Nontargeted Identification of Organic Components in Fine Particulate Matter Related to Lung Tumor Metastasis Based on an Adverse Outcome Pathway Strategy.

Emerging studies implicate fine particulate matter (PM2.5) and its organic components (OCs) as urgent hazard factors for lung cancer progression in nonsmokers. Establishing the adverse outcome pathway (AOP)-directed nontargeted identification method, this study aimed to explore whether PM2.5 exposure in coal-burning areas promoted lung tumor metastasis and how we identify its effective OCs to support traceability and control of regional PM2.5 pollution. First, we used a nude mouse model of lung cancer for PM2.5 exposure and found that the exposure significantly promoted the hematogenous metastases of A549-Luc cells in lung tissues and the adverse outcomes (AOs), with key events (KEs) including the changed expression of epithelial-mesenchymal transition (EMT) markers, such as suppression of E-cad and increased expression of Fib. Subsequently, using AOs and KEs as adverse outcome directors, we identified a total of 35 candidate chemicals based on the in vitro model and nontargeted analysis. Among them, tributyl phosphate (C12H27O4P), 2-bromotetradecane (C14H29Br), and methyl decanoate (C11H22O2) made greater contributions to the AOs. Finally, we clarified the interactions between these OCs and EMT-activating transcription factors (EMT-ATFs) as the molecular initiation event (MIE) to support the feasibility of the above identification strategy. The present study updates a new framework for identifying tumor metastasis-promoting OCs in PM2.5 and provides solid data for screening out chemicals that need priority control in polluted areas posing higher lung cancer risk.

Real-world data on patients with early breast cancer who were prescribed abemaciclib adjuvant therapy in Japan.

Aim: To understand the real-world use of abemaciclib in Japanese patients with early breast cancer (EBC). Methods: This retrospective observational study was conducted using a Japanese administrative claims database in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative EBC who received abemaciclib adjuvant therapy from December 2021-March 2023. Patient characteristics and treatment patterns were summarized. Results: Among 374 patients, 38.2, 51.6 and 63.4% patients received neoadjuvant chemotherapy, adjuvant chemotherapy and radiotherapy, respectively; 13.1% were chemotherapy naive. Tamoxifen (37.7%), letrozole (35.6%), anastrozole (24.3%) were the commonly prescribed concomitant adjuvant endocrine therapies. Abemaciclib dose reductions were observed in 42.0% patients. Conclusion: Use of abemaciclib for treatment of high-risk EBC was described, which could help inform patient selection and treatment patterns.

Abemaciclib (150 mg twice daily) is prescribed with hormonal therapy for the treatment of early breast cancer (EBC) with high risk of recurrence. We used a big database from Japan that has anonymized information about 44 million patients from 480 hospitals. We aim to describe the characteristics of patients with EBC who receive abemaciclib and their treatment patterns in Japan.We included 374 patients with EBC who had breast cancer surgery and were prescribed abemaciclib with hormonal therapy between December 2021 and March 2023. The median age of patients is 54 years, almost all (99.2%) are female. The most commonly prescribed hormonal therapy with abemaciclib is tamoxifen (37.7%), letrozole (35.6%) and anastrozole (24.3%).Of the 374 patients who were prescribed abemaciclib, 38.2% patients received chemotherapy before surgery, 51.6% received chemotherapy after surgery and 63.4% received radiation therapy after surgery; whereas, 13.1% received no perioperative chemotherapy before abemaciclib therapy. Around 42% of patients reduced their dose from starting dose of abemaciclib. Higher proportion of older patients and patients with low body weight, had dose reduction. Majority of the patients are prescribed either an antidiarrheal agent or probiotic within a day of starting abemaciclib.This is the first study describing patient characteristics and treatment patterns of Japanese patients who are prescribed abemaciclib in the clinical practice. The results will help understand who can benefit from abemaciclib, and to choose the most appropriate patients to receive abemaciclib for the treatment of EBC.

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.

Real-World Patient Characteristics, Treatment Patterns, and Outcomes of HR+, HER2- Early Breast Cancer Patients in Japan: An Analysis with National Database(NDB).

