Real-world Analyses Research Articles

Advancing Interpretable Regression Analysis for Binary Data: A Novel Distributed Algorithm Approach.

Sparse data bias, where there is a lack of sufficient cases, is a common problem in data analysis, particularly when studying rare binary outcomes. Although a two-step meta-analysis approach may be used to lessen the bias by combining the summary statistics to increase the number of cases from multiple studies, this method does not completely eliminate bias in effect estimation. In this paper, we propose a one-shot distributed algorithm for estimating relative risk using a modified Poisson regression for binary data, named ODAP-B. We evaluate the performance of our method through both simulation studies and real-world case analyses of postacute sequelae of SARS-CoV-2 infection in children using data from 184 501 children across eight national academic medical centers. Compared with the meta-analysis method, our method provides closer estimates of the relative risk for all outcomes considered including syndromic and systemic outcomes. Our method is communication-efficient and privacy-preserving, requiring only aggregated data to obtain relatively unbiased effect estimates compared with two-step meta-analysis methods. Overall, ODAP-B is an effective distributed learning algorithm for Poisson regression to study rare binary outcomes. The method provides inference on adjusted relative risk with a robust variance estimator.

Doxycycline Post-Exposure Prophylaxis for Bacterial Sexually Transmitted Infections: The Current Landscape and Future Directions.

The incidence of bacterial sexually transmitted infections (STI) continues to rise particularly among men who have sex with men (MSM). Doxycycline post-exposure prophylaxis (doxy-PEP) has emerged as a promising biomedical prevention strategy. This review aims to summarize the results of recent studies, highlight the current normative guidance on the use of doxy-PEP, and discuss remaining questions. In the past decade, there have been four randomized controlled trials and three real-world analyses of doxy-PEP, which consistently demonstrated a reduction in Chlamydia trachomatis and Treponema pallidum infections among MSM. Questions remain regarding the efficacy of doxy-PEP for Neisseria gonorrhoeae infection and among cisgender women. Possible detrimental impacts include an increase in antimicrobial resistance as well as alterations to the gut microbiome Doxy-PEP is an effective strategy for preventing Chlamydia trachomatis and Treponema pallidum among MSM. Further work is needed to investigate the benefits among other populations, as well as to monitor for adverse effects.

Working on new applications: Use of economic evaluation in burden of disease estimates

Abstract Burden of disease (BoD) analyses provide policy-makers with useful evidence to prioritise policy responses to major public health threats. Increasingly, however, epidemiological data alone is not considered as sufficient to inform decisions, particularly when funding is allocated within a single government approach and different sectors compete for a larger share of the overall budget. Similarly, other funders, such as charities and foundations, may want to prioritise budget allocation between health and non-health objectives. In all these cases, traditional BoD analyses need to be complemented by economic evaluations. In its simplest form, the economic component may mean adding an assessment of the healthcare costs caused by the diseases in the study. A more comprehensive, though still with limitations, approach is to use monetary values to measure the extent to which individuals are willing to exchange their income - which can be spent on other things - for the health outcomes they experience. Finally, in its most advanced and comprehensive form, analyses can include assessments of a number of relevant dimensions, such as those in the OECD’s Better Life Index. The latter approach is also consistent with, and its results support the implementation of, a health in all policies approach. This presentation will look at traditional and innovative approaches that can be used to add an economic dimension to BoD analyses. After introducing the rationale and key methodological issues of each approach, the presentation will discuss the advantages and disadvantages of each methodology and will identify areas where their use can be beneficial in guiding the decision-making process. Examples of the use of these methodologies in real-world analyses will also be presented to support the theoretical part of the discussion.

