Drugs - Real World Outcomes最新文献

Background: There is limited real-world evidence regarding the safety of ramucirumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC).

Objective: We evaluated the safety of ramucirumab plus FOLFIRI in patients with mCRC by age and initial dose of irinotecan.

Patients and methods: This single-arm, prospective, multicenter, non-interventional, observational study was conducted between December 2016 and April 2020. Patients were observed for 12 months.

Results: Of 366 enrolled Japanese patients, 362 were eligible for study inclusion. The frequency of grade ≥ 3 adverse events (AEs) by age (≥ 75 years vs < 75 years) was 56.1% versus 50.2%, indicating no substantial differences between age groups. Grade ≥ 3 notable AEs, including neutropenia, proteinuria, and hypertension, were also similar in both age groups, but the frequency of any grade venous thromboembolic events was higher in those aged ≥ 75 years than in those aged < 75 years (7.0% vs 1.3%). The frequency of grade ≥ 3 AEs was slightly lower in patients receiving > 150 mg/m² of irinotecan than in those receiving ≤ 150 mg/m² of irinotecan (42.1% vs 53.6%); however, the frequency of grade ≥ 3 diarrhea, but not any grade diarrhea, and liver failure/injury was higher in patients receiving > 150 mg/m² of irinotecan than in those receiving ≤ 150 mg/m² of irinotecan (4.6% vs 1.9% and 9.1% vs 2.3%, respectively).

Conclusions: The safety profile of ramucirumab plus FOLFIRI in mCRC patients was similar in subgroups by age and initial irinotecan dose in real-world settings.

Background: Patients with overactive bladder (OAB) experience sudden, intense urges to urinate, which may include urge urinary incontinence and nocturia. Pharmacotherapy includes β₃-adrenergic receptor agonists such as mirabegron; however, mirabegron contains a label warning for cytochrome P450 (CYP) 2D6 inhibition, making coadministration with CYP2D6 substrates require monitoring and dose adjustment to avoid unintended increases in substrate concentration.

Objective: To understand the codispensing patterns of mirabegron among patients using ten predefined CYP2D6 substrates with and before mirabegron dispensing.

Methods: This retrospective claims database analysis used the IQVIA PharMetrics^® Plus Database to assess codispensing of mirabegron with ten predefined CYP2D6 substrate groups identified on the basis of medications most frequently prescribed in the United States, those with high susceptibility to CYP2D6 inhibition, and those with evidence for exposure-related toxicity. Patients had to be ≥ 18 years old before initiation of the CYP2D6 substrate episode that overlapped with mirabegron. The cohort entry period was November 2012 to September 2019, and the overall study period was 1 January 2011 to 30 September 2019. Comparisons of patient profiles at dispensing were made between time periods with and before mirabegron use in the same patient. Descriptive statistics were used to assess the number of exposure episodes, total duration of exposure, and median duration of exposure of CYP2D6 substrate dispensing with and before mirabegron.

Results: CYP2D6 substrate exposure periods totaling ≥ 9000 person-months were available before overlapping exposure to mirabegron for all ten CYP2D6 substrate cohorts. Median codispensing duration for chronically administered CYP2D6 substrates was 62 (interquartile range [IQR] 91) days for citalopram/escitalopram, 71 (105) days for duloxetine/venlafaxine, and 75 (115) days for metoprolol/carvedilol; median codispensing duration for acutely administered CYP2D6 substrates was 15 (33) days for tramadol and 9 (18) days for hydrocodone.

Conclusions: In this claims database analysis, the dispensing patterns of CYP2D6 substrates with mirabegron displayed frequent overlapping of exposure. Thus, a need exists to better understand the outcomes experienced by patients with OAB who are at increased risk for drug‒drug interactions when taking multiple CYP2D6 substrates concurrently with a CYP2D6 inhibitor.

Background: Knowledge of patient outcomes and treatment effectiveness associated with acute migraine treatments in Japan is lacking.

Objective: To describe patient-reported outcomes (PROs) and treatment effectiveness in three acute treatment groups from OVERCOME (Japan): over-the-counter (OTC) only, prescription nonsteroidal anti-inflammatory drugs/acetaminophen (Rx-NSAIDs/ACE) only, and triptans.

Methods: OVERCOME (Japan) was an observational, cross-sectional, population-based web survey of people with migraine (July-September 2020). PROs, including the Migraine-Specific Quality of Life Questionnaire (MSQ), Migraine Interictal Burden Scale (MIBS-4), Migraine Disability Assessment (MIDAS), and Work Productivity and Activity Impairment Questionnaire: Migraine (WPAI-M), were compared pairwise between treatment groups. Logistic regression was used to examine treatment effectiveness.

