Real-world Effectiveness Research Articles

Effectiveness of Ustekinumab for patients with moderate to severe Ulcerative Colitis: A Multi-Center Real-World Canadian Study

Background: We aimed to evaluate the real-world effectiveness and safety of ustekinumab for the treatment of both bio-naïve and bio-exposed ulcerative colitis (UC) patients in a real-world setting. Methods: Retrospective, Canadian multicenter cohort study. Primary outcomes were clinical remission and endoscopic remission. Key secondary outcomes included composite clinical and endoscopic response, safety, and persistence. Univariable logistic regression was conducted to examine associations between baseline factors and 12 month clinical and endoscopic response and remission. The primary focus was on the association between these outcomes and bio-exposure status. Results: A total of 198 patients were included, of whom 47.5% were female and 85.9% under 65 years. The majority had severe endoscopic activity at baseline (47.5%, n=87) and were bio-exposed (88.8%, n=176; 33%, n=66 prior failure of 3 or more biologics). Patients were followed for a median of 12.8 (IQR 8.2 to 22.1) months after induction. The overall clinical remission rates were 41.3% (69/167), 38.1% (56/147), and 43.6% (58/133) at 3, 6 and 12 months, respectively. Endoscopic remission rates (MES=0) were 8.0% (7/88), 18.7% (23/123), and 12.5% (11/88) at 3, 6, and 12 months, respectively, and consistently higher in bio-naïve patients compared to bio-exposed patients through 12 months (p<0.05 at all time points). Bio-naive patients were more likely to achieve endoscopic remission compared to bio-exposed (HR=5.40, 95% CI: 1.08-26.93). Adverse events were reported in 14.1% (18/198). Discussion: In a highly refractory and largely bio-exposed population, a substantial proportion of patients with UC treated with ustekinumab can achieve clinical and endoscopic outcomes of importance after 12 months. Prior biologic exposure is associated with lower rates of endoscopic remission.

Maternal Mortality in Missosuri: A Comparison of Definitions and Data Sources

There are multiple surveillance systems working to address the issue of maternal mortality in Missouri. These surveillance systems have key methodological differences in their definitions, terminology, inclusion criteria, and purpose. This study aims to provide an understanding of the practical effects of these programmatic differences regarding what cases are included and how this can impact the interpretations of the data and influence policy decisions. To accomplish this, death certificates identified by the Missouri Vital Statistics program, the Pregnancy Mortality Surveillance System, and the Pregnancy-Associated Mortality Review (PAMR) program were compared. Commonalities and differences were noted, demonstrating the real-world effects of the methodological differences between programs. In particular, the PAMR program includes injury deaths in the count of pregnancy-related deaths, which are not included by other surveillance systems. These differences highlight the importance of understanding the methodology and limitations of a dataset.

Budget impact analysis of subcutaneous infliximab (CT-P13 SC) for treating inflammatory bowel disease in Saudi Arabia: Analysis from payer perspective

Background The Saudi Food and Drug Authority (SFDA) has approved the subcutaneous (SC) administration of infliximab, presenting a more convenient alternative with reduced outpatient visits and diminished expenses compared to the intravenous (IV) administration. However, the financial implications of this formulation have not been examined from the perspective of Saudi payers. Methods and materials A prevalence-based budget impact model was developed to evaluate the financial effects of introducing "environment without" versus "with infliximab SC." The model’s time horizon spanned over 2 years (2021–2023), aligning with the biennial national pharmaceutical procurement cycle. The comparison focused on infliximab SC versus all available formulations of infliximab IV in the Saudi market for two inflammatory bowel diseases (IBD): Ulcerative Colitis (UC) and Crohn’s Disease (CD). Treatment comparators’ comparability and dose escalations were substantiated by published studies, utilizing dosing information from the summary of product characteristics. Drug acquisition costs were derived from SFDA registered prices, with IV formulation administration costs included. Scenario analysis assessed the budget impact of infliximab SC introduction at uptake rates ranging from 0% to 100%. Results Introducing infliximab SC demonstrated cost-saving potential in the treatment of IBD. At 100% uptake with UC patients for 2 years, infliximab SC resulted in savings of -SAR-31.9 million (-SAR29,145 per patient). Similarly, for CD, introducing infliximab SC at 100% uptake over 2 years yielded savings of -SAR106.2 million (-SAR36,585 per patient). Conclusion This study reveals that infliximab SC is associated with cost-saving potential when compared to infliximab IV formulations available in Saudi Arabia. Future research should address uncertainties related to real-world comparative effectiveness, the convenience of administration, patient tolerability, and physician acceptance of the SC formulation of infliximab, alongside comparisons with other TNF-alpha inhibitors.