Real-world evidence for clinical outcomes and treatment patterns in patients with hormone receptor-positive(HR+)and human epidermal growth factor receptor 2-negative(HER2-)early breast cancer(EBC)in Japan is limited. We aimed to provide recent evidence in this population using the National Database of Health Insurance Claims and Specific Health Check-ups of Japan(NDB). Adults ≥20 years old who were diagnosed with HR+/HER2- breast cancer and underwent breast resection surgery were followed up. Patient characteristics and treatment patterns were evaluated. Durations of overall post-operative endocrine therapy(ET)and luteinizing hormone-releasing hormone(LH-RH)agonist therapy, and time to metastasis/recurrence after surgery were analyzed using Kaplan-Meier method. Overall, 294,904 patients were included. Cyclophosphamide and tamoxifen were the most common peri-operative chemotherapeutic and ET drugs. Median(95% confidence interval[CI])duration of post-operative ET and LH-RH agonist therapy was 5.01(5.01-5.01)years and 2.13 (2.12-2.14)years, respectively. Five-year cumulative rate(95% CI)of any recurrence was 8.6%(8.5-8.7), visceral metastasis being the most common. Nation-wide treatment patterns were described, which were consistent with guideline recommendations for patients with HR+, HER2- EBC. Further discussion is required to delay metastasis/recurrence and improve clinical outcomes(Fig. 1: Plain language summary of the study).

Patients' Preferences for Attributes of Molecular Targeting Therapies for Advanced Non-Small Cell Lung Cancer with EGFR Mutations in Japan-A Discrete-Choice Experiment.

AIM: This study aims to evaluate Japanese patients' preferences in first-line therapy choice for advanced non-small cell lung cancer(NSCLC)with epidermal growth factor receptor(EGFR)mutations. METHODS: A cross-sectional discrete-choice experiment was conducted on advanced NSCLC patients in Japan. Participants completed the online questionnaire that included different levels of 5 treatment attributes: time to disease progression, chance of rash, next therapy option, frequency of health care visits and administration route. The primary analysis estimated the relative attribute importance. The preferences of EGFR mutation-positive patients were compared with those of EGFR mutation-negative/unknown patients to observe whether preference differs by mutation status. RESULTS: A total of 158 participants completed the survey. The analysis on the overall study population revealed next therapy option(mean relative attribute importance[SD]: 39.30 [17.07])as the most important attribute, followed by time to disease progression(25.52[10.51]), chance of rash(21.58 [11.74]), with administration route(7.63[6.99])and frequency of health care visits(5.96[3.40])the least preferred. The results in the subgroups by EGFR mutation status were similar. CONCLUSION: Next therapy option is the major influencing factor for treatment choice of molecular targeting therapy among advanced NSCLC patients in Japan, emphasizing the importance of communicating the next treatment options to patients at the time of their first treatment.

Assessment of discordance of treatment satisfaction between patients with rheumatoid arthritis in low disease activity or in remission and their treating physicians: A cross-sectional survey.

OBJECTIVES: To assess discordance in overall treatment satisfaction between patients with rheumatoid arthritis (RA) and their physicians. METHODS: This was a multicenter, cross-sectional, observational study of patients with RA (in low disease activity or remission) and their board-certified treating physicians in Japan; 202 patient-physician pairs were analyzed. Treatment satisfaction and perceptions were assessed using a structured questionnaire. RESULTS: Using a two-level ('satisfied' or 'unsatisfied') assessment of satisfaction, 195 patients (96.5%) and 190 physicians (94.1%) answered 'satisfied' with a high level of concordance (184 pairs, 91.1%). Using a four-level assessment, the ratio of 'satisfied' to 'somewhat satisfied' was higher in patients (66.3%/30.2%) than physicians (43.6%/50.5%). Satisfaction with treatment outcomes (e.g. joint conditions, subjective symptoms) was generally high in patients and physicians; relatively less satisfaction was reported for medication cost, especially among patients. Shared treatment decision-making was reported in ≥96% of patient-physician pairs. The most common 'most important' treatment target differed between patients ('Have a social life without worrying about RA') and physicians ('Prevent joint damage, deformity, and joint swelling'). CONCLUSIONS: Treatment satisfaction and concordance were high between patients in low activity/remission and physicians. Some differences between patients and physicians were reported in satisfaction for specific treatment outcomes and important treatment targets.

