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Aim: To evaluate real-world treatment patterns, survival and healthcare-resource utilization in US patients with advanced biliary tract cancers (BTC) receiving systemic therapy. Patients & methods: This study used claims data from the Healthcare Integrated Research Database (HIRD®) linked to clinical data from the Cancer Care Quality Program (January 1, 2015–September 30, 2020). Results: Of 413 patients, 84.5% received gemcitabine-based first-line (1L) treatment, 46% received second-line treatment, and 16.5% received third-line (3L) treatment. All-cause mortality was 53% and approximately 70% of patients had ≥1 inpatient visit. The total mean per-patient-per-month all-cause costs were $19,589 for 1L and $33,534 for 3L treatment. Conclusion: Results showed poor survival, significant resource use and high costs as treatment line progresses for patients with advanced BTC. Plain Language Summary Our research explored which treatments US patients with advanced biliary tract cancers (BTC) received and how long they lived for. We analyzed information from a US database, called the Healthcare Integrated Research Database (HIRD®), which holds information related to healthcare insurance claims. Out of 413 patients in the database, 84.5% were initially given a combination treatment involving a chemotherapy called gemcitabine. We also found that 46% of patients received a type of second treatment (also known as second-line therapy), and 16.5% received a third treatment (third-line therapy). During treatment, around 70% of patients needed to stay in hospital at least once. The cost of healthcare was more expensive for patients receiving later lines of therapy, with the average monthly cost per patient for first-line treatment being $19,589 and third-line treatment being $33,534. Furthermore, just over half of the 413 patients died from any causes, showing the poor outlook these patients face. This information is important for understanding the real-world management of patients with BTC, so that their care can be improved in the future. Article highlights This study evaluated real-world treatment patterns, survival, healthcare-resource utilization (HCRU) and costs in patients with advanced biliary tract cancers (BTC) receiving systemic therapy in the US before the recent approval of immuno-oncology (IO)-based regimens. The study was an observational, retrospective cohort study among adults with advanced BTC, identified through medical and pharmacy claims from the Healthcare Integrated Research Database (HIRD®), linked to clinical data from the Cancer Care Quality Program (CCQP). Among 413 patients included in the study, 84.5% of patients received gemcitabine-based first-line (1L) therapy, 46% of patients received a second-line therapy and 16.5% received a third-line (3L) therapy. All-cause mortality was 53% with a median survival of 11.5 months. Approximately 70% of patients had ≥1 inpatient visit and hospitalization was the key driver for HCRU. The total mean per-patient-per-month, all-cause cost increased with progression of line of treatment from 1L treatment ($19,589) to 3L treatment ($33,534). The results highlight poor patient outcomes coupled with high HCRU and costs before the recent approval of IO-based regimens, indicating the need for novel treatment options. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate the predictive factors for persistent disease activity following anti-vascular endothelial growth factors (anti-VEGF) and their long-term effects in patients to be treated for neovascular age-related macular degeneration (nAMD) under real-world conditions. Methods: Retrospective data analysis of the PROOF study, a multi-center real-world retrospective chart review conducted across Korea in patients with nAMD included treatment-naive patients with nAMD who received first anti-VEGF (ranibizumab, bevacizumab, or aflibercept) between January 2017 and March 2019 was performed. All 600 patients (cohort 1) had a minimum follow-up of 12 months of which 453 patients (cohort 2) were followed-up for 24 months from baseline. Results: At month 12 after anti-VEGF therapy, 58.10% (95% confidence interval [CI]: 54.09, 62.12) of patients and at month 24, 66.02% of patients continued to have persistent retinal fluid. At both months 12 and 24, predictive factors for persistent disease activity were fibrovascular pigment epithelial detachments (PED) (P = 0.0494) and retinal fluid at month 3 after loading phase (P = 0.0082). The mean changes in visual acuity were + 6.2, + 10.1, and + 13.3 letters and in the central subfield thickness were − 79.1 µm, − 96.3 µm, and − 134.4 µm at 12 months from baseline, in the bevacizumab, aflibercept, and ranibizumab groups, respectively. Conclusions: The presence of retinal fluid after loading phase and fibrovascular PED were predictors of persistent disease activity after at least 1 year of anti-VEGF treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma is the most common type of liver cancer and is often seen in people with chronic liver diseases. For patients with hepatocellular carcinoma who cannot receive surgery, other treatments include atezolizumab plus bevacizumab, sorafenib, or lenvatinib. We compared the length of life among 1874 United States veterans who received these therapies, both in the overall population of patients and in groups by race/ethnicity. The results showed that the risk of death was 30% lower with atezolizumab plus bevacizumab compared with sorafenib, and 26% lower compared with lenvatinib. These trends were consistent across White, Black, and Hispanic patients. Thus, patients who received atezolizumab plus bevacizumab had improved survival outcomes compared with those treated with sorafenib or lenvatinib, regardless of race or ethnicity. Background/Objectives: This study evaluated comparative overall survival (OS) of United States veterans with unresectable hepatocellular carcinoma (uHCC) receiving first-line (1L) atezolizumab plus bevacizumab vs. sorafenib or lenvatinib, overall and across racial and ethnic groups. Methods: In this retrospective study, patients with uHCC who initiated atezolizumab plus bevacizumab (post-2020) or sorafenib or lenvatinib (post-2018) were identified from the Veterans Health Administration National Corporate Data Warehouse (1 January 2017–31 December 2022). Patient characteristics were evaluated in the year prior to 1L treatment initiation. Kaplan–Meier and multivariable Cox regression methods were used to compare OS starting from treatment between cohorts, both overall and by race and ethnicity. Results: Among the 1874 patients included, 405 (21.6%) received 1L atezolizumab plus bevacizumab, 1016 (54.2%) received sorafenib, and 453 (24.2%) received lenvatinib, with a median follow-up time of 8.5, 7.6, and 8.2 months, respectively. Overall, patients receiving atezolizumab plus bevacizumab had longer unadjusted median OS (12.8 [95% CI: 10.6, 17.1] months) than patients receiving sorafenib (8.0 [7.1, 8.6] months) or lenvatinib (9.5 [7.8, 11.4] months; both log-rank p < 0.001). After adjustment, atezolizumab plus bevacizumab was associated with a reduced risk of death by 30% vs. sorafenib (adjusted HR: 0.70 [95% CI: 0.60, 0.82]) and by 26% vs. lenvatinib (0.74 [0.62, 0.88]; both p < 0.001). OS trends in the White, Black, and Hispanic patient cohorts were consistent with that of the overall population. Conclusions: Atezolizumab plus bevacizumab was associated with improved survival outcomes compared with sorafenib and lenvatinib in patients with uHCC, both overall and across racial and ethnic subgroups. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the real-world efficacy and safety of combining pembrolizumab, a novel immunotherapy agent, with chemotherapy in early-stage triple-negative breast cancer treatment. We specifically aimed to validate clinical trial results in routine practice. A total of 108 Turkish patients receiving neoadjuvant therapy were examined. The combined regimen demonstrated high efficacy, with 64% of patients achieving pathological complete response, and exhibited generally favorable safety profiles with predominantly mild adverse events. These findings support the use of this combination as a standard treatment for this aggressive breast cancer subtype. However, the results underscore the need for further research to identify optimal patient selection criteria, which can inform oncologists' decision-making and potentially enhance outcomes for patients with triple-negative breast cancer. Background/Objectives: Following the results of the phase 3 KEYNOTE-522 trial, the U.S. Food and Drug Administration approved pembrolizumab, a humanized IgG4 kappa monoclonal antibody, in combination with neoadjuvant chemotherapy as a new standard of care for high-risk early-stage triple-negative breast cancer (TNBC). This retrospective, multicenter study in Türkiye assessed the real-world efficacy and safety of neoadjuvant pembrolizumab combined with chemotherapy in early-stage TNBC. Methods: The study included 108 patients treated between 2021 and 2023 across 14 oncology centers. Three distinct neoadjuvant regimens incorporating pembrolizumab were administered at the discretion of the treating physicians. The primary outcomes were the pathological complete response (pCR) rate after neoadjuvant therapy and the 2-year event-free survival (EFS) and overall survival (OS) rates. Results: The observed pCR rate was 63.9%, closely mirroring the 64.8% reported in the KEYNOTE-522 trial. At the two-year mark, the EFS rate was 87.2% and the OS rate was 92.3%. Multivariable analysis identified pCR as the sole independent predictor of both EFS and OS. The safety profile was consistent with previous clinical trial data, with most adverse events being of grade 1–2 in severity. Conclusions: These findings provide valuable real-world confirmation of the efficacy and safety of neoadjuvant pembrolizumab–chemotherapy in early-stage TNBC, complementing evidence from randomized trials. [ABSTRACT FROM AUTHOR]

Background: Low-intensity psychological interventions may be a cost-effective, accessible solution for treating depression and anxiety in patients with long-term conditions, but evidence from real-world service settings is lacking. This study examined the effectiveness of low-intensity psychological interventions provided in the Improving Access to Psychological Therapies programme in England for patients with and without long-term conditions. Methods: A retrospective analysis was conducted on patients (total N = 21,051, long-term conditions n = 4024) enrolled in three low-intensity psychological interventions, i.e. Internet-delivered cognitive behavioural therapy (iCBT), guided self-help (GSH), and psychoeducational group therapy (PGT) within a Talking Therapies service from 2016 to 2020. Primary outcomes included pre–post-treatment changes in depression (Patient Health Questionnaire-9) and anxiety (Generalised Anxiety Disorder-7). Results: Overall, both cohorts significantly improved on all outcomes post-treatment, with large effect sizes. Patients with long-term conditions experienced a greater reduction in depression while those without experienced a greater reduction in anxiety, but these differences were marginal (< 1 score difference on both measures). No difference between the cohorts was shown when comparing the differential effectiveness across interventions, but those engaging in iCBT showed greater reduction in depression and anxiety than those in GSH and PGT, while those in GSH improved more than PGT. Conclusions: Low-intensity psychological interventions, particularly iCBT, were effective in treating depression and anxiety in patients with long-term conditions in a real-world service setting. Our large-scale study supports the continued and increased implementation of low-intensity psychological interventions for this subpopulation via integrated care. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to evaluate the efficacy and safety of escalating the dosage of intravitreal brolucizumab in patients with refractory neovascular age-related macular degeneration (AMD). Methods: This retrospective study included 17 eyes of 17 patients with refractory AMD treated with high-dose brolucizumab (12 mg/0.1 ml) for over 12 months. Patients initially received at least one anti-vascular endothelial growth factor (anti-VEGF) agent and were switched to standard-dose brolucizumab (6 mg/0.05 ml). Those who showed a suboptimal response to standard-dose treatment had their dosage of brolucizumab escalated. Results: Visual acuity was maintained from 68.3 ± 3.4 letters to 70.7 ± 3.2 letters after 12 months of high-dose treatment (P = 0.128). Central subfield thickness was 343.7 ± 17.0 μm before high-dose treatment and 316.7 ± 18.5 μm at 12 months (P = 0.083). The proportions of patients with subretinal fluid and serous pigment epithelial detachment significantly decreased from 82.4% to 41.2% and from 52.9% to 17.6%, respectively, after high-dose treatment (P = 0.039 and P = 0.031, respectively). The treatment interval extended from 7.2 ± 2.4 weeks to 10.2 ± 2.2 weeks after switching to standard-dose brolucizumab (P < 0.001) and was maintained at 13.5 ± 2.8 weeks after increasing the dose (P = 0.154). No severe ocular adverse events were observed. Conclusions: High-dose brolucizumab was effective in patients who did not respond to standard-dose brolucizumab after switching from previous anti-VEGF agents. Increasing the dosage could offer sustained disease control and reduce the treatment burden for patients with refractory AMD. [ABSTRACT FROM AUTHOR]

