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BACKGROUND: Treatment persistence among patients with psoriatic arthritis (PsA) is essential for achieving optimal treatment outcomes. Guselkumab, a fully human interleukin-23p19-subunit inhibitor, was approved by the United States (US) Food and Drug Administration for the treatment of active PsA in July 2020, with a dosing regimen of 100 mg at week 0, week 4, then every 8 weeks. In the Phase 3 DISCOVER-1 and DISCOVER-2 studies of patients with active PsA, 94% of guselkumab-randomized patients completed treatment through 1 year and 90% did so through 2 years (DISCOVER-2). Real-world evidence is needed to compare treatment persistence while following US prescribing guidelines (i.e., on-label persistence) for guselkumab versus subcutaneous (SC) tumor necrosis factor inhibitors (TNFis). METHODS: Adults with PsA receiving guselkumab or their first SC TNFi (i.e., adalimumab, certolizumab pegol, etanercept, or golimumab) between 14 July 2020 and 31 March 2022 were identified in the IQVIA PharMetrics® Plus database (first claim defined the treatment start date [index date]). Baseline characteristics and biologic use (biologic-naïve/biologic-experienced) were assessed during the 12-month period preceding the index date. Baseline characteristics were balanced between cohorts using propensity-score weighting based on the standardized mortality ratio approach. The follow-up period spanned from the index date until the earlier of the end of continuous insurance eligibility or end of data availability. On-label persistence, defined as the absence of treatment discontinuation (based on a gap of 112 days for guselkumab or 56 days for SC TNFi) or any dose escalation/reduction during follow-up, was assessed in the weighted treatment cohorts using Kaplan-Meier (KM) curves. A Cox proportional hazards model, further adjusted for baseline biologic use, was used to compare on-label persistence between the weighted cohorts. RESULTS: The guselkumab cohort included 526 patients (mean age 49.8 years; 61.2% female) and the SC TNFi cohort included 1953 patients (mean age: 48.5 years; 60.2% female). After weighting, baseline characteristics were well balanced with a mean follow-up of 12.3-12.4 months across cohorts; 51.5% of patients in the guselkumab cohort and 16.7% in the SC TNFi cohort received biologics in the 12-month baseline period. Respective rates of treatment persistence at 3, 6, 9, and 12 months were 91.2%, 84.1%, 75.9%, and 71.5% for the guselkumab cohort versus 77.3%, 61.6%, 50.0%, and 43.7% for the SC TNFi cohort (all log-rank p < 0.001). At 12 months, patients in the guselkumab cohort were 3.0 times more likely than patients in the SC TNFi cohort to remain persistent on treatment (p < 0.001). Median time to discontinuation was not reached for the guselkumab cohort and was 8.9 months for the SC TNFi cohort. CONCLUSION: This real-world study employing US commercial health-plan claims data to assess on-label treatment persistence in PsA demonstrated that, at 12 months, guselkumab was associated with a 3 times greater likelihood of persistence compared with SC TNFi.
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AIMS: To assess US payers' per-patient cost of testing associated with next-generation sequencing (NGS) versus polymerase chain reaction (PCR) biomarker testing strategies among patients with metastatic non-small cell lung cancer (mNSCLC), including costs of testing, delayed care, and suboptimal treatment initiation. METHODS: A decision tree model considered biomarker testing for genomic alterations using either NGS, sequential PCR testing, or hotspot panel PCR testing. Literature-based model inputs included time-to-test results, costs for testing/medical care, costs of delaying care, costs of immunotherapy [IO]/chemotherapy [CTX] initiation prior to receiving test results, and costs of suboptimal treatment initiation after test results (i.e. costs of first-line IO/CTX in patients with actionable mutations that were undetected by PCR that would have been identified with NGS). The proportion of patients testing positive for a targetable alteration, time to appropriate therapy initiation, and per-patient costs were estimated for NGS and PCR strategies combined. RESULTS: In a modeled cohort of 1,000,000 members (25% Medicare, 75% commercial), an estimated 1,119 had mNSCLC and received testing. The proportion of patients testing positive for a targetable alteration was 45.9% for NGS and 40.0% for PCR testing. Mean per-patient costs were lowest for NGS ($8,866) compared to PCR ($18,246), with lower delayed care costs of $1,301 for NGS compared to $3,228 for PCR, and lower costs of IO/CTX initiation prior to receiving test results (NGS: $2,298; PCR:$5,991). Cost savings, reaching $10,496,220 at the 1,000,000-member plan level, were driven by more rapid treatment with appropriate therapy for patients tested with NGS (2.1 weeks) compared to PCR strategies (5.2 weeks). LIMITATIONS: Model inputs/assumptions were based on published literature or expert opinion. CONCLUSIONS: NGS testing was associated with greater cost savings versus PCR, driven by more rapid results, shorter time to appropriate therapy initiation, and minimized use of inappropriate therapies while awaiting and after test results.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anciano , Humanos , Estados Unidos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Medicare , Pruebas Genéticas , Genómica , Mutación , Secuenciación de Nucleótidos de Alto Rendimiento , Reacción en Cadena de la PolimerasaRESUMEN
Aim: To investigate real-world time to next treatment in patients with chronic lymphocytic leukemia initiating first-line (1L) ibrutinib or acalabrutinib. Materials & methods: US specialty pharmacy electronic medical records (21/11/2018-30/4/2022) were used; patients initiated 1L on/after 21/11/2019 (acalabrutinib approval). Results: Among 710 patients receiving ibrutinib, 5.9% initiated next treatment (mean time to initiation = 9.2 months); among 373 patients receiving acalabrutinib, 7.5% initiated next treatment (mean time to initiation = 5.9 months). Adjusting for baseline characteristics, acalabrutinib-treated patients were 89% more likely to initiate next treatment (hazard ratio = 1.89; p = 0.016). Conclusion: This study addresses a need for real-world comparative effectiveness between 1L ibrutinib and acalabrutinib and shows that next treatment (a clinically meaningful measure for real-world progression) occurred less frequently with 1L ibrutinib.