Dose-finding study of the checkpoint kinase 1 inhibitor, prexasertib, in Japanese patients with advanced solid tumors.

Prexasertib is a novel inhibitor of checkpoint kinase 1. The primary objective of this study was to evaluate prexasertib tolerability in Japanese patients with advanced solid tumors. This nonrandomized single-arm open-label phase 1 study of prexasertib consisted of 2 dose levels, 80 mg/m2 and the global-recommended dose based on a US study of 105 mg/m2 , administered intravenously once every 14 days (n = 6 for each dose). Transition to the higher dose proceeded if the frequency of dose-limiting toxicity observed in cycle 1 was <33% at the lower dose. Safety measures, pharmacokinetics and antitumor activity were assessed. A total of 12 patients were treated. Two patients, one in each dose group, experienced dose-limiting toxicities of febrile neutropenia, one grade 4 and the other grade 3; both patients recovered and continued the study treatment. The grade 4 treatment-emergent adverse events related to study treatment were neutropenia (6 patients [50.0%]), leukopenia (4 patients [33.3%]), and 1 instance each (8.3%) of anemia, febrile neutropenia and thrombocytopenia. Neutropenia was generally transient and reversible; 11 patients (91.7%) required granulocyte colony-stimulating factor treatment during the study. There were no discontinuations due to adverse events or deaths. The prexasertib pharmacokinetics displayed dose-independent and time-independent behavior across both dose levels, similar to the profile observed in the US-based phase 1 study. Eight patients had a best overall response of stable disease. These data are consistent with the known safety profile for prexasertib and confirm its tolerability in Japanese patients with advanced solid tumors.

Efficacy and safety of baricitinib in Japanese patients with active rheumatoid arthritis: A 52-week, randomized, single-blind, extension study.

OBJECTIVES: The objective of this study is to evaluate the efficacy and safety of long-term (64 weeks; 52-week extension of a 12-week study) baricitinib treatment in Japanese patients with active rheumatoid arthritis (RA) despite methotrexate therapy. METHODS: Patients (N = 145) with active RA were randomized to placebo, 1mg, 2mg, 4mg, or 8mg baricitinib for the first 12 weeks. During the 52-week extension period, patients on 4mg or 8mg baricitinib remained on the same dose and all other patients were re-randomized to 4mg or 8mg baricitinib. Most patients on 8mg baricitinib were switched to 4mg by week 64 (protocol amendment); data analysis was based on the treatment group at the beginning of the extension period. RESULTS: Increases in the American College of Rheumatology (ACR) response rates (ACR20, ACR50, and ACR70) observed during the first 12 weeks were maintained during the extension period, accompanied by improvements in ACR core components. At week 64, a large proportion of patients (>40%) had low disease activity. Most treatment-related adverse events were mild or moderate; herpes zoster was the most common reason (11/27 patients) for discontinuation. CONCLUSIONS: The efficacy and safety profile of baricitinib was maintained during long-term treatment of Japanese patients with RA and background methotrexate therapy. Clinicaltrials.gov NCT01469013; Funding: Eli Lilly and Incyte.

Relationship between disease activity and patient-reported outcomes in rheumatoid arthritis: Post hoc analyses of overall and Japanese results from two phase 3 clinical trials.

