Treatment sequencing after failure to alectinib in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer.

Alectinib is the first-line therapy for anaplastic lymphoma kinase-positive non-small-cell lung cancer. Although some guidelines have recommended using other anaplastic lymphoma kinase inhibitors after alectinib failure, evidence for such regimens in patients who fail to respond to alectinib is limited. This study involved using administrative claims data from acute care hospitals in Japan. We extracted the data of 634 patients diagnosed with lung cancer between September 1, 2014, and January 31, 2023, who received alectinib treatment before treatment with another anaplastic lymphoma kinase inhibitor. We assessed distributions of patients according to their treatment sequencing and prognosis among three periods defined based on the initial marketing dates of lorlatinib and brigatinib. The type of anaplastic lymphoma kinase inhibitors after alectinib failure changed over time. In the most recent period, lorlatinib (58%) and brigatinib (40%) became predominant. Two-year overall survival improved over time (47%-84%), accompanied by an increased 2-year proportion of patients who continuously used anaplastic lymphoma kinase inhibitors after alectinib failure (13%-44%). The times to treatment discontinuation of the regimen between patients treated with lorlatinib and brigatinib were similar, with a hazard ratio of 1.02 (95% confidence interval, 0.64-1.64) in the period after marketing brigatinib. This study provides insights into the evolving treatment landscape for patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer who experience failed alectinib treatment and highlights the need for further studies and data accumulation to determine the optimal treatment strategy.

Treatment patterns and clinical outcomes in patients with metastatic triple-negative breast cancer: a large-scale data analysis using the Japanese claims database.

PURPOSE: This study evaluated treatment patterns and clinical outcomes among patients with metastatic triple-negative breast cancer (mTNBC) in real-world clinical settings in Japan. METHODS: The treatment patterns, time to next treatment or death (TTNTD), time to treatment discontinuation, adverse events of interest, and medical costs of treating patients with mTNBC in first-, second-, and third-line settings were investigated using data of patients meeting the inclusion criteria between January 2017 and March 2022 in a Japanese medical claims database. The treatment regimens for mTNBC were defined according to the Japanese Breast Cancer Society Clinical Practice Guidelines. RESULTS: In this study, 2236 patients with mTNBC (median age 66.0 years; 99.8% female) were included in the first-line cohort. Of these, 46.6% and 20.8% were included in the second- and third-line cohorts, respectively. The two most frequently used treatments were capecitabine (19.1%) and S-1 (tegafur-gimeracil-oteracil) (14.5%) in the first-line cohort, eribulin (18.3%) and bevacizumab/paclitaxel (14.4%) in the second-line cohort, and eribulin (19.4%) and bevacizumab/paclitaxel (17.5%) in the third-line cohort. The TTNTD shortened as the line of therapy progressed (median 8.0, 6.5, and 5.2 months for the first-, second-, and third-line treatments, respectively). Nausea/vomiting and neutropenia/leukopenia occurred in 62.8% and 18.3% of all patients, respectively. The medical total costs per day were 6.7, 10.2, and 12.9 thousand yen during the first-/second-/third-line treatments, respectively. CONCLUSION: This study provides insight into current treatment patterns for mTNBC in Japan. The cost-benefit balance worsens with later-line treatment and a high unmet need for mTNBC drug treatment remains.

Cardiovascular and renal diseases in type 2 diabetes patients: 5-year cumulative incidence of the first occurred manifestation and hospitalization cost: a cohort within the French SNDS nationwide claims database.