Ibrutinib and acalabrutinib are oral medications taken once-daily and twice-daily, respectively. They are recommended as initial treatment for chronic lymphocytic leukemia (CLL). The goal of this study was to compare the efficacy of these treatments as initial treatment for CLL. To meet this goal, real-world US specialty pharmacy electronic medical records between 11/21/20184/30/2022 were used. Patients treated with ibrutinib or acalabrutinib as initial treatment for CLL were studied. Treatment had to be started on or after the date of acalabrutinib approval for CLL (11/21/2019). Time to next treatment was used to estimate real-world disease progression. It was defined as the time from the initiation of initial treatment with ibrutinib or acalabrutinib to the initiation of a next treatment. Study results showed that patients were observed for a median of up to 1.5 years. Over this period, next treatment was more likely for acalabrutinib (7.5%) compared with ibrutinib (5.9%). After adjusting for differences in patient characteristics, next treatment was 89% more likely with acalabrutinib than ibrutinib. This study addresses a need to compare the effectiveness of initial treatment with ibrutinib and acalabrutinib in the real-world. It helps better contextualize results from clinical trial data and shows that next treatment occurred less frequently with ibrutinib.
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Adenina/análogos & derivados , Leucemia Linfocítica Crónica de Células B , Pirazinas , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Piperidinas , Benzamidas/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
Purpose: Increased dosing frequency adversely affects treatment adherence and outcomes in chronic diseases; however, such data related to treatment adherence is lacking in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). This study compared adherence between patients treated with ibrutinib (once-daily) versus acalabrutinib (twice-daily) as first-line (1L) therapy for CLL/SLL. Patients and Methods: Specialty pharmacy electronic medical records were used to identify adults with CLL/SLL initiating 1L ibrutinib or acalabrutinib between 01/01/2018 and 11/30/2020. Adherence was measured by the proportion of days covered (PDC) and medication possession ratio (MPR) and was compared between cohorts using odds ratios (ORs) obtained from logistic regression models adjusted for baseline characteristics. Results: Between 01/01/2018 and 11/30/2020, 1374 and 140 patients initiated ibrutinib and acalabrutinib, respectively. Based on PDC/MPR ≥80%, patients treated with once-daily ibrutinib were more likely to be adherent than those treated with twice-daily acalabrutinib (OR ranges: PDC: 1.04-1.76; MPR: 1.03-1.58). At 6 months, patients on ibrutinib had a 58-76% higher likelihood of staying adherent compared to patients on acalabrutinib (PDC: 75.9% for ibrutinib vs 63.6% for acalabrutinib, OR: 1.76, P=0.008; MPR: 76.8% vs 66.9%, OR: 1.58, P=0.036) with a similar trend noted for the entire line of treatment (LOT) (PDC: 53.0% vs 41.4%, OR: 1.53, P=0.021; MPR: 58.7% vs 47.1%, OR: 1.50, P=0.027). Conclusion: In this real-world analysis, CLL/SLL patients initiating 1L once-daily ibrutinib had >50% higher treatment adherence than those initiating twice-daily acalabrutinib during their LOT. Given the importance of sustained adherence for disease control in CLL/SLL, dosing frequency may be an important consideration for patients and physicians.
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OBJECTIVE: To evaluate the time to discontinuation (TTD) and baseline characteristics among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) treated with first-line (1L) venetoclax + obinutuzumab (VO) in the United States. METHODS: A nationwide electronic health record-derived database was used to select adults with CLL/SLL initiating a 1L venetoclax-based regimen between April 11, 2016-July 31, 2020. Study measures included TTD (defined as >120-day treatment gap or switching therapy) and baseline characteristics by discontinuation status. RESULTS: A total of 113 patients receiving 1L VO on/before July 31, 2020 were eligible for analysis (mean age: 65.9 years; 31.9% women). During the first 60 days post-treatment initiation, 3.5% had tumor lysis syndrome (TLS). The proportion of patients using corticosteroids, anti-hyperuricemics, and anti-emetics was higher during the first 60 days post-treatment initiation (100.0%, 78.8%, and 52.2%, respectively) than the period from day 61 onward (67.0%, 45.5%, and 33.9%, respectively). Mean (median) duration of active treatment was 11.6 (12.1) months; 16.8% discontinued treatment before completing 12 cycles, 68.1% completed ≥12 cycles (among which 29.9% completed ≥15 cycles), and 15.0% who did not discontinue treatment were censored before completing 12 cycles. Kaplan-Meier analysis showed that median TTD was 13.8 months. Relative to those completing ≥12 cycles, patients discontinuing treatment before completing the prescribed 12 cycles were older (70.4 vs. 65.1 years) and had poorer renal function (36.8% vs. 13.0% with creatinine clearance <60 mL/min). CONCLUSION: A small proportion of CLL/SLL patients who were older and had poorer baseline renal function discontinued 1L VO prior to completing 12 treatment cycles. Additionally, treatment utilization, including medications related to TLS mitigation and management, was more intense during the initiation phase of VO. Further research with longer follow-up to assess long-term outcomes of VO treatment after early discontinuation is warranted.