Temporal trends in lipid management among Korean patients following acute myocardial infarction from 2011 to 2020

Abstract Background/Purpose Real-world data trends on dyslipidaemia prevalence and lipid management for patients following acute myocardial infarction (AMI) are lacking in South Korea, one of the Asia-Pacific nations. Our study aimed to evaluate the 10-year temporal trends of dyslipidaemia prevalence and lipid management in this patient population. Methods The study utilized datasets from two Korean AMI observational cohort (2011–2020) including a total of 26,751 participants (Figure 1A). The primary endpoints were as follows: (1) absolute low-density lipoprotein cholesterol (LDL-C) target of <70 mg/dL; (2) relative LDL-C target of >50% LDL-C reduction from the baseline; (3) absolute or relative LDL-C target (American target); and (4) both absolute and relative LDL-C targets (European target). Results The prevalence of dyslipidaemia increased from 11.1% to 17.1% (Table 1, Figure 1B), while the statin prescription rates increased from 92.9% to 97.0% from 2011 to 2020. High-intensity statin use increased from 12.80% in 2012 to 69.30% in 2020 (Table 1) Interestingly, the yearlong substantial increases in the prescription rates of high-intensity statins were prominent between 2013 (21.9%) and 2014 (37.7%) and between 2018 (52.4%) and 2019 (66.1%), which may have been influenced by major revisions to the international lipid management guidelines and their adoption (Figure 1C). Ezetimibe use increased from 4.50% in 2016 to 22.50% in 2020. The achievement rate of the absolute and relative LDL-C targets increased from 41.4% and 20.8% in 2012 to 62.5% and 39.5% in 2019, respectively (Table 1). The achievement rates of the American (45.7% in 2012 to 68.6% in 2019) and European (16.5% in 2012 to 33.8% in 2019) targets showed similar increasing trends (Table 1, Figure 1D). Conclusions Despite the adoption of lipid management guidelines in clinical practice has improved, some patients some patients are unable to reduce their LDL-C concentrations to their target levels. Our real-world analyses emphasise the need for multidirectional and continued efforts to optimise lipid management and improve the clinical outcomes in these patients.Figure 1

Hybrid random projection technique for enhanced representation in high-dimensional data

This paper introduces a novel hybrid random projection method (HRP) that effectively combines the strengths of normal random projection (NRP) and plus-minus one random projection (PMRP). By incorporating a blending parameter, HRP optimises the contributions of the NRP and PMRP, reducing the dimensions of the data while ensuring that the structure of the data is preserved. Conventional methods, such as NRP and PMRP, are recognised for their benefits; however, they also have limitations. NRP is generally accurate but can encounter difficulties with certain data types or noise. The PMRP is simple, but occasionally fails to capture complex relationships within the data. The performance of HRP is investigated through comprehensive evaluations, including simulations and real-world data analyses from key machine learning datasets, such as period change, toxicity, MNIST, and human activity recognition (HAR). We examine various factors such as sample size, dimensions of the original and reduced data, and sparsity. Distance distortion is the primary metric utilised to measure performance, and indicates how well the dataset structure is maintained after dimension reduction. In every test, HRP consistently demonstrates the least distance distortion, performing superiorly to the NRP and PMRP. This is true for a range of scenarios and datasets. HRP represents a significant advancement in dimension reduction techniques. Its ability to minimise information loss during the reduction process demonstrates its potential as a powerful tool for managing complex high-dimensional data in practical applications. This renders HRP an important development in the fields of machine learning, intelligent systems, and artificial intelligence, offering improved efficiency and precision in data analyses.

A review of serious adverse events linked with GLP-1 agonists in type 2 diabetes mellitus and obesity treatment.

Glucagon-like peptide-1 (GLP-1) agonists play a crucial role in treating type 2 diabetes mellitus and obesity by providing glycemic control and aiding weight management. Despite their widespread use, concerns about serious adverse events have prompted extensive research. This review aims to describe the current understanding of serious adverse events associated with GLP-1 agonists. A comprehensive search of PubMed, Google Scholar and Embase databases was performed starting from 2010. Studies reporting evidence of an association between GLP-1 agonists and serious adverse events from 22 articles (5 case reports, 5 randomized controlled trials (RCTs), 9 real-world data cohort analyses, 2 meta-analyses and 1 systematic review and meta-analysis) were included and categorized by the type of adverse event. While some studies reported risks, including anaphylaxis, cardiovascular, gastrointestinal, psychiatric and thyroid-related events, others found no significant associations. The evidence remains mixed, necessitating further research to fully understand the safety profile of GLP-1 agonists and inform clinical practice.