Abstract 4139196: Long-term effectiveness and safety of mavacamten in a real-world, multi-center, global study: Preliminary results of COLLIGO-HCM from a diverse cohort in the United States

Introduction: The mavaCamten ObservationaL evIdence Global cOnsortium in hypertrophic cardiomyopathy (COLLIGO-HCM; ClinicalTrials.gov ID NCT06372457) is a multinational, multicenter observational research initiative aiming to describe the real-world outcomes of mavacamten for the treatment of obstructive HCM. Aims: Describe the real-world effectiveness and safety of mavacamten, measured by echo measurements and NYHA class. Methods: This retrospective study used data from medical records from two participating HCM centers in the US. Patient-level data was extracted to assess the effectiveness and safety of mavacamten post-treatment initiation through 60 weeks. Patient characteristics and outcomes were described, including echocardiogram measurements, New York Heart Association (NYHA) functional class, and safety. Results: A total of 93 patients were treated with mavacamten (mean age 60.6 ± 13.9 years, 23.7% black, 57.0% female, and 77.4% NYHA class III at baseline) with a mean follow-up of 37.0 ± 28.1 weeks ( Table ). From baseline to week 60, 3 (3.2%) patients experienced temporary treatment discontinuation, and 3 (3.2%) discontinued mavacamten due to left ventricular ejection fraction (LVEF) <50%. By week 12, 77.1% of patients had improved by ≥1 NYHA class. The percentage increased to 89.5% by week 24 and remained stable through week 60. Mean changes from baseline in resting and Valsalva left ventricular outflow tract gradients were 31.8 ± 32.8 and 57.3 ± 47.3 mmHg, respectively, at week 24, and remained similar through week 60. Mean change in LVEF from baseline was 4.1 ± 7.1% at week 12 and remained largely unchanged through week 60 (Figure) . Conclusions: This study demonstrated the early and sustained effectiveness of mavacamten with one of the longest follow-ups to date, in a real-world population with a higher racial diversity and disease burden than those in the clinical trials. This data further substantiates the effectiveness and safety profile of mavacamten.

Lecanemab's Path Forward: Navigating the Future of Alzheimer's Treatment in Europe Amidst the EMA's Rejection.

Lecanemab (Leqembi©, Biogen), a humanized anti-amyloid-beta monoclonal antibody, has been approved for early-stage Alzheimer's disease (AD) in several countries, including the US and Japan. However, the European Medicines Agency (EMA) recently issued a negative opinion on its marketing authorization, reflecting concerns over the clinical value and manageability of anti-amyloid treatments. This decision highlights the ongoing disconnect between research advancements and clinical practice, where the focus on biological markers over tangible clinical improvements remains contentious. Despite promising biological effects, lecanemab's clinical outcomes have been modest, raising questions about its therapeutic role. The EMA's refusal underscores the need to address doubts surrounding the real-world effectiveness and safety of such treatments, especially concerning amyloid-related imaging abnormalities (ARIAs), a common side effect observed in clinical trials. The recent approval of lecanemab by the UK's Medicines and Healthcare products Regulatory Agency, despite the National Institute for Health and Care Excellence's rejection on cost-effectiveness grounds, further fuels the debate on the feasibility of anti-amyloid therapies. This commentary emphasizes the importance of real-world data on lecanemab's impact on cognitive decline, daily functioning, and side-effect management. As the global clinical use of lecanemab increases, continuous and standardized reporting on its outcomes is crucial for guiding future regulatory decisions and for potentially bridging the gap between research and practice in AD treatment.