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Leucemia Linfocítica Crónica de Células B , Adulto , Humanos , Femenino , Anciano , Masculino , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
Introduction: Integrase strand transfer inhibitor-based regimens (eg, containing dolutegravir [DTG]) are associated with weight/body mass index (BMI) increases among people living with HIV-1 (PLWH). Assessing antiretroviral therapy (ART)-related weight/BMI changes is challenging, as PLWH may experience return-to-health weight gain as a result of viral suppression. This retrospective, longitudinal real-world study compared weight/BMI outcomes among overweight/obese (BMI ≥25 kg/m2; thus excluding return-to-health weight/BMI changes), treatment-naïve PLWH who initiated darunavir (DRV)/cobicistat (c)/emtricitabine (FTC)/tenofovir alafenamide (TAF) or DTG + FTC/TAF. Methods: Treatment-naïve PLWH with BMI ≥25 kg/m2 who initiated DRV/c/FTC/TAF or DTG + FTC/TAF (index date) had ≥12 months of baseline observation and ≥1 weight/BMI measurement in baseline and post-index periods in the Symphony Health IDV® database (07/17/2017-12/31/2021) were included. Inverse probability of treatment weighting (IPTW) was used to balance differences in baseline characteristics between cohorts. On-treatment time-to-weight/BMI increases ≥5% were compared between cohorts using weighted adjusted Cox models. Results: Post-IPTW, 76 overweight/obese DRV/c/FTC/TAF-treated (mean age = 51.2 years, 30.7% female, 35.6% Black, mean baseline BMI = 33.2 kg/m2) and 88 overweight/obese DTG + FTC/TAF-treated PLWH (mean age = 51.5 years, 31.4% female, 31.4% Black, mean baseline BMI = 32.7 kg/m2) were included. The median [interquartile range] time from ART initiation to weight/BMI increase ≥5% was shorter for the DTG + FTC/TAF cohort (21.8 [9.9, 32.3] months) than the DRV/c/FTC/TAF cohort (median and interquartile times not reached; Kaplan-Meier rate at 21.8 months = 20.8%). Over the entire follow-up, overweight/obese PLWH initiating DTG + FTC/TAF had a more than twofold greater risk of experiencing weight/BMI increase ≥5% compared to those initiating DRV/c/FTC/TAF (hazard ratio [95% confidence interval]=2.43 [1.02; 7.04]; p = 0.036). Conclusion: Overweight/obese PLWH who initiated DTG + FTC/TAF had significantly greater risk of weight/BMI increase ≥5% compared to similar PLWH who initiated DRV/c/FTC/TAF and had shorter time-to-weight/BMI increase ≥5%, suggesting a need for additional monitoring to assess the risk of weight gain-related cardiometabolic disease.
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INTRODUCTION: Integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART) has been associated with weight gain, though there is limited information on associations between ART-related weight gain and cardiometabolic outcomes among people living with HIV-1 (PLWH). We, therefore, evaluated risks of incident cardiometabolic outcomes following INSTI versus non-INSTI-based ART initiation in the United States. METHODS: We conducted a retrospective study using IBM MarketScan Research Databases (12 August 2012-31 January 2021). Treatment-naïve PLWH initiating ART (index date) on/after 12 August 2013 (approval date of the first second-generation INSTI, dolutegravir) were included and censored at regimen switch/discontinuation, end of insurance eligibility or end of data availability. We used inverse probability of treatment weights constructed with baseline (12 months pre-index) characteristics to account for differences between INSTI- and non-INSTI-initiating cohorts. Doubly robust hazard ratios (HRs) obtained from weighted multivariable Cox regression were used to compare time to incident cardiometabolic outcomes (congestive heart failure [CHF], coronary artery disease, myocardial infarction, stroke/transient ischemic attack, hypertension, type II diabetes, lipid disorders, lipodystrophy and metabolic syndrome) by INSTI-initiation status. RESULTS: Weighted INSTI (mean age = 39 years, 23% female, 70% commercially insured, 30% Medicaid insured) and non-INSTI (mean age = 39 years, 24% female, 71% commercially insured, 29% Medicaid insured) cohorts included 7059 and 7017 PLWH, respectively. The most common INSTI-containing regimens were elvitegravir-based (43.4%), dolutegravir-based (33.3%) and bictegravir-based (18.4%); the most common non-INSTI-containing regimens were darunavir-based (31.5%), rilpivirine-based (30.4%) and efavirenz-based (28.3%). Mean±standard deviation follow-up periods were 1.5±1.5 and 1.1±1.2 years in INSTI- and non-INSTI-initiating cohorts, respectively. INSTI initiators were at a clinically and significantly increased risk of experiencing incident CHF (HR = 2.12, 95% confidence interval [CI] = 1.08-4.05; p = 0.036), myocardial infarction (HR = 1.79, 95% CI = 1.03-5.65; p = 0.036) and lipid disorders (HR = 1.26, 95% CI = 1.04-1.58; p = 0.020); there was no evidence of an increased risk for other individual or composite outcomes. CONCLUSIONS: Over a short average follow-up period of <2 years, INSTI use among treatment-naïve PLWH was associated with an increased risk of several cardiometabolic outcomes, such as CHF, myocardial infarction and lipid disorders, compared to non-INSTI use. Further research accounting for additional potential confounders and with longer follow-up is warranted to more accurately and precisely quantify the impact of INSTI-containing ART on long-term cardiometabolic outcomes.