OBJECTIVE: To examine patient-reported outcomes (PROs) in patients with different rheumatoid arthritis (RA) disease activity levels and identify residual symptoms. METHODS: Post hoc analyses of overall and Japanese data from two randomized controlled trials including RA patients with previous inadequate responses to methotrexate (NCT01710358) or no/minimal previous disease-modifying antirheumatic drug treatment (NCT01711359) (sponsor: Eli Lilly and Company). Week 24 assessments were disease activity (Simplified Disease Activity Index, Disease Activity Score/Disease Activity Score 28 joints-erythrocyte sedimentation rate) and PROs (pain visual analog scale [VAS], morning joint stiffness [MJS], Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue, and Medical Outcomes Study Short Form 36 Health Survey Physical and Mental Component Scores). RESULTS: Patients achieving remission/low disease activity (LDA) at Week 24 had larger/significant improvements from baseline in pain, MJS, disability, fatigue, and physical and emotional quality of life versus patients with high/moderate disease activity. Some patients achieving remission and LDA, reported residual pain (pain VAS >10 mm): 20.8-39.3% and 48.7-70.0% (overall study populations), 16.0-34.5% and 47.1-62.0% (Japanese patients). Residual MJS and fatigue were also reported. CONCLUSION: Remission/LDA were associated with improvements in PROs in overall and Japanese patient populations; however, some patients achieving remission had residual symptoms, including pain.

Determinants of Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity in patients with rheumatoid arthritis: A post hoc analysis of overall and Japanese results from phase 3 clinical trials.

OBJECTIVES: To assess the determinants of Patient's Global Assessment of Disease Activity (PtGA) and Physician's Global Assessment of Disease Activity (PhGA) in overall and Japanese patients with rheumatoid arthritis (RA) from two large randomized controlled trials. METHODS: Post hoc analysis of overall and Japanese RA patients who had previous inadequate responses to methotrexate or who had no/minimal previous disease-modifying antirheumatic drug treatment. We examined correlations between PtGA/PhGA and tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), inflammatory markers, pain visual analog scale (VAS), and other patient-reported outcomes at baseline, Week 12, and Week 24. Determinants of PtGA/PhGA were identified. RESULTS: In overall populations, pain VAS was the main determinant of PtGA, whereas TJC28 was the main determinant of PhGA in both studies. In Japanese populations, consistent with overall populations, pain VAS was the main determinant of PtGA in both studies; in contrast to overall populations, pain VAS and SJC28/TJC28 played an important role in PhGA. CONCLUSION: Pain was the most important determinant of PtGA, whereas determinants of PhGA varied between populations/studies and were mostly explained by pain/joint counts. Physicians should be aware of patients' perceptions of disease activity when performing assessments/prescribing treatments.

Coupling bioleaching and electrokinetics to remediate heavy metal contaminated soils.

In this study, bioleaching was coupled with electrokinetics (BE) to remove heavy metals (Cu, Zn, Cr and Pb) from contaminated soil. For comparison, bioleaching (BL), electrokinetics (EK), and the chemical extraction method were also applied alone to remove the metals. The results showed that the BE method removed more heavy metals from the contaminated soil than the BL method or the EK method alone. The BE method was able to achieve metal solubilization rates of more than 70 % for Cu, Zn and Cr and of more than 40 % for Pb. Within the range of low current densities (<1 mA cm(-2)), higher current density led to more metal removal. However, the metal solubilization rates did not increase with increasing current density when the current density was higher than 1 mA cm(-2). Therefore, it is suggested that bioleaching coupled with electrokinetics can effectively remediate heavy metal-contaminated soils and that preliminary tests should be conducted before field operation to detect the lowest current density for the greatest metal removal.

Enhanced dewaterability of waste-activated sludge by combined cationic polyacrylamide and magnetic field pretreatment.

The potential function of combining magnetic field (MF) pretreatment with cationic polyacrylamide (CPAM) additive on enhancing the dewaterability of waste-activated sludge was investigated in the present work. Two reactors were involved in a specially designed experimental apparatus, one of which was built with MF accessories. Several parameters were conducted, including CPAM dosages, MF strengths and processing times, respectively. Capillary suction time (CST) and specific resistance to filtration (SRF) were used to evaluate sludge dewaterability. Extracellular polymeric substances (EPS) concentration was also determined in an attempt to identify the observed changes in dewaterability. It was indicated by the results that both CPAM conditioning and MF pretreatment on sludge can lower CST and SRF values. However, subjecting to a combination of MF pretreatment and CPAM conditioning, sludge dewaterability was significantly enhanced beyond the level observed of CPAM addition alone. The lowest CST and SRF values of 36.5 s and 0.75×10(12) m kg(-1), respectively, were obtained when sludge was co-conditioned by CPAM (at a dosage of 40 mg L(-1)) and MF (at an induction of 40 mT) for 30 min, suggesting the optimal condition for enhancing sludge dewaterability. It is also shown from the significant correlations between EPS, protein, polysaccharide and CST/SRF that the increment of EPS concentration in sludge supernatant may be the major reason for the enhancement of dewaterability.

