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.

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.

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.).

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.

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.

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.

Treatment patterns in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma post covalent Bruton tyrosine kinase inhibitor treatment: a Japanese claims database study.

Standard treatment has not been established for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after discontinuation of covalent Bruton tyrosine kinase inhibitor (cBTKi) therapy. This retrospective, administrative database (Medical Data Vision) study described the patient characteristics, treatment patterns, and factors associated with receiving post-first-cBTKi treatment in Japanese patients with CLL/SLL. Patients aged ≥18 years with confirmed CLL/SLL diagnosis and treated with anti-neoplastic drugs indicated for CLL/SLL between March 2013 and February 2022 were included. Patient characteristics at baseline (first line), first cBTKi exposure (first-cBTKi), post-first-cBTKi treatment received, and the treatment sequence of CLL drugs received first line through third line, were described. Time-to-event analyses used the Kaplan-Meier method. Multivariable logistic regression analysis was used to explore factors associated with receiving post-first-cBTKi treatment among patients who discontinued first-cBTKi treatment. Among 2,424 eligible patients (median age: 72.0 years, 61.9% male), 450 (18.6%) received cBTKi in any treatment line. Among patients treated with cBTKi, 273 (60.7%) discontinued treatment; 56.0% of them (n = 153/273) received subsequent treatment. Median duration of post-first-cBTKi treatment was 2.2 months (95% confidence interval [CI]: 1.8, 3.5). The most common regimens post-first-cBTKi were cBTKi therapy (47.7%), bendamustine-based therapy (17.0%), and venetoclax-based therapy (13.1%). Patients aged <75 years (odds ratio [OR] [95% CI]: 2.0 [1.2, 3.4]) and those who did not receive blood transfusion during cBTKi treatment (OR [95% CI]: 2.3 [1.3, 4.1]) were more likely to receive post-first-cBTKi treatment. In conclusion, Japanese patients with CLL/SLL received various treatments for short duration after first-cBTKi discontinuation.

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.

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.

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.

Outcomes for Recurrent Mantle Cell Lymphoma Post-Ibrutinib Therapy: A Retrospective Cohort Study from a Japanese Administrative Database.

INTRODUCTION: Treatment options in patients with mantle cell lymphoma (MCL) failing ibrutinib are limited, with no standard therapies defined. This study aimed to investigate real-world treatment patterns and outcomes for patients with MCL following ibrutinib. METHODS: This study utilized a de-identified hospital-based claims database (Medical Data Vision) in Japan. Eligible patients were adults who were diagnosed with MCL and had received antitumor drugs between December 2010 and July 2020. Patients were followed from the first antitumor drug treatment until the end of available data up to July 2021. Time-to-event analyses utilized the Kaplan-Meier method. Factors for receiving post-ibrutinib therapy were explored with logistic regression analysis. RESULTS: Of the 1386 patients who started antitumor drug therapy, 247 patients received and discontinued ibrutinib at any line of therapy. Among them, 137 patients (55.5%) received subsequent therapy. The median age at the end of ibrutinib therapy was 77 (range 42-95), and 44 patients had a dependent activity of daily living (ADL). Factors negatively associated with receiving post-ibrutinib therapy after discontinuation of ibrutinib were age ≥ 75 years (odds ratio [95% CI] 0.46 [0.26-0.80]) and emergency hospital admissions (0.37 [0.17-0.84]). Immediate post-ibrutinib therapy regimens were highly diverse, with BR (bendamustine, rituximab) only prescribed in more than 10% of patients. The median duration of post-ibrutinib therapy was 1.5 months (95% CI 1.07-2.07). The median overall survival from the end of ibrutinib therapy in patients regardless of the receipt of post-ibrutinib therapy (n = 247), in those who did not receive post-ibrutinib therapy (n = 110), and in those who received post-ibrutinib therapy (n = 137) was 5.6 months (95% CI 3.8-8.7), 2.3 months (95% CI 1.2-3.9), and 8.7 months (95% CI 5.6-13.8), respectively. The most common adverse event during post-ibrutinib therapy was infection, with the use of anti-infectives (17%). CONCLUSIONS: Patients with MCL previously treated with ibrutinib have poor ability to carry out ADL and experience very poor outcomes. New safe, effective therapies are needed.