Background and objective: Multiple randomized controlled studies have shown that pirfenidone and nintedanib are effective and safe for treating idiopathic pulmonary fibrosis. This study aimed to evaluate their efficacy, safety, and tolerability in a real-world setting. Methods: We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases for real-world studies published up to March 3, 2023, on pirfenidone and nintedanib for idiopathic pulmonary fibrosis. Results: A total of 74 studies with 23,119 participants were included. After 12 months of treatment, the change from baseline in percent predicted FVC (%FVC) was − 0.75% for pirfenidone and − 1.43% for nintedanib. The change from baseline in percent predicted DLCO (%DCLO) was − 2.32% for pirfenidone and − 3.95% for nintedanib. The incidence of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) was 12.5% for pirfenidone and 14.4% for nintedanib. The IPF-related mortality rates of pirfenidone and nintedanib were 13.4% and 7.2%, respectively. The all-cause mortality was 20.1% for pirfenidone and 16.6% for nintedanib. In the pirfenidone group, 16.6% of patients discontinued treatment because of adverse events, and in the nintedanib group, 16.2% of patients discontinued treatment because of adverse events. The incidence of adverse events was 56.4% and 69.7% for pirfenidone and nintedanib, respectively. Conclusion: The results of this study indicate that pirfenidone and nintedanib are both effective in slowing down the decline of lung function in IPF patients in real-world settings. The incidence of adverse events with pirfenidone is lower than that with nintedanib, but both are below the clinical trial data, and no new major adverse events have been observed. The discontinuation rates due to adverse reactions of the two drugs are consistent with clinical trial data, indicating good tolerability. However, the mortality rates and AE-IPF incidence rates of these two drugs in real-world settings are higher than those in previous clinical trials, with pirfenidone patients showing a higher mortality rate. Further large-sample studies are needed to investigate the risks of these drugs in these aspects. Additionally, we recommend that future real-world studies pay more attention to patients' subjective symptoms and conduct stratified analyses of the efficacy and safety of pirfenidone and nintedanib based on factors such as patients' baseline lung function, comorbidities, and age, in order to provide more personalized medication advice for IPF patients in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: As the COVID-19 pandemic becomes an endemic state, still many questions remain regarding the risks and impact of SARS-CoV-2 infection and vaccination in patients with immune-mediated inflammatory diseases (IMIDs) who were excluded from the phase 3 COVID-19 vaccination trials. Methods: The BELCOMID study collected patient data and serological samples from a large, multicentric IMID patient cohort that was prospectively followed during sequential stages of the pandemic. Patients were stratified according to vaccination status into five groups across three sampling periods. Interactions between SARS-CoV-2 infection, COVID-19 vaccination status, IMID-treatment modalities and IMID course were explored. Results: In total, 2165 patients with IBD, a dermatological or rheumatological IMID participated. SARS-CoV-2 infection rates increased over the course of the pandemic and were highest in IMID patients that had refused every vaccine. After baseline COVID-19 vaccination, serologic spike (S)-antibody responses were attenuated by particular types of immune-modulating treatment: anti-TNF, rituximab, JAKi, systemic steroids, combined biologic/immunomodulator treatment. Nonetheless, S-antibody concentration increased progressively in patients who received a booster vaccination, reaching 100% seroconversion rate in patients who had received two booster vaccines. Previous SARS-CoV-2 infection was found as a predictor of higher S-antibody response. Patients who had refused every vaccine showed the lowest rates of S-seroconversion (53.8%). Multiple logistic regression did not identify previous SARS-CoV-2 infection as a risk factor for IMID flare-up. Furthermore, no increased risk of IMID flare-up was found with booster vaccination. Conclusions: Altogether, the BELCOMID study provides evidence for the efficacy and safety of COVID-19 vaccination and confirms the importance of repeated booster vaccination in IMID patients. [ABSTRACT FROM AUTHOR]

Introduction: Persistence on advanced therapies in ulcerative colitis (UC) is a useful real-world treatment performance measure. This study compared real-world persistence during the maintenance phase among advanced therapy-naïve and -experienced patients with UC initiated on ustekinumab or adalimumab. Methods: Claims data from the IQVIA PharMetrics® Plus de-identified database (01/01/2015–06/30/2022) were used to select adult patients with UC treated with ustekinumab or adalimumab based on the agent first initiated (index date) after 10/21/2019. Inverse probability of treatment weighting was used to balance cohorts on baseline characteristics. Persistence on the index agent (no gaps in days of supply of > 120 days for ustekinumab or > 60 days for adalimumab), persistence while corticosteroid-free, while on monotherapy, and persistence on the US labeled dose were described and compared during the 12-month period post-index using Kaplan–Meier analysis and Cox proportional hazards models. Outcomes were analyzed separately among advanced therapy-naïve and advanced therapy-experienced patients. Results: At 12 months post-index, advanced therapy-naïve patients receiving ustekinumab (n = 371) had higher persistence on the index agent [83.8% vs. 57.6%, hazard ratio (95% confidence interval) = 3.09 (2.29–4.16); p < 0.001), persistence while corticosteroid-free [2.00 (1.63–2.45); p < 0.001], persistence while on monotherapy [2.67 (2.07–3.44); p < 0.001], and persistence on the labeled dose [4.21 (2.76–6.44); p < 0.001] versus those receiving adalimumab (n = 1726). At 12 months post-index, advanced therapy-experienced patients receiving ustekinumab (n = 693) had higher persistence on the index agent [78.1% vs. 59.2%, 2.44 (1.82–3.26); p < 0.001], persistence while corticosteroid-free [1.24 (1.01–1.54); p = 0.0447], persistence while on monotherapy [2.53 (2.00–3.21); p < 0.001], and persistence on the labeled dose [4.77 (3.09–7.35); p < 0.001] versus those receiving adalimumab (n = 254). Conclusion: This claims-based analysis demonstrated significantly higher treatment persistence, including persistence while corticosteroid-free, persistence while on monotherapy, and persistence on the labeled dose, among both advanced therapy-naïve and advanced therapy-experienced patients with UC initiated on ustekinumab compared to adalimumab. [ABSTRACT FROM AUTHOR]

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Objective: Alzheimer's Disease (AD) is increasingly recognized as being associated with metabolic disorders, including Metabolic Associated Steatotic Liver Disease (MASLD). This study aimed to assess the relative risk of AD in individuals with MASLD. Methods: In this retrospective cohort study, we analyzed data from individuals aged over 65 who underwent health check-ups between January 2018 and June 2023. MASLD was diagnosed based on ultrasound findings and cardiometabolic criteria. AD incidence was identified using ICD-10 codes and self-reports. Poisson regression models estimated the relative risk of AD in relation to MASLD, adjusting for age, BMI, sex, SBP, HbA1c, HDL-c, triglycerides, hs-CRP, GGT, and estimated GFR. Results: The study included 4,582 MASLD patients and 6,318 controls. MASLD patients showed a higher incidence of AD (127 cases) compared to controls (61 cases). The fully adjusted Poisson regression model indicated an increased AD risk in MASLD patients [RR: 2.80 (95% CI: 1.79-4.38)]. Conclusion: Our findings suggested MASLD as an independent risk factor for AD, underlining the role of metabolic dysfunctions in AD pathogenesis. The study emphasized the need for comprehensive metabolic health management in AD prevention strategies, particularly among high-risk groups. [ABSTRACT FROM AUTHOR]

Background: Real-world data on the implementation and prognostic impact of glucose-lowering drugs with proven cardiovascular benefits in patients with type 2 diabetes (T2D) following acute coronary syndrome (ACS) are limited. We investigated the utilization and treatment patterns of sodium–glucose contrasporter-2 inhibitors (SGLT2Is) and glucagon-like peptide-1 recepto-agonists (GLP1RAs) in patients with T2D experiencing ACS and analyzed their association with mortality and major adverse cardiovascular events (MACEs) including recurrent ACS, acute revascularization, heart failure, or ischemic stroke. Methods: We carried out a retrospective analysis of 9756 patients with T2D from a nationwide healthcare organization in Israel who were hospitalized with ACS between 01/2019 and 01/2022. Drug prescriptions were estimated pre-hospitalization, 90 days, and 1 year following hospitalization. The association between SGLT2I and/or GLP1RA treatment with MACE and mortality was investigated using a time-dependent Cox regression analysis with multivariable adjustment. Results: The prescription rates (pre-hospitalization, 90 days, and 1 year post-hospitalization) of GLP1RAs were 13%, 13.2%, and 18%, and those of SGLT2Is were 23.9%, 33.6%, and 42.7%, respectively. At 1 year, 13.9% of patients were prescribed both treatments. The use of SGLT2Is and/or GLP1RAs was higher in younger age groups and increased from 2019 to 2021 (38.1% to 59.2%). The adjusted hazard ratio for the association of pre- or post-hospitalization SGLT2I and/or GLP1RA treatment with mortality and MACE was 0.724 (0.654–0.801) and 0.974 (0.909–1.043), respectively. Conclusions: In the real-world practice of treating patients with T2D experiencing ACS, the implementation of SGLT2Is, particularly GLP1RAs, was suboptimal when prescribed both early and 1 year following hospitalization, emphasizing the need to improve medical care. Treatment with SGLT2Is and/or GLP1RAs was associated with a favorable impact on mortality but not MACE. [ABSTRACT FROM AUTHOR]