Adopting a Framework for Rapid Real-World Data Analyses in Safety Signal Assessment

The expanding availability of real-world data (RWD) has led to an increase in both the interest and possibilities for using this information in postmarketing safety analyses and signal management. While there is enormous potential value from the safety insights generated through RWD, the analysis preparation, execution, and communication required to reliably deliver the evidence can be time consuming. Since the safety signal assessment process is a regulated and timebound process, any supporting RWD analyses require a rapid turnaround of well-designed and informative results. To address this challenge, a TransCelerate BioPharma working group was formed and developed a framework to help teams responsible for safety signal assessment overcome the challenges of working with RWD rapidly to deliver analyses within regulatory timelines. Here, a previously performed safety assessment was evaluated within the context of the developed framework to illustrate how the framework may be adopted in practice.

Fruquintinib in metastatic colorectal cancer: a multicenter real-world analysis on efficacy, safety, and predictive and prognostic factors.

Randomized trials have shown a survival benefit for fruquintinib over placebo in patients with metastatic colorectal cancer (mCRC) that progressed after standard therapies, but real-world prognostic analyses have been seldom reported. We evaluated survival, safety outcomes, and predictive and prognostic factors in patients treated with fruquintinib in a real-life setting. We conducted a multi-center study by collecting relevant data on patients with advanced colorectal cancer (CRC) who received fruquintinib, focusing on progression-free survival (PFS), overall survival (OS), and L3 skeletal muscle index (SMI), including safety follow-up. From January 2020 to January 2022, a total of 140 patients were selected and included in this study. The cut-off date was 30 July 2022. The median follow-up time was 18.3 months (range, 6-29.3 months) and the median age of included cases was 63 years (range, 32-81 years). The median PFS and OS for the 140 patients was 6.3 and 12.6 months, respectively. The median PFS and OS for the 76 patients who were included in SMI analysis was 6.0 and 12.0 months, respectively. Multivariate analysis suggested brain metastasis {hazard ratio (HR) [95% confidence interval (CI)]: 2.779 (1.162-6.646), P=0.02}, decrease in SMI of >5% [HR (95% CI): 9.732 (2.201-43.028), P=0.003], and baseline carcinoembryonic antigen (CEA) level [HR (95% CI): 4.061 (1.391-11.858), P=0.01] as independent predictors of OS. The most common treatment-related adverse events (TRAEs) were hypertension (24, 17.1%), fatigue (21, 15%), and hand-foot syndrome (20, 14.3%); 9 (13.6%) and 15 (10.7%) patients had dose reduction and treatment discontinuation due to TRAEs respectively. The real-world efficacy and safety of fruquintinib in advanced CRC patients are numerically superior to that in the previous phase III studies. SMI, brain metastasis and CEA could serve as potential markers for patient selection.

Source inference for misinformation spreading on hypergraphs

Source inference aims at revealing the seed of the misinformation spreading on social networks, and attracted great attention in the field of network science and cybersecurity. Extensive real-world data analyses have certificated that individual interactions exist pairwise and higher-order interactions, and thus should be described using the hypergraph. Previous studies about the source inference algorithms are mainly focused on simple graphs (i.e., a graph only has pairwise interactions) while neglecting the higher-order interactions. In this article, we propose a dynamical message-passing (DMP) algorithm to infer the misinformation spreading on hypergraphs. As a comparison, we also extend jordan centrality (JC), betweenness centrality (BC), closeness centrality (CC), and eigenvector centrality (EIG) algorithm to hypergraphs. The results show that our proposed DMP algorithm can accurately and effectively infer the propagation source on both artificial and real-world hypergraphs compared to the centrality algorithms. Even if the increase in propagation scale renders the other centrality algorithms completely ineffective, the DMP algorithm can still distinguish the real propagation sources in the form of a rank smaller than 10% of the network size. In general, our DMP algorithm provides an effective solution for inferring the misinformation source on high-order networks.