Real-World Data Analysis of Second-Line Antiangiogenic Targeted Treatments Following Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies and First-Line FOLFOX for Patients with Metastatic Colorectal Cancer.

INTRODUCTION: Evidence is lacking on second-line and later treatments for patients with RAS wild-type colorectal cancer (CRC) who receive first-line anti-epidermal growth factor receptor (EGFR) antibody therapy. In this study, we explored the real-world treatment sequences, treatment duration, and factors associated with treatment sequences and durations in Japanese patients with CRC. METHODS: This retrospective observational cohort study used a Japanese administrative claims database (April 2008 to July 2021). Patients with confirmed CRC (presumed RAS wild-type) who received first-line FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) plus anti-EGFR therapy in or after May 2016, followed by second-line irinotecan-based chemotherapy plus an antiangiogenic drug, were included. Treatment durations were estimated by the Kaplan-Meier method. Cox regression analysis was used to identify factors associated with treatment duration. RESULTS: Analysis populations consisted of 1163 (first-line and second-line) and 645 (third-line) patients. At the start of first-line therapy, 67.8% of patients were male, the mean age was 64 years, 83.4% had left-sided CRC, and 84.3% were prescribed FOLFOX plus panitumumab. For second-line therapy, patients were prescribed bevacizumab (63%), ramucirumab (27%), or aflibercept beta (10%). Median (95% CI) treatment durations from the start of second-line therapy to the end of antitumor drug therapies were similar for bevacizumab (12.5 months [11.2, 14.0]), ramucirumab (12.5 months [11.2, 14.8]), and aflibercept beta (14.0 months [10.4, 17.0]). Treatment duration from second-line was positively associated with first-line treatment duration of 6 months or more, CRC surgery before starting first-line therapy, and liver surgery during first-line therapy, and was negatively associated with use of nonsteroidal anti-inflammatory drugs before second-line therapy. CONCLUSION: Real-world data revealed that all three antiangiogenic drugs were used as second-line therapy after first-line anti-EGFR antibodies and showed similar treatment durations.

Current status of shared decision making for rheumatoid arthritis treatment in Japan: a web-based survey on physicians and patients.

OBJECTIVE: To assess the current status of shared decision making (SDM) in rheumatoid arthritis (RA) clinical practice in Japan from the perspectives of physicians and patients. METHODS: A web-based survey was conducted to recruit patients with RA who were prescribed, for the first time, a conventional synthetic disease-modifying antirheumatic drug (csDMARD) or a biological drug/Janus kinase (JAK) inhibitor, and physicians who prescribed these treatments to patients with RA. The SDM Questionnaire-Physician version (SDM-Q-Doc) and the 9-item SDM Questionnaire (SDM-Q-9) were used to assess the SDM levels of physicians and patients, respectively. The scale ranged from 0 to 100, and higher scores indicated better SDM status. RESULTS: The responses from 107 physicians who treat patients with RA, 107 patients prescribed a csDMARD, and 110 patients prescribed a biological drug/JAK inhibitor were collected. The mean SDM score for SDM-Q-Doc was 74.5 when physicians decided to prescribe a csDMARD and 77.2 when they decided to prescribe a biological drug/JAK inhibitor. However, the mean SDM score for SDM-Q-9 was 62.3 when patients were prescribed csDMARDs and 72.6 when they were prescribed biological drugs/JAK inhibitors. CONCLUSIONS: The results showed differences in SDM level between patients and physicians and, from the patient perspective, between treatment types.

Rheumatoid arthritis (RA) is a long-term disease that causes swelling and pain, mainly in the joints of the hands and feet. Because RA cannot be cured, treatment usually continues for a long time. Shared decision making (SDM) involves people and their doctors deciding on the best treatment together. This study was done to understand how SDM is used for RA treatment in Japan. We sent one survey to 107 doctors who treat RA and a different survey to 217 people with RA. Each survey asked the doctors or the people with RA to score, on a scale of 0 to 100, how involved the person with RA was in making the decision on what treatment to use. A higher score meant more involvement in SDM. Doctors gave higher SDM scores than people with RA did, which meant doctors thought there was more SDM than what people with RA thought. This was true whether the person started treatment with a conventional RA drug or a newer RA drug (biological/JAK inhibitor). However, for both doctors and people with RA, the SDM scores were higher when a newer drug was used than when a conventional drug was used. This may be because the newer drugs are often prescribed for people with more severe RA or because there are more treatment types available. This was the first study to look at SDM in RA treatment in Japan. Increasing SDM will help improve treatment satisfaction in people with RA and increase patient-centered medical care.[Figure: see text].