Objectives: To document the real-world experience with the use of pneumatic pulsatile mechanical circulatory support (MCS) with the PulseCath iVAC2L during high-risk percutaneous coronary interventions (HR-PCIs). Background: The use of MCS in HR-PCIs may reduce the rate of major adverse cardiovascular events (MACEs) at 90 days. The PulseCath iVAC2L is a short-term pulsatile transaortic left ventricular (LV) assist device that has been in use since 2014. The iVAC2L Registry tracks its safety and efficacy in a variety of hospitals worldwide. Methods: The iVAC2L Registry is a multicenter, observational registry that aggregates clinical data from patients treated with the iVAC2L worldwide. A total of 293 consecutive cases were retrospectively collected and analyzed. Estimated rates of in-hospital clinical endpoints were described. All-cause mortality was used as the primary endpoint and other outcomes of interest were used as secondary endpoints. The rates obtained were reported and contextualized. Results: The in-hospital rate of all-cause mortality was 1.0%, MACE was 3.1%. Severe hypotension occurred in 8.9% of patients. Major bleeding and major vascular complications occurred in 1.0% and 2.1%, respectively. Acute myocardial infarction occurred in 0.7% of patients. Cerebrovascular events occurred in 1.4% of patients. Cardiac arrest occurred in 1.7% of patients. A statistically significant improvement in blood pressure was observed with iVAC2L activation. Conclusions: The results of the present study suggest that the iVAC2L is capable of improving hemodynamics with a low rate of adverse events. However, confirmatory studies are needed to validate these findings. [ABSTRACT FROM AUTHOR]

For patients with locally advanced/metastatic urothelial carcinoma (la/mUC), first-line (1L) treatment with platinum-based chemotherapy (PBC) followed by avelumab 1L maintenance (1LM) is a recommended therapy per treatment guidelines in patients without disease progression. However, contemporary real-world (rw) data among patients receiving this treatment are necessary to understand clinical outcomes and optimal treatment sequencing. This retrospective cohort study analyzed rw treatment patterns and clinical outcomes, including overall survival (rwOS) and progression-free survival (rwPFS), in patients with la/mUC receiving avelumab 1LM. From the Flatiron Health database, 214 patients who received avelumab 1LM following 1L PBC were included. From the start of avelumab 1LM, median rwOS was 23.8 months (95% CI: 18.2—not estimable [NE]) and median rwPFS was 5.1 months (95% CI: 4.1–7.0). A total of 96 patients received second-line (2L) therapy, with 53 receiving enfortumab vedotin (EV). From the start of 2L EV, median rwOS was 11.2 months (95% CI: 6.8—NE) and median rwPFS was 4.9 months (95% CI: 3.9–8.8). Treatment patterns and clinical outcomes in this study align with guidelines and outcomes observed in the JAVELIN Bladder 100 and EV-301 clinical trials and other rw studies, supporting the use of 1L PBC followed by avelumab 1LM and 2L EV for eligible patients. [ABSTRACT FROM AUTHOR]

Background: In the phase 3 clinical trials FIGARO-DKD and FIDELIO-DKD, finerenone reduced the risk of cardiovascular and kidney events among people with chronic kidney disease (CKD) and type 2 diabetes (T2D). Evidence regarding finerenone use in real-world settings is limited. Methods: A retrospective cohort study (NCT06278207) using two Japanese nationwide hospital-based databases provided by Medical Data Vision (MDV) and Real World Data Co., Ltd. (RWD Co., Kyoto Japan), converted to the OMOP common data model, was conducted. Persons with CKD and T2D initiating finerenone from 1 July 2021, to 30 August 2023, were included. Baseline characteristics were described. The occurrence of hyperkalemia after finerenone initiation was assessed. Results: 1029 new users of finerenone were included (967 from MDV and 62 from RWD Co.). Mean age was 69.5 and 72.4 years with 27.3% and 27.4% being female in the MDV and RWD Co. databases, respectively. Hypertension (92 and 95%), hyperlipidemia (59 and 71%), and congestive heart failure (60 and 66%) were commonly observed comorbidities. At baseline, 80% of persons were prescribed angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers. Sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists were prescribed in 72% and 30% of the study population, respectively. The incidence proportions of hyperkalemia were 2.16 and 2.70 per 100 persons in the MDV and RWD Co. databases, respectively. There were no hospitalizations associated with hyperkalemia observed in either of the two datasets. Conclusions: For the first time, we report the largest current evidence on the clinical use of finerenone in real-world settings early after the drug authorization in Japan. This early evidence from clinical practice suggests that finerenone is used across comorbidities and comedications. [ABSTRACT FROM AUTHOR]

Objectives: Fingolimod is approved in Turkey or the treatment of cases of multiple sclerosis (MS) which cannot be controlled with first-line treatments. There is limited information about its efficacy and safety in clinical practice in Turkey. The aim of this study was to evaluate the efficacy and safety of fingolimod treatment in patients with relapsing-remitting multiple sclerosis who were prescribed fingolimod by the Multiple Sclerosis specialists of Bursa Uludağ University Department of Neurology. Methods: This is a single-center observational study evaluating 142 patients using fingolimod who were followed up for at least 12 months in our center between April 2015 and October 2022. Efficacy results were evaluated in terms of mean number of attacks, annualized relapse rate, relapse-free patient rate, disease progression, clinical and radiological disease activity, and no evidence of disease activity (NEDA-3). The safety outcomes are the rates of treatment-related severe adverse events and patients' continuation rates. Results: Over 12 months of treatment with fingolimod, the average number of attacks decreased by 94.6%, the annual relapse rate decreased by 87%, and most patients did not relapse (83.1%). Alongside this, in 76.4% of cases, there was no disability progression and in 83.3% of cases, magnetic resonance imaging (MRI) activation was not observed. Excluding replacement due to ineffectiveness, 89.4% of patients continued fingolimod therapy. Cardiac events, treatment-related infections and a decreased lymphocyte count were observed as side effects. Conclusion: In our center, switching from first-line treatments to fingolimod was effective in reducing disease activity in patients with multiple sclerosis. [ABSTRACT FROM AUTHOR]

Objectives: This study is aimed to compare the effectiveness of modern therapy including angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) with conventional heart failure treatment in the real world. Background: Since ARNI and SGLT2i were introduced to treat heart failure (HF), its therapeutic regimen has modernized from previous treatment with beta-blocker (BB) and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) with mineralocorticoid receptor antagonist (MRA) as added-on in HF with reduced ejection fraction (HFrEF). However, a comparison between conventional and modern treatment strategies with drugs in combination has not been performed. Methods: This observational study (2013–2020), using the Swedish HF Registry, involved 20,849 HF patients. Patients received either conventional (BB, ACEi/ARB, with/without MRA, n = 20,140) or modern (BB, ACEi/ARB, MRA, SGLT2i or BB, ARNI, MRA with/without SGLT2i, n = 709) treatment at the index visit. The endpoints were all-cause and cardiovascular (CV) mortality. Results: Modern HF therapy was associated with a significant 28% reduction in all-cause mortality (adjusted HR [aHR], 0.72 (0.54–0.96); p = 0.024) and a significant 62% reduction in CV mortality (aHR, 0.38 (0.21–0.68); p = 0.0013) compared to conventional HF treatment. Similar results emerged in a sensitivity analysis using propensity score matching. The interaction analyses did not reveal any trends for EF (< 40% and ≥ 40%), sex, age (< 70 and ≥ 70 years), eGFR (< 60 and ≥ 60 ml/min/1.73 m2), and etiology of HF subgroups. Conclusion: In this nationwide study, modern HF therapy was associated with significantly reduced all-cause and CV mortality, regardless of EF, sex, age, eGFR, and etiology of HF. [ABSTRACT FROM AUTHOR]

For patients with locally advanced/metastatic urothelial carcinoma (la/mUC), first-line (1L) treatment with platinum-based chemotherapy (PBC) followed by avelumab 1L maintenance (1LM) is a recommended therapy per treatment guidelines in patients without disease progression. However, contemporary real-world (rw) data among patients receiving this treatment are necessary to understand clinical outcomes and optimal treatment sequencing. This retrospective cohort study analyzed rw treatment patterns and clinical outcomes, including overall survival (rwOS) and progression-free survival (rwPFS), in patients with la/mUC receiving avelumab 1LM. From the Flatiron Health database, 214 patients who received avelumab 1LM following 1L PBC were included. From the start of avelumab 1LM, median rwOS was 23.8 months (95% CI: 18.2—not estimable [NE]) and median rwPFS was 5.1 months (95% CI: 4.1–7.0). A total of 96 patients received second-line (2L) therapy, with 53 receiving enfortumab vedotin (EV). From the start of 2L EV, median rwOS was 11.2 months (95% CI: 6.8—NE) and median rwPFS was 4.9 months (95% CI: 3.9–8.8). Treatment patterns and clinical outcomes in this study align with guidelines and outcomes observed in the JAVELIN Bladder 100 and EV-301 clinical trials and other rw studies, supporting the use of 1L PBC followed by avelumab 1LM and 2L EV for eligible patients.