Real-World, Observational, Retrospective Study to Evaluate the Effectiveness and Safety of Treatment with Sorafenib in Patients with Advanced Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) accounts for approximately 90% of liver cancer cases. Sorafenib, the first drug to demonstrate survival benefits for advanced HCC, was validated through the SHARP randomized clinical trial (RCT). While RCTs are essential for assessing new therapies, real-world studies provide additional insights into their effectiveness in routine clinical practice. This study aimed to evaluate sorafenib’s real-world effectiveness by analyzing overall survival (OS) and the time to radiological and symptomatic progression. Methods: Data from 368 patients treated with sorafenib at a Brazilian Cancer Center between 2009 and 2020 were retrospectively reviewed. Results: The median OS was 9.6 months, and the time to radiological progression was 5.3 months, similar to the SHARP trial. However, the time to symptomatic progression was shorter (2.3 months) than the SHARP study (4.1 months). In terms of safety, 27.4% of patients presented clinically relevant toxicities, and 24.5% needed to discontinue treatment due to toxicity. Conclusions: Overall, sorafenib demonstrated effectiveness in the studied population, with OS and radiological progression times comparable to SHARP study results. The difference in symptomatic progression may be due to the study’s retrospective nature and limitations.

Assessing Atorvastatin’s Real-World Effectiveness in Patients with Type 2 Diabetes Mellitus for the Primary Prevention of Cardiovascular Events

Assessing Atorvastatin’s Real-World Effectiveness in Patients with Type 2 Diabetes Mellitus for the Primary Prevention of Cardiovascular Events

Real-world effectiveness and safety of simnotrelvir/ritonavir for COVID-19: A nationwide, multicenter, prospective, observational cohort study in China

Real-world effectiveness and safety of simnotrelvir/ritonavir for COVID-19: A nationwide, multicenter, prospective, observational cohort study in China

Tumor Necrosis Alpha (TNF-α) Antagonists Used in Chronic Inflammatory Rheumatic Diseases: Risks and their Minimization Measures.

Tumor necrosis factor alpha (TNF- α) inhibitors are widely employed for the management of chronic inflammatory rheumatism. However, their usage carries significant risks, including site and infusion reactions, serious infections, malignancy, heart failure autoimmune and demyelinating disorders. These risks are comprehensively outlined in risk management plans (RMPs) associated with these molecules. RMP provides information on the safety profile of a medicinal product as well as the measures that will be taken to minimize risks; these are known as risk minimization measures. These measures are divided into routine measures related to elements, such as the summary of product characteristics, labeling, pack size, package leaflet, or legal supply status of the product, while additional measures may include educational programs, including tools for healthcare providers and patients, controlled access or pregnancy prevention programs, among others. Additional measures can consist of one or more interventions that need to be implemented in a sustainable way in a defined target group, while respecting the timing and frequency of any intervention and procedures to reach the target population. An evaluation of the effectiveness of these measures is required to determine whether or not an intervention has been effective. This comprehensive review offers an in-depth exploration of the current treatment, uses, and associated risks of TNF-α inhibitors. Additionally, it provides a detailed account of risk minimization measures and risk management practices while shedding light on their real-world implementation and effectiveness.

Real-World safety and effectiveness of evolocumab in primary hypercholesterolemia and mixed dyslipidemia in Saudi Arabia