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Diabetes Mellitus Tipo 2 , Infecciones por VIH , VIH-1 , Infarto del Miocardio , Estados Unidos/epidemiología , Femenino , Humanos , Adulto , Masculino , Estudios Retrospectivos , Incidencia , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Antirretrovirales/efectos adversos , LípidosRESUMEN
Background: Literature describing respiratory syncytial virus (RSV)-related complications in older adults in the United States is scarce. This study described risk factors of RSV-related complications and healthcare costs of Medicare-insured patients aged ≥60 years with medically attended RSV. Methods: 100% Medicare Research Identifiable Files (1 January 2007-31 December 2019) were used to identify adults aged ≥60 years with RSV (index: first diagnosis date). Predictors of ≥1 RSV-related complication (ie, pneumonia, acute respiratory failure, congestive heart failure, hypoxia/dyspnea, non-RSV lower/upper respiratory tract infections, or chronic respiratory disease) during the up to 6-month post-RSV diagnosis period were identified. Patients with all aforementioned diagnoses during the 6 months pre-index could not be evaluated for a complication and were therefore ineligible for analyses. Differences between 6-month pre- and post-index total all-cause and respiratory/infection-related healthcare costs were assessed. Results: Overall, 175 392 patients with RSV were identified. Post-RSV diagnosis, 47.9% had ≥1 RSV-related complication, with mean time-to-event of 1.0 month. The most common complications were pneumonia (24.0%), chronic respiratory disease (23.6%), and hypoxia or dyspnea (22.0%). Baseline predictors of ≥1 RSV-related complication included having previous diagnoses for complication/comorbidity listed in the Methods, hypoxemia, chemotherapy, chest radiograph, stem cell transplant, and anti-asthmatic and bronchodilator use. Total all-cause and respiratory/infection-related healthcare costs were $7797 and $8863 higher, respectively, post-index versus pre-index (both P < .001). Conclusions: In this real-world study, almost half of patients with medically attended RSV experienced an RSV-related complication within 1 month post-RSV diagnosis, and costs significantly increased post-diagnosis. Having a complication/comorbidity pre-RSV predicted a higher risk of developing a different complication post-RSV infection.
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BACKGROUND: Prostate cancer (PC) is more likely to develop in men ≥65 years old than in those <65 years old. This study aimed to generate real-world evidence on treatment patterns, clinical outcomes, health care resource utilization (HCRU), and costs among older patients with metastatic castration-resistant PC (mCRPC). MATERIALS AND METHODS: A claims algorithm based on treatments expected for mCRPC was used to identify men ≥65 years old with mCRPC in the SEER-Medicare data between 2007 and 2019. The index date was defined as the date of the start of first-line therapy (1L). Treatment patterns and all-cause and PC-specific HCRU and costs were measured in the 12 months preindex period and the postindex follow-up period. Time to next treatment or death (TNTD) and overall survival (OS) were assessed in the follow-up period. RESULTS: A total of 4758 patients met the eligibility criteria and received 1L treatment. Among these 1L patients, 57.4% subsequently received second-line (2L) treatment; among patients receiving 2L treatment, 49.3% subsequently received third-line (3L) treatment. Abiraterone, enzalutamide, and docetaxel were most common regimens in 1L (41.9%, 22.0%, 22.0%, respectively), 2L (33.3%, 32.7%, 13.6%, respectively), and 3L (17.9%, 25.1%, 22.3%, respectively). On average, patients had 1.2 inpatient admissions, 1.1 emergency room visits, and 27.6 outpatient visits per year during follow-up. The mean total all-cause and PC-related costs during the follow-up period were $111,060 and $99,540 per-patient-per-year, respectively. Median TNTD was 9.3, 6.5, and 5.7 months for 1L, 2L, and 3L, respectively. Median OS from the start of 1L treatment for mCRPC was 21.5 months. DISCUSSION: Among older patients with mCRPC, high attrition from 1L to subsequent lines of therapy was observed. Median TNTD was <1 year and median OS was <2 years. These results highlight a need to introduce more effective mCRPC therapies in 1L to improve clinical outcomes for older patients.