BACKGROUND: Myocardial infarction (MI), stroke, peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD) are common cardiovascular renal diseases (CVRD) manifestations for type 2 diabetes. The objective was to estimate the incidence of the first occurring CVRD manifestation and cumulative hospitalization costs of each CVRD manifestation for type 2 diabetes without CVRD history. METHODS: A cohort study of all type 2 diabetes free of CVRD as of January 1st 2014, was identified and followed-up for 5 years within the French SNDS nationwide claims database. The cumulative incidence of the first occurring CVRD manifestation was estimated using the cumulative incidence function, with death as a competing risk. Cumulative hospitalization costs of each CVRD manifestations were estimated from the perspective of all payers. RESULTS: From 2,079,089 type 2 diabetes without cancer or transplantation, 76.5% were free of CVRD at baseline with a mean age of 65 years, 52% of women and 7% with microvascular complications history. The cumulative incidence of a first CVRD manifestation was 15.3% after 5 years of follow-up with a constant linear increase over time for all CVRD manifestations: The most frequent was CKD representing 40.6% of first occurred CVRD manifestation, followed by HF (23.0%), then PAD (13.5%), stroke (13.2%) and MI (9.7%). HF and CKD together reached about one patient out of ten after 5 years and represented 63.6% of first CVRD manifestations. The 5-year global cost of all CVRD hospitalizations was 3.9 billion euros (B€), i.e. 2,450€ per patient of the whole cohort, with an exponential increase over time for each specific CVRD manifestation. The costliest was CKD (2.0 B€), followed by HF (1.2 B€), then PAD (0.7 B€), stroke (0.6 B€) and MI (0.3 B€). CONCLUSIONS/INTERPRETATION: While MI, stroke and PAD remain classic major risks of complications for CVRD-free type 2 diabetes, HF and CKD nowadays represent individually a higher risk and cost than each of these classic manifestations, and jointly represents a risk and a cost twice as high as these three classic manifestations all together. This should encourage the development of specific HF and CKD preventive strategies.

Average daily glucocorticoid dose, number of prescription days, and cumulative dose in the initial 90 days of glucocorticoid therapy are associated with subsequent hip and clinical vertebral fracture risk: a retrospective cohort study using a nationwide health insurance claims database in Japan.

PURPOSE: Fracture risk assessment is recommended at three months after glucocorticoid (GC) therapy initiation. This study aimed to assess whether GC exposure in the initial 90 days of GC therapy is associated with subsequent hip and clinical vertebral fracture risk using the nationwide health insurance claims database of Japan (NDBJ). METHODS: Patients aged ≥ 50 years who were prescribed GC (≥ 70 mg prednisolone or equivalent; PSL) in the initial 90 days of GC therapy and were followed for hip and clinical vertebral fracture incidences for the subsequent 1080 days were selected from NDBJ. Associations of GC exposure with hip or clinical vertebral fracture risk were evaluated by Cox regression analysis adjusted for potential confounders. RESULTS: We selected 316,396 women and 299,871 men for the GC-exposed group and 43,164 women and 33,702 men for the reference group. Higher GC doses and longer prescription days in the initial 90 days of GC therapy were significantly and dose-dependently associated with increased fracture risk relative to the reference group. Patients receiving GC ≥ 5 mg PSL/day had a significantly increased fracture risk in the stratum of 30-59 days of GC prescription. In addition, female patients who received GC (≥ 1 and < 2.5 mg PSL/day) for 90 days in the initial 90 days of GC therapy had a significantly increased fracture risk. CONCLUSIONS: GC exposure in the initial 90 days of GC therapy was dose-dependently associated with hip and clinical vertebral fracture risk. GC may increase fracture risk with lower doses for shorter durations than previously reported. Fracture risk assessment three months after glucocorticoid (GC) therapy initiation is recommended. We found that GC exposure in the initial 90 days of GC therapy at lower daily doses for shorter durations than previously reported were significantly and dose-dependently associated with fracture risk using a nationwide health insurance claims database.

A retrospective observational study of ibrutinib in chronic lymphocytic leukaemia in a real-life setting in France using the national claims database (OSIRIS).

