the utility of data for research. OBJECTIVE: This study aims to describe and evaluate a process of integrating data from several complementary sources to conduct health outcomes research in patients with non-small cell lung cancer (NSCLC). The integrated data set is also used to describe patient demographics, clinical characteristics, treatment patterns, and mortality rates. METHODS: This retrospective cohort study integrated data from 4 sources: administrative claims from the HealthCore Integrated Research Database, clinical data from a Cancer Care Quality Program (CCQP), clinical data from abstracted medical records (MRs), and mortality data from the US Social Security Administration. Patients with lung cancer who initiated second-line (2L) therapy between November 01, 2015, and April 13, 2018, were identified in the claims and CCQP data. Eligible patients were 18 years or older and received atezolizumab, docetaxel, erlotinib, nivolumab, pembrolizumab, pemetrexed, or ramucirumab in the 2L setting. The main analysis cohort included patients with claims data and data from at least one additional data source (CCQP or MR). Patients without integrated data (claims only) were reported separately. Descriptive and univariate statistics were reported. RESULTS: Data integration resulted in a main analysis cohort of 2195 patients with NSCLC; 2106 patients had CCQP and 407 patients had MR data. The claims-only cohort included 931 eligible patients. For the main analysis cohort, the mean age was 62.1 (SD 9.27) years, 48.56% (1066/2195) were female, the median length of follow-up was 6.8 months, and for 37.77% (829/2195), death was observed. For the claims-only cohort, the mean age was 66.6 (SD 12.69) years, 52.1% (485/931) were female, the median length of follow-up was 8.6 months, and for 29.3% (273/931), death was observed. The most frequent 2L treatment was immunotherapy (1094/2195, 49.84%), followed by platinum-based regimens (472/2195, 21.50%) and single-agent chemotherapy (441/2195, 20.09%); mean duration of 2L therapy was 5.6 (SD 4.9, median 4) months. We describe challenges and learnings from the data integration process, and the benefits of the integrated data set, which includes a richer set of clinical and outcome data to supplement the utilization metrics available in administrative claims. CONCLUSIONS: The management of patients with NSCLC requires care from a multidisciplinary team, leading to a lack of a single aggregated data source in real-world settings. The availability of integrated clinical data from MRs, health plan claims, and other sources of clinical care may improve the ability to assess emerging treatments.

Real-world characteristics and outcomes of advanced non-small-cell lung cancer patients with EGFR exon 19 deletions or exon 21 mutations.

Aim: To estimate real-world (rw) outcomes for first-line therapy in patients with advanced EGF receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), focusing on specific mutation types. Patients & methods: Retrospective observational study (n = 244 patients). Results: Univariate/multivariate analyses showed longer rw progression-free survival (rwPFS) and rwPFS2 in patients with ex19del versus Leu858Arg mutations. Median overall survival was 12.3 months longer with ex19del versus Leu858Arg mutations (HR: 1.47 [95% CI: 0.96-2.25]; p = 0.074). With EGFR-tyrosine kinase inhibitor monotherapy, unadjusted rwPFS for ex19del mutations was longer than for Leu858Arg mutations (HR: 1.62 [95% CI: 1.03-2.56]; p = 0.036). Conclusion: In this rw cohort of patients with advanced EGFR+ NSCLC, ex19del mutations conferred a prognostic advantage over Leu858Arg mutations, with significantly better rwPFS and rwPFS2.

Treatment patterns for patients with advanced/metastatic cancers by site of care.

OBJECTIVES: To compare treatments, overall survival (OS), and total costs among patients receiving anticancer therapy in hospital outpatient vs physician office settings. STUDY DESIGN: This retrospective observational study utilized claims data from a large national health plan to identify patients with advanced/metastatic non-small cell lung cancer (aNSCLC), metastatic colorectal cancer (mCRC), or metastatic breast cancer (mBC) treated in hospital outpatient or physician office settings. METHODS: Patients enrolled in Medicare Advantage Prescription Drug or commercial plans for at least 180 days prior to and at least 30 days after start of first-line (1L) therapy were included. Treatments by lines of therapy, OS, and total costs were evaluated by site of care. RESULTS: Eligible patients included 4618 with aNSCLC, 2304 with mCRC, and 1411 with mBC. There were no major differences in 1L, second-line, or third-line therapy by site of care. Patients with aNSCLC in physician office had longer 1L duration (hospital outpatient, 96 days vs physician office, 102 days; P < .01), but there were no differences in duration of therapy by site of care for mBC or mCRC. Costs were higher in the hospital outpatient setting for mCRC and mBC, but there were no differences in OS for any of the cancers. CONCLUSIONS: Although patients received similar care in hospital outpatient and physician office settings, the differences in duration of treatment and costs warrant further evaluation.