Abstract Introduction The aim of this study was to evaluate the efficacy and safety of escalating the dosage of intravitreal brolucizumab in patients with refractory neovascular age-related macular degeneration (AMD). Methods This retrospective study included 17 eyes of 17 patients with refractory AMD treated with high-dose brolucizumab (12 mg/0.1 ml) for over 12 months. Patients initially received at least one anti-vascular endothelial growth factor (anti-VEGF) agent and were switched to standard-dose brolucizumab (6 mg/0.05 ml). Those who showed a suboptimal response to standard-dose treatment had their dosage of brolucizumab escalated. Results Visual acuity was maintained from 68.3 ± 3.4 letters to 70.7 ± 3.2 letters after 12 months of high-dose treatment (P = 0.128). Central subfield thickness was 343.7 ± 17.0 μm before high-dose treatment and 316.7 ± 18.5 μm at 12 months (P = 0.083). The proportions of patients with subretinal fluid and serous pigment epithelial detachment significantly decreased from 82.4% to 41.2% and from 52.9% to 17.6%, respectively, after high-dose treatment (P = 0.039 and P = 0.031, respectively). The treatment interval extended from 7.2 ± 2.4 weeks to 10.2 ± 2.2 weeks after switching to standard-dose brolucizumab (P

Abstract Background The randomized, dose-optimization, open-label ReDOS study in US patients with metastatic colorectal cancer (CRC) showed that, compared with a standard dosing approach, initiating regorafenib at 80 mg/day and escalating to 160 mg/day depending on tolerability increased the proportion of patients reaching their third treatment cycle and reduced the incidence of adverse events without compromising efficacy. Subsequently, the ReDOS dose-escalation strategy was included as an alternative regorafenib dosing option in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. A retrospective analysis was conducted using a US claims database to assess whether inclusion of this dose-escalation strategy in NCCN Guidelines has influenced the use of flexible dosing in routine US clinical practice, and to describe clinical outcomes pre- and post-inclusion in NCCN Guidelines. Methods Patients with CRC in the Optum’s de-identified Clinformatics® Data Mart database initiating regorafenib for the first time between January 2016 and June 2020 were stratified based on whether they initiated regorafenib pre- or post-inclusion of ReDOS in NCCN Guidelines, and in two groups: flexible dosing (

Objective To explore the effectiveness and safety of belimumab in Chinese adult lupus nephritis (LN) patients under a real-world setting. Methods For this retrospective cohort study, 30 LN patients received belimumab plus standard of care (SoC) due to a new onset or a relapse of LN from June 2021 to December 2022. And 30 matched patients only treated with SoC after propensity score matching (PSM) at the same period were also enrolled. After 24-week follow-ups, renal complete remission (CR), disease activity index, 24 h urine protein level, dose of prednisone and incidence of adverse events were compared. Results No statistically significant differences existed in baseline demographics, complement C3/C4, anti-dsDNA autoantibody titer, 24 h urine protein level or disease activity index. At Week 24, 21/30 patients achieved renal CR and it was higher than that of SoC group (21 vs 12, P=0.037). As compared with SoC group, belimumab group had lower levels of 24 h urine protein[346.50(183.75，571.00) mg vs 611.50(360.00，1450.00) mg], SLEDAI-2K (SLE disease activity index, SLEDAI-2K) score[(3.93±2.79) vs (5.70±3.14)] and daily prednisone dose [(11.67±4.34) mg/d vs (22.42±9.23) mg/d](P＜0.05). Furthermore, the incidence of adverse events between two group was comparable (P>0.05). Conclusions Belimumab plus SoC may alleviate LN, boost the rate of renal CR, lower 24 h urine protein levels, improve disease activity and reduce the intake of prednisone.

Abstract Background Single-pill combination (SPC) of three antihypertensive drugs has been shown to improve adherence to therapy compared with free combinations, but little is known about its long-term costs and health consequences. This study aimed to evaluate the lifetime cost-effectiveness profile of a three-drug SPC of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic vs the corresponding two-pill administration (a two-drug SPC plus a third drug separately) from the Italian payer perspective. Methods A cost-effectiveness analysis was conducted using multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged ≥ 40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug dispensation until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies, assigning each of them to each cohort member. Costs and life-years gained were discounted by 3%. Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty. Results Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61–1.14), with a mean cost differential of -€12 (95% CI -9,719–8,131), making it the dominant strategy (ICER = -14, 95% CI -€15,871–€7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17–7,813) and €2,027 (95% CI 19–8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574–10,640 vs. €3,710, 95% CI 263–11,955). The cost-effectiveness profile did not significantly change according to age, sex, and clinical status. Conclusions The SPC was projected to be cost-effective compared with the two-pill combination at almost all reasonable willingness-to-pay thresholds. As it is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system.

Kristin Kahle-Wrobleski,1 Bonnie KH Bui,2 Jennifer Friderici,2 Kristin J Moore,2 Maureen Carlyle,2 Noah S Webb,2 Carolyn K Martin,2 Wilson D Pace,3,4 John M Westfall3,4 1US Value Evidence and Outcomes, GSK, Philadelphia, PA, USA; 2Health Economics and Outcomes Research, Optum Life Sciences, Eden Prairie, MN, USA; 3DARTNet Institute, Research Department, Aurora, CO, USA; 4Family Medicine, University of Colorado Medical School, Denver, CO, USACorrespondence: Kristin Kahle-Wrobleski, US Value Evidence and Outcomes, GSK, 2929 Walnut Street, Philadelphia, PA, 19104, USA, Tel +1-463-224-4001, Email kristin.k.wrobleski@gsk.comPurpose: Current guidelines recommend triple therapy maintenance inhalers for patients with recurrent exacerbations of chronic obstructive pulmonary disease (COPD); however, these maintenance therapies are underutilized. This study aimed to understand how physicians make COPD treatment decisions, and how combination maintenance therapies are utilized in a real-world setting.Patients and Methods: This exploratory, hypothesis-generating, non-interventional study used a cross-sectional online survey that was administered to a sample of practicing physicians in the United States. The survey included five fictitious vignettes detailing common symptoms experienced by patients with COPD. Survey questions included factors physicians consider in their decisions, and perceived barriers to prescribing treatments. Repeated measures multivariable analyses were conducted to evaluate how likely physicians were to switch to triple therapy versus no change to patient’s current maintenance therapy or change to another maintenance therapy.Results: In total, 200 physicians completed the survey. Cost of treatment and patient access to treatment were reported as the most common barriers physicians consider in their prescribing decisions. Physicians were more likely to switch a patient’s maintenance inhaler to triple therapy versus no change to maintenance inhaler if they considered the patient’s history of new symptoms, insurance status, and clinical guidelines in their decision. Physicians with more experience treating patients with COPD, and those who treat more patients with COPD per week, were more likely to switch to triple therapy versus no change to maintenance inhaler.Conclusion: This study demonstrates the complexity of factors that can influence physicians’ decisions when prescribing treatments for patients with COPD, including considerations of treatment cost, patient access and adherence, patient comorbidities, efficacy of current treatment, clinical guidelines, and provider’s level of experience treating COPD. Further research may help elucidate the relative importance of the factors influencing physicians’ decisions and inform what types of decision-support tools would be most beneficial.Plain Language Summary: Chronic obstructive pulmonary disease (COPD) symptoms can be effectively managed with maintenance therapies, which are treatments that are taken routinely to help improve symptoms. A combination of three different therapies (triple therapy maintenance) has been shown to be more effective than a combination of two different therapies (dual therapy maintenance) in patients with moderate-to-severe COPD. However, maintenance therapies, including triple therapy, are underutilized. This study aimed to explore how physicians make their treatment decisions for patients with COPD, and how combination maintenance therapies are utilized. To do so, we administered a survey to a sample of practicing physicians in the United States. The survey included five clinically based, fictitious profiles, or vignettes, of patients with COPD, with common symptoms and patient characteristics being described. Physicians were then asked to answer questions about what treatment they would prescribe for each patient, and any factors they considered when deciding on a treatment for a patient. We found that cost of treatment and patient access to treatment were the most common barriers that physicians considered when choosing a treatment. Physicians were also more likely to switch a patient’s maintenance inhaler to a triple therapy maintenance inhaler if they considered the patient’s history of new symptoms, patient’s insurance status, and clinical guidelines when making their decisions. Our study shows that there are many complex factors that influence physicians’ decisions when deciding on a treatment for patients with COPD.Keywords: maintenance therapy, patient vignette, pharmacotherapy, physician survey, real world, triple therapy

Abstract Objective To report the interim results of the PERPRISE study (Study 509; NCT04202159), which is evaluating perampanel as the only adjunctive anti‐seizure medication (ASM) in adults with focal to bilateral tonic–clonic seizures (FBTCS) or primary generalized tonic–clonic seizures (GTCS). Methods PERPRISE is an ongoing 12‐month multicenter, prospective, observational, non‐interventional study of perampanel in a real‐world setting in Germany. Patients are aged ≥18 years with FBTCS or GTCS due to focal or idiopathic generalized epilepsy. Perampanel, as an adjunctive therapy to ASM monotherapy (‘add‐on therapy’) or as a substitute for one ASM in dual therapy (‘substitution therapy’), is prescribed in line with its SmPC. The Interim Analysis Set comprises the first 100 patients who received ≥1 dose of perampanel and attended or discontinued prior to the ~6‐month visit. Interim endpoints include retention rate, measures of effects on seizure frequency, and treatment‐emergent adverse events (TEAEs). Results One hundred patients were included in the Interim Analysis Set (add‐on, n = 43 [43.0%]; substitution, n = 55 [55.0%]; unknown, n = 2). The 6‐month retention rate was 78.0% (add‐on, 83.7%; substitution, 72.7%). For the overall population with GTCS and/or FBTCS, seizure‐freedom rate at 6 months was 58.8% (add‐on, 72.2%; substitution, 47.9%) and 50% responder rate at 6 months was 82.6% (add‐on, 89.2%; substitution, 76.6%). Retention rates and seizure outcomes were better with perampanel as an early‐line treatment than as a late‐line treatment. TEAEs were reported by 48 patients (48.0%), most commonly dizziness (n = 9), fatigue (n = 7), and irritability (n = 7). Sixteen patients (16.0%) withdrew from perampanel treatment due to TEAEs. Significance The interim analysis of PERPRISE offers insight into the real‐world use of perampanel in Germany, including for the first time, clinical practice data from patients with GTCS and switching ASMs within a dual therapy. Further data from PERPRISE will be of value to inform clinical decision‐making in this patient cohort. Plain Language Summary Patients with epilepsy often take more than one medication for seizure control. This 12month study looked at patients in Germany receiving perampanel as only add‐on medication. The interim analysis shows, that at 6 months, over 70% of the 100 patients continued to use perampanel; 59% experienced no seizures during treatment with perampanel, and in 83%, seizure frequency was reduced by half. Side effects occurred in 48% of patients (most commonly dizziness, fatigue, and irritability) and caused 16% to withdraw from the study. Overall, perampanel was a suitable as only add‐on medication for patients with epilepsy.