BACKGROUND: Ibrutinib is a Bruton's tyrosine kinase inhibitor indicated for the first-line treatment and relapse of chronic lymphocytic leukaemia (CLL), Waldenström's macroglobulinemia (WM) and mantle cell lymphoma (MCL). This study aimed to describe the characteristics of CLL patients treated with ibrutinib and its effectiveness, safety, and treatment pattern in real life. METHODS: All patients covered by the general health scheme (approximately 80% of the French population) with a first ibrutinib dispensation from August 1, 2017 (date of reimbursement in France) to December 31, 2020, were identified in the French National Health Insurance database (SNDS). An algorithm was developed to identify the disease (CLL, MCL or WM) for which ibrutinib was prescribed. This article focused on CLL patients. The time to next treatment (TTNT) was plotted using Kaplan‒Meier curves. RESULTS: During this period, 6,083 patients initiated ibrutinib, among whom 2,771 (45.6%) patients had CLL (mean age of 74 years; 61% of men). At ibrutinib initiation, 46.6% of patients had a cardiovascular comorbidity. Most patients (91.7%) were not hospitalized during the exposure period for one of the cardiovascular or bleeding events studied. Hospitalizations were more frequent in patients with a cardiovascular comorbidity (5.9% versus 11.0%, p-value < 0.0001) and aged over 70 (5.9% versus 9.4%, p-value < 0.0001). The median TTNT was not reached. CONCLUSION: This is one of the largest cohorts of ibrutinib-treated patients in the world. The profile of CLL patients treated with ibrutinib was in accordance with the marketing authorization and reimbursement. This study confirmed effectiveness and safety data.

Association Between Arterial Pulse Waveform Analysis and Mortality in Patients With Septic Shock: A Retrospective Cohort Study Using Japanese Diagnosis Procedure Combination Data.

Purpose: Specialized pressure transducers for arterial pulse waveform analysis (S-APWA) devices are dedicated kits connected to an arterial pressure catheter that monitors hemodynamic parameters, such as cardiac output, pulse pressure variation, and stroke volume variation, less invasively. While the association between the use of S-APWA devices and clinical outcomes in perioperative patients has been previously evaluated, its assessment in patients with septic shock remains inadequate. Materials and Methods: This retrospective cohort study utilized a nationwide Diagnosis Procedure Combination database in Japan. Adult patients with septic shock admitted to the intensive care unit (ICU) with arterial pressure catheter placement on the admission day from August 2012 to February 2021 were included. Hospitalizations meeting the eligibility criteria were categorized into groups based on S-APWA device usage. The primary outcome, evaluated using Cox regression analysis, was 30-day all-cause mortality in the propensity score overlap-weighted population. Secondary outcomes included in-hospital mortality, ICU duration, and overall hospital stay. Results: Among 5130 eligible hospitalizations, 643 were in the S-APWA group and 4487 were in the conventional pressure transducer group. Cox regression analysis within the propensity score overlap-weighted population showed no significant difference in 30-day mortality (adjusted hazard ratio: 0.94; 95% confidence interval: 0.9-1.38; P = .58). Logistic regression analysis indicated no significant differences in the in-hospital mortality. While the S-APWA group had prolonged ICU stays, no significant difference in the overall hospital stay was observed according to linear regression analyses. Conclusions: Our study found no significant association between S-APWA use and 30-day mortality in patients with septic shock. These findings offer insights into optimizing monitoring systems in ICUs.

Application of multiple validated algorithms for identifying incident breast cancer among individuals with atopic dermatitis.

PURPOSE: Validated algorithms (VAs) in insurance claims databases are often used to estimate the prevalence and incidence of comorbidities and evaluate safety signals. However, although they are then used in different data sources or subpopulations from those in which they were developed the replicability of these VAs are rarely tested, making their application and performance in these settings potentially unknown. This paper describes testing multiple VAs used to identify incident breast cancer cases in a general population and in an indication-specific population, patients with atopic dermatitis (AD). METHODS: Two algorithms were tested in multiple insurance claims databases and four cohorts were created. Modifications were made to account for the US insurance setting. The resulting incidence rates (IRs) were then compared across algorithms and against surveillance, epidemiology, and end results (SEER) estimates to assess reliability. RESULTS: Algorithm 1 produced low IRs compared to Algorithm 2. Algorithm 2 provided similar estimates to those of SEER. Individuals in the AD cohorts experienced lower incident breast cancer cases than those in the general population cohorts. CONCLUSION: Regardless of an algorithm's reported accuracy, the original study setting and targeted population for the VAs may matter when attempting to replicate the algorithm in an indication-specific subpopulation or varying data sources. Investigators should use caution and conduct sensitivity analyses or use multiple algorithms when attempting to calculate incidence or prevalence estimates using VAs.