Assessing olaparib efficacy in U.S. Veterans with metastatic prostate cancer utilizing a time-indifferent g-rate method ideal for real-world analyses

We aimed to assess real-world efficacy of the PARP inhibitor, olaparib, in US Veterans with metastatic prostate cancer (mPC) by leveraging the national data repository and evaluate a novel approach to assess treatment efficacy in tumors considered rare or harboring rare mutations. Included Veterans had 1) mPC with somatic or germline alterations/mutations in genes involved in homologous recombination repair (HRR), 2) received olaparib monotherapy as well as a novel hormonal therapy/androgen receptor pathway inhibitors (NHT/ARPI), and/or chemotherapy, and 3) estimable rates of tumor growth (g-rate) using PSA values obtained while receiving treatment. Previous work has shown an excellent inverse correlation of g-rate with survival. Using g-rate, we determined tumor doubling time (DT) and DT ratios (DT on olaparib/DT on prior medication). We postulated that a DT ratio≥ 1 was associated with benefit. We identified 139 Veterans, including 42 Black males with tumors harboring mutations/alterations in HRR genes who received olaparib: BRCA2 (50), ATM (32), BRCA1 (10), other mutations (47). 62/139 (45%) of all and 21/42 (50%) of Black Veterans had DT ratios ≥1, including 31, 10, 2, and 19 with BRCA2, ATM, BRCA1, and other mutations, respectively (p=0.006). Median survival with DT ratios ≥1 was superior, being 24.5 vs. 11.4 months for DT ratio <1 (p=0.01, HR 0.50, 95% CI 0.29-0.85). Benefit from olaparib, defined as DT ratio ≥1, was not observed for germline status, starting PSA value, number of prior therapies, or immediate prior therapy. Compared to matched cohorts, tumors in the olaparib cohort had shorter DTs with enzalutamide in first line (367 vs. 884 days; p=0.0043). Using equations indifferent to timing of assessments ideal for real-world efficacy analyses, we showed DT ratio ≥1 representing slower tumor growth on olaparib relative to the prior therapy correlates with improved survival. Olaparib efficacy in Veterans with mPC harboring mutations/alterations in HRR genes emulates clinical trial results. Black men had comparable results. Compared to matched cohorts, in first line, enzalutamide was less efficacious in tumors harboring mutations/alterations in HRR genes. American Society of Clinical Oncology Conquer Cancer Foundation (ASCO CCF), the Blavatnik Family Foundation and the Prostate Cancer Foundation (PCF).

Decomposing Impact on Longitudinal Outcome of Time-Varying Covariate into Baseline Effect and Temporal Effect

Longitudinal processes are often associated with each other over time; therefore, it is important to investigate the associations among developmental processes and understand their joint development. The traditional latent growth curve model (LGCM) with a time-varying covariate (TVC) provides a method to estimate the TVC effect on a longitudinal outcome while modeling the outcome’s change. However, it does not allow the TVC to predict variations in the random growth coefficients. We propose decomposing the TVC into initial trait and temporal states using three methods to address this limitation. In each method, the baseline of the TVC is viewed as an initial trait, and the corresponding effects are obtained by regressing random intercepts and slopes on the baseline value. Temporal states are characterized as (a) interval-specific slopes, (b) interval-specific changes, or (c) changes from the baseline at each measurement occasion, depending on the method. We demonstrate our methods through simulations and real-world data analyses, assuming a linear–linear functional form for the longitudinal outcome. The results demonstrate that LGCMs with a decomposed TVC can provide unbiased and precise estimates with target confidence intervals. We also provide OpenMx and Mplus 8 code for these methods with commonly used linear and nonlinear functions.

Higher prevalence of dupilumab-induced ocular adverse events in atopic dermatitis compared to asthma: A daily practice analysis.