Results: The analysis included 9075 survey respondents (OTC only: n = 5791; Rx-NSAIDs/ACE only: n = 751; triptans: n = 2533). Triptan users reported the lowest MSQ scores, most severe disability (MIDAS: 20.7% versus 6.3% and 11.6%) and severe interictal burden (MIBS-4: 50.1% versus 21.2% and 19.8%), and greatest work impairment (WPAI-M: 50.4% versus 32.2% and 30.8%) compared with the OTC and Rx-NSAIDs/ACE groups, respectively. Treatment effectiveness was very poor-to-poor for 60.9%, 43.1%, and 47.6% of the triptan, OTC, and Rx-NSAIDs/ACE groups, respectively. Severe interictal burden was significantly associated with insufficient treatment effectiveness (odds ratios, severe versus no burden: 0.47 [95% confidence interval: 0.40-0.54], 0.56 [0.35-0.89], and 0.41 [0.32-0.52], for the OTC, Rx-NSAIDs/ACE, and triptan groups, respectively).

Conclusion: People with high migraine burden used triptans for acute treatment, but many reported poor treatment effectiveness. Education may be required to promote better treatments, including earlier introduction of migraine-specific acute and preventive medications.

Background: Trastuzumab in combination with chemotherapy is the standard first-line (1L) treatment for HER2+ metastatic gastric cancer (mGC) in the USA.

Objective: This study characterizes the real-world treatment patterns, healthcare resource use (HRU), and costs in patients with HER2+ mGC post-1L trastuzumab before approval of fam-trastuzumab deruxtecan-nxki.

Patients and methods: This retrospective study used the IQVIA PharMetrics^® Plus Database (October 2014-September 2019) to identify adults with HER2+ mGC who discontinued trastuzumab-based regimens in 1L. Patient characteristics, second-line (2L) treatment patterns, and treatment duration were summarized. HRU and costs before and after discontinuation of 1L trastuzumab-based regimens as well as during 2L treatment were described.

Results: Of the 190 HER2+mGC patients who discontinued 1L trastuzumab-based regimens, 136 (71.58%) initiated 2L treatments. Trastuzumab-based regimens were the most common in 2L (50.74%), followed by ramucirumab + paclitaxel (19.85%). The median time to 2L discontinuation was 2.37 months. During a mean follow-up of 9.8 months, mean per-patient-per-month (PPPM) healthcare costs post-1L trastuzumab-based regimens were higher in patients receiving 2L treatment than those without subsequent treatment (US$25,178 vs. US$14,812). The mean PPPM cost during 2L treatment was US$30,838, primarily driven by outpatient infusion costs (US$22,262).

Conclusions: The short duration of 2L treatment observed in this study is consistent with a lack of effective treatments post-1L trastuzumab prior to 2020. Re-use of trastuzumab treatment was common despite its limited efficacy and high treatment cost. The findings highlight the unmet medical needs and substantial burden faced by patients with HER2 +mGC previously treated with trastuzumab.

Background: Patient affordability is an important nonclinical consideration for treatment access among patients with schizophrenia.

Objective: This study evaluated and measured out-of-pocket (OOP) costs for antipsychotics (APs) among Medicaid beneficiaries with schizophrenia.

Methods: Adults with a schizophrenia diagnosis, ≥ 1 AP claim, and continuous Medicaid eligibility were identified in the MarketScan^® Medicaid Database (1 January 2018-31 December 2018). OOP AP pharmacy costs ($US 2019) were normalized for a 30-day supply. Results were descriptively reported by route of administration [ROA; orals (OAPs), long-acting injectables (LAIs)], generic/branded status within ROAs, and dosing schedule within LAIs. The proportion of total (pharmacy and medical) OOP costs AP-attributable was described.

Results: In 2018, 48,656 Medicaid beneficiaries with schizophrenia were identified (mean age 46.7 years, 41.1% female, 43.4% Black). Mean annual total OOP costs were $59.97, $6.65 of which was AP attributable. Overall, 39.2%, 38.3%, and 42.3% of beneficiaries with a corresponding claim had OOP costs > $0 for any AP, OAP, and LAI, respectively. Mean OOP costs per patient per 30-day claim (PPPC) were $0.64 for OAPs and $0.86 for LAIs. By LAI dosing schedule, mean OOP costs PPPC were $0.95, $0.90, $0.57, and $0.39 for twice-monthly, monthly, once-every-2-months, and once-every-3-months LAIs, respectively. Across ROAs and generic/branded status, projected OOP AP costs per-patient-per-year for beneficiaries assumed fully adherent ranged from $4.52 to $13.70, representing < 25% of total OOP costs.

Conclusion: OOP AP costs for Medicaid beneficiaries represented a small fraction of total OOP costs. LAIs with longer dosing schedules had numerically lower mean OOP costs, which were lowest for once-every-3-months LAIs among all APs.