Treatment sequencing for the care of patients with advanced or metastatic non-small cell lung cancer in the United States.

OBJECTIVES: Therapeutic advances for the treatment of patients with advanced/metastatic non-small cell lung cancer (NSCLC) have led to additional options for care. This observational study was designed to describe emerging treatment patterns and survival outcomes. MATERIALS AND METHODS: Flatiron Health's oncology electronic health records database was to identify eligible patients who were age 18+ who initiated second-line therapy for NSCLC Survival analyses were conducted using Kaplan Meier methods and Cox proportional hazard model using SAS 9.4. both unadjusted and adjusted, using generalized propensity score, to account for imbalances between groups. RESULTS: The 10,060 eligible patients from Dec 2014 to Feb 2019 were 52.6% male; mean age 67.1 years; 70.3% white; 26.0% squamous/70.0% non-squamous (4.1% not specified); and 92.7% were treated at community practices. Immune checkpoint inhibitors (ICIs) were used by 79.9% of the cohort during any line of therapy; 12.1% and 53.7% used ICIs during first- and second-line therapy, respectively. There was heterogeneity in treatment sequencing, as the three most common first→second line sequences accounted for 7.7% (carboplatin + paclitaxel→nivolumab), 5.0% (carboplatin + pemetrexed→nivolumab), and 3.8% (carboplatin + nab-paclitaxel→nivolumab) of the total population, respectively. Unadjusted median overall survival was 21.1 months (95% confidence interval, CI: 20.5-21.6) from metastatic diagnosis. Median survival was 23.0 months (95% CI, 22.3-23.6) for non-squamous and 18.1 months (95% CI, 17.3-18.8) for squamous disease. CONCLUSION: There is heterogeneity in sequencing strategies that limit the ability to conduct robust comparative effectiveness research of treatment sequences. Since few patients follow a similar treatment trajectory, comparative effectiveness research will be challenged to identify treatment sequences with sufficient sample size.

Healthcare resource utilization in advanced non-small-cell lung cancer: post hoc analysis of the randomized phase 3 REVEL study.

PURPOSE: In REVEL, patients with advanced non-small-cell lung cancer (aNSCLC) and patients with increased tumor aggressiveness (rapid disease progression (RDP), platinum-refractory disease (PRD), and high symptom burden (HSB)) benefited from second-line treatment with ramucirumab plus docetaxel over placebo plus docetaxel. This post hoc analysis describes healthcare resource utilization (HCRU) associated with the treatment. METHODS: aNSCLC patients who had progressed during or after first-line platinum-based chemotherapy were randomized to receive docetaxel and either ramucirumab or placebo until disease progression, unacceptable toxicity, withdrawal, or death. HCRU included hospitalizations, transfusions, and concomitant medications. Categorical variables (counts and percentages) were compared using Fisher's exact test. Continuous variables (mean, standard deviation (SD), median, minimum, and maximum) were compared using the Wilcoxon rank sum test. RESULTS: Patient characteristics were largely similar between treatment arms. Within the intent-to-treat (ITT) population (n = 1253), the mean treatment duration was 19.7 and 16.9 weeks in the ramucirumab and control arms, respectively; 51.0% versus 54.9% of patients received subsequent anticancer therapy, respectively. Hospitalization rates were 41.9% versus 42.6% (p = 0.863), mean length of hospital stay was 14.5 days versus 11.3 days (p = 0.066), transfusion rates were 9.9% versus 12.3% (p = 0.206), and use of granulocyte colony-stimulating factors was 41.8% versus 36.6% (p = 0.063), respectively. No significant difference was observed in HCRU between treatment arms in both ITT population and in aggressive disease subgroups including RDP (n = 209), PRD (n = 360), and HSB (n = 497). CONCLUSION: In REVEL, the addition of ramucirumab to docetaxel did not increase HCRU among patients with aggressive aNSCLC disease. These results may help inform economic evaluation of treatment for patients with aNSCLC.