Dupilumab has been shown to be an effective treatment in moderate-to-severe atopic dermatitis (AD) and severe asthma (SA). However, comparative real-world analyses of adverse events (AE), particularly dupilumab-associated ocular surface disease (DAOSD), are lacking. This is the first real-world study to provide insight into the prevalence of AEs associated with dupilumab in AD compared with SA. Secondary objectives were to assess the prevalence, onset and therapeutic strategies of DAOSD and evaluate dupilumab discontinuation rates. Data from two daily practice registries including AD and SA patients receiving dupilumab treatment were analyzed. Adverse events, including DAOSD, were evaluated. In total, 322 AD and 148 SA patients were included. Headaches (23.6%), injection site reactions (10.1%), and influenza-like symptoms (13.5%) were more prevalent in SA patients. Interestingly, ocular AEs were significantly more prevalent in AD patients (62.1%, p<0.001), including conjunctivitis (17.1%, p=0.004). 88% AD and 47% SA patients with ocular AEs received one or more ophthalmic treatment(s). Additionally, 20% of AD and 17.6% of SA patients discontinued dupilumab treatment due to ocular AEs, while only 65% of these AD and none of these SA patients were referred to an ophthalmologist. The higher incidence of DAOSD in AD patients compared with SA patients in this real-world study highlights the importance of physician awareness, especially when prescribing dupilumab to AD patients. Conversely, the findings of this study help alleviate potential concerns about ocular AEs in patients with SA who do not have comorbid AD. Furthermore, the effective management of most ocular AEs with ophthalmic treatments suggests favorable tolerability of dupilumab in daily practice, and multidisciplinary collaboration is essential to proactively manage ocular AEs before discontinuing dupilumab.

Adherence and persistence to tafamidis treatment among Medicare beneficiaries in the presence of a patient assistance program

Tafamidis is the only disease-modifying therapy approved to treat patients in the United States with transthyretin amyloid cardiomyopathy (ATTR-CM), which most commonly affects patients aged ≥ 65 years. The manufacturer operates a patient assistance program (PAP) to support access to tafamidis. This study conducted Privacy Preserving Record Linking (PPRL) using Datavant tokens to match patients across Medicare prescription drug plan (PDP) and PAP databases to evaluate the impact of PAPs on treatment exposure classification, adherence, and persistence determined using Medicare PDP data alone. We found 35% of Medicare PDP patients received tafamidis through the PAP only; 14% through both Medicare PDP and the PAP, and 51% through Medicare PDP only. Adherence and persistence were comparable between these cohorts but underestimated among patients who received ≥ 2 prescriptions through Medicare PDP and ≥ 1 through the PAP when solely using Medicare data versus pooled Medicare and PAP data (modified Medication Possession Ratio: 84% [69% ≥ 80% adherent] vs. 96% [93%]; Proportion of Days Covered: 77% [66% ≥ 80% adherent] vs. 88% [88%]; mean days to discontinuation: 186 vs. 252; total discontinuation: 13% vs. 11%). Cross-database PPRL is a valuable method to build more complete treatment journeys and reduce the risk of exposure misclassification in real-world analyses.

DeepPIG: deep neural network architecture with pairwise connected layers and stochastic gates using knockoff frameworks for feature selection

Selecting relevant feature subsets is essential for machine learning applications. Among the feature selection techniques, the knockoff filter procedure proposes a unique framework that minimizes false discovery rates (FDR). However, employing a deep neural network architecture for a knockoff filter framework requires higher detection power. Using the knockoff filter framework, we present a Deep neural network with PaIrwise connected layers integrated with stochastic Gates (DeepPIG) for the feature selection model. DeepPIG exhibited better detection power in synthetic data than the baseline and recent models such as Deep feature selection using Paired-Input Nonlinear Knockoffs (DeepPINK), Stochastic Gates (STG), and SHapley Additive exPlanations (SHAP) while not violating the preselected FDR level, especially when the signal of the features were weak. The selected features determined by DeepPIG demonstrated superior classification performance compared with the baseline model in real-world data analyses, including the prediction of certain cancer prognosis and classification tasks using microbiome and single-cell datasets. In conclusion, DeepPIG is a robust feature selection approach even when the signals of features are weak. Source code is available at https://github.com/DMCB-GIST/DeepPIG.