IntroductionEvolocumab’s short-term efficacy and safety were proven in phase-3 clinical trial, but its long-term safety and effectiveness in the Saudi population are yet to be studied. The aim of this study was to assess the long-term safety and effectiveness of evolocumab in Saudi patients with primary hypercholesterolemia or mixed dyslipidemia. MethodA retrospective cohort study evaluated adult patients who had newly been prescribed evolocumab for hypercholesterolemia or mixed dyslipidemia. Safety events included myocardial infarction, unstable angina, stroke, transient ischemic attack, heart failure, rhabdomyolysis, renal dysfunction, and myalgia. Effectiveness outcomes included changes in lipid profiles from baseline, assessed at 6-, 12-, 18-, and 24-month. ResultsThe study sample were 469 who newly prescribed evolocumab, from which 69.1 % being male, were included. The most prevalent comorbidities were coronary artery disease, diabetes, and hypertension. Statin was the most commonly used therapy. The most common adverse events at 6-month follow-up, based on the incidence rate per 1000 person-years, were coronary revascularization (63.20), myalgia (44.96), myocardial infarction (31.53), unstable angina (31.49), heart failure (26.94), rhabdomyolysis without renal dysfunction (8.93), transient ischemic attack (4.46), and rhabdomyolysis with renal dysfunction (4.46). Stroke incidence increased with follow-up length, from 8.87 per 1000 person-years at 6 months to 12.84 per 1000 person-years at 24 months. Evolocumab use significantly reduced LDL and total cholesterol levels at 6, 12, 18, and 24 months follow-up, while having no significant effect on HDL or triglycerides levels. ConclusionEvolocumab appeared to be safe and effective therapeutic option for patients with primary hypercholesterolemia or mixed dyslipidemia to potentially reduce LDL levels to therapeutic levels when statins are insufficient.

Real world effectiveness of oral semaglutide: Focus on patients with type 2 diabetes older than 75 years

AimData on the efficacy of oral semaglutide (OS) in elderly patients with type 2 diabetes are still lacking. This study evaluates the effectiveness of OS in a real world setting with a large ≥75 year old population. MethodsThis study includes all type 2 diabetic patients who started OS between October 2021 and December 2023 in seven diabetes centers. Data were collected at baseline, 6 (T6) and 12 (T12) months. Effectiveness measures were assessed on the total sample and by patient age (<65, 65–75, >75 years). ResultsOverall 1824 patients started OS, of those 18.7 % were over 75 years (>75 yr). OS resulted in a significant reduction in rate of patients using sulphonylureas, rapid and basal insulin therapy, HbA1c reduced by 0.87 % at T6 and at T12 (both p < 0.0001), body weight by 2.78 Kg (p < 0.0001) at T6 and 3.89 Kg (p < 0.0001) at T12. Similarly, >75 yr showed HbA1c reduction at T6 (p < 0.0001) and T12 (p = 0.0003), body weight significantly reduced (p for interaction 0.005) both at T6 (−1.57 Kg; p = 0.0003) and T12 (−2.74 Kg; p < 0.0001). ConclusionIn our study, OS results efficacy in non-elderly and elderly patients, making it an effective treatment option also for very elderly type 2 diabetic patients.

Tele-collaborative outreach to rural patients with chronic pain: pragmatic effectiveness trial protocol for the CORPs study.

Despite the increased availability of evidence-based treatments for chronic pain, many patients in rural areas experience poor access to services. Patients receiving care through the VA may also need to navigate multiple systems of care. To examine the effectiveness of a remotely delivered collaborative care intervention for improving pain interference among veterans with high-impact chronic pain living in rural areas. We will conduct a four-site pragmatic effectiveness trial of remotely delivered collaborative care for high-impact chronic pain. Participants (n = 608) will be randomized to the Tele-Collaborative Outreach to Rural Patients (CORPs) intervention or to minimally enhanced usual care (MEUC). Participants randomized to CORPs will complete a biopsychosocial assessment and five follow-up sessions with a nurse care manager (NCM), who will collaborate with a consulting clinician to provide personalized recommendations and care management. CORP participants will also be invited to a virtual 6-session pain education group class. Participants randomized to MEUC will receive a one-time education session with the NCM to review available pain services. All participants will complete quarterly research assessments for one year. The primary study outcome is pain interference. This trial will oversample veterans of female birth sex and minoritized race or ethnicity to test heterogeneity of treatment effects across these patient characteristics. We will conduct an implementation process evaluation and incremental cost-effectiveness analysis. This pragmatic trial will test the real-world effectiveness of a remotely delivered collaborative care intervention for chronic pain. Study findings will inform future implementation efforts to support potential uptake of the intervention.

Atezolizumab/bevacizumab and lenvatinib for hepatocellular carcinoma: A comparative analysis in a European real-world cohort.