Sequential therapy with ramucirumab and/or checkpoint inhibitors for non-small-cell lung cancer in routine practice.

Aim: To describe treatment patterns and outcomes for advanced/metastatic non-small-cell lung cancer (aNSCLC) treated with single-agent or combination ramucirumab (ramucirumab-based) and/or immune checkpoint inhibitor (ICI-based) therapy. Materials & methods: Retrospective study of aNSCLC patients (n = 4054) identified in the Flatiron Health database, who received at least two treatment lines including ramucirumab- and/or ICI-based regimens between December 2014 and May 2017. Results: Median overall survival (95% CI) from aNSCLC diagnosis was 29.3 (25.5-33.0) months for patients receiving sequential ramucirumab- and ICI-based therapy (n = 245), 15.1 (12.6-18.2) months for patients receiving sequences including ramucirumab- without ICI-based therapy (n = 112), and 23.1 (21.9-24.2) months for patients receiving ICI-based therapy without ramucirumab-based therapy in sequence (n = 3697). Conclusion: Results provide real-world survival estimates for aNSCLC treated with sequences including ramucirumab- and/or ICI-based therapies.

The Budget Impact of Including Necitumumab on the Formulary for First-Line Treatment of Metastatic Squamous Non-Small Cell Lung Cancer: U.S. Commercial Payer and Medicare Perspectives.

BACKGROUND: Necitumumab (Neci) was the first biologic approved by the FDA for use in combination with gemcitabine and cisplatin (Neci + GCis) in first-line treatment of metastatic squamous non-small cell lung cancer (msqNSCLC). The potential financial impact on a health plan of adding Neci + GCis to drug formularies may be important to value-based decision makers in the United States, given ever-tightening budget constraints. OBJECTIVE: To estimate the budget impact of introducing Neci + GCis for first-line treatment of msqNSCLC from U.S. commercial and Medicare payer perspectives. METHODS: The budget impact model estimates the costs of msqNSCLC before and after adoption of Neci + GCis in hypothetical U.S. commercial and Medicare health plans over a 3-year time horizon. The eligible patient population was estimated from U.S. epidemiology statistics. Clinical data were obtained from randomized clinical trials, U.S. prescribing information, and clinical guidelines. Market share projections were based on market research data. Cost data were obtained from online sources and published literature. The incremental aggregate annual health plan, per-patient-per-year (PPPY), and per-member-per-month (PMPM) costs were estimated in 2015 U.S. dollars. One-way sensitivity analyses were conducted to assess the effect of model parameters on results. RESULTS: In a hypothetical 1,000,000-member commercial health plan with an estimated population of 30 msqNSCLC patients receiving first-line chemotherapy, the introduction of Neci + GCis at an initial market share of approximately 5% had an overall year 1 incremental budget impact of $88,394 ($3,177 PPPY, $0.007 PMPM), representing a 2.9% cost increase and reaching $304,079 ($10,397 PPPY, $0.025 PMPM) or a 7.4% cost increase at a market share of 14.7% in year 3. This increase in total costs was largely attributable to Neci drug costs and, in part, due to longer survival and treatment duration for patients treated with Neci+GCis. Overall, treatment costs increased by $81,812 (13.5%), and disease costs increased by $7,951 (0.4%), whereas adverse event costs decreased by $1,368 (0.5%) in year 1. From the Medicare perspective, the overall year 1 incremental budget impact was $438,056 ($0.037 PMPM, $3,112 PPPY), representing a 3.0% cost increase. The higher incremental budget in Medicare, compared with commercial plans, was due to higher msqNSCLC incidence in the older Medicare patients (154 vs. 30 patients, respectively). Results were most sensitive to Neci drug costs. CONCLUSIONS: Based on projected market shares, coverage for first-line therapy with Neci + GCis appeared to modestly affect overall U.S. health care budgets for msqNSCLC-related care. Given the small eligible patient population, the PMPM budgetary impact on a commercial health plan of reimbursing Neci + GCis in the first year was less than $0.01, rising with increased use of Neci + GCis to $0.025 in the third year. The real-world effect of Neci + GCis needs to be evaluated to validate this analysis; however, these findings may help policymakers in making coverage decisions for Neci + GCis. DISCLOSURES: This study was funded by Eli Lilly and Company. Molife, Brown, Tawney, and Cuyun Carter are equity holders and employees of Eli Lilly and Company. Bly, Cinfio, and Klein are employees of Medical Decision Modeling, which received funding from Eli Lilly and Company to conduct this research and prepare this manuscript.