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Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Anciano , Estados Unidos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Estudios Retrospectivos , Medicare , Costos y Análisis de Costo , Atención a la Salud , Resultado del Tratamiento , Costos de la Atención en SaludRESUMEN
BACKGROUND: An estimated 10-15% of non-small cell lung cancer (NSCLC) cases present with epidermal growth factor receptor mutation (EGFRm). While EGFR tyrosine kinase inhibitors (EGFR-TKIs) such as osimertinib have become first-line (1L) standard of care for these patients, limited chemotherapy use still occurs in real-world practice. Studies of healthcare resource use (HRU) and cost of care provide a means by which the value of various treatment regimens, healthcare efficiency, and disease burden can be assessed. These studies are important for population health decision makers and health systems that prioritize value-based care to drive population health. OBJECTIVE: The aim of this study was to descriptively assess HRU and costs among patients with EGFRm advanced NSCLC initiating 1L therapy in the United States. METHODS: IBM MarketScan Research Databases (January 1, 2017 to April 30, 2020) were used to identify adult patients with advanced NSCLC, based on a diagnosis for lung cancer (LC) and initiation of 1L therapy or diagnosis of metastases within 30 days of the first LC diagnosis. All patients had ≥ 12 months of continuous insurance eligibility prior to the first LC diagnosis and initiated (in 2018 or after) an EGFR-TKI during any line of therapy to proxy EGFRm status. Per-patient-per-month all-cause HRU and costs were described during 1L for patients initiating 1L osimertinib or chemotherapy. RESULTS: A total of 213 patients with advanced EGFRm NSCLC were identified (mean age at 1L initiation: 60.9 years; 69.0% female). In 1L, 66.2% initiated osimertinib, 21.1% chemotherapy, and 12.7% another regimen. Mean 1L therapy duration was 8.8 months (osimertinib) and 7.6 months (chemotherapy), respectively. Among osimertinib recipients, 28% had an inpatient admission, 40% an emergency room (ER) visit, and 99% an outpatient visit. Among chemotherapy recipients, these proportions were 22%, 31%, and 100%. Mean monthly all-cause healthcare costs among osimertinib and chemotherapy patients were US$27,174 and US$23,343, respectively. Among osimertinib recipients, drug-related costs (including pharmacy and outpatient antineoplastic drug and administration costs) made up 61% (US$16,673) of total costs, inpatient costs 20% (US$5462), and other outpatient costs 16% (US$4432). In chemotherapy recipients, 59% (US$13,883) of total costs were drug-related, 5% (US$1166) were inpatient costs, and 33% (US$7734) other outpatient costs. CONCLUSIONS: Higher mean total cost of care was observed among patients receiving 1L TKI (osimertinib) than 1L chemotherapy in EGFRm advanced NSCLC. However, descriptive differences in type of spending and HRU were identified: higher inpatient costs and inpatient days for osimertinib versus higher outpatient costs for chemotherapy. Findings suggest that significant unmet needs may remain for 1L treatment of EGFRm NSCLC, and despite significant advances in targeted care, further individualized therapies are needed to balance benefits, risks, and total cost of care. Furthermore, observed descriptive differences in inpatient admissions may have implications for quality of care and patient quality of life, for which additional research is warranted.
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This study assessed the total costs of testing, including the estimated costs of delaying care, associated with next-generation sequencing (NGS) versus single-gene testing strategies among patients with newly diagnosed metastatic non-small cell lung cancer (mNSCLC) from a Canadian public payer perspective. A decision tree model considered testing for genomic alterations using tissue biopsy NGS or single-gene strategies following Canadian guideline recommendations. Inputs included prevalence of mNSCLC, the proportion that tested positive for each genomic alteration, rebiopsy rates, time to test results, testing/medical costs, and costs of delaying care based on literature, public data, and expert opinion. Among 1,000,000 hypothetical publicly insured adult Canadians (382 with mNSCLC), the proportion of patients that tested positive for a genomic alteration with an approved targeted therapy was 38.0% for NGS and 26.1% for single-gene strategies. The estimated mean time to appropriate targeted therapy initiation was 5.1 weeks for NGS and 9.2 weeks for single-gene strategies. Based on literature, each week of delayed care cost CAD 406, translating to total mean per-patient costs of CAD 3480 for NGS and CAD 5632 for single-gene strategies. NGS testing with mNSCLC in current Canadian practice resulted in more patients with an identified mutation, shorter time to appropriate targeted therapy initiation, and lower total testing costs compared to single-gene strategies.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Ahorro de Costo , Canadá , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
This retrospective study evaluated the benefit of following different long-acting injectable (LAI) initiation strategies based on the timing of behavioral and clinical events among Medicaid beneficiaries with schizophrenia. Adults with schizophrenia initiating oral antipsychotics (OAPs) after 12 months without antipsychotic use or schizophrenia-related inpatient/emergency room (ER) visits (index date) were identified. Patients were categorized into four event-driven LAI initiation strategy cohorts based on observed sequences of behavioral (i.e., OAP adherence) and clinical (i.e., schizophrenia-related inpatient/ER visits) events between index and LAI initiation or censoring-strategy #1: adherent to OAPs without schizophrenia-related inpatient/ER visits; strategy #2: nonadherent to OAPs without schizophrenia-related inpatient/ER visits; strategy #3: one schizophrenia-related inpatient/ER visit; strategy #4: ≥2 schizophrenia-related inpatient/ER visits. Clinical outcomes (i.e., all-cause inpatient/ER visits) were evaluated between OAP initiation and end of follow-up. Comparisons between LAI initiation strategy cohorts were conducted using a dynamic marginal structural model adjusting for baseline characteristics and time-varying confounders. Among 13,444 eligible patients, 13.1%, 53.6%, 15.7%, and 17.6% were following strategies #1-4, respectively; of these, 21.9%, 4.3%, 9.2%, and 6.5% started an LAI (the remaining were censored). Strategy #1 was associated with a greater clinical benefit, with 43%, 69%, and 80% fewer inpatient days (all p < 0.05); and 57%, 59%, and 79% fewer ER visits (all p < 0.01) vs strategies #2-4, respectively; the clinical benefit was also observed for strategy #2 vs #3-4. Therefore, starting an LAI prior to OAP nonadherence or occurrence of a schizophrenia-related inpatient/ER visit was associated with fewer all-cause inpatient days of inpatient stay and ER visits.