Validity of self-reported Helicobacter pylori eradication treatment from questionnaire and interview surveys of the JPHC-NEXT study: comparison with prescription history from insurance claims data.

BACKGROUND: We aimed to evaluate the validity of self-administered questionnaire surveys and face-to-face interview surveys for the detection of Helicobacter pylori eradication therapy. METHODS: Participants were a cohort, aged 40-74 years, living in three different locations of Japan, who took part in the baseline survey (2011-2012) of the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT). Five years after the baseline survey, a questionnaire and interview survey were independently conducted to determine the history of Helicobacter pylori eradication treatment over the 5-year period. Prescription of Helicobacter pylori eradication medications in national insurance claims data from the baseline survey to the 5-year survey was used as a reference standard. RESULTS: In total, 15,760 questionnaire surveys and 8,006 interview surveys were included in the analysis. There were 3,471 respondents to the questionnaire and 2,398 respondents to the interview who reported having received Helicobacter pylori eradication treatment within the past five years. Comparison of the questionnaire survey to national insurance claims data showed a sensitivity of 95.1% (2213/2328), specificity of 90.6% (12174/13432), positive predictive value of 63.8% (2213/3471), negative predictive value of 99.1% (12174/12289), and Cohen's Kappa value of 0.71. Respective values of the interview survey were 94.4% (1694/1795), 88.7% (5507/6211), 70.6% (1694/2398), 98.2% (5507/5608), and 0.74. CONCLUSION: Both the questionnaire and the interview showed high sensitivity, high specificity, and good agreement with the insurance claim prescriptions data. Some participants may have received eradication treatment without going through the public insurance claim database, resulting in a low positive predictive value.

Factors associated with death, hospitalization, resignation, and sick leave from work among patients with schizophrenia in Japan: a nested case-control study using a large claims database.

BACKGROUND: Premature mortality, frequent relapse that easily leads to hospitalization, and discontinuous employment are key challenges for the treatment of schizophrenia. We evaluated risk factors for important clinical outcomes (death, hospitalization, resignation, and sick leave from work) in patients with schizophrenia in Japan. METHODS: A nested case-control study was conducted for patients with schizophrenia identified in a Japanese claims database. For each outcome, the case was matched with up to four controls of the same age, sex, index year, and enrollment status (employee or dependent family). Potential risk factors were defined by prescriptions or diagnoses within 3 months prior to or in the month of the event. The association among potential risk factors and each outcome was evaluated using multivariable conditional logistic regression analysis with stepwise variable selection. RESULTS: The number of cases and eligible patients for each outcome were 144 and 38,451 (death), 1,520 and 35,225 (hospitalization), 811 and 18,770 (resignation), and 4,590 and 18,770 (sick leave), respectively. Depression was a risk factor for death (odds ratio [OR]: 1.92; 95% confidence interval [CI]: 1.12, 3.29), hospitalization (OR: 1.22; 95% CI: 1.05, 1.42), and sick leave from work (OR: 1.46; 95% CI: 1.36, 1.57). Other risk factors for death were hospitalization history, Charlson Comorbidity Index (CCI) score, and prescription for laxatives. Prescriptions for hypnotics, laxatives, and anticholinergics were risk factors for hospitalization. Prescriptions for hypnotics and anticholinergics were risk factors for resignation. CCI score, prescription for hypnotics, laxatives, and antidiabetics were risk factors for sick leave from work. CONCLUSIONS: Our findings suggest that depression and some physical symptoms, such as constipation and extrapyramidal symptoms, are risk factors for important clinical outcomes in patients with schizophrenia. Attention should be paid to both depression and physical symptoms for the treatment of schizophrenia.

Incidence and potential risk factors of human cytomegalovirus infection in patients with severe and critical coronavirus disease 2019.