Background: Psychoactive medications play an important role for the mental health and risk of suicidal behaviour in the oldest segment of the population (75+). A better understanding of psychoactive medication use is advocated to prevent suicide in this age group.

Purpose: We investigated the risk of suicide associated with the use of psychoactive medications in the total population aged ≥ 75 years, with and without exposure to antidepressants.

Method: A national population-based register study, including all Swedish residents aged ≥ 75 years between 2006 and 2014 (N = 1,413,806). A nested case-control design was used to investigate psychoactive medications associated with suicide among users and non-users of antidepressants. Risk estimates were calculated in adjusted conditional logistic regression models for the entire cohort and by gender.

Results: Suicide occurred in 1305 persons (907 men and 398 women). Among them, 555 (42.5%) were on an antidepressant at the time of suicide. Adjusted incidence rate ratio (aIRR) for suicide was increased in those who were on hypnotics in the total cohort (aIRR 2.05, 95% confidence interval 1.74 to 2.41), in both users and non-users of antidepressants and for both genders. Elevated suicide risk was observed in those who concomitantly used anxiolytics with antidepressants (1.51, 1.25 to 1.83). Decreased risk of suicide was observed among those who were on anti-dementia drugs, in the total cohort (0.33, 0.21 to 0.52) and in both users and non-users of antidepressants. Use of antipsychotics and mood stabilisers showed no effect on suicide risk.

Conclusion: Use of hypnotics and concomitant use of anxiolytics with antidepressants was associated with increased risk of late-life suicide. Our findings suggest the need for careful evaluation of the benefit-risk balance of psychoactive medications as well as their availability as a possible suicide means. Future research should consider the indication of use of the psychoactive medications and the severity of psychiatric and medical illnesses of the patients.

Background: Understanding the demographic and clinical characteristics of patients with Inflammatory Bowel Disease (IBD) who are likely to experience poor disease outcomes may allow early interventions that can improve health outcomes.

Objectives: To describe demographic and clinical characteristics of patients with ulcerative colitis (UC) and Crohn's disease (CD) with the presence of at least one Suboptimal Healthcare Interaction (SOHI) event, which can inform the development of a model to predict SOHI in members with IBD based on insurance claims, with the goal of offering these patients some additional intervention.

Methods: We identified commercially insured individuals with IBD between 01 January 2019 and 31 December 2019 using Optum Labs' administrative claims database. The primary cohort was stratified on the presence or absence of ≥ 1 SOHI event (a SOHI-defining data point or characteristic at a specific time point) during the baseline observation period. SOHI was deployed as the basis for the development of a model to predict which individuals with IBD were most likely to continue to have SOHI within a 1-year timeframe (follow-up SOHI) using insurance claims data. All baseline characteristics were analyzed descriptively. Multivariable logistic regression was used to examine the association of follow-up SOHI with baseline characteristics.

Results: Of 19,824 individuals, 6872 (34.7%) were found to have follow-up SOHI. Individuals with follow-up SOHI were more likely to have had similar SOHI events in the baseline period than those with non-SOHI. A significantly greater proportion of individuals with SOHI had ≥ 1 claims-based C-reactive protein (CRP) test order and ≥ 1 CRP lab results compared with non-SOHI. Individuals with follow-up SOHI were more likely to incur higher healthcare expenditures and resource utilization as compared with non-SOHI individuals. A few of the most important variables used to predict follow-up SOHI included baseline mesalamine use, count of baseline opioid fills, count of baseline oral corticosteroid fills, baseline extraintestinal manifestations of disease, proxy for baseline SOHI, and index IBD provider specialty.

Conclusion: Individuals with SOHI are likely to have higher expenditures, higher healthcare resource utilization, uncontrolled disease, and higher CRP lab results as compared with non-SOHI members. Distinguishing SOHI and non-SOHI patients in a dataset could efficiently identify potential cases of poor future IBD outcomes.

The generation of real-world evidence (RWE), which describes patient characteristics or treatment patterns using real-world data (RWD), is rapidly growing more popular as a tool for decision-making in Japan. The aim of this review was to summarize challenges to RWE generation in Japan related to pharmacoepidemiology, and to propose strategies to address some of these challenges. We first focused on data-related issues, including the lack of transparency of RWD sources, linkage across different care settings, definitions of clinical outcomes, and the overall assessment framework of RWD when used for research purposes. Next the study reviewed methodology-related challenges. As lack of design transparency impairs study reproducibility, transparent reporting of study design is critical for stakeholders. For this review, we considered different sources of biases and time-varying confounding, along with potential study design and methodological solutions. Additionally, the implementation of robust assessment of definition uncertainty, misclassification, and unmeasured confounders would enhance RWE credibility in light of RWD source-related limitations, and is being strongly considered by task forces in Japan. Overall, the development of guidance for best practices on data source selection, design transparency, and analytical methods to address different sources of biases and robustness in the process of RWE generation will enhance credibility for stakeholders and local decision-makers.