Immunotherapy-based combinations are currently the standard of care in the systemic treatment of patients with HCC. Recent studies have reported unexpectedly long survival with lenvatinib (LEN), supporting its use in first-line treatment for HCC. This study aims to compare the real-world effectiveness of LEN to atezolizumab/bevacizumab (AZ/BV). A retrospective analysis was conducted to evaluate the effectiveness and safety of frontline AZ/BV or LEN therapy in patients with advanced HCC across 18 university hospitals in Europe. The study included 412 patients (AZ/BV: n=207; LEN: n=205). Baseline characteristics were comparable between the 2 treatment groups. However, patients treated with AZ/BV had a significantly longer median progression-free survival compared to those receiving LEN. The risk of hepatic decompensation was significantly higher in patients with impaired baseline liver function (albumin-bilirubin [ALBI] grade 2) treated with AZ/BV compared to those with preserved liver function. Patients with alcohol-associated liver disease had poorer baseline liver function compared to other etiologies and exhibited a worse outcome under AZ/BV. In this real-world cohort, survival rates were similar between patients treated with LEN and those treated with AZ/BV, confirming that both are viable first-line options for HCC. The increased risk of hepatic decompensation in patients treated with AZ/BV who have impaired baseline liver function underscores the need for careful monitoring. Future trials should aim to distinguish more clearly between metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease.

Real-world effectiveness of nirmatrelvir-ritonavir and molnupiravir in non-hospitalised adults with Covid-19: a population-based, retrospective cohort study cohort study

ObjectivesThe real-world effectiveness of the oral antivirals nirmatrelvir-ritonavir and molnupiravir against the SARS-CoV-2 Omicron variant remains uncertain. We aimed to estimate their effectiveness in non-hospitalised adults with Covid-19. MethodsThis retrospective cohort study used data from the Municipal Department for Public Health Services of Vienna, Austria, to identify non-hospitalised adults with confirmed SARS-CoV-2 infection between Jan-2022–May-2023. Nirmatrelvir-ritonavir users were compared with untreated controls and molnupiravir users with untreated controls by calculating adjusted risk differences (aRDs) using a covariate-adjusted logistic regression model with inverse probability weighting. Outcomes were hospitalisation and all-cause death within 28 days. ResultsWe identified 113,399 eligible cases (90,481 untreated controls, 12,166 nirmatrelvir-ritonavir users, and 10,752 molnupiravir users). Over 96% of the patients were immunised by previous infection or vaccination. In the nirmatrelvir-ritonavir analysis, the estimated risk of hospitalisation was 0.57% (95%CI, 0.35–0.78) in nirmatrelvir-ritonavir users and 1.09% (95%CI, 0.86–1.32) in untreated controls (aRD -0.53%; 95%CI, -0.77–-0.28). The estimated risk of death was 0.0% (95%CI, 0.0–0.0) in nirmatrelvir-ritonavir users and 0.13% (95%CI, 0.08–0.18) in untreated controls (aRD -0.13%, 95%CI, -0.18–-0.08). The number needed to treat to prevent hospitalisation and death was 190 (95%CI, 130–356) and 792 (95%CI, 571–1289), respectively. These statistically significant aRDs were restricted to the subgroup of patients ≥60 years. In the molnupiravir analysis, the estimated risk of hospitalisation was 1.36% (95%CI, 0.95–1.77) in molnupiravir users and 1.16% (95%CI, 0.93–1.39) in untreated controls (aRD 0.2%; 95%CI, -0.08–0.49). The estimated risk of death was 0.12% (95%CI, 0.01–0.23) in molnupiravir users and 0.14% (95%CI, 0.06–0.21) in untreated controls (aRD, -0.01%; 95%CI, -0.08–-0.06). ConclusionsAmong outpatients aged ≥60 years with Covid-19 in an Omicron-dominated era, treatment with nirmatrelvir-ritonavir was associated with a lower risk of hospitalisation and all-cause death within 28 days, albeit with wide confidence intervals and high numbers needed to treat. This finding was not observed in molnupiravir users and younger nirmatrelvir-ritonavir users.