Therapy-Related Satisfaction and Quality of Life for Japanese People with Diabetes Using Rapid-Acting Insulin Analogs: A Web-Based Survey.

INTRODUCTION: People with diabetes require insulin to regulate blood glucose (BG); rapid-acting insulin analogs (RAIA) represent one approach for BG management. New fast-acting RAIA administered at the start of a meal suppress postprandial BG better than conventional RAIA. New RAIA are expected to confer higher treatment satisfaction and improved quality of life (QOL) than conventional RAIA. METHODS: This cross-sectional, web-based survey in Japan (November 2022) included people with diabetes (type 1/2), aged ≥ 18 years, registered in the Rakuten Insight Diabetes Panel, using new and/or conventional RAIA. RAIA-specific satisfaction was evaluated by questions on RAIA use (scores: 1 [not at all satisfied]; 7 [very satisfied]) and QOL by the Diabetes Therapy-Related (DTR)-QOL questionnaire (scores: 0-100, 100 = best) for the whole population (primary endpoint) and for new versus conventional RAIA users (secondary endpoint). Multiple regression models were used to compare new versus conventional RAIA users. RESULTS: The analysis population comprised 217 people with diabetes (new RAIA, n = 109; conventional RAIA, n = 108). Mean (standard deviation) RAIA-specific satisfaction scores ranged from 5.1 (1.2) to 5.4 (1.2); DTR-QOL total score was 51.6 (20.4). RAIA satisfaction scores were numerically higher for new versus conventional RAIA users; no difference in DTR-QOL total score was observed. DTR-QOL satisfaction with treatment domain score was significantly higher in new versus conventional RAIA users (least squares mean difference [standard error]: 7.3 [3.1]; 95% confidence interval: 1.2, 13.4; P = 0.0197). RAIA-specific satisfaction was higher among patients who discussed BG sufficiently with their doctor versus those who did not. CONCLUSIONS: New RAIA users have greater treatment satisfaction than conventional RAIA users. QOL was similar among new and conventional RAIA users, except for satisfaction with treatment, which was significantly higher among new RAIA users. Detailed explanations from the doctor to the person with diabetes about the relationship between new RAIA and BG status are essential. A graphical plain language summary is available with this article.

Prevalence of Metabolic Syndrome in Patients with Type 2 Diabetes in Japan: A Retrospective Cross-Sectional Study.

INTRODUCTION: Recent data on the prevalence of metabolic syndrome in Japanese patients with type 2 diabetes (T2D) are limited. METHODS: This retrospective, cross-sectional, observational study investigated the prevalence of metabolic syndrome in patients with T2D using a Japanese administrative claims database. Patients with a T2D diagnosis, prescription of a hypoglycemic agent, and one or more annual health checkups in 2020 were included. Trends in the prevalence of metabolic syndrome by sex and body mass index (BMI) subgroup were assessed. RESULTS: The study cohort consisted of 155,653 patients (men, 81.6%; mean age 54.6 ± 8.5 years). Patients with metabolic syndrome had a higher mean BMI (29.1 ± 4.5 kg/m2 versus 25.2 ± 4.5 kg/m2) and mean waist circumference (98.3 ± 10.0 cm versus 87.9 ± 11.2 cm) compared to those without metabolic syndrome. Overall, the prevalence of metabolic syndrome was 43.0% in patients with T2D, with prevalence higher in men (46.6%) than women (27.0%). The prevalence increased across BMI subgroups from 17.3% in the < 25 kg/m2 subgroup, to 54.6% and 66.1% in the 25 to < 30 and ≥ 30 kg/m2 subgroups, respectively. A greater proportion of patients with metabolic syndrome had cardiovascular or renal comorbidities (BMI < 25, 0.3-2.0%; BMI 25 to < 30, 0.7-6.2%; BMI ≥ 30 kg/m2, 0.7-6.8%) and cardiovascular drug usage (BMI < 25, 1.3-9.0%; BMI 25 to < 30, 3.8-31.1%; BMI ≥ 30 kg/m2, 3.5-37.0%) in the higher BMI subgroups compared to the BMI < 25 kg/m2 subgroup. CONCLUSION: The prevalence of metabolic syndrome in Japanese patients with T2D was 43.0% and increased with higher BMI. In patients with T2D and metabolic syndrome, cardiovascular drug usage and comorbidities increased in patients with a higher BMI. These data highlight the importance of managing metabolic parameters in addition to glycemic control in Japanese patients with T2D, particularly in patients with metabolic syndrome and BMI ≥ 25 kg/m2.