BACKGROUND: Human cytomegalovirus (HCMV) infection occurs in immunosuppressed individuals and is known to increase mortality. Patients with coronavirus disease 2019 (COVID-19) are often treated with steroids, require intensive care unit (ICU) treatment, and may therefore be at risk for HCMV infection. However, which factors predispose severely ill patients with COVID-19 to HCMV infection and the prognostic value of such infections remain largely unexplored. This study aimed to examine the incidence and potential risk factors of HCMV infection in patients with severe or critical COVID-19 and evaluate the relationship between HCMV infection and mortality. METHODS AND FINDINGS: We used administrative claims data from advanced treatment hospitals in Japan to identify and analyze patients with severe or critical COVID-19. We explored potential risk factors for HCMV infection using multivariable regression models and its contribution to mortality in patients with COVID-19. Overall, 33,151 patients who progressed to severe or critical COVID-19 illness were identified. The incidence of HCMV infection was 0.3-1.7 % depending on the definition of HCMV infection. Steroids, immunosuppressants, ICU admission, and blood transfusion were strongly associated with HCMV infection. Furthermore, HCMV infection was associated with patient mortality independent of the observed risk factors for death. CONCLUSIONS: HCMV infection is a notable complication in patients with severe or critical COVID-19 who are admitted to the ICU or receive steroids, immunosuppressants, and blood transfusion and can significantly increase mortality risk.

Impact of long-term macrolide therapy on the evaluation indicator of outpatient oral antimicrobial use according to the AWaRe classification.

The WHO recently proposed a new indicator for judging the appropriateness of antimicrobial selection according to the AWaRe classification. Although macrolides are often administered for long-term macrolide therapy, the impact of this therapy on the indicator remains unclear. This study examined the impact of this therapy on the indicator for outpatient oral antimicrobial use. Using the JMDC claims database, outpatients who were prescribed an oral antimicrobial at least once between January and December 2022 (n = 2.66 million) were included in the study. The ratio of patient numbers and antimicrobial usage (AMU) were calculated based on age group (<15, 15-64, and ≥65 years) and prescription days (1-15, 16-30, 31-60, 61-90, and ≥91 days), and AMU of each drug was corrected for defined daily doses and classified according to the AWaRe. Patients with chronic airway disease for whom macrolides were prescribed for 91 days and more were defined as long-term macrolide therapy. Macrolides accounted for more than 30 % of total oral AMU in all age groups. In the elderly, 11.2 % of patients were prescribed macrolides for 91 days or more, accounting for 66.4 % of macrolide use. With regard to diseases that were associated with macrolide prescriptions, the percentage of patients prescribed for chronic airway diseases increased as the number of days of prescription increased. These results suggest that the impact of long-term macrolide therapy should be considered when assessing the appropriateness of outpatient oral AMU according to the AWaRe classification.

Nationwide epidemiology and health resource use among children with COVID-19 in Japan.

BACKGROUND: The COVID-19 pandemic posed substantial challenges to healthcare systems. Understanding the responses of pediatric health services is crucial for future pandemic planning and preparedness, yet such data remains limited. METHODS: In this retrospective cohort study, we analyzed data from administrative databases developed by Japan Medical Data Center and DeSC Healthcare Inc. The dataset comprised records of 2,612,511 children, totaling 60,224,888 person-months, from January 2020 to May 2022. Multivariate generalized estimation equations were used to examine the incidence rates of COVID-19 and associated health resource use. RESULTS: Our analysis revealed that the incidence rates of COVID-19 gradually increased from Wave I (2.2 cases per 100,000 person-months) to Wave V (177.8cases per 100,000 person-months), with a notable elevation during Wave VI (2367.7 cases per 100,000 person-months). While nucleic acid amplification tests were primarily used during Waves I-V, the use of rapid antigen tests markedly increased in Wave VI. The hospitalization rates increased gradually from 0.2 in Wave I to 10.2 events per 100,000 person-months in Wave VI, and the case-hospitalization risk decreased from 14.9% in Wave II to 0.7% in Wave VI. Additionally, we observed decreasing trends in the use of antibiotics (Wave I, 31.8%; Wave VI, 9.0%), whereas antipyretic use rose from Wave I (56.1%) to Wave VI (86.6%). CONCLUSIONS: Our study highlighted essential changes in the nationwide pediatric healthcare system's response to the COVID-19 pandemic. These findings provide valuable insights into the future pandemic planning and preparedness.