Background and Objective: Chronic atrophic gastritis (CAG) is a complex chronic disease caused by multiple factors that frequently occurs disease in the clinic. The worldwide prevalence of CAG is high. Interestingly, clinical CAG patients often present with a variety of symptom phenotypes, which makes it more difficult for clinicians to treat. Therefore, there is an urgent need to improve our understanding of the complexity of the clinical CAG population, obtain more accurate disease subtypes, and explore the relationship between clinical symptoms and medication. Therefore, based on the integrated platform of complex networks and clinical research, we classified the collected patients with CAG according to their different clinical characteristics and conducted correlation analysis on the classification results to identify more accurate disease subtypes to aid in personalized clinical treatment. Method: Traditional Chinese medicine (TCM) offers an empirical understanding of the clinical subtypes of complicated disorders since TCM therapy is tailored to the patient's symptom profile. We gathered 6,253 TCM clinical electronic medical records (EMRs) from CAG patients and manually annotated, extracted, and preprocessed the data. A shared symptom-patient similarity network (PSN) was created. CAG patient subgroups were established, and their clinical features were determined through enrichment analysis employing community identification methods. Different clinical features of relevant subgroups were correlated based on effectiveness to identify symptom-botanical botanical drugs correspondence. Moreover, network pharmacology was employed to identify possible biological relationships between screened symptoms and medications and to identify various clinical and molecular aspects of the key subtypes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: 5,132 patients were included in the study: 2,699 males (52.60%) and 2,433 females (47.41%). The population was divided into 176 modules. We selected the first 3 modules (M29, M3, and M0) to illustrate the characteristic phenotypes and genotypes of CAG disease subtypes. The M29 subgroup was characterized by gastric fullness disease and internal syndrome of turbidity and poison. The M3 subgroup was characterized by epigastric pain and disharmony between the liver and stomach. The M0 subgroup was characterized by epigastric pain and dampness-heat syndrome. In symptom analysis, The top symptoms for symptom improvement in all three subgroups were stomach pain, bloating, insomnia, poor appetite, and heartburn. However, the three groups were different. The M29 subgroup was more likely to have stomach distention, anorexia, and palpitations. Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon were the most popular botanical drugs. The M3 subgroup has a higher incidence of yellow urine, a bitter tongue, and stomachaches. Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora were the botanical drugs used. Vomiting, nausea, stomach pain, and appetite loss are common in the M0 subgroup. The primary medications are Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia. Through GO and KEGG pathway analysis, We found that in the M29 subgroup, Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon may exert their therapeutic effects on the symptoms of gastric distension, anorexia, and palpitations by modulating apoptosis and NF-κB signaling pathways. In the M3 subgroup, Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora may be treated by NF-κB and JAK-STAT signaling pathway for the treatment of stomach pain, bitter mouth, and yellow urine. In the M0 subgroup, Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia may exert their therapeutic effects on poor appetite, stomach pain, vomiting, and nausea through the PI3K-Akt signaling pathway. Conclusion: Based on PSN identification and community detection analysis, CAG population division can provide useful recommendations for clinical CAG treatment. This method is useful for CAG illness classification and genotyping investigations and can be used for other complicated chronic diseases. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the long-term outcomes of stage I breast cancer (BC) patients diagnosed during the current era of screening mammography, immunohistochemistry receptor testing, and systemic adjuvant therapy. Methods: A retrospective cohort study was conducted on 328 stage I BC patients treated consecutively in a single referral center with a follow-up period of at least 12 years. The primary endpoints were invasive disease-free survival (IDFS) and overall survival (OS). The influence of tumor size, grade, and subtype on the outcomes was analyzed. Results: Most patients were treated by lumpectomy, sentinel node biopsy, and adjuvant endocrine therapy, and most (82%) were of subtype luminal A. Adjuvant chemotherapy was administered to 25.6% of our cohort. Only 24 patients underwent gene expression testing, which was introduced toward the end of the study period. Mean IDFS was 14.64 years, with a 15-year IDFS of 75.6%. Mean OS was 15.28 years with a 15-year OS of 74.9%. In a Cox multivariate analysis, no clinical or pathologic variable impacted on OS and only tumor size (<1 cm vs. 1–2 cm) impacted significantly on IDFS. During follow-up, 20.1% of the cohort developed second primary cancers, including BC. The median time to diagnosis of a second BC was 6.49 years. Conclusion: The study results emphasize the importance of long-term follow-up and screening for subsequent malignancies of patients with stage I BC and support the need for using prognostic and predictive indicators beyond the routine clinicopathological characteristics in luminal A patients. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to evaluate the real-world drug survival, adherence, and discontinuation risk of biologics disease-modifying anti-rheumatic drugs (bDMARDs) among patients with ankylosing spondylitis (AS). Methods: This was a retrospective study using a computerized database. Biologic-naïve and biologic-experienced AS patients who initiated treatment with bDMARDs (tumor necrosis factor alpha inhibitors {TNF-αis} or interleukin-17 inhibitor {IL-17i}) during 2015–2018 were included. Adherence was assessed using the proportion of days covered (PDC) method. Drug survival was analyzed using Kaplan–Meier estimates. Risk of discontinuation was estimated by the Cox proportional hazard model. Results: We identified 343 eligible patients utilizing 481 lines of therapy. The mean age was 44.6 years (SD ± 13.4), 57.7% were males, and 69.7% were biologic-naïve at baseline. The proportion of highly adherent patients (PDC ≥ 0.8) in the biologic-naïve group was 63.5% for golimumab, 69.2% for etanercept, and 71.6% for adalimumab (p > 0.9). Among the biologic-experienced group, secukinumab had the highest proportion of adherent patients (75.7%) and etanercept the lowest (50.0%) reaching statistical difference (p < 0.001). The Kaplan–Meier analysis did not show a significant difference in drug survival in either the biologic-naïve or the biologic-experienced groups (p = 0.85). Multivariable analysis demonstrated a similar risk for discontinuation for etanercept, golimumab, and secukinumab compared with adalimumab, regardless of biologic-experience status. Conclusions: Adherence, drug survival, and risk for discontinuation were similar for all TNF-αis and the IL-17i SEC, regardless of biologic-experience status. As drug survival is an indirect measure of drug efficacy, n, in real-world settings, we believe caregivers can integrate these results into treatment considerations. [ABSTRACT FROM AUTHOR]

Randomized controlled trials have demonstrated responses to clinical parameters, but a significant proportion of allergy patients in real-life settings would have been excluded from such studies. Therefore, real-world research is needed, and there is a growing body of information on allergen immunotherapy's long-term effectiveness and safety. Real-world evidence can be a valuable instrument to better understand the patient's journey and the effectiveness and safety of therapies. For this purpose, a registry will be used for the first time in Italy to evaluate the impact of allergen immunotherapy on several outcomes, including quality of life and disease-related effects in the pediatric and adult allergic population with a socio-economic assessment and respect to real-world health. [ABSTRACT FROM AUTHOR]

In this study, we compared the similarities and differences in adverse events (AEs) among CAR T-cell products through signal mining via the FDA Adverse Event Reporting System (FAERS) and identified unknown AEs to provide a reference for safe clinical medication. Data from the FAERS database spanning from the fourth quarter of 2017 to the first quarter of 2024 were extracted. Signals were identified using the reporting odds ratio (ROR) method and the Medicines and Healthcare Products Regulatory Agency (MHRA) method. A total of 11,386 AE reports related to six CAR T-cell products were selected. The top three categories of AEs reported were nervous system disorders, immune system disorders, and general disorders and administration site conditions. However, there were variations in the AE spectra among the different CAR T-cell products. The BCMA-targeting drugs idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel) were found to be associated with parkinsonism, which were not observed in CD19-targeting drugs. Tisagenlecleucel (Tisa-cel) and axicabtagene ciloleucel (Axi-cel) exhibited cerebrovascular accident-related AEs, graft versus host disease, and abnormal coagulation indices. Cilta-cel was associated with cerebral hemorrhage, intracranial hemorrhage, cranial nerve disorder, and facial nerve disorder. Cardiopulmonary toxicity, including hypoxia, tachypnoea, cardiorenal syndrome, and hypotension, exhibited strong signal intensities and considerable overlap with CRS. The number of positive signals for cardiopulmonary toxicity associated with drugs targeting CD-19 is greater. Clinicians should assess patients prior to medication and closely monitor their vital signs, mental status, and laboratory parameters during treatment. [ABSTRACT FROM AUTHOR]

Background: The randomized, dose-optimization, open-label ReDOS study in US patients with metastatic colorectal cancer (CRC) showed that, compared with a standard dosing approach, initiating regorafenib at 80 mg/day and escalating to 160 mg/day depending on tolerability increased the proportion of patients reaching their third treatment cycle and reduced the incidence of adverse events without compromising efficacy. Subsequently, the ReDOS dose-escalation strategy was included as an alternative regorafenib dosing option in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. A retrospective analysis was conducted using a US claims database to assess whether inclusion of this dose-escalation strategy in NCCN Guidelines has influenced the use of flexible dosing in routine US clinical practice, and to describe clinical outcomes pre- and post-inclusion in NCCN Guidelines. Methods: Patients with CRC in the Optum's de-identified Clinformatics® Data Mart database initiating regorafenib for the first time between January 2016 and June 2020 were stratified based on whether they initiated regorafenib pre- or post-inclusion of ReDOS in NCCN Guidelines, and in two groups: flexible dosing (< 160 mg/day; < 84 tablets in the first treatment cycle) and standard dosing (160 mg/day; ≥ 84 tablets in the first treatment cycle). The primary endpoints were the proportion of patients who initiated their third treatment cycle and the mean number of treatment cycles per group. Results: 703 patients initiated regorafenib during the study period, of whom 310 (44%) initiated before and 393 (56%) initiated after inclusion of ReDOS in NCCN Guidelines. After inclusion in the guidelines, the proportion of patients who received flexible dosing increased from 21% (n = 66/310) to 45% (n = 178/393), the proportion who received standard dosing decreased from 79% (n = 244/310) to 55% (n = 215/393), the proportion who initiated their third treatment cycle increased from 36% (n = 113/310) to 46% (n = 179/393), and the mean (standard deviation) number of treatment cycles increased from 2.6 (2.9) to 3.2 (3.1). Conclusions: Following inclusion of ReDOS in NCCN Guidelines, real-world data suggest that US clinicians have markedly increased use of flexible dosing in clinical practice, potentially maximizing clinical benefits and safety outcomes for patients with metastatic CRC receiving regorafenib. [ABSTRACT FROM AUTHOR]