Real-World Evidence of FOLFIRI Combined with Anti-Angiogenesis Inhibitors or Anti-EGFR Antibodies for Patients with Early Recurrence Colorectal Cancer After Adjuvant FOLFOX/CAPOX Therapy: A Japanese Claims Database Study.

BACKGROUND: Oxaliplatin-containing adjuvant regimens (folinic acid, fluorouracil, and oxaliplatin/capecitabine and oxaliplatin [FOLFOX/CAPOX]) are used after curative resection of colorectal cancer (CRC). However, real-world evidence regarding treatment sequences and outcomes in patients with early recurrence CRC after adjuvant chemotherapy is limited. OBJECTIVE: We aimed to describe the patient characteristics, treatment sequence, and overall duration of second-line (2L) therapy in patients with early recurrence CRC who received adjuvant chemotherapy (FOLFOX/CAPOX) followed by folinic acid, fluorouracil, and irinotecan (FOLFIRI) + anti-angiogenesis drugs (AA) or FOLFIRI + anti-epidermal growth factor receptor (EGFR) antibodies. METHODS: This retrospective study analyzed Japanese administrative data from November 2014 to March 2023 of adult patients who underwent CRC resection surgery, started FOLFOX/CAPOX ≤3 months (mo) after surgery, and had early CRC recurrence. Early recurrence was defined as initiation of FOLFIRI+AA or FOLFIRI+anti-EGFR antibodies as 2L therapy, ≤12 mo of discontinuing adjuvant chemotherapy. Patient characteristics, treatment sequence, median time to treatment discontinuation (mTTD), i.e., duration between the start and end dates of 2L therapy (Kaplan-Meier method), and factors associated with 2L time to treatment discontinuation constituted the study outcomes (Cox regression model). Subgroup analyses were performed for timing of early CRC recurrence (≤6 mo and 6-12 mo) and tumor sidedness. RESULTS: Among the 832 selected patients (median age [minimum-maximum] 67 (24-86) years, 56.4% male), CAPOX (71.3%) was more commonly used than FOLFOX (28.7%) as adjuvant therapy. FOLFIRI+AA (72.5%) was used more commonly than FOLFIRI+anti-EGFR antibodies (27.5%) in 2L. AA and anti-EGFR antibodies groups had similar mTTD: 6.2 mo (95% confidence interval 5.8, 6.9) and 6.1 mo (95% confidence interval 5.2, 7.4). Age ≥70 years showed significant association with shorter 2L treatment duration (hazard ratio 1.2, 95% confidence interval 1.0, 1.4; p = 0.03). The AA cohort's mTTD was numerically shorter in the ≤6 mo recurrence subgroup compared with the 6-12 mo recurrence subgroup (6.1 mo vs 8.1 mo); the anti-EGFR antibodies cohort had similar mTTD (5.8 mo vs 6.2 mo). The AA and anti-EGFR antibodies cohorts also had similar mTTD in the left-sided CRC subgroup (6.5 mo vs 6.2 mo), but not in the right-sided subgroup (5.6 mo vs 3.9 mo). CONCLUSIONS: This is the first administrative data-based real-world evidence on treatment sequence and outcomes for patients with early recurrence CRC treated with FOLFIRI+AAs or FOLFIRI+ anti-EGFR antibodies after adjuvant FOLFOX/CAPOX therapy in Japan. Both regimens had similar TTD, but relapse timing and tumor sidedness may influence their efficacy.