Fast and furious: Changing gears on the road to cure with chimeric antigen receptor T cells in multiple myeloma

Based on the pivotal KarMMa-1 and CARTITUDE-1 studies, Idecabtagene vicleucel (Ide-cel) and Ciltacabtagene autoleucel (Cilta-cel) have been approved to treat multiple myeloma patients, who have been exposed to at least 1 proteasome inhibitor, immunomodulatory drug and anti-CD38 antibody after 4 or 3 lines of therapy, respectively. The unprecedented rates of deep and long-lasting remissions have been meanwhile confirmed in multiple real-world analyses and more recently, the KarMMa-3 and CARTITUDE-4 studies lead to the approval in earlier lines of therapy. It is currently believed that ultimately all patients with relapsed/refractory multiple myeloma experience relapse after anti-BCMA CAR T-cell therapies. There is a plethora of CAR T-cell therapies targeting novel antigens, with the aim to overcome current CAR T-cell resistance. In this review, we will summarize current evidence of novel antigens and their clinical potential. Together with current CAR T-cell therapy and T-cell engagers, these approaches might lead us to the next frontier in multiple myeloma: total immunotherapy and the road to chemotherapy-free cure.

Persistent effectiveness of CGRP antibody therapy in migraine and comorbid medication overuse or medication overuse headache - a retrospective real-world analysis

BackgroundManagement of patients with migraine who have concomitant medication overuse (MO) or medication overuse headache (MOH) is a major problem in clinical practice. Detoxification of acute analgesics before or during initiation of prophylactic therapy has long been recommended although this concept has recently been questioned. Additionally, relapse after detoxification is a common problem. This real-world study analyses the initial and sustained effectiveness of prophylactic migraine therapy with CGRP (receptor) antibodies without prior detoxification in patients with comorbid MO or MOH for up to one year.MethodsA retrospective real-world analysis was performed on 291 patients (episodic migraine (EM) with MO (EM-MO; n = 35), EM without MO (EM-noMO; n = 77), chronic migraine (CM) with MOH (CM-MOH; n = 109), CM without MOH (CM-noMOH; n = 70). All patients began treatment with either erenumab (n = 173), fremanezumab (n = 70) or galcanezumab (n = 48) without prior detoxification. Data were available for up to 12 months of treatment. Responder rates for monthly headache days (MHD), monthly migraine days (MMD) and monthly acute medication intake (AMD) were analysed.ResultsAll groups showed a significant reduction in MHD, MMD and AMD at the last observed time point compared to baseline. In patients with CM and MOH, 60.6% (66/109) no longer fulfilled the definition of MO or MOH and a further 13.8% (15/109) had only EM-MO. In the EM cohort, 89% (31/35) of MO patients lost their MO during therapy. MHD and AMD 30% responder rates were comparable for CM-MOH and CM-noMOH (MHD: CM-MOH: 56.0% vs. CM-noMOH: 41.4%, p = 0.058, AMD: CM-MOH: 66.1% vs. CM-noMOH: 52.9%, p = 0.077). MMD responder rate did not differ significantly (after Bonferroni adjustment) (CM-MOH: 62.4% vs. CM-noMOH: 47.1%, p = 0.045, α = 0.017). After successful initiation of therapy, 15.4% of the initial CM-MOH patients relapsed and met the criterion for CM-MOH at the end of follow-up. There were no antibody specific differences in response to therapy.ConclusionsOur data confirms the effectiveness of CGRP antibody treatment in migraine patients with additional MOH or MO in a real-world setting. Low relapse rates after initial successful therapy support an early start of CGRP antibody treatment in patients with MOH or MO.Trial registrationNo registration, retrospective analysis.Graphical

Retrospective Database Analysis of Liver-Related Clinical Events in Adult and Pediatric Patients with Alpha-1 Antitrypsin Deficiency in the United States.