Healthcare utilization and costs of children with attention deficit/hyperactivity disorder initiating atomoxetine versus extended-release guanfacine.

OBJECTIVES: To compare 1-year direct healthcare costs and utilization among children and adolescents initiating non-stimulant medications atomoxetine (ATX) or extended-release guanfacine (GXR). METHODS: In this retrospective, observational cohort study, children and adolescents aged 6-17 years with attention deficit/hyperactivity disorder (ADHD) who had ≥1 prescription claim for ATX or GXR between December 31, 2009 and January 1, 2011 were identified in the MarketScan Commercial or Multi-State Medicaid claims databases. The first claim was set as the index. Patients with no claims for other ADHD medications that overlapped with the days' supply for the index therapy during the post-period were classified as initiating monotherapy. All-cause and ADHD-related utilization and costs (2011 US$) and treatment patterns (adherence and persistence) were evaluated during the 12 months following index. Propensity score adjustment accounted for differences in patient characteristics, and bootstrapping was used for comparisons. RESULTS: A total of 13,239 children and adolescents with ADHD met the study criteria (4,411 ATX initiators and 8,828 GXR initiators). There were 2,699 ATX monotherapy patients. In propensity-score-adjusted analyses, mean all-cause total costs were significantly less for monotherapy ATX initiators than for GXR initiators ($7,553 vs $10,639; difference = -$3,086, p < .0001), as were mean ADHD-related total costs ($3,213 vs $4,544; difference = -$1,330, p < .0001). Monotherapy ATX initiators had significantly fewer all-cause and ADHD-related total medical visits and ∼22 days shorter persistence to index therapy (p < .0001). Results were similar for secondary analyses comparing all ATX with all GXR initiators, regardless of monotherapy or combination regimen, and comparing only monotherapy initiators. CONCLUSIONS: Children and adolescents with ADHD who initiated ATX monotherapy incurred lower all-cause and ADHD-related total healthcare costs than patients who initiated GXR. This was due in part to less healthcare resource utilization and slightly shorter persistence for ATX patients. These findings may aid decision-making and inform future studies, but must be tempered due to inherent observational research limitations.

One-Year Clinical Effectiveness Comparison of Prasugrel with Ticagrelor: Results from a Retrospective Observational Study using an Integrated Claims Database.

BACKGROUND: No direct comparisons of ticagrelor and prasugrel with 1-year clinical follow-up have been reported. OBJECTIVES: Our objective was to compare 1-year clinical outcomes among patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with either ticagrelor or prasugrel in a real-world setting. METHODS: This retrospective study included patients from a payer database who were aged ≥18 years and had ACS managed with PCI with no history of transient ischemic attack (TIA)/stroke. Data were propensity matched for prasugrel use with a 3:1 prasugrel:ticagrelor ratio. Post-discharge net adverse clinical event (NACE) rate at 1 year was evaluated for noninferiority using a pre-defined 20% margin. NACE was a composite of major adverse cardiovascular events (MACE) or rehospitalization for bleeding. RESULTS: In total, 15,788 ACS-PCI patients were included (prasugrel 12,797; ticagrelor 2991). Prasugrel-treated patients were younger; less likely to be female, have prior myocardial infarction (MI), diabetes, or non-ST-segment elevation MI (NSTEMI); and more likely to have unstable angina (UA) than ticagrelor-treated patients. Prior to matching, NACE and MACE (P < 0.01) were lower, with no difference in bleeding with prasugrel compared with ticagrelor. After matching, there was no significant difference in baseline characteristics. Noninferiority was demonstrated for NACE, MACE, and bleeding between prasugrel and ticagrelor. NACE and MACE were significantly lower with prasugrel use, primarily driven by heart failure, with no significant difference in all-cause death, MI, UA, revascularization, TIA/stroke, or bleeding. CONCLUSIONS: In this retrospective study, physicians preferentially used prasugrel rather than ticagrelor in younger ACS-PCI patients with lower risk of bleeding or comorbidities. After propensity matching, clinical outcomes associated with prasugrel were noninferior to those with ticagrelor.