Trends of HbA1c and BMI in People with Type 2 Diabetes: A Japanese Claims-Based Study.

INTRODUCTION: Obesity prevalence has increased in Japan in recent years. Given the strong association of obesity with poor glycemic control, and increased risk of type 2 diabetes (T2D) with central obesity, this study describes the current trends and relationships between glycated hemoglobin (HbA1c), body mass index (BMI), and waist circumference in the Japanese people with T2D. METHODS: This was a retrospective, cross-sectional study of people with T2D who had at least one recorded HbA1c and BMI (or waist circumference) value in the Japan Medical Data Center Claims database. Five annual cohorts of the study population were formed between January 2017 and December 2021. Annual trends of HbA1c across BMI categories (obesity class I [≥ 25 ~ < 30 kg/m2]-IV [≥ 40 kg/m2]) and in people with central obesity (waist circumference: ≥ 85 cm in men; ≥ 90 cm in women) were described by sex and age groups. RESULTS: Overall, 106,089 people with T2D (HbA1c and BMI data: 106,079; HbA1c and waist circumference data: 105,424) were included, with the majority of people belonging to obesity class I (range: 39.7-40.6%) and obesity class II (range: 16.2-17.7%) categories across all annual cohorts. People in higher BMI categories had higher mean HbA1c, with > 50% of people with T2D in obesity class I-IV (54.8-56.5%) having HbA1c ≥ 7%. Between 2017 and 2021, BMI and waist circumference increased in the age group 18-44 years. More than 50% of people with T2D and central obesity in both sexes and people of age group 18-44 years across obesity class I-IV or with central obesity had HbA1c ≥ 7%. CONCLUSION: More than half of the people with T2D belonging to obesity class I-IV or central obesity had poor glycemic control (HbA1c ≥ 7%), especially in the 18-44 age group. This highlights the need for body weight management for better glycemic control in relatively young Japanese people with T2D and obesity.

Risk factors for recurrence in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer in Japan: a systematic literature review and meta-analysis.

BACKGROUND: The clinicopathological factors indicating risk of recurrence are used to guide the choice of perioperative therapy in patients with breast cancer. Although several risk factors for recurrence have been reported in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer in Japan, there has been no systematic review quantifying potential risk factors. METHODS: We performed a systematic literature review and meta-analysis using the MEDLINE, Embase, Cochrane CENTRAL, and Japan Medical Abstract Society databases to identify risk factors for recurrence in HR+/HER2- early breast cancer in Japan. The primary outcome was relapse-free or disease-free survival (RFS/DFS), and the secondary outcomes were overall survival and breast cancer-specific survival (BCSS). RESULTS: Searches identified 42 eligible publications. Meta-analyses identified lymph node metastasis (hazard ratio: 2.76 [95% confidence interval: 1.97-3.88]), large tumor size (1.67 [1.24-2.23]), high histological grade (1.50 [1.04-2.16]), and high nuclear grade (2.02 [1.61-2.54]) as risk factors for RFS/DFS. Lymph node metastasis (2.43 [1.28-4.63]), large tumor size (1.80 [1.24-2.62]), and high histological grade (2.02 [1.44-2.84]) were also risk factors for overall survival, and high progesterone status was a possible favorable prognostic factor for BCSS (0.20 [0.10-0.42]). CONCLUSIONS: Identified risk factors were consistent with the previous reports, and this study provides quantitative summary of risk factors for HR+/HER2- early breast cancer recurrence in Japan. (PROSPERO Registration ID, CRD42022338391.).

Comparison of two ethnic populations using distribution adjusted mean.