Real-world analyses on burden of illness in patients with alpha-1 antitrypsin deficiency (AATD) are limited. We investigated the real-world burden of liver-related clinical events among adult and pediatric patients with AATD in the USA. This was a retrospective, observational analysis of administrative claims data from the IQVIA PharMetrics® Plus and Ambulatory Electronic Medical Records databases from 2011 to 2022. Patients had a diagnosis of liver and/or lung disease with ≥180 days of continuous enrollment in the IQVIA PharMetrics Plus database before and ≥90 days after their first diagnosis. Follow-up time was assigned to the AATD with liver disease health state or AATD with both liver and lung disease health state (for patients aged ≥18 years only). Baseline demographic characteristics and liver-related clinical events of interest were reported. Of 5136 eligible patients, 771 adult and 123 pediatric patients contributed time to the AATD with liver disease health state; 541 adults contributed time to the AATD with both liver and lung disease health state. Among adults, patients with both liver and lung disease had higher rates of liver-related clinical events than patients with liver disease alone. Ascites was the most frequently observed clinical event among adults in both health states, and the median time to the composite of any liver-related clinical event was 26.5 days among all adults combined. Across all pediatric age groups, ascites, gastrointestinal bleed and hepatic encephalopathy were more common than spontaneous bacterial peritonitis and hepatocellular carcinoma, but median time to liver-related clinical event varied by age group at index date and type of event. No liver transplantations occurred in patients aged 6-17 years. Diagnosed AATD with liver disease carries a substantial burden on adult and pediatric patients; new treatment options are warranted to avoid disease progression to decompensating events.

House dust mite immunotherapy: A real-world, prescription data-based analysis.

House dust mite (HDM) sensitisation can contribute to the development of allergic rhinoconjunctivitis (AR) or allergic asthma (AA). As treatment, allergen immunotherapy (AIT) is a promising approach, since it aims building immunotolerance against allergens, therewith establishing long-term efficacy. The evaluation of AIT has been investigated in many randomised controlled trials, whereas few real-world evidence studies are available. We used data from the longitudinal prescription data base IQVIA™ LRx. Data on initial AIT prescriptions against HDM from January 2009 to December 2013 was analysed regarding treatment (subcutaneous AIT with either depigmented polymerised allergen extract [dSCIT] or other allergens [oSCIT], or sublingual immunotherapy [SLIT]) and treatment duration. Treatment groups were compared with a control group of AR patients not receiving AIT. Data on symptomatic medication was collected until February 2017 and progression of AR and AA was compared. Data of 7260 patients with AIT prescriptions and of 21,780 control patients was analysed. AIT was associated with a significant decrease of AR medication intake compared with control (dSCIT: -34.0%, p<0.0001; oSCIT: -25.7%, p<0.0001; SLIT: -37.7%, p=0.0026). In asthmatics, SCIT was associated with a significant decrease of asthma medication compared with control (dSCIT: -45.2%, p<0.0001; oSCIT: -32.9%, p<0.0001). Further, a significantly reduced likelihood for onset of asthma medication was demonstrated in patients treated with SCIT compared with controls (dSCIT OR: 0.759, p=0.0476; oSCIT OR: 0.815, p=0.0339). Real-world data analyses indicate that AIT, particularly given via a subcutaneous route, reduces the need of medication against AR and AA and might delay the onset of asthma medication in patients with AR.

Real-world comparison of the efficacy of three CDK4/6 inhibitors (CDK4/6i) in the first-line treatment of endocrine-sensitive advanced breast cancer (aBC): Single institution experience.