"Real-World" Comparison of Prasugrel With Ticagrelor in Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention in the United States.

OBJECTIVES: The 30-day clinical outcomes with prasugrel or ticagrelor were compared using a US payer database in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). BACKGROUND: Prasugrel and ticagrelor demonstrated superior efficacy with increased non-coronary artery bypass graft major bleeding compared with clopidogrel in randomized clinical trials. No direct randomized or observational studies have compared clinical outcomes between prasugrel and ticagrelor. METHODS: Patients hospitalized for ACS-PCI between August 1, 2011 and April 30, 2013 and prescribed prasugrel or ticagrelor were selected. Drug treatment cohorts were propensity matched based upon demographic and clinical characteristics. The primary objective compared 30-day net adverse clinical events (NACE) in prasugrel- and ticagrelor-treated patients using a prespecified 20% noninferiority margin. Secondary objectives included comparisons of major adverse cardiovascular events (MACE) and major bleeding. RESULTS: Data were available for 16,098 patients (prasugrel, n = 13,134; ticagrelor, n = 2,964). In unmatched cohorts, prasugrel-treated patients were younger with fewer comorbidities than ticagrelor-treated patients, and 30-day NACE rates were 5.6 and 9.3%, respectively (P < 0.001). Following propensity matching, NACE was noninferior (P < 0.001) and 22% lower in prasugrel-treated than in ticagrelor-treated patients (RR, 0.78; 95% CI, 0.64-0.94). A 30-day adjusted MACE (RR, 0.80; 95% CI, 0.64-0.98) and major bleeding (RR, 0.65; 95% CI, 0.45-0.95) were also lower in prasugrel-treated patients compared with ticagrelor-treated patients. CONCLUSIONS: In this "real-world," retrospective, observational study, physicians appear to preferentially use prasugrel in younger patients with lower risk of bleeding or comorbidities compared with ticagrelor. Following adjustment, clinical outcomes associated with prasugrel use appear as good, if not better, than those associated with ticagrelor in ACS-PCI patients. © 2015 Wiley Periodicals, Inc.

One-year post-discharge resource utilization and treatment patterns of patients with acute coronary syndrome managed with percutaneous coronary intervention and treated with ticagrelor or prasugrel.

OBJECTIVE: Our objective was to compare 1-year real-world healthcare resource utilization (HRU), associated charges, and antiplatelet treatment patterns among patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with ticagrelor or prasugrel. METHODS: Using the ProMetis-Lx database, adult ACS-PCI patients treated with ticagrelor or prasugrel post-discharge were identified between 1 August 2011 and 31 May 2013 and propensity matched to adjust for baseline differences. RESULTS: Before matching, ticagrelor-treated patients (n = 2991) were older with increased baseline ischemic and bleeding risks compared with prasugrel-treated patients (n = 12,797). After matching, ticagrelor patients had higher all-cause HRU (2.5 vs. 2.4 per patient per month; P = 0.012) and cardiovascular (CV) HRU (0.4 vs. 0.3 per patient per month; P = 0.026), with the difference in CV rehospitalizations (17.7 vs. 15.7 %; P = 0.011) primarily driven by congestive heart failure (CHF) (4.9 vs. 3.8 %; P = 0.02). All-cause charges within 1 year did not significantly differ between groups ($US5456 vs. 4844 per patient per month; P = 0.37), but dyspnea-related total charges were significantly higher with ticagrelor ($US139 vs. 95 per patient per month; P = 0.005). Although infrequent, switching was slightly higher with ticagrelor (8.3 vs. 6.0 %; P < 0.001) at 1 year, and mean persistence was slightly longer with prasugrel (150 vs. 159 days; P = 0.002), with no significant difference in mean adherence (61 vs. 63 %; P = 0.17). CONCLUSION: Overall monthly HRU was slightly lower with prasugrel than with ticagrelor, with no significant difference in bleeding HRU. Prasugrel was associated with slightly higher pharmacy charges, but lower dyspnea charges, resulting in no significant difference in total charges. Patients receiving prasugrel tended to use it for longer than those receiving ticagrelor as less switching occurred. These findings may aid decision making, but must be tempered due to inherent study limitations.