In similarly designed clinical trials conducted in different regions or a multiregional trial, we sometimes observe different mean responses between trials or regions due to differences in distributions of an ethnic factor. Uesaka et al. ( 2003 ) used adjusted means for covariate, the distribution adjusted mean, to deal with such a situation. This paper examines distributional properties of the distribution adjusted mean and shows its applicability to comparison of mean responses from clinical trials where the distribution of an ethnic factor is different between regions. A real example and simulation results are shown. The results of this paper enable us to evaluate the similarity of different responses in clinical trials from different ethnic populations.

Multikinase Inhibitor Treatment Patterns for Advanced Thyroid Cancer in Japan: An Administrative Claims Database Study.

BACKGROUND: The multikinase inhibitors (MKIs) sorafenib, lenvatinib, and vandetanib are approved for advanced thyroid cancer (TC) in Japan. How sequential treatment with MKIs is conducted in Japanese clinical practice is unknown. METHODS: This retrospective observational cohort study used a Japanese administrative claims database (April 2008-September 2021). Patients with a confirmed TC subtype diagnosis of papillary (PTC), follicular (FTC), medullary (MTC), or anaplastic (ATC), who received MKI treatment after TC diagnosis within the index period (June 2014-August 2021), were included. Overall MKI treatment duration was estimated by Kaplan-Meier analysis. RESULTS: The analysis population included 795 patients (PTC, N = 447; FTC, N = 86; MTC, N = 32; ATC, N = 230). Median age was ≥ 64 years; most patients (> 60%) were female except for the MTC subgroup (43.8%). First-line (1L) MKI treatment was mainly lenvatinib for PTC (81.7%), FTC (83.7%), and ATC (97.8%), and vandetanib for MTC (62.5%). Among patients discontinuing 1L MKI treatment and evaluable for subsequent therapy [PTC: 57.9% (259/447); FTC: 48.8% (42/86); MTC: 62.5% (20/32); ATC: 70.4% (162/230)], 26.3% (68/259), 21.4% (9/42), 50.0% (10/20), and 4.9% (8/162) of PTC, FTC, MTC, and ATC patients, respectively, received second-line (2L) treatment. Median (95% CI) overall MKI treatment duration was 21.2 (17.9-27.5), 43.9 (30.9-not assessable), 39.0 (17.7-not assessable), and 4.0 (3.0-4.8) months for PTC, FTC, MTC, and ATC, respectively. CONCLUSION: Advanced TC treatment options are limited. In this study, most patients received only 1L MKI treatment; of those who discontinued 1L, ≤ 50% progressed to 2L.

Treatment persistence of interleukin-17 inhibitor class drugs among patients with psoriasis in Japan: a retrospective database study.

BACKGROUND AND OBJECTIVE: Real-world evidence on persistence of interleukin-17 inhibitors (IL-17i) as a drug class among Japanese patients with psoriasis is lacking. Hence, we aimed to describe persistence rates of IL-17is among patients with psoriasis including psoriasis vulgaris (PsO), psoriatic arthritis (PsA), and generalized pustular psoriasis (GPP) or erythrodermic psoriasis (EP) in Japan. METHODS: We analyzed claims data from the Medical Data Vision database. Patients ≥15 years old with a psoriasis diagnosis and an IL-17i prescription between November 2016 and August 2020 were included and followed through August 2021. Persistence rates of the IL-17i class among patients with psoriasis and its subtypes (PsO, PsA, and GPP or EP), and persistence rates of ixekizumab, secukinumab, or brodalumab among patients with PsO or PsA were analyzed using Kaplan-Meier method. Analyses were conducted in the bio-naïve and bio-experienced subgroups. RESULTS: The IL-17i class had >50% persistence rates up to 36 months among patients with psoriasis and its subtypes (PsO, PsA, and GPP or EP). 36-Month persistence rates for ixekizumab, secukinumab, and brodalumab were 46.2% to 57.7% in patients with PsO and 43.0% to 48.4% in patients with PsA. Across analyses, bio-naïve patients demonstrated similar or greater persistence rates than bio-experienced patients. CONCLUSION: IL-17is' persistence rates over 36 months were >50% among patients with psoriasis and its subtypes (PsO, PsA, and GPP or EP) in Japan.