Characteristics of pediatric patients claimed with acute upper respiratory infection during otorhinolaryngology consultations: A descriptive study of a large Japanese medical claims database.

This study aimed to clarify other diseases claimed simultaneously with acute upper respiratory infection (URI), antibiotic prescriptions, and examinations associated with infectious diseases in pediatric patients with acute URI insurance claims at otorhinolaryngology outpatient visits. Pediatric patients who visited an otolaryngology department between 2019 and 2021 and were definitively diagnosed with URI were selected using a large Japanese medical claims database. Patient backgrounds, antibiotic use, and examinations were descriptively evaluated. In total, 8010 patients were included in the analysis. The median number (interquartile range) of diseases claimed in the same month as acute URI was 4 (3-6). Only 519 (6.5 %) patients were claimed as acute URI alone. Regardless of the prescription of antibiotics, the most commonly redundantly claimed disease in these patients was allergic rhinitis, followed by acute bronchitis, acute sinusitis, and earwax impaction. The frequently prescribed antibiotics were third-generation cephalosporins, macrolides, and penicillins with extended-spectrum, including amoxicillin which was recommended by the Japanese manual; the proportion of patients with examinations was low (2.9-21.7 %). Among patients with acute URI, diagnoses requiring antibiotics were also claimed; therefore, when evaluating acute URI using the Japanese medical claims database, care must be taken in patient selection. Moreover, the implementation rate of examinations necessary for diagnosis was low, so there is an urgent need to develop an environment where examinations can be conducted in outpatient settings.

Evaluating the association of body mass index with COVID-19 severity and mortality using Japanese administrative claims data.

INTRODUCTION: Obesity is a risk factor for aggravation of and mortality from coronavirus disease 2019 (COVID-19). We aimed to investigate the relationship between COVID-19 and Body Mass Index (BMI) in the Japanese population. METHODS: We used administrative claims data from an advanced treatment hospital in Japan and extracted data from patients hospitalized for COVID-19. The exposure variable was BMI measured at the time of admission, and the study outcomes were progression to critical illness and death. Analyses were performed for each age group. RESULTS: Overall, 58,944 patients met the inclusion criteria. The risk of critical illness increased monotonically with higher BMI. In contrast, the relationship between BMI and mortality follows a J-shaped curve; being underweight and obese are risk factors for mortality. When stratified by age, similar trends were observed for both critical illness and mortality. CONCLUSION: A higher BMI is a risk factor for the progression of COVID-19 severity, whereas both lower and higher BMIs are risk factors for mortality in the Japanese population.

Incidence and risk factors for coronavirus disease 2019-associated pulmonary aspergillosis using administrative claims data.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is one of the noticeable complications of COVID-19 and its incidence varies widely. In Japan, research on the incidence, risk factors and mortality associated with CAPA is limited. OBJECTIVES: This study aimed to explore the incidence and potential risk factors for CAPA in patients with severe or critical COVID-19 and evaluate the relationship between CAPA and mortality of patients with severe or critical COVID-19. METHODS: We investigated the incidence of CAPA in patients with severe and critical COVID-19 using administrative claims data from acute care hospitals in Japan. We employed multivariable regression models to explore potential risk factors for CAPA and their contribution to mortality in patients with severe and critical COVID-19. RESULTS: The incidence of CAPA was 0.4%-2.7% in 33,136 patients with severe to critical COVID-19. Age, male sex, chronic lung disease, steroids, immunosuppressants, intensive care unit admission, blood transfusion and dialysis were potential risk factors for CAPA in patients with severe to critical COVID-19. CAPA was an independent factor associated with mortality. CONCLUSIONS: CAPA is a serious complication in patients with severe and critical COVID-19 and may increase mortality.

Validation of Claims-Based Algorithm for Lyme Disease, Massachusetts, USA.