Health-related quality of life (HRQoL) data are important indicators of health status in patients with lymphoma. The objective of this analysis was to assess the impact of treatment with Sandoz rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on HRQoL in treatment-naïve adult patients with diffuse large B-cell lymphoma (DLBCL) included in the prospective, real-world REFLECT study. REFLECT is the first prospective study to assess HRQoL in patients with DLBCL treated with a rituximab biosimilar. HRQoL was assessed via the patient-reported European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire at baseline, mid-treatment (month 3), end of treatment (month 6), and follow-up (months 9 and 12). Subgroup analyses were performed to evaluate the influence of baseline characteristics on HRQoL, and associations between baseline HRQoL and treatment response. HRQoL was assessed in 169 patients. Mean global health status score remained stable from baseline (54.8) to mid-treatment (month 3; 54.7), before steadily improving through to end of treatment (month 6; 61.4), and follow-up month 9 (64.9) and month 12 (68.8). Similar trends were observed across most functional and symptom subscales. Higher cognitive, physical, or role functioning, and less appetite loss, diarrhea, fatigue, or pain at baseline, were all associated with an improved likelihood of reaching a complete versus partial response at the end of treatment. Overall, these findings confirm the HRQoL benefits of R-CHOP therapy in treatment-naïve adult patients with DLBCL, and suggest that baseline HRQoL may be predictive of treatment response. [ABSTRACT FROM AUTHOR]

Open set recognition (OSR) constitutes a critical endeavor within the domain of computer vision, frequently deployed in applications, such as autonomous driving and medical imaging recognition. Existing OSR methodologies predominantly center on the acquisition of a profound association between image data and corresponding labels, facilitating the extraction of discriminative features instrumental for distinguishing novel categories. Nevertheless, real-world scenarios often introduce not only novel classes (referred to semantic shift) but also intricate environmental modifications that engender alterations in the distribution of established classes (termed as covariate shift). The latter phenomenon has the potential to undermine the robust correlation between images and labels established by conventional statistical correlation modeling approaches, consequently resulting in significant degradation of OSR performance. Causal correlation stands as the fundamental linkage between entities, routinely harnessed by humans to enhance their cognitive capacities for a more profound comprehension of the intricate world. With inspiration drawn from this perspective, our work herein introduces the causal inference-inspired open set recognition (CISOR) approach tailored for real-world OSR (RWOSR). CISOR represents the pioneering initiative to leverage the stability inherent in causal correlation to construct two pivotal modules: the covariate causal independence (CCI) module and the semantic causal uniqueness (SCU) module, both instrumental in addressing the RWOSR problem. The CCI module adeptly confronts the challenge of covariate shift by imposing constraints on the correlations between inter-class causal features. This strategy effectively mitigates the impact of spurious correlations between distinct categories on the generalization capacity of discriminative features. Furthermore, in order to counteract the issue of semantic shift, the SCU module harnesses correlations between causal features within the same class as constraints, thereby facilitating the extraction of resilient causal features endowed with superior discriminative capabilities. Empirical findings substantiate the superior efficacy of the proposed CIOSR method when compared to state-of-the-art approaches across diverse RWOSR benchmark datasets. The source code of this article will be available at https://github.com/yangzhen1252/RWOSR1. [ABSTRACT FROM AUTHOR]

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Background: Venlafaxine is frequently prescribed for patients with depression. To control the concentration of venlafaxine within the therapeutic window for the best treatment effect, a model to predict venlafaxine concentration is necessary. Aim: Our objective was to develop a prediction model for venlafaxine concentration using real-world evidence based on machine learning and deep learning techniques. Method: Patients who underwent venlafaxine treatment between November 2019 and August 2022 were included in the study. Important variables affecting venlafaxine concentration were identified using a combination of univariate analysis, sequential forward selection, and machine learning techniques. Predictive performance of nine machine learning and deep learning algorithms were assessed, and the one with the optimal performance was selected for modeling. The final model was interpreted using SHapley Additive exPlanations. Results: A total of 330 eligible patients were included. Five influential variables that affect venlafaxine concentration were venlafaxine daily dose, sex, age, hyperlipidemia, and adenosine deaminase. The venlafaxine concentration prediction model was developed using the eXtreme Gradient Boosting algorithm (R2 = 0.65, mean absolute error = 77.92, root mean square error = 93.58). In the testing cohort, the accuracy of the predicted concentration within ± 30% of the actual concentration was 73.49%. In the subgroup analysis, the prediction accuracy was 69.39% within the recommended therapeutic range of venlafaxine concentration within ± 30% of the actual value. Conclusion: The XGBoost model for predicting blood concentration of venlafaxine using real-world evidence was developed, guiding the adjustment of regimen in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Relapse and refractory (R/R) rates after first‐line R‐CHOP in diffuse large B cell lymphomas (DLBCL) are ~40% and ~15% respectively. Aims: We conducted a retrospective real‐world analysis aimed at evaluating clinical outcomes of R/R DLBCL patients. Material and Methods: Overall, 403 consecutive DLBCL patients treated in two large hematological centers in Torino, Italy were reviewed. Results: At a median follow up of 50 months, 5‐year overall survival from diagnosis (OS‐1) was 66.5%, and 2‐year progression free survival (PFS‐1) was 68%. 134 (34.4%) patients relapsed (n = 46, 11.8%) or were refractory (n = 88, 22.6%) to R‐CHOP. Most employed salvage treatments included platinum salt‐based regimens in 38/134 (28.4%), lenalidomide in 14 (10.4%). Median OS and PFS after disease relapse or progression (OS‐2 and PFS‐2) were 6.7 and 5.1 months respectively. No significant difference in overall response rate, OS‐2 or PFS‐2 in patients treated with platinum‐based regimens versus other regimens was observed. By multivariate analysis, age between 60 and 80 years, germinal center B cell type cell of origin and extranodal involvement of <2 sites were associated with better OS‐2. Discussion: Our findings confirm very poor outcomes of R/R DLBCL in the rituximab era. Widespread approval by national Medicine Agencies of novel treatments such as CAR‐T cells and bispecific antibodies as second‐line is eagerly awaited to improve these outcomes. [ABSTRACT FROM AUTHOR]

Background: Single-pill combination (SPC) of three antihypertensive drugs has been shown to improve adherence to therapy compared with free combinations, but little is known about its long-term costs and health consequences. This study aimed to evaluate the lifetime cost-effectiveness profile of a three-drug SPC of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic vs the corresponding two-pill administration (a two-drug SPC plus a third drug separately) from the Italian payer perspective. Methods: A cost-effectiveness analysis was conducted using multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged ≥ 40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug dispensation until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies, assigning each of them to each cohort member. Costs and life-years gained were discounted by 3%. Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty. Results: Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61–1.14), with a mean cost differential of -€12 (95% CI -9,719–8,131), making it the dominant strategy (ICER = -14, 95% CI -€15,871–€7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17–7,813) and €2,027 (95% CI 19–8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574–10,640 vs. €3,710, 95% CI 263–11,955). The cost-effectiveness profile did not significantly change according to age, sex, and clinical status. Conclusions: The SPC was projected to be cost-effective compared with the two-pill combination at almost all reasonable willingness-to-pay thresholds. As it is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system. [ABSTRACT FROM AUTHOR]

Serum neurofilament light chain (sNfL) levels have been proposed as a biomarker of the clinical activity, disability progression, and response to treatment of people with multiple sclerosis (PwMS); however, questions remain about its implementation in clinical practice. Ocrelizumab (OCR) has proven effective in improving clinical and radiological outcomes and reducing sNfL levels. This real-life study followed the sNfL levels of 30 PwMS treated for 12 months with OCR and evaluated the usefulness of this biomarker for their short-term prognosis, considering expanded disability status scale (EDSS), annualized relapse rate (ARR), radiological activity, and NEDA-3 values. OCR reduced ARR in 83% of PwMS and radiological activity in 80%. EDSS was maintained, while NEDA-3 was achieved in 70% at 12 months. OCR produced an early reduction in sNfL levels (at 3 months). At baseline, greater MRI-evaluated radiological activity was associated with higher sNfL levels. sNfL levels over the first 12 months of treatment did not predict a suboptimal response or sustained control of the disease. Longer-term studies are needed to explore the predictive usefulness of sNfL levels in PwMS treated with high-efficacy drugs. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to assess the clinical effectiveness and safety profile of omalizumab as a therapeutic intervention for chronic urticaria (CU). Methods: From March 1, 2023, to September 30, 2023, data on a cohort comprising 96 patients with CU, who underwent treatment with omalizumab at our medical institution's allergy clinic, were systematically compiled. Subsequent to the administration of omalizumab, the therapeutic efficacy was assessed utilizing the 7-day urticaria activity score and the urticaria control test. Results: Based on the statistical analysis, the mean duration of therapeutic intervention was 2.4 ± 1.3 months, with a corresponding mean cumulative dosage of 765 ± 450 mg. Of the subset of 42 patients with CU who were subjected to a follow-up period exceeding 3 months, it was observed that the treatment led to complete symptom remission, and no instances of recurrence were documented. Notably, there were statistically significant differences in the treatment duration and the cumulative dosage between patients who experienced co-morbid conditions and those who did not (p < 0.01, 95% CI: 0.280–1.326; p < 0.01, 95% CI: 0.597–2.997). Furthermore, there were significant differences in the treatment duration and cumulative dosage between patients in the combined allergic rhinitis group and those in the non-combined allergic rhinitis group (p < 0.01, 95% CI: 0.204–1.305; p = 0.01, 95% CI: 0.326–2.860). Conclusion: Omalizumab demonstrates efficacy in the management of CU among Chinese patients by exerting effective symptom control and facilitating the regression of skin lesions. The assessment of its therapeutic efficacy typically requires a 12-week treatment period. Moreover, the co-occurrence of CU with other allergic disorders serves as a pertinent consideration for the adjustment of omalizumab dosing regimens. [ABSTRACT FROM AUTHOR]

Introduction: Oral semaglutide improves cardiovascular risk factors in people with type 2 diabetes (T2D) in clinical trials, though real-world evidence is limited. We aimed to determine the real-world impact of oral semaglutide on routinely collected clinical data in our practice. Methods: People with T2D initiated on oral semaglutide in secondary care diabetes clinics at two hospital sites in Wales (United Kingdom) were included. Data were collected on reasons for oral semaglutide initiation and changes in bodyweight, blood pressure, glycemic control, and lipid profiles over follow-up at 3–6 months, and at 6–12 months. Data were collected to determine the safety of oral semaglutide. Results: Seventy-six patients were included, with a median age 59.3 [51.4–67.6] years, and 38 (50.0%) patients were female. The most common reasons for oral semaglutide were need for weight loss and improved glycemia (69.8%), and improved glycemia alone (25.0%). Oral semaglutide associated with significantly reduced bodyweight (− 3.3 kg), body mass index (BMI) (– 0.9 kg/m2), glycated hemoglobin (HbA1c) (− 11 mmol/mol), and total cholesterol (− 0.4 mmol/l) by 3–6 months follow-up. At 6–12 months, there was a significant reduction in systolic blood pressure (− 7.0 mmHg), in addition to sustained reductions in other metabolic parameters. By 12 months, 18 (23.6%) patients had discontinued the drug, largely resulting from gastrointestinal disturbance, but there were no serious events in this cohort. Conclusions: Oral semaglutide was effective in improving cardiovascular risk factors in this real-world population living with T2D, and no serious events were identified related to oral semaglutide in this patient group. [ABSTRACT FROM AUTHOR]