Background: Pre-operative hypoalbuminemia is known to predict negative outcomes for patients undergoing major surgeries. However, various cut-off points for starting exogenous albumin have been recommended.

Objective: This study investigated the association between pre-operative severe hypoalbuminemia, in-hospital death, and length of hospital stay in patients undergoing gastrointestinal surgery.

Methods: A retrospective cohort study using a database analysis was undertaken on hospitalized patients who underwent major gastrointestinal surgery. The pre-operative serum albumin level was classified into three groups: severe hypoalbuminemia (< 2.0 mg/dL) and non-severe hypoalbuminemia (≥ 2.0-3.4 g/dL) and normal level (3.5-5.5 g/dL). To compare between different cut-offs, a sensitivity analysis using another albumin level classification as severe hypoalbuminemia (< 2.5 mg/dL) and non-severe hypoalbuminemia (≥ 2.5-3.4 g/dL) and normal level (3.5-5.5 g/dL) was applied. The primary outcome was post-operative in-hospital death. Propensity-score adjusted regression analyses were applied.

Results: A total of 670 patients were included. Their average age was 57.4 ± 16.3 years, and 56.1% were men. Only 59 patients (8.8%) had severe hypoalbuminemia. Overall, a total of 93 in-hospital deaths (13.9%) occurred among all included patients, but there were 24/59 (40.7%) deaths among patients with severe hypoalbuminemia, 59/302 (19.5%) deaths among patients with non-severe hypoalbuminemia, and 10/309 (3.2%) deaths among patients with normal albumin level. The adjusted odds ratio for post-operative in-hospital death comparing patients with severe hypoalbuminemia and patients with normal albumin level was 8.11 (3.31-19.87; p < 0.001), while the odds ratio for in-hospital death comparing patients with non-severe and patients with normal albumin level was 3.89 (1.87-8.10; p < 0.001). A sensitivity analysis showed similar findings, the odds ratio for in-hospital death for severe hypoalbuminemia (cut-off as < 2.5 g/dL) was 7.44 (3.38-16.36; p < 0.001), while the odds ratio for in-hospital death for severe hypoalbuminemia (cut-off as 2.5-3.4 g/dL) was 3.02 (1.40-6.52; p = 0.005).

Conclusions: Severe pre-operative hypoalbuminemia in patients undergoing gastrointestinal surgery was associated with an increased risk of in-hospital mortality. The risk of death for patients with severe hypoalbuminemia was relatively similar when using different cut-offs such as < 2.0 and <2.5 g/dL.

Background: Medications with anticholinergic and/or sedative properties are commonly used in the management of psychiatric illnesses. The burden of anticholinergic and sedative medication use has been measured by the Drug Burden Index (DBI) score tool. A higher DBI score has been associated with increased risk of falls, bone and hip fractures, and functional and cognitive impairment, among other serious health outcomes, especially in older adults.

Objectives: We aimed to describe the drug burden in older adults with psychiatric illnesses using DBI, determine the factors that are associated with the drug burden measured by DBI, and examine the association between DBI score and Katz for activities of daily living (ADL) index.

Methods: A cross-sectional study was conducted in the psychogeriatric division of an aged-care home. The study sample comprised all inpatients, aged ≥ 65 years, diagnosed with psychiatric illness. The data obtained included demographic characteristics, duration of hospital stay, primary psychiatric diagnosis and comorbidities, functional status using the Katz ADL index, and cognitive status using the Mini-Mental State Examination (MMSE) score. DBI score was calculated for each anticholinergic and sedative medication used.

Results: Of the 200 patients eligible for analysis, 106 (53.1%) were females and the mean age was 76 ± 9 years. The most commonly encountered chronic disorders were hypertension 102 (51%) and schizophrenia 94 (47%). The use of drugs with anticholinergic and/or sedative effects was seen in 163 (81.5%) patients; the mean DBI score was 1.25 ± 1. The results of the multinomial logistic regression showed that schizophrenia (odds ratio (OR) = 2.1 (95% confidence interval (CI) 1.57-4.45), p = 0.01), level of dependency (OR = 3.50 (95% CI 1.38-5.70), p = 0.001), and polypharmacy (OR = 2.99 (95% CI 2.15-4.29), p = 0.003) were significantly associated with DBI score ≥ 1 compared to DBI score 0.

Conclusions: The study showed that anticholinergic and sedative medication exposure measured by DBI was associated with higher levels of dependency on the Katz ADL index in a sample of older adults with psychiatric illnesses from an aged-care home.