Comparison of healthcare resource utilization and costs in patients hospitalized for acute coronary syndrome managed with percutaneous coronary intervention and receiving prasugrel or ticagrelor.

OBJECTIVE: To compare healthcare resource utilization (HCRU) and healthcare costs in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with prasugrel or ticagrelor. METHODS: Hospital charge master data were used to identify ACS-PCI patients aged ≥ 18 years with ≥ 1 in-hospital claim for prasugrel or ticagrelor between August 1, 2011-April 30, 2013. Treatment groups were propensity matched for baseline and index hospitalization characteristics. HCRU and costs were assessed through 90-days post-discharge. Costs were determined based on hospital-specific cost-to-charge ratios and adjusted to 2013 US dollars. RESULTS: Before matching, ticagrelor patients were older, more-often female, and had increased cardiovascular (CV) and bleeding risks compared with prasugrel patients. Propensity-matched length of index hospital stay (4.7 vs 4.9 days, p = 0.23) and risk for all-cause [30-day: relative risk (RR) = 0.86; 95% CI = 0.73-1.0; 90-day: RR = 0.90; 95% CI = 0.80-1.0, and CV-related (30-day: RR = 0.77; 95% CI = 0.59-1.0; 90-day: RR = 0.89; 95% CI = 0.73-1.1) re-hospitalizations did not significantly differ between prasugrel and ticagrelor, respectively. Compared to ticagrelor, the propensity-matched risk of re-hospitalization for myocardial infarction (MI) (30-day: RR = 0.39; 95% CI = 0.21-0.75; 90-day: RR = 0.53; 95% CI = 0.34-0.81) and an outpatient medical encounter for dyspnea (30-day: RR = 0.49; 95% CI = 0.33-0.74; 90-day: RR = 0.60; 95% CI = 0.46-0.80) were significantly lower for prasugrel patients, with no significant differences in bleeding encounters between groups (30-day: RR = 0.87; 95% CI = 0.54-1.40; 90-day: RR = 1.0; 95% CI = 0.71-1.50). Matched total healthcare costs were not significantly different between groups during the index hospitalization ($36,011 vs $37,247, p = 0.21), 30-days post-discharge ($2007 vs $2522, p = 0.48), 90-days post-discharge ($4564 vs $5242, p = 0.49), and aggregate of the index hospitalization through 90-day follow-up ($40,576 vs $42,494, p = 0.09) timeframes. CONCLUSIONS: Re-hospitalization for MI and outpatient encounters for dyspnea were lower in prasugrel treated than in ticagrelor treated ACS-PCI patients up to 90-days post-index hospitalization discharge, with no difference in bleeding encounters or healthcare costs between the two populations. This data supports the utility of prasugrel in routine clinical practice. These findings should be considered within limitations of observational research.

Adherence and persistence with prasugrel following acute coronary syndrome with percutaneous coronary intervention.