Use, perceptions, and effectiveness of e-cigarettes for smoking cessation among older adults in England: a population study, 2014–2024

BackgroundThis study aimed to characterise patterns of tobacco smoking and vaping among older adults (≥ 65 years) in England, to explore harm perceptions of e-cigarettes among those who smoke, and to estimate the real-world effectiveness of e-cigarettes for helping older adults to stop smoking.MethodsData were collected as part of a representative monthly cross-sectional household survey in England between April 2014 and April 2024 (n = 197,219). We analysed differences between older (≥ 65 years) and younger/middle-aged adults (18–64 years) in (a) time trends in tobacco smoking and vaping, (b) harm perceptions of e-cigarettes vs. cigarettes (adjusting for gender, socioeconomic position, and vaping status), and (c) the real-world effectiveness of e-cigarettes for smoking cessation (adjusting for gender, socioeconomic position, characteristics of the quit attempt, and use of other evidence-based cessation aids).ResultsTobacco smoking prevalence remained relatively unchanged over time among older adults (at ~ 9%; 9.5% [8.5–10.6%] in April 2014 and 8.7% [7.7–9.8%] in April 2024) but vaping prevalence increased (from 2.1% [1.6–2.7%] to 3.7% [3.0–4.6%], respectively). These trends differed from those observed among younger/middle-aged adults, among whom there was a clear decline in smoking (from 21.8% [21.0–22.7%] to 18.2% [17.3–19.0%]) and a larger increase in vaping (from 5.6% [5.2–6.1%] to 16.2% [15.3–17.0%]). Older adults were consistently less likely than younger/middle-aged adults to use e-cigarettes to support attempts to quit smoking (26.8% [17.2–39.3%] vs. 43.7% [39.6–48.0%] in April 2024). Older smokers reported greater uncertainty about the harms of e-cigarettes compared with cigarettes (ORadj = 2.48 [2.28–2.69]). E-cigarettes appeared to be effective for helping older adults to stop smoking (ORadj = 1.50 [0.96–2.34]); whether effectiveness was lower than for younger/middle-aged adults was inconclusive.ConclusionsOver the past decade, smoking prevalence has remained stable among older adults while decreasing among the rest of the adult population in England. Older adults are more unsure about the relative harms of e-cigarettes and less likely to use them to support attempts to quit smoking, despite evidence that they are effective for smoking cessation in this population.

Robust Evidence in Integrative Medicine: Innovations, Challenges, and Future Directions

Integrative Medicine (IM), which includes therapies such as acupuncture, herbal medicine, yoga, and meditation, is gaining attention for managing chronic pain conditions. However, concerns about the quality of evidence supporting the use of these interventions persist. The 5th Annual Jaseng Academic conference 2024, in Seoul, South Korea, themed "Robust Evidence in Integrative Medicine: Innovations, Challenges, and Future Directions," addressed these concerns by focusing on advancements in study design, evidence synthesis, and open science practices. This conference proceeding summarizes key insights from the conference, emphasizing the role of pragmatic randomized controlled trials (pRCTs) in evaluating real-world effectiveness, and addressing the complexities involved in IM research such as sham controls. The integration of IM therapies into comprehensive pain management strategies (particularly in Korea), supported by government-backed research and policy initiatives was also discussed. Advancements in methodologies were addressed, such as bibliometric analysis, evidence mapping, and the development of clinical practice guidelines (CPGs) for integrative therapies. These methodologies offer valuable insights but face challenges due to the heterogeneity of IM interventions, and potential synergistic or antagonistic effects when combined with conventional medicine. Finally, the potential of open science to enhance transparency, reporting, and reproducibility in IM was explored, emphasizing the increased role of adherence to reporting guidelines (CONSORT and PRISMA). The future of IM research is built upon the continued efforts of refined study designs, rigorous evidence synthesis, and the integration of open science principles, for a robust and more credible evidence base.

Real-world effectiveness of palbociclib plus endocrine therapy in HR+/HER2- advanced breast cancer: final results from the POLARIS trial.