Treatment Pattern for Advanced Gastric Cancer in Japan and Factors Associated with Sequential Treatment: A Retrospective Administrative Claims Database Study.

INTRODUCTION: Clinical trials have proven the efficacy and safety of new therapies for advanced gastric cancer (AGC), but how those therapies are used in the real world is poorly described. Real-world treatment patterns of antitumor therapies and factors associated with overall therapy duration in patients with AGC in Japan were investigated. METHODS: This retrospective cohort study used a Japanese administrative claims database (June 2014 to September 2019). Patients with AGC who started the guideline-recommended first-line combination regimens with platinum and fluoropyrimidine agents between June 2015 and July 2019 were included. Cox regression analysis was performed to identify factors associated with overall therapy duration (first line to last administration of guideline-listed agent). RESULTS: Of the 10,581 patients included, the most common first-line combination regimen without trastuzumab was S-1 plus oxaliplatin (4327/9069 patients; 47.7%) and with trastuzumab was capecitabine plus cisplatin (608/1512 patients; 40.2%). Most common second- and third-line regimens were ramucirumab plus taxane (3650/5358 patients; 68.1%) and nivolumab (1229/2390 patients; 51.4%), respectively. Factors positively associated with longer overall therapy duration were: oral fluoropyrimidine in first line (hazard ratio [95% confidence interval]: 0.63 [0.57-0.69]); trastuzumab in any line (0.73 [0.68-0.78]); treatment at a designated cancer hospital (0.89 [0.84-0.94]); dietary consultation within 1 month before/after start of first line (0.92 [0.86-0.98]); and treatment at a surgical department (0.94 [0.89-0.99]). Negatively associated factors were: edema (1.21 [1.07-1.37]); physical therapy (1.21 [1.12-1.31]); nutritional intervention (1.21 [1.14-1.28]) within 1 month before/after start of first line; thrombosis (1.13 [1.04-1.23]); renal disease (1.11 [1.02-1.21]); age (1.07 [1.02-1.13]); and peritoneal metastasis/ascites (1.06 [1.01-1.13]). CONCLUSIONS: In real-world treatment practice for AGC in Japan, therapy choice after the recommended first-line chemotherapy was consistent with guidelines. Factors associated with overall therapy duration were identified, which may assist in optimizing treatment sequence.

Association of Albumin-Bilirubin Grade and Sequential Treatment with Standard Systemic Therapies for Advanced Hepatocellular Carcinoma: A Retrospective Cohort Study Using a Japanese Administrative Database.

BACKGROUND: Evidence about the relationship between albumin-bilirubin (ALBI) grade and sequential systemic therapy for advanced hepatocellular carcinoma in real-world Japanese clinical practice is limited. OBJECTIVE: The objective of this study was to investigate ALBI grades and sequential treatment for advanced hepatocellular carcinoma in Japanese clinical practice. METHODS: We conducted a retrospective cohort study using a Japanese hospital-based administration database to assess treatment sequence in patients with confirmed advanced hepatocellular carcinoma and first prescription (index line) of lenvatinib (July 2014-June 2019; N = 1558) or sorafenib (July 2014-June 2016 [sorafenib-A; N = 1511] or June 2017-June 2019 [sorafenib-B; N = 1276]). Transition to subsequent line was assessed in patients who completed the index line without transarterial chemoembolization. The ALBI grade and sequential treatment relationships were analyzed in patients with baseline and/or end of index line ALBI scores. RESULTS: Transition to a subsequent line was low (sorafenib-A [n = 1320]: 12.6%; sorafenib-B [n = 1049]: 40.7%; lenvatinib [n = 786]: 27.2%). In patients with baseline ALBI data (combined cohorts; n = 385), overall treatment duration was shorter in those with baseline ALBI grade 2b or 3 vs grade 1 or 2a (median: 7.1, 6.7, 4.5, and 3.0 months for grades 1, 2a, 2b, and 3, respectively). In patients with baseline and end of index line ALBI data (combined cohorts; n = 222), ALBI grade worsened during index line regardless of baseline grade. Of these patients in the sorafenib-B or lenvatinib cohorts who completed the index line without transarterial chemoembolization (n = 120), transition to a subsequent line was higher with the end of index line grade 1/2a (66.7/68.4%) than with grade 2b/3 (34.0/11.1%). CONCLUSIONS: Adequate liver function, indicated by ALBI grade, at the start and end of first-line treatment is associated with successful sequential therapy in Japanese clinical practice.