e13080 Background: The combination of CDK4/6i and endocrine therapy (ET) is the standard of care in the first-line treatment of hormone receptor positive (HR+), HER2- aBC. In registrational studies, the progression-free survival (PFS) of all three CDK4/6i ranged from 23.8 to 28.12 months and overall survival (OS) from 53.9 to 66.8. In Croatia, both ribociclib and palbociclib were approved for clinical use in August 2018 and abemaciclib in November 2019. Methods: This retrospective study included patients with endocrine-sensitive HR+, HER2- aBC treated with aromatase inhibitor (AI) and CDK4/6i in the first-line setting between August 2018 and October 2023 at University Hospital Centre Zagreb. Ethics committee approval was obtained before the study was commenced. Patient demographics, clinical presentation, tumor characteristics and treatment data were collected. Real-world PFS (rwPFS) and OS analyses were done with the final data cut-off date of December 31, 2023, using type 1 right censoring. Data were analyzed using the Kaplan-Meier method. Results: Of the 274 patients treated with a combination of CDK4/6i and ET in the first-line setting, 172 with endocrine-sensitive tumors (98 de novo metastatic and 74 with treatment-free interval longer than 12 months) were eligible for the study, of which 41.86% (72/172) received ribociclib, 44.19% (76/172) palbociclib, and 13.95% (24/172) abemaciclib. Overall rwPFS was 48 months (95% CI:35-53). In the abemaciclib group, median rwPFS and OS were not reached in the follow-up period. The rwPFS was 48 (95% CI:27-53) for ribociclib and 47 (95% CI:30-49) for palbociclib. The overall OS was 62 months (95% CI:47-62). Median OS in the ribociclib group was 62 months (95% CI:40-62) and in the palbociclib group 52 (95% CI:42-54) months. Conclusions: The PFS and OS results for palbociclib and ribociclib in this retrospective real-world study correlate with results from randomized clinical trials, confirming some inferiority of palbociclib compared to ribociclib in the context of OS. Due to the later availability of the drug, larger sample size and longer follow-up will be needed to make definitive conclusions on the efficacy of abemaciclib.

Real-world outcomes of osimertinib (Osi) vs. afatinib or erlotinib in patients with classical vs. atypical EGFR-mutated metastatic non-small cell lung cancer (mNSCLC).

8566 Background: Limited data are available on the efficacy of osi for mNSCLC with atypical EGFR mutations (AM) such as L861Q, G719X, S768I, and exon20 insertions. Afatinib is FDA approved for mNSCLC harboring L861Q, G719X, and S768I. Real-world analyses comparing osi to afatinib and erlotinib for AM have yielded mixed results. Methods: We performed a single-institution retrospective analysis of patients with EGFR-mutated mNSCLC treated from 2007-2023 with EGFRTKIs. Clinical trial patients were excluded. Patients with classical EGFRmutations (CM) were compared to those with AM. Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the EMR. Median PFS and OS were estimated and compared via Kaplan-Meier log-rank analysis. Independent sample t-tests and chi-square analyses were used for univariate comparisons. P-values&lt;0.05 were considered statistically significant. Results: Among 355 patients with 1L EGFR-mutated mNSCLC, 315 (90%) had CM (exon19 del [N=182; 51%] and L858R [N=119; 34%]), while 36 (10%) harbored AM in G719X (N=21; 6%), Exon 20 (N=11; 3%), L861Q (N=7; 2%), and S768I (N=4; 1%). Patients with CM vs AM had similar median age at diagnosis (63, p=0.406), gender (65% F; p=0.213), racial composition (p=0.653), and history of smoking (44%, p=0.167). At diagnosis, 45% vs 48% of patients had CNS involvement (p=0.434). 52% vs 41% received osi, 36% vs 20% patients received erlotinib, and 11% vs 37% received afatinib (p&lt;0.001). Patients with CM had superior mPFS (29 vs 15m; p=0.021) and mOS (49 vs 13m; p&lt;0.001) vs AM (Table). In AM patients (N=36), osi had superior mPFS (15m [7-23]) vs afatinib (11m [8-15]; p=0.005) or erlotinib (8m [6-10]; p=0.001). mOS was likewise superior for osi (29m [6-50]) vs afatinib (13m [9-17]; p&lt;0.001) or erlotinib (14m [6-21]; p&lt;0.001). 121 CM and 7 AM patients were rechallenged with a TKI; mPFS2 for AM was 13m for osi (N=4) vs 4m for afatinib (N=3; p=0.114). Dose-reduction due to AE was lower for osi (19%) vs afatinib (24%; p=0.003) or erlotinib (23%; p=0.002). Discontinuation due to AE was lower for osi vs afatinib (1% vs 2%; p&lt;0.001) or erlotinib (2%; p=0.004). Conclusions: Retrospectively, AM were associated withinferior PFS and OS compared to CM. Osi demonstrated superior survival and tolerability compared to afatinib or erlotinib for AM. [Table: see text]