Strict eligibility criteria for participation in randomized clinical trials (RCTs) often limit the generalizability of data when applied to a more heterogeneous real-world population. Thus, evidence generated directly from real-world populations, including subgroups underrepresented in RCTs, can help inform routine clinical practice. POLARIS (NCT03280303), a prospective, observational, multicenter, cohort study, evaluated patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) receiving palbociclib + endocrine therapy (ET) in routine care. Demographics, baseline characteristics, and treatment patterns were summarized descriptively. Real-world response and clinical benefit rates, real-world progression-free survival (rwPFS), and overall survival (OS) were summarized descriptively by line of therapy and endocrine partner in the overall cohort and various subgroups. Between January 2017 and October 2019, 1250 patients (median age of 64.0 years) initiated treatment with palbociclib-based therapy, including 901 in the first-line (1L) setting and 349 in the second-line or later (≥2L) settings. Real-world response and clinical benefit rates with palbociclib + ET were 34.0% and 69.4%, respectively, in 1L, and 21.8% and 57.9% in ≥2L. Median rwPFS was 20.9 (95% CI, 18.7-24.7) and 13.5 (10.6-17.1) months, and median OS was 48.5 (42.0-not estimable) and 37.2 (31.2-40.8) months, with 1L and ≥2L palbociclib + ET, respectively. Outcomes in this large, heterogeneous, real-world population are generally consistent with previously reported results from clinical trials and other real-world studies, further supporting the use of palbociclib + ET in patients with HR+/HER2- ABC. NCT03280303 (ClinicalTrials.gov).

Real world effectiveness of early ensitrelvir treatment in patients with SARS-CoV-2, a retrospective case series

BackgroundEnsitrelvir, a 3C-like protease inhibitor, received emergency approval in Japan in November 2022 for treating non-hospitalized patients with mild-to-moderate COVID-19. However, confirmation of its real-world clinical effectiveness is limited. MethodsThis retrospective study evaluated 18 vaccinated outpatients (15 men; median age, 39.5 years; range, 26–56), treated with a 5-day oral ensitrelvir regimen (375 mg loading dose, followed by 125 mg daily) between December 1, 2022, and January 31, 2023. Nasal swabs were collected on days 0, 3, 6, and 9 for RT-qPCR to assess viral load. Variants were identified by Sanger sequencing, and outcomes were compared to historical controls. Patients were followed for 60 days to monitor for post-acute sequelae of COVID-19 (PASC). ResultsSymptoms such as mild fever and sore throat improved rapidly after one day of ensitrelvir treatment, with 66 % of patients recovering within six days. All individuals were infected with the BA.5 Omicron variant. Viral loads, as measured by Ct values, increased significantly from 21.82 at symptom onset to 37.65 b y day 6, with SARS-CoV-2 RNA undetectable in most patients by day 9. Those treated within 48 h of symptom onset showed the viral load reduction. Compared to historical controls, where symptom resolution took 8.5 days, ensitrelvir shortened recovery time to as little as 1.4 days for over 66 % of patients. ConclusionEnsitrelvir treatment resulted in rapid symptom relief and significant viral load reduction, with no adverse events, viral rebound, or PASC symptoms, demonstrating its potential efficacy and safety. Larger studies are needed for further confirmation.

Positive effects from the introduction of fully subsidised nicotine replacement therapy in Ireland