Compared with notifiable disease surveillance, claims-based algorithms estimate higher Lyme disease incidence, but their accuracy is unknown. We applied a previously developed Lyme disease algorithm (diagnosis code plus antimicrobial drug prescription dispensing within 30 days) to an administrative claims database in Massachusetts, USA, to identify a Lyme disease cohort during July 2000-June 2019. Clinicians reviewed and adjudicated medical charts from a cohort subset by using national surveillance case definitions. We calculated positive predictive values (PPVs). We identified 12,229 Lyme disease episodes in the claims database and reviewed and adjudicated 128 medical charts. The algorithm's PPV for confirmed, probable, or suspected cases was 93.8% (95% CI 88.1%-97.3%); the PPV was 66.4% (95% CI 57.5%-74.5%) for confirmed and probable cases only. In a high incidence setting, a claims-based algorithm identified cases with a high PPV, suggesting it can be used to assess Lyme disease burden and supplement traditional surveillance data.

Patient characteristics, treatment patterns, and outcomes of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer patients prescribed cyclin-dependent kinase 4 and 6 inhibitors: large-scale data analysis using a Japanese claims database.

PURPOSE: The aim was to understand real-world cyclin-dependent kinase (CDK) 4 and 6 inhibitor use in Japan. METHODS: This retrospective observational study used a Japanese administrative claims database and included patients with presumptive hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) prescribed CDK4 and 6 inhibitor therapy between December 2017 and March 2021. Patient characteristics, treatment patterns, and selected clinical and safety outcomes were descriptively summarized. Time to discontinuation (TTD) and chemotherapy-free survival (CFS) were examined using Kaplan-Meier estimates. RESULTS: The study cohort (N = 6442) was predominantly female (99.4%; median [range] age 64 [26-99] years) with records of metastases (79.6%) within 1 year prior to initiating CDK4 and 6 inhibitor therapy. In total, 4463 (69.3%) and 1979 (30.7%) were prescribed palbociclib and abemaciclib, respectively, as their first CDK4 and 6 inhibitor, most commonly in combination with fulvestrant (n = 3801; 59.0%). Overall, 3756 patients initiated a subsequent anticancer treatment, of whom 748 (19.9%) initiated a different CDK4 and 6 inhibitor in combination with the same or different endocrine therapy. Median TTD (95% confidence interval) was 9.7 (9.3, 10.1) months for the first CDK4 and 6 inhibitor therapy. Median CFS was 26.1 (24.6, 27.8) months. Incidence of clinically relevant diarrhea was higher after abemaciclib initiation (9.8%) than after palbociclib initiation (1.5%). More patients experienced dose reduction with palbociclib (69.3%) than with abemaciclib (53.0%). CONCLUSION: The data provide insights into current clinical practices for CDK4 and 6 inhibitor use in Japan that could help establish future treatment strategies for ABC.

Prevalence and Clinical Characteristics of Patients with Moderate-to-Severe Asthma in Japan Using a JMDC Claims Database.

INTRODUCTION: Although the prevalence and burden of asthma are continuously increasing, there is a lack of evidence on the landscape of moderate-to-severe asthma in Japan. Here, we report the prevalence of moderate-to-severe asthma and describe patient's demographics and clinical characteristics from 2010 to 2019 using the JMDC claims database. METHODS: Patients (≥12 years) from the JMDC database with ≥2 asthma diagnoses in 2 different months in each index year were stratified as moderate-to-severe asthma based on the definition of asthma prevention and management guideline (Japanese Guidelines for Asthma, JGL) or Global Initiative for Asthma (GINA). PRIMARY OBJECTIVE: 10-year trend (2010-2019) in the prevalence of moderate-to-severe asthma. SECONDARY OBJECTIVE: Demographics and clinical characteristics of patients from 2010 to 2019. RESULTS: Of 7,493,027 patients from the JMDC database, 38,089 and 133,557 were included in JGL and GINA cohorts, respectively, by 2019. Both cohorts presented an increasing trend in the prevalence rate of moderate-to-severe asthma from 2010 to 2019, irrespective of age groups. Demographics and clinical characteristics were consistent across the cohorts in each calendar year. Majority of patients were in the age group of 18-60 years in both JGL (86.6%) and GINA (84.2%) cohorts. Allergic rhinitis was the most frequent comorbidity and anaphylaxis the least frequent comorbidity reported in both the cohorts. CONCLUSIONS: In Japan, the prevalence rate of patients with moderate-to-severe asthma, as per JGL or GINA in the JMDC database, increased from 2010 to 2019. The demographics and clinical characteristics were similar in both cohorts over the assessment duration.