PURPOSE: To measure the adherence and persistence of patients with acute coronary syndrome (ACS) initiating prasugrel after percutaneous coronary intervention (PCI). METHODS: Using the Thomson Reuters MarketScan Commercial and Medicare Supplemental database, a retrospective cohort study identified patients initiating prasugrel following ACS-PCI hospitalization in 2009-2011. Prasugrel adherence over 12 months was measured using the medication possession ratio (MPR); predictors of adherence were identified using a logistic regression model. Persistence was defined as time on continuous therapy; a Cox model identified predictors of prasugrel discontinuation. RESULTS: Among 1,340 patients, the mean age was 57 years; 79.5 % were male. Median prasugrel MPR was 93.2 %; 69.0 % of patients had an MPR ≥80 %. Predictors of adherence <80 % included prior PCI [odds ratio (OR) 0.60; 95 % confidence interval (CI) 0.40-0.90], prior depression (OR 0.37; 95 % CI 0.16-0.84), prior bleeding (OR 0.41; 95 % CI 0.19-0.86), and baseline anticoagulant use (OR 0.13; 95 % CI 0.03-0.55). Baseline statin use predicted higher adherence (OR 1.56; 95 % CI 1.21-2.02). The median duration of prasugrel therapy was 259 days. Predictors of discontinuation included prior anemia [hazard ratio (HR) 1.63; 95 % CI 1.21-2.21], prior cardiomyopathy (HR 2.72; 95 % CI 1.44-5.13), and prior ischemic heart disease (HR 1.15; 95 % CI 1.00-1.32); baseline statin use predicted reduced risk of discontinuation (HR 0.85; 95 % CI 0.75-0.97). CONCLUSIONS: Although adherence to prasugrel was generally high, the duration of therapy was frequently below recommendations. An awareness of risk factors for low adherence or early discontinuation can point to appropriate targets for intervention.

Combination therapy patterns and predictors of ADHD in commercially insured and Medicaid populations.

OBJECTIVES: Several stimulant and nonstimulant medications are used alone or in combination to treat attention-deficit/hyperactivity disorder (ADHD). Little is known about the current prevalence and predictors of combination therapy. This analysis describes ADHD medication use focusing on combination versus monotherapy. METHODS: Health insurance claims from the Truven Health MarketScan® Commercial Database and Multi-State Medicaid Database were analyzed for patients with an ADHD diagnosis (International Classification of Diseases, Ninth Revision codes 314.0x). Patients included were aged ≥ 6 years as of January 2010, continuously enrolled from July 2009 through December 2010, and had a claim for an ADHD medication in 2010. Medication use was measured in treatment months during 2010. Baseline demographic and clinical predictors of combination therapy (> 1 ADHD medication class in the same month) involving atomoxetine, long-acting stimulants, and α2-adrenergic agonists were explored using logistic regression, with generalized estimating equations to account for within-patient correlation between months. RESULTS: Commercially insured patients with ADHD (N = 211 226) were primarily aged 6 to 17 years (58.4%) and male (61.5%). Attention-deficit/hyperactivity disorder with hyperactivity was present in 15.8% of these patients. Combination therapy was used in 10.3% of 1 125 119 treatment months. Short-acting stimulants and α2-adrenergic agonists had the highest combination use (45.3% and 54.0%, respectively). Patients with ADHD insured through Medicaid (N = 125 104) were primarily aged 6 to 17 years (94.4%) and male (69.5%). Hyperactivity was present in 39.7% of these patients. Combination therapy was used in 24.0% of 721 986 treatment months. Short-acting stimulants, α2-adrenergic agonists, and intermediate-acting stimulants had the highest combination use (70.0%, 63.8%, and 51.8%, respectively). In multivariate models for both data sources, female patients were less likely to use combination therapy. Patients with hyperactivity were more likely to use combination therapy. Tics/Tourette's syndrome was associated with combination therapy for atomoxetine and long-acting stimulants. CONCLUSION: In commercially insured and Medicaid ADHD populations, combination therapy rates differed by medication class, as did the demographic and clinical characteristics statistically significantly associated with combination therapy. This suggests that these medications may be used differently in clinical practice.

Is depression a modifiable risk factor for diabetes burden?

The purpose of this review article was to examine the empirical evidence supporting depression as a risk factor for diabetes complications and associated burden. A database search using keywords located recent clinical and population studies addressing the association between depression and type 2 diabetes. Both cross-sectional and cohort studies were reviewed. Depression appears to exacerbate the progression of type 2 diabetes. The evidence is strong supporting the hypothesis that depression in persons with diabetes increases the risk of diabetes-related burden, including suboptimal glycemic control, complications, functionality, mortality, and health care utilization. Screening for depression among patients with diabetes should be increased in primary care. Newer approaches to diabetes care management may help to slow the progression of diabetes.