Aim: Evaluation of the real-world effectiveness and safety of 8-week glecaprevir/pibrentasvir (G/P) in treatment-naive Canadian individuals with hepatitis C and compensated cirrhosis. Patients & methods: Analysis of Canadian people enrolled in the CREST study. Primary end point was sustained virologic response at posttreatment Week 12 (SVR12) rates; safety end points were also assessed. Results: Fifty-three individuals received ≥1 dose of G/P. In the modified analysis set (MAS; which excluded those who discontinued G/P [n = 1] or with missing SVR12 data [n = 12]), 98% (39/40) achieved SVR12; 1 person experienced virologic failure. No individuals experienced or discontinued treatment due to a serious adverse event. Conclusion: In this real-world Canadian cohort, 8-week G/P was well tolerated, with SVR12 rates similar to those in clinical trials. Plain Language Summary What is this article about? Clinical research studies have shown that a high proportion of individuals infected with hepatitis C virus (HCV) and with advanced liver disease who had not been treated before, were cured after treatment for 8–12 weeks with the oral medication glecaprevir/pibrentasvir (G/P). However, data in real-life are limited. To support these studies, we present the effectiveness and safety of G/P given for 8 weeks, in a real-life setting, in Canadian people with HCV infection and advanced liver disease who have not previously received HCV treatment. Our population included people who use drugs, those with excessive alcohol use and those with mental health conditions. These individuals represent a population at high risk for HCV infection and transmission. What were the results? Our findings show that treatment with G/P for 8 weeks was effective and well tolerated in the general population as well as in vulnerable individuals. What do the results mean? The results in this real-world setting were similar to those seen in clinical research studies, and more importantly in populations that are often underrepresented. This supports the use of G/P for treating HCV infection in underserved populations, which will be key to achieving global HCV elimination. Article highlights Hepatitis C remains a global health concern. In Canada it is estimated that approximately 194,500 people are still living with hepatitis C virus (HCV) infection despite widespread availability of highly effective and well tolerated therapies. The World Health Organization has set a goal for the elimination of HCV as a public health concern by 2030. There are limited real-world data in patients with HCV infection and compensated cirrhosis (CC). This study examined the real-world effectiveness and safety of 8-week glecaprevir/pibrentasvir (G/P) in 53 Canadian, treatment-naive people with CC, including those with drug use disorder, excessive alcohol use and mental health conditions. In the overall population, 98% of patients achieved sustained virologic response at posttreatment Week 12 (SVR12). SVR12 rates remained high in patients including those with substance use disorder, excessive alcohol use, depression, FibroScan® ≥12.5 kPa and FibroScan >20 kPa or platelet count <150 × 109/l. Most common adverse events (AEs) were fatigue (26%, n = 14) and headache (11%, n = 6), with no serious or drug-related AEs reported and no AEs leading to treatment discontinuation. Our findings confirm the effectiveness and safety of G/P therapy in treatment-naive people with HCV genotype 1–6 and CC, including those who may be underserved in clinical trials. If strategies to optimize screening for HCV infection and linkage to care are implemented, we can be confident that an 8-week course of treatment with G/P can be offered to patients with CC, irrespective of co-morbidities and concomitant medications. [ABSTRACT FROM AUTHOR]

Introduction: Vitiligo, a chronic autoimmune skin depigmentation disease with an unpredictable course, has been associated with several comorbid autoimmune and psychological conditions. Our current understanding of vitiligo burden and management in the real world is limited. This real-world analysis presents data on vitiligo epidemiology, comorbidities, and treatment of patients in Israel. Methods: This retrospective study analyzed data from the Maccabi Health Services database. Prevalent patients with vitiligo in 2021 were matched to patients in the general population on the basis of age group, gender, and socioeconomic status. Patient demographics, vitiligo incidence and prevalence, comorbidities, and treatment patterns are reported. Data are presented as percentages, mean, median, P values, and standard mean differences (SMD). Results: In this analysis, 11,412 patients with vitiligo were matched to patients from the general population. Incidence and prevalence rates increased over time from 2005 to 2021. Compared to the general population, patients with vitiligo were more likely to have an immune-mediated comorbidity (29.7% vs 18.4% [P < 0.001; SMD 0.27]) or psychological comorbidity (18.7% vs 15.9% [P < 0.001; SMD 0.07]). Comorbidities included atopic dermatitis (patients with vitiligo vs general population 12.5% vs 8.4%), psoriasis (5.8% vs 3.6%), Hashimoto's thyroiditis (2.9% vs 1.1%), alopecia areata (2.2% vs 0.9%), depression (10.8% vs 9.5%), and sleep disorder/insomnia (5.9% vs 4.4%). Only 74.8% of all patients with vitiligo had ever received treatment, with topical corticosteroids (51.5%) and calcineurin inhibitors (36.5%) most commonly prescribed. At the end of 2021, 83.7% of patients were untreated. Conclusion: Patients with vitiligo are more likely to have various immune-related and psychological comorbidities, highlighting the significant impact of the condition on well-being. Nearly a quarter of patients had never received treatment, with many receiving only topical treatments, and medication persistence was low. This highlights the lack of adequate treatment in this population and the need for more effective management options. [ABSTRACT FROM AUTHOR]

Introduction: Cyclin-dependent kinases 4/6 inhibitors (CDK 4/6i) combined with endocrine therapy have become the gold standard in hormone receptor-positive (HR +) HER2-negative (HER2-) metastatic breast cancer (MBC). However, there is a significant lack of data regarding the efficacy and safety of these treatments in elderly patients. We present the results of a real-world data (RWD) cohort stratified by age at treatment initiation (≥ 70 years compared to patients < 70 years). Methods: Clinico-pathological data of HR + HER2- MBC patients who were candidates for CDK4/6i therapy between January 2017 and December 2020 at the Institut Català d'Oncologia (Spain) were retrospectively collected. The primary goal was to assess Progression-Free Survival (PFS), Overall Survival (OS), and safety outcomes within this patient population. Results: A total of 274 patients with MBC who received CDK4/6i treatment were included in the study. Among them, 84 patients (30.8%) were aged ≥ 70 years, with a mean age of 75, while 190 patients (69.2%) were under the age of 70, with a mean age of 55.7 years. The most frequently observed grade 3–4 toxicity was neutropenia, with similar rates in both the < 70 group (43.9%) and the ≥ 70 group (47.9%) (p = 0.728). The median Progression-Free Survival (mPFS) for the first-line CDK4/6i treatment was 22 months (95% CI, 15.4–39.8) in the < 70 group and 20.8 months (95% CI 11.2–NR) in the ≥ 70 group (p = 0.67). Similarly, the median PFS for the second-line CDK4/6i treatment was 10.4 months (95% CI, 7.4–15.1) and 7.1 months (95% CI 4.4–21.3) (p = 0.79), respectively. Median overall survival (mOS) was not reached either for the first- and second-line treatment. Conclusions: Our RWD suggests that elderly patients, when compared to those under 70, experience similar survival outcomes and exhibit comparable tolerance for CDK4/6i therapy. [ABSTRACT FROM AUTHOR]

Introduction: There are limited data on the burden of newly diagnosed patients with heart failure (HF) in Thailand. Thus, this study aimed to fully understand the hospitalization, rehospitalization, mortality rates, demographics and characteristics, and quality of care in these patients. Method: A retrospective review of all eligible adult patients' medical records from 2018 and 2019 was conducted at five hospitals. The patients were newly diagnosed with HF, as indicated by the International Classification of Diseases (ICD)-10 code "I50." Descriptive statistics was used to investigate patients' hospital burden and clinical outcome data. Results: There were 1134 patients newly diagnosed with HF, classified as HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) (44.0, 40.0, and 16.0%, respectively). The male-to-female ratios in HFmrEF and HFpEF were similar. In contrast, the proportion of men with HFrEF was greater. The mean age of all patients was 66.0 years. The hospitalization rate was 1.3. Rehospitalization rates for HF-related issues were 0.1, 0.2, 0.4, and 0.5 at 30 days, 60 days, 180 days, and 1 year, respectively. The percentage of deaths from all causes among these patients was 9.8%, while the percentage of deaths from cardiovascular-related causes was 8.5%. Only a small proportion of patients received a target dose of guideline-directed medical therapy (GDMT). Conclusions: The study revealed that the characteristics, hospitalization rate for HF, and in-hospital mortality rate among newly diagnosed patients with HF were higher compared to similar studies conducted in Thailand and other countries. Moreover, a high quality of care is needed to improve the morbidity and mortality associated with HF in Thailand. [ABSTRACT FROM AUTHOR]