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Aim: Compare weight changes between people living with HIV-1 (PLWH) at high risk of weight gain (females, Blacks or Hispanics) switching from an integrase strand transfer inhibitor (INSTI) to a protease inhibitor (PI) or another INSTI. Materials & methods: Mean weight changes from pre-switch to up-to-12 months post-switch were retrospectively compared between PLWH switching to a PI or INSTI. Results: 356 PLWH were eligible. At 9- and 12-month post-switch, weight increases were observed for INSTI (weight: +1.55 kg and +1.59 kg), while decreases were observed for PI (-0.23 kg and -1.59 kg); differences between cohorts widened over time. Conclusion: These data suggest that switching off an INSTI may be a management tool to mitigate or reverse weight gain.
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Infecciones por VIH , Inhibidores de Integrasa VIH , VIH-1 , Femenino , Humanos , Hispánicos o Latinos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de Integrasa VIH/farmacología , Integrasas/uso terapéutico , Estudios Retrospectivos , Aumento de Peso , Negro o AfroamericanoRESUMEN
INTRODUCTION: Antiretroviral therapy (ART) has been associated with weight gain in people living with HIV-1 (PLWH); however, limited research has assessed whether early weight gain post-ART initiation is associated with metabolic or cardiovascular outcomes among PLWH at high risk of weight gain (i.e., female, Black or Hispanic). This study aimed to evaluate the incidence of metabolic and cardiovascular outcomes between PLWH at high risk of weight gain following an observed ≥ 5% or < 5% weight/body mass index (BMI) gain within 6 months following ART initiation. METHODS: A retrospective longitudinal study using Symphony Health, an ICON plc Company, IDV® electronic medical records (October 1, 2014-March 31, 2021) identified adult female, Black, or Hispanic treatment-naïve PLWH who initiated ART and who had ≥ 1 weight or BMI measurement pre- and within 6 months post-treatment (landmark period). Inverse probability of treatment weighting was used to account for differences between PLWH who experienced ≥ 5% and < 5% weight/BMI gain. The time to each outcome was compared between cohorts using weighted hazard ratios (HRs) after the landmark period. RESULTS: Weighted ≥ 5% and < 5% cohorts included 620 and 632 patients, respectively; baseline characteristics were similar between the two cohorts (mean age: ~ 48 years, ~ 59% female, ~ 49% Black, ~ 17% Hispanic). During a mean 2-year follow-up, PLWH with ≥ 5% weight/BMI gain were significantly more likely to be diagnosed with type 2 diabetes mellitus (T2DM; HR = 2.19; p = 0.044). There were no significant differences in the incidence of any other outcomes between the study cohorts. CONCLUSION: Despite a short 2-year follow-up, female, Black or Hispanic PLWH experiencing ≥ 5% weight/BMI increase within 6 months following ART initiation had an increased risk of T2DM, but not other metabolic or cardiovascular outcomes, likely due to the short follow-up period. Further research with longer follow-up and specific ART regimens is warranted to examine the impact of ART-related weight gain on long-term clinical outcomes.
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OBJECTIVE: Evaluate systemic therapy utilization patterns and outcomes by line of therapy among patients with advanced/recurrent endometrial cancer (EC) treated in the United States. METHODS: This retrospective observational study used the Optum Clinformatics Extended Data Mart Date of Death database (1 January 2004-31 December 2019) and included de-identified data from adult patients with advanced/recurrent EC who were treated with first-line (1L) platinum-based chemotherapy and initiated second-line (2L) anti-neoplastic therapy. The index date was the date of 1L therapy initiation. The number and sequence of treatments received and the proportion of patients who received each type of treatment for each line of therapy were evaluated. To account for new drug approvals, patients first treated in 2018 or 2019 were also assessed separately. RESULTS: Among the 1317 patients who met all eligibility criteria, 520 (39.5%) and 235 (17.8%) patients received 3 or 4+ lines of treatment, respectively, during a median total follow-up time of 25.2 months (range, 2.5-173.3 months) following the index date. Chemotherapy, including platinum- and non-platinum-based regimens, was the most common treatment across all lines of therapy: 2L, 80.0%; 3L, 66.2%; 4L+, 80.4%. Overall, 2.5%, 2.3%, and 8.9% of 2L, 3L, and 4L + patients, respectively, received anti-program death 1 (anti-PD-1) immunotherapies. In patients first treated in 2018 and 2019 (n = 163), 9.8% of patients received anti-PD-1 immunotherapy in the 2L. In the overall population, median time to next treatment (TTNT) was 19.3, 10.5, and 8.1 months for patients undergoing 2L, 3L, and 4L treatment, respectively. CONCLUSIONS: Among patients with advanced/recurrent EC treated with 1L platinum-based therapy in clinical practice, chemotherapy was the most common treatment choice across all lines of therapy. Immunotherapy use was low overall but increased in patients who started treatment in 2018 or 2019. Overall, median TTNT decreased as lines of therapy increased.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Endometriales , Adulto , Humanos , Estados Unidos , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Inmunoterapia , Estudios Retrospectivos , Neoplasias Endometriales/tratamiento farmacológicoRESUMEN
BACKGROUND: Atrial fibrillation (AF) is a recognized adverse consequence associated with all Bruton's tyrosine kinase inhibitors used to treat chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); however, real-world time to discontinuation (TTD) and time to next treatment (TTNT) of CLL/SLL patients with a high baseline AF/stroke risk remain unknown. MATERIALS AND METHODS: Patients with CLL/SLL from a nationwide electronic health record-derived database (February 12, 2013-January 31, 2021) initiating first-line (1L) or second or later-line (2L+) treatment with ibrutinib or other regimens on or after February 12, 2014 (index date) were analyzed. Kaplan-Meier survival analysis was used to assess TTD and TTNT among all patients, patients with high AF risk (CHARGE-AF risk score ≥10.0%), and patients at high risk of stroke (CHA2DS2-VASc risk score ≥3 [females] or ≥2 [males]). RESULTS: In 1L/2L+, 2190/1851 patients received ibrutinib and 4388/4135, were treated with other regimens. Median TTD for ibrutinib was similar regardless of AF/stroke-related risk (1L: all patients, 15.7 months; high AF risk, 11.7 months; high stroke risk, 13.7 months; similar results in 2L+). Median TTNT was significantly longer for ibrutinib vs. other regimens (1L: not reached vs. 45.9 months; 2L+: not reached vs. 23.6 months; both P < .05), including among those with high AF/stroke risk. TTNT was similar between all patients and high-risk cohorts in 1L and 2L+ (all P > .05). CONCLUSION: This study highlights that elevated baseline AF/stroke-related risk does not adversely impact TTD and TTNT outcomes associated with ibrutinib use. Additionally, TTNT was significantly longer for patients treated with ibrutinib vs. other regimens.