Risk of a second cancer and infection in patients with indolent B-cell lymphoma exposed to first-line bendamustine plus rituximab: A retrospective analysis of an administrative claims database.

Bendamustine has a potent immunosuppressive effect because it causes T-cell lymphopenia, which might lead to a second primary malignancy (SPM) and would increase the risk of infection. Using the Medical Data Vision administrative claims database, we compared the cumulative incidence of SPM, infections within 6 months, and overall survival (OS) among untreated patients with indolent B-cell lymphomas (iBCL) who received rituximab-based chemotherapy between 2009 and 2020. Patients with grade 3b follicular lymphoma or a previous history of malignancy were excluded. Eligible 5234 patients were assigned to three cohorts: rituximab monotherapy (N = 780), RCHOP/RCVP/RTHPCOP (doxorubicin replaced with pirarubicin) (N = 2298), or bendamustine/rituximab (BR) (N = 2156). There were 589 recorded SPMs, of which myelodysplastic syndromes were the most common (1.7%). The cumulative incidence of SPM was significantly higher in patients treated with BR than in those treated with rituximab monotherapy (p < 0.01) or RCHOP/RCVP/RTHPCOP (p < 0.0001): the 5-year cumulative incidence function was 18.1%, 12.5%, and 12.9%, respectively. In the Fine-Gray subdistribution hazards model, BR showed a significantly higher cumulative incidence of SPM than RCHOP/RCVP/RTHPCOP (subhazard ratio, 1.33; 95% confidence interval [CI], 1.10-1.61). Furthermore, in sensitivity analysis, a nested case-control study using an entire cohort showed consistent results: the SPM odds ratios (95% CI) of first-line bendamustine, bendamustine after first-line, and any-line bendamustine were 1.43 (1.14-1.78), 1.26 (0.96-1.64), and 1.33 (1.09-1.62), respectively. Regarding infections, adjusted odds ratios (95% CI) of BR compared to RCHOP/RCVP/RTHPCOP were as follows: cytomegalovirus infection, 13.7 (4.88-38.4); bacterial pneumonia, 0.63 (0.50-0.78); and pneumocystis pneumonia, 0.24 (0.11-0.53). There was no significant difference in OS between RCHOP/RCVP/RTHPCOP and BR in patients with follicular, mantle cell, marginal zone, or lymphoplasmacytic lymphomas. In conclusion, treatment strategies that consider the risk of SPM and infections after chemotherapy are warranted in patients with iBCL.

Odds of Medical Comorbidities in Essential Tremor: Retrospective Analysis of a Large Claims Database in the United States.

INTRODUCTION: Essential tremor (ET) is the most common tremor disorder, estimated to affect 7 million individuals in the USA. There is little empirical evidence on comorbidities among this population beyond higher prevalence of brain-related and stress-related disorders. This study aims to examine differences in the prevalence of the 31 Elixhauser comorbidities among ET patients compared to statistically similar control patients. METHODS: An extract from Optum's de-identified Clinformatics® Data Mart Database (CDM) from 2018 to 2019 of adults aged 40-80 years with at least one claim with an ET diagnosis was propensity score matched to controls. Logistic regression was used to generate doubly robust adjusted odds ratios for each of the 31 Elixhauser comorbidities. RESULTS: In these analyses, ET patients had significantly greater adjusted odds of depression, alcohol abuse, and other neurological disorders, as well as chronic pulmonary disease, renal failure, hyperthyroidism, and cardiac arrhythmias relative to controls. They also had lower odds of uncomplicated diabetes, congestive heart failure, metastatic cancer, paralysis, peripheral vascular disease, and fluid and electrolyte disorders. CONCLUSION: A number of recent studies, including our own, suggest that psychiatric, neurologic, and stress-related disorders may be more prevalent among ET patients than controls. Additional differences in the prevalence of a range of medical comorbidities have also been variably reported across studies, suggesting that some combination of these might be more prevalent. Further studies would be of value in sorting through these associations.