Clinical trials and real world studies demonstrated benefit of mepolizumab treatment in severe asthma but data on its effectiveness beyond 2 years remain limited. Herein, we provide mepolizumab treatment evaluation up to 4 years. we studied all patients initiated on mepolizumab in our center from June 2017 to August 2018. Clinical outcomes data were retrieved from the local dendrite systems registry. Comparison analyses and logistic regression were conducted to explore longevity and predictors of response to mepolizumab treatment. a total of 66 patients initiated on mepolizumab with a median follow-up of 45.8 (42.4,48.1) months were included in the study [mean age 50.3 years (range 18-79), females 50 (73%) ]. At 20.7 months of treatment, 42 patients (63.6%) had positive response, 13 (19.7%) negative response, and 11 (16.7%) discontinued due to other factors. At 45.8 months, 35 (53%) patients were still on mepolizumab, 21 (31.8%) switched to a different biologic, and 10 (15.2%) discontinued biologics. Two deaths were recorded during the study period. The median blood eosinophil was reduced from 0.43x109/L (0.27, 0.75) to 0.04 (0.0, 0.1) (p < 0.00001)]. The median annual exacerbations were reduced from 6.0 (4,8) to 1.0 (0.0,3.0) (p < 0.00001), and mOCS use was reduced from59% to 29%, p = 0.001. The mean asthma control questionnaire-6 (ACQ6) improved from 3.1 ± 1.7 to 2.1 ± 1.3 (p < 0.00001). mepolizumab clinical benefit was sustained over 4 years. However, approximately half of the cohort discontinued the treatment prompting the need for further research into the treatment response longevity. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness and tolerability of brivaracetam (BRV) in adults with epilepsy by specific comorbidities and epilepsy etiologies. Methods: EXPERIENCE/EPD332 was a pooled analysis of individual patient records from several non-interventional studies of patients with epilepsy initiating BRV in clinical practice. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within prior 3 months), continuous seizure freedom (no seizures since baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Analyses were performed for all adult patients (≥ 16 years of age) and stratified by comorbidity and by etiology at baseline (patients with cognitive/learning disability [CLD], psychiatric comorbidity, post-stroke epilepsy, brain tumor−related epilepsy [BTRE], and traumatic brain injury−related epilepsy [TBIE]). Results: At 12 months, ≥ 50% seizure reduction was achieved in 35.6% (n = 264), 38.7% (n = 310), 41.7% (n = 24), 34.1% (n = 41), and 50.0% (n = 28) of patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, respectively; and continuous seizure freedom was achieved in 5.7% (n = 318), 13.7% (n = 424), 29.4% (n = 34), 11.4% (n = 44), and 13.8% (n = 29), respectively. During the study follow-up, in patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, 37.1% (n = 403), 30.7% (n = 605), 33.3% (n = 51), 39.7% (n = 68), and 27.1% (n = 49) of patients discontinued BRV, respectively; and TEAEs since prior visit at 12 months were reported in 11.3% (n = 283), 10.0% (n = 410), 16.7% (n = 36), 12.5% (n = 48), and 3.0% (n = 33), respectively. Conclusions: BRV as prescribed in the real world is effective and well tolerated among patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE. [ABSTRACT FROM AUTHOR]

Introduction: Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). Methods: The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. Results: A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. Conclusion: Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status. [ABSTRACT FROM AUTHOR]

Introduction: Efficacy and safety of the fixed ratio combination of insulin degludec and liraglutide (IDegLira) has been largely documented. However, long-term data are limited. This study aimed at describing persistence in therapy and the effectiveness at 48 months of IDegLira. Methods: We conducted an observational study based on retrospective chart review. All patients treated with IDegLira during 2018–2022 were included. Data on treatment approaches and clinical outcomes were collected at the first prescription of IDegLira (T0) and after 6, 12, 24, 36, and 48 months. Results: Overall, 156 patients (mean age 68 years, 64.1% men) started IDegLira, of whom 88 (56.4%) were previously treated with basal-oral therapy (BOT) and 68 (43.6%) with basal-bolus schemes (BB). Before starting IDegLira, 23.8% were treated with ≥ 2 oral antihyperglycemic agents in association with insulin; at T0, the proportion decreased to 3.2%. Short-acting insulin was discontinued after the first week. After 48 months, levels of HbA1c were significantly reduced by 1.34% in the BOT group and 1.07% in the BB group (p < 0.0001 in both groups). In the BOT group, FBG levels decreased by about 50 mg/dl and body weight was unchanged. In the BB group, FBG levels decreased by about 40 mg/dl and body weight was significantly reduced by an average of 7.7 kg. Five patients (3.2%) interrupted therapy with IDegLira during 48 months, and no severe hypoglycemia occurred. Conclusions: Our study emphasizes the important role of IDegLira in maintaining a good metabolic control while minimizing the risk of major hypoglycemia and weight gain in the long term. The substantial simplification of treatment schemes can increase adherence. [ABSTRACT FROM AUTHOR]

Elranatamab efficacy in the single-arm, registrational MagnetisMM-3 trial (NCT04649359) was compared with that of physician's choice of treatment (PCT) for triple-class refractory multiple myeloma. MagnestisMM-3 eligibility criteria were applied to two USA-based oncology electronic health record databases, COTA and Flatiron Health (FH), to identify cohorts for this study (NCT05932290). Applied statistical techniques accounted for cohort imbalances. MagnetisMM-3 (BCMA-naive; n = 123) outcomes were compared with those from COTA (n = 239) and FH (n = 152). Elranatamab was associated with a significantly higher objective response rate (risk ratios, 1.88–2.25), significantly longer progression-free survival (hazard ratios [HRs], 0.37–0.57), and, across most analyses, significantly longer overall survival (HRs, 0.46–0.66) versus PCT. BCMA-naive patients who were treated with elranatamab exhibited significantly better outcomes than patients treated in real-world clinical practice. Elranatamab is a new medicine for the treatment of people with multiple myeloma. In the ongoing clinical trial MagnetisMM-3, most people had fewer myeloma cells when treated with elranatamab. However, MagnetisMM-3 only looks at the effects of elranatamab without comparing it to other myeloma treatments. Therefore, a new study was designed to compare the effectiveness of elranatamab in the MagnetisMM-3 study with other treatments used in real-world clinical practice (not in a clinical trial). Data from people in MagnetisMM-3 was compared with data from two US databases (COTA and Flatiron Health) containing health records of patients treated for multiple myeloma in real-life clinical practice. The same criteria used to select patients for the MagnetisMM-3 trial (123 people) were used to identify people with similar characteristics in COTA (239 people) and Flatiron Health (152 people). More people treated with elranatamab had fewer myeloma cells in their bodies after treatment than people who received their doctor's choice of treatment in clinical practice. In fact, six out of ten people treated with elranatamab had fewer myeloma cells versus about three in ten people from each real-world database. People treated with elranatamab versus physician's choice of treatment lived longer without their disease getting worse and lived longer overall. In conclusion, this study found that more people treated with elranatamab responded to treatment and lived longer than similar people from the COTA and Flatiron Health databases who were given treatments available in a real-world clinical setting. Clinical Trial Registration: NCT05932290 (ClinicalTrials.gov) Executive summary Elranatamab is a BCMAxCD3 bispecific antibody under investigation for the treatment of relapsed or refractory multiple myeloma in the single-arm, registrational phase II MagnetisMM-3 trial (NCT04649359) of elranatamab. Although favorable clinical outcomes have been observed in patients treated with elranatamab in MagnetisMM-3, it can be difficult to compare these clinical results with those of other available therapies due to the single-arm design. The aim of this study (NCT05932290) was to contextualize efficacy data from patients naive to BCMA-directed therapy who received elranatamab in the MagnetisMM-3 trial with data from similar patients from two USA-based oncology electronic health record databases, COTA and Flatiron Health, as external real-world control arms. Trial inclusion and exclusion criteria were applied to each real-world database to obtain comparable patient populations. Statistical techniques (e.g., inverse probability of treatment weighting) were used to account for imbalances across cohorts on key confounding variables, including age, sex, cytogenetic risk, number of prior lines of therapy, Eastern Cooperative Oncology Group performance status, time since initial multiple myeloma diagnosis, penta-drug refractory status and International Staging System disease stage. Ultimately, outcomes of 123 patients from MagnetisMM-3 Cohort A (BCMA naive) were compared with those of 239 and 152 similar patients from the COTA and Flatiron Health databases, respectively. Elranatamab was associated with a significantly higher objective response rate, longer progression-free survival and generally longer overall survival compared with real-world treatments. Among BCMA-naive patients, those treated with elranatamab exhibited improved clinical outcomes compared with patients who received treatments used in real-world clinical practice. [ABSTRACT FROM AUTHOR]

Patients with lung cancer under treatment have been associated with a high risk of COVID‐19 infection and potentially worse outcome, but real‐world data on patient‐reported outcomes (PROs) are rare. We assess patients' characteristics and PROs before and during the COVID‐19 pandemic in an advanced non‐small cell lung cancer (NSCLC) cohort in Germany. Patients with locally advanced or metastatic NSCLC from the prospective, multicentre, observational CRISP Registry (NCT02622581) were categorised as pre‐pandemic (March 2019 to Feb 2020, n = 1621) and pandemic (March 2020 to Feb 2021, n = 1317). From baseline to month 15, patients' health‐related quality of life (HRQoL) was assessed by FACT‐L, anxiety and depression by PHQ‐4. Association of pandemic status with time to deterioration (TTD) in QoL scales adjusted for potential covariates was estimated using Cox modelling. PROs were documented for 1166 patients (72%) in the pre‐pandemic, 979 (74%) in the pandemic group. Almost 60% of patients were male, median age was 66 years, comorbidities occurred in 85%. Regarding HRQoL, mean‐change‐from‐baseline plots hardly differed between both samples. Approximately 15%–21% of patients reported anxiety, about 19%–27% signs of depression. For the pandemic group, TTD was slightly, but statistically significantly, worse for the physical well‐being‐FACT‐G subscale (HR 1.15 [95%CI 1.02–1.30]) and the anxiety‐GAD‐2 subscale (HR 1.14 [95%CI 1.01–1.29]). These prospectively collected real‐world data provide valuable insights into PROs before and during the COVID‐19 pandemic in advanced NSCLC. For the patients, the pandemic seemed to be less of a burden than the disease itself, as there was a considerable proportion of patients with anxiety and depression in both groups. [ABSTRACT FROM AUTHOR]

A 52‐week postmarketing surveillance study was initiated to evaluate the safety and effectiveness of guselkumab, a human anti–interleukin 23 subunit p19 monoclonal antibody, in Japanese patients with psoriasis vulgaris, psoriatic arthritis, generalized pustular psoriasis, and erythrodermic psoriasis in real‐world practice. Here, we report results of the 20‐week interim analysis of the ongoing postmarketing surveillance study. Patients who received guselkumab between May 2018 (the date of commercial launch in Japan) and October 2020 were registered in this study. In total, 411 and 245 patients were included in the safety and effectiveness analysis sets, respectively. Adverse drug reactions (ADRs) occurred in 6.6% (27 of 411) and serious ADRs in 2.2% (nine of 411) of patients. The most frequent ADRs by System Organ Class were "Infections and infestations" (2.4%), with nasopharyngitis being the most frequently observed ADR (0.7%). The mean Psoriasis Area Severity Index score decreased from 11.6 at baseline to 6.5 at week 4 and 2.2 at week 20, with improvements achieving statistical significance at each time point. Clinical Global Impression, Dermatology Life Quality Index, and Nail Psoriasis Severity Index outcomesalso showed substantial improvements. Our findings demonstrate that guselkumab is well tolerated and effective in Japanese patients with psoriasis through 20 weeks of treatment in real‐world clinical practice, showing significant effectiveness observed as early as 4 weeks. The study was officially registered with the University Hospital Medical Information Network Clinical Trials Registry with the identifier UMIN000032969. [ABSTRACT FROM AUTHOR]