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Fibrilación Atrial , Leucemia Linfocítica Crónica de Células B , Linfoma de Células B , Accidente Cerebrovascular , Masculino , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Pirimidinas/efectos adversos , Pirazoles/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Accidente Cerebrovascular/etiologíaRESUMEN
INTRODUCTION: Atopic dermatitis (AD) is associated with significant quality-of-life and economic burdens. Real-world evidence is needed to identify optimal treatment pathways for AD. Here we evaluate real-world effectiveness of systemic therapies for moderate-to-severe AD in the USA. METHODS: Data (September 2016 to December 2019) were from the IQVIA Health Plan Claims data set (IQVIA, Danbury, CT) from patients aged 12 years or older with AD (ICD-9/10-CM, 691.8/L20.x) initiating a systemic immunosuppressive (SIS) agent (methotrexate, cyclosporine, mycophenolate, or azathioprine) or dupilumab and continuously enrolled for at least 6 months before and after the index date. Indicators of non-response (i.e., adding on/switching systemic therapy, AD-related inpatient/emergency room visits, or incident staphylococcal/streptococcal skin infection) and predictors of non-response were evaluated. Descriptive statistics and Kaplan-Meier rates and times were obtained; Cox regression models were used. RESULTS: In 3249 patients, 45.4% exhibited at least one indicator of non-response, with median time to non-response being longer for dupilumab than for any SIS therapy (27.0 vs 4.0-7.7 months, respectively). Key non-response predictors were age, geographic region, and baseline number of annual AD-related medical visits. CONCLUSION: Non-response was common in patients with AD who required systemic treatment, and non-response indicators occurred significantly more frequently with SIS treatment than with dupilumab treatment.
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Dermatitis Atópica , Inmunosupresores , Dermatitis Atópica/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Revisión de Utilización de Seguros , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Tumor lysis syndrome (TLS) is a potentially fatal complication of antineoplastic treatments for hematologic malignancies, including chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients developing TLS require intensive care, adding to the overall clinical and economic burden of CLL/SLL. OBJECTIVE: To analyze TLS-associated health care resource utilization (HCRU) and costs in patients with CLL/SLL treated with regimens associated with a high TLS risk (per treatment guidelines), ie, anti-CD20-based chemoimmunotherapy (CIT), lenalidomide, obinutuzumab, or venetoclax. METHODS: Adult patients with CLL/SLL in the MarketScan Databases (January 1, 2006, to April 30, 2020) initiated on CIT, lenalidomide, obinutuzumab, or venetoclax (index date) on or after January 1, 2007, were included in the analysis. Treatment-emergent TLS was defined as TLS occurring in the first 90 days of active treatment. The post-index period was divided into 30-day intervals until the end of the index regimen; intervals pre-TLS were non-TLS intervals and those starting from the TLS event were TLS intervals. Per-patient-per-month (PPPM) HCRU and costs were compared between TLS and non-TLS intervals using generalized linear models adjusted for baseline and time-varying confounders. The proportion of patients in the TLS cohort (patients with treatment-emergent TLS) and non-TLS cohort (patients with no treatment-emergent TLS) who switched treatment within 90 days post-index was compared using Kaplan-Meier rates with logrank P values. RESULTS: Among 6,343 patients with CLL/SLL, 71 (1.1%) developed treatment-emergent TLS (venetoclax: 11.5%; other regimens: 0.8%) after a mean (median) of 12.7 (7.0) days following treatment initiation (mean [median] duration of index regimen: 16.0 [10.0] months); 12 (0.2%) developed clinical TLS (venetoclax: 3.1%; other regimens: 0.1%). TLS was associated with 1.7 times more inpatient admissions (P < 0.001), 2 times more days of inpatient stay (P = 0.012), 22% fewer days of antineoplastic drug administration (P = 0.020), and $3,062 PPPM higher health care costs (P = 0.016), which were mainly driven by $1,688 PPPM higher inpatient costs (P = 0.044). Higher costs were observed among both patients who initiated venetoclax (TLS: $24,170; non-TLS: $20,091) and those who initiated other regimens (TLS: $8,746; non-TLS: $6,915). More patients in the TLS vs non-TLS cohort switched treatment in the first 90 days of treatment (12.6% vs 5.1%, P = 0.006). CONCLUSIONS: TLS was associated with a substantial cost burden (driven by inpatient costs) and higher rate of treatment switching (vs non-TLS cohort) in patients with CLL/SLL treated with CIT, obinutuzumab, lenalidomide, or venetoclax. The risk of treatment-emergent TLS and associated incremental HCRU and costs, as well as the potential impact on quality of life, should be weighed when evaluating the risk-benefit of therapies in CLL/SLL management. DISCLOSURES: Dr Rogers has received research funding from Genentech, AbbVie, Novartis, and Janssen (not for the present study); consulting fees from Acerta Pharma, AstraZeneca, Innate Pharma, Pharmacyclics, Genentech, and AbbVie; and travel funding from AstraZeneca. Mr Emond, Mr Kinkead, Ms Lafeuille, and Mr Lefebvre are employees of Analysis Group, Inc., which has provided paid consulting services to Janssen Scientific Affairs, LLC. Drs Lu and Huang are employees of Janssen Scientific Affairs, LLC, and stockholders of Johnson & Johnson. Ms Côté-Sergent was an employee of Analysis Group, Inc., at the time the study was conducted. This study was funded by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design; data collection, analysis, and interpretation; manuscript writing; and the decision to publish the article.