Which patient-reported outcomes do rheumatology patients find important to track digitally? A real-world longitudinal study in ArthritisPower.

BACKGROUND: Patient-reported outcomes (PROs) are increasingly used to track symptoms and to assess disease activity, quality of life, and treatment effectiveness. It is therefore important to understand which PROs patients with rheumatic and musculoskeletal disease consider most important to track for disease management. METHODS: Adult US patients within the ArthritisPower registry with ankylosing spondylitis, fibromyalgia syndrome, osteoarthritis, osteoporosis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus were invited to select between 3 and 10 PRO symptom measures they felt were important to digitally track for their condition via the ArthritisPower app. Over the next 3 months, participants (pts) were given the option to continue tracking their previously selected measures or to remove/add measures at 3 subsequent monthly time points (month [m] 1, m2, m3). At m3, pts prioritized up to 5 measures. Measures were rank-ordered, summed, and weighted based on pts rating to produce a summary score for each PRO measure. RESULTS: Among pts who completed initial selection of PRO assessments at baseline (N = 253), 140 pts confirmed or changed PRO selections across m1-3 within the specified monthly time window (28 days ± 7). PROs ranked as most important for tracking were PROMIS Fatigue, Physical Function, Pain Intensity, Pain Interference, Duration of Morning Joint Stiffness, and Sleep Disturbance. Patient's preferences regarding the importance of these PROs were stable over time. CONCLUSION: The symptoms that rheumatology patients prioritized for longitudinal tracking using a smartphone app were fatigue, physical function, pain, and morning joint stiffness.

Treatment sequences of patients with advanced colorectal cancer and use of second-line FOLFIRI with antiangiogenic drugs in Japan: A retrospective observational study using an administrative database.

The objectives were to describe treatment sequences for advanced colorectal cancer (CRC), use of second-line FOLFIRI (leucovorin, 5-fluorouracil, irinotecan) plus antiangiogenic drug (bevacizumab, ramucirumab, aflibercept beta) therapy, and the factors associated with the duration of antitumor drug treatment from second-line antiangiogenic therapy in Japan. This retrospective observational study was conducted using a Japanese hospital-based administrative database. Patients were enrolled if they started adjuvant therapy (and presumably experienced early recurrence) or first-line treatment for advanced CRC between May 2016 and July 2019, and were analysed until September 2019. Factors associated with overall treatment duration from second-line treatment with FOLFIRI plus antiangiogenic drugs were explored with multivariate Cox regression analysis. The most common first-line treatments were FOLFOX (leucovorin, 5-fluorouracil, oxaliplatin) or CAPOX (capecitabine, oxaliplatin) with bevacizumab (presumed RAS-mutant CRC) and FOLFOX with panitumumab (presumed RAS-wild type CRC). The most common second-line treatments were FOLFIRI-based. Many patients did not transition to subsequent lines of therapy. For second-line treatment, antiangiogenic drugs were prescribed more often for patients with presumed RAS-mutant CRC, right-sided CRC, and independent activities of daily living (ADL). The median duration of second-line FOLFIRI plus antiangiogenic drug treatment was 4.5 months; 66.2% of patients transitioned to third-line therapy. Low body mass index and not fully independent ADL were significantly associated with shorter overall duration of antitumor drug treatment from second-line therapy. Left-sided CRC, presumed RAS-wild type CRC, previous use of oral fluoropyrimidines and use of proteinuria qualitative tests, antihypertensives, or anticholinergics during second-line therapy were significantly associated with longer treatment. Treatment of advanced CRC in Japan is consistent with both international and Japanese guidelines, but transition rates to subsequent therapies need improvement. In addition to antitumor drug treatment, better ADL, higher body mass index, management of hypertension, and proteinuria tests were associated with continuation of sequential therapy that included antiangiogenic drugs.

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.