Abstract Smoking remains a leading cause of preventable death in the Europe. Despite recent declines in prevalence, the adverse health and economic effects of smoking are felt disproportionately by disadvantaged groups. Nicotine replacement therapy (NRT) is well established as an effective smoking cessation aid; however, its financial cost may act as a barrier to uptake. In February 2023, eligibly for fully subsidised NRT was expanded to all users of smoking cessation services in Ireland. This study evaluated the impact of universal access to NRT on smoking cessation. This study utilised secondary analysis of routinely collected data from service users attending Irish smoking cessation services. Individuals were followed for twelve weeks. Changes in self-reported quit status and NRT use were analysed before (January 2021 - February 2023) and after (March 2023 - December 2023) the introduction of fully subsidised NRT. Logistic regression modelling identified factors associated with smoking cessation. The total number of participants was 19,717. There was higher uptake of NRT among service users who were eligible for free NRT (59% vs 40%, p &amp;lt; 0.001) and higher quit rates at four (41% vs 29%, p &amp;lt; 0.001) and twelve (29% vs 20%, p &amp;lt; 0.001) weeks. Logistic regression models demonstrated that NRT use was significantly associated with smoking cessation at four (aOR 1.88, 95%CI 1.47 - 2.41) and twelve (aOR 1.76, 95%CI 1.37 - 2.28) weeks. This study confirms the effectiveness of NRT in an Irish context and illustrates the benefits of universal access to this life saving medicine. Targeted interventions are required to intensify services offered to disadvantages groups if the ambitious objectives of Tobacco Endgame are to be achieved. These findings represent an urgent call to action for European policy makers to deliver equitable access to NRT across the continent. Such action can transform the public health landscape and help bring us closer to achieving a tobacco free Europe. Key messages • This study confirms the real-world effectiveness of NRT use as a smoking cessation aid. • The removal of financial barriers is associated with increased NRT use and successful smoking cessation.

The effects of angiotensin receptor-neprilysin inhibitors on clinical outcomes in heart failure with mildly reduced or preserved ejection fraction: real-world evidence from the CCA Database-HF Center

Abstract Background Recent clinical trials have demonstrated the potential efficacy and safety of angiotensin receptor-neprilysin inhibitors (ARNI) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction. Nevertheless, the generalizability of these findings in real-world clinical settings remains to be determined. We aimed to compare the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB)on clinical outcomes in HF patients with mildly reduced or preserved ejection fraction. Methods Patient-level data was derived from the China Cardiovascular Association Database-HF Center Registry. We included exclusively a subpopulation of HF patients with left ventricular ejection fraction (LVEF) &amp;gt;40% and comorbid with hypertension. Patients prescripted with ARNI at discharge and sustaining to ARNI therapy during follow-up were categorized as the ARNI group, while those maintaining the usage of ACEI/ARB after discharge were designated as the ACEI/ARB group. In complete cases, the primary endpoint of all-cause mortality at one year was assessed by the 1:1 propensity score matching (PSM) method. Results In all HF patients with LVEF &amp;gt;40% comorbid with hypertension, the usage of ARNI has increased from 0.9% in 2017 to 37.2% in 2021. A total of 3348 patients in the ARNI group and 7688 patients in the ACEI/ARB group were identified for comparative effectiveness. After 1:1 PSM, 5482 patients were included in the primary analysis, with 2741 patients in each treatment arm. The proportion of patients receiving higher dosages of ARNI (200mg/d and 400mg/d) was 20.9%, 26.6%, 29.2%, and 30.3% at discharge, 1-month, 3-month, and 1-year, respectively. Over the 1-year follow-up, ARNI was associated with a 20% relative reduction in all-cause death compared to the ACEI/ARB therapy (10.5% vs. 12.9%, adjusted hazard ratio [HR], 0.80 [95% CI, 0.69-0.94], P=0.005). The absolute risk difference in all-cause death between ARNI and ACEI/ARB arms was 2.88 per 100 patient-years (incidence rate difference, -2.88 [95% CI, -4.86 to -0.9]). Cardiovascular death also tended to decrease in the ARNI group but with missed statistical significance (4.5% vs. 4.9%, adjusted HR, 0.89 [95% CI, 0.70-1.14], P=0.373). Treatment benefits were more significant in those with LVEF between 40-50% (adjusted HR, 0.62 [95% CI, 0.48-0.79]), 50-60% (adjusted HR, 0.85 [95% CI, 0.68-1.06]), but not observed in HF patients with LVEF&amp;gt;60% (adjusted HR, 1.80 [95% CI, 1.08-2.98]; Pinteraction&amp;lt;0.001). Conclusion In real-world clinical settings, treatment with ARNI was associated with a significant relative risk reduction in all-cause mortality compared with ACEI/ARB in HF patients with mildly reduced or preserved LVEF. The cardiovascular benefit was concentrated in patients with LVEF ≤60%.