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Antineoplásicos , Leucemia Linfocítica Crónica de Células B , Síndrome de Lisis Tumoral , Adulto , Antineoplásicos/efectos adversos , Estrés Financiero , Costos de la Atención en Salud , Humanos , Lenalidomida/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Calidad de Vida , Estudios Retrospectivos , Síndrome de Lisis Tumoral/tratamiento farmacológico , Síndrome de Lisis Tumoral/etiologíaRESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) is a common, contagious, and seasonal pathogen causing 64 million acute respiratory infections annually in adults and children worldwide. High-risk adults, including older adults and those with cardiopulmonary conditions or weakened immune systems, are more likely to be infected. However, limited information exists on RSV incidence and associated costs among adults, including high-risk patients. OBJECTIVE: To evaluate the annual incidence of medically attended, International Classification of Diseases (ICD)-coded RSV among commercially insured adults and assess health care costs among adults with ICD-coded RSV in the United States. METHODS: Optum's deidentified Clinformatics Data Mart Database (January 01, 2007, to June 30, 2020) and IBM's MarketScan Databases (January 01, 2000, to July 31, 2020) were used. Medically attended, ICD-coded RSV incidence among adults was assessed from July 1 of a given year to June 30 of the next year and reported per 100,000 population. Trends in all-cause mean weekly costs pre-RSV and post-RSV diagnosis were reported. Results were reported overall and among patients aged 60-64 years, 65 years or older, 85 years or older, and 18-59 years at high risk of severe RSV (defined as having cardiopulmonary conditions or a weakened immune system). RESULTS: Annual incidence of medically attended, ICD-coded RSV in adults overall was 22.0-52.9 in Optum and 23.4-63.6 in MarketScan. Incidence rates were higher among patients aged 60-64 years (Optum: 25.2-66.1; MarketScan: 31.9-82.1), 65 years or older (Optum: 37.3-75.5; MarketScan: 54.1-97.3), 85 years or older (Optum: 92.4-140.6; MarketScan: 79.4-234.7), and 18-59 years at high risk of severe RSV (Optum: 41.3-135.9; MarketScan: 46.3-112.4). Mean weekly costs increased during the week before (Optum: $2,325; MarketScan: $2,080) and post-RSV diagnosis (Optum: $9,523; MarketScan: $3,551), compared with those in weeks 2-8 pre-RSV diagnosis (Optum: $1,350; MarketScan: $872). The increases in mean weekly costs during the week before and the week following RSV diagnosis were higher among patients aged 60-64 years (mean weekly costs in weeks 2-8 pre-RSV, week 1 pre-RSV, week 1 post-RSV; Optum: $1,623, $2,690, $10,823; MarketScan: $1,259, $2,992, $5,069), 65 years or older (Optum: $1,731, $3,067, $12,866; MarketScan: $1,517, $3,571, $5,268), 85 years or older (Optum: $1,563, $2,430, $18,134; MarketScan: $1,613, $4,113, $6,231), and 18-59 years at high risk of severe RSV (only for MarketScan: $1,237, $3,294, $5,531; costs were similar for Optum). CONCLUSIONS: Incidence of medically attended, ICD-coded RSV in adults was 22.0-63.6 per 100,000 population, a likely underestimation since RSV was not systematically tested and only RSV-coded cases were observed. Incremental costs associated with RSV were substantial. Incidence rates and costs were higher among patients aged 60 years or older and patients at high risk of severe RSV. DISCLOSURES: This study was sponsored by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design, interpretation of results, manuscript preparation, and publication decisions. B. Brookhart and D. Anderson are employees of Janssen Scientific Affairs, LLC, and are stockholders of Johnson & Johnson. C. Rossi, B. Emond, J. Wang, P. Lefebvre, and M.-H. Lafeuille are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study and manuscript. M. Mesa-Frias. and S. Drummond are former employees of Janssen Scientific Affairs, LLC. L. Lamerato is an employee of Henry Ford Health System and received research funding from Janssen Scientific Affairs, LLC.