Real-world Cohort Of Patients Research Articles

Remote monitoring is an independent predictor of better survival in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators

Abstract Introduction Despite improvements in pharmacotherapy and advancements in invasive techniques, patients with ischemic cardiomyopathy are at high risk of adverse events and death. Strategies aimed at improving prognosis, including patient-centered individualization of care are needed. Remote monitoring (RM) of patients with heart failure, which allows for a continuous assessment of device- and some patient-related parameters, has been shown to reduce the risk of hospitalization and death, although no analyses were focused specifically on patients with ischemic cardiomyopathy after percutaneous coronary intervention (PCI). Purpose To determine whether RM is associated with outcomes in patients with ischemic cardiomyopathy after percutaneous coronary intervention. Methods The clinical, echocardiographic and angiographic data of consecutive patients with ICM and ICD or CRT-D, who had undergone PCI were obtained from the single-centre COMMIT-HF registry. Each consecutive patient with ICM was offered RM at the discretion of the treating physician. The RM center in our facility monitors patients with cardiac implantable devices in all working days. In case of any clinical, or device-related events potentially requiring reaction, patients are telephonically invited to contact healthcare system, either in the local emergency departments, or in our hospital, or outpatient clinic. Patients supervised with RM undergo routine in-person visits in the outpatient device clinic every 12 months. In the conventional arm, routine visits in the outpatient clinic occur every 6 months. The long-term data were acquired from the National Health Fund – the sole Polish healthcare provider. The primary outcome of the study was 36-month all-cause mortality. Results In the years 2009-2017, there were a total of 1019 patients with ICM and ICD, who underwent PCI, and those constituted the study group. Of those, 227 (22.3%) were monitored remotely, while the remaining were treated conventionally. The studied groups did not differ significantly, apart from that the patients with RM had a history of CABG, and had a lower mean left ventricular ejection fraction (LVEF, 26% vs 32%, p<0.001) than subjects without RM, while the percentage of CRT-D devices was significantly higher in patients with RM (36.2% vs 6.2%, p<0.001). The 36-month all-cause mortality rate was 18.9% in patients monitored remotely and 25.3% in subjects without RM (p log rank = 0.028). In the multivariable analysis, RM was identified as an independent predictor of lower mortality. The other variables independently associated with higher survival were lower age, absence of anemia, optimal glomerular filtration rate, and higher LVEF. Conclusions Remote monitoring of patients with ischemic cardiomyopathy is independently associated with lower all-cause mortality in a real-world cohort of patients with ICDs.Baseline characteristicsMultivariable analysis

Treatment patterns in a real-world cohort of patients with Wilson disease in the United States

BackgroundWilson disease (WD) is a rare and potentially fatal genetic disorder caused by accumulation of toxic levels of copper. Current treatments include chelating agents and/or zinc. We characterized real-world US treatment patterns in patients with WD.MethodsThis retrospective, observational medical chart review utilized deidentified clinical data, including treatment patterns, abstracted from patient medical charts between 01/2012 and 06/2017. Line of therapy was assessed based on disease presentation and aggregated. Index treatment was defined as the first line of therapy, followed by second line of therapy and third line of therapy. Results were summarized using descriptive statistics.ResultsA total of 225 patients were included (mean [SD] age at diagnosis: 24.7 [9.8] years). Initial disease presentation was both neurologic/psychiatric and hepatic in 52.9%, followed by neurologic/psychiatric (20.0%), hepatic (16.9%), and asymptomatic (10.2%). Median (first and third quartiles) duration of follow-up from diagnosis was 39.5 (33.8–60.4) months. The most common first line of therapy was penicillamine monotherapy in 45.5%, followed by trientine monotherapy (26.1%) and chelator/zinc combination therapy (21.2%). A total of 167/222 (75.2%) patients remained on first line of therapy during the follow-up period. Of the 13.5% who switched to second line of therapy, most changed to trientine monotherapy (53.3%). All those who switched to third line of therapy transitioned to zinc monotherapy (100.0%). Unexpectedly, 11.3% discontinued first line of therapy without transitioning to a subsequent therapy. The primary rationale for index monotherapy selection was improved efficacy (61.6%). Most discontinuations were due to side effects/tolerability (40.8%). Treatment patterns varied by initial disease presentation, practice setting, physician specialty, and geographic location.ConclusionThese results demonstrate a lack of consensus in the US regarding first-line treatment for patients with WD. Evidence-based treatment pathways informed by high-quality clinical trials for improved health outcomes are needed.

Diagnostic accuracy of smartwatches for automated atrial fibrillation detection over time: insights from the basel wearable study

Abstract Background The first smart-watch (SW) able to record a single lead ECG (SL-ECG) with automated atrial fibrillation (AF) detection algorithm was introduced 2018. Multiple other manufacturers followed. While manufacturers claim to continuously improve their devices’ algorithm, little is known about the impact on diagnostic accuracy on AF detection over time in a real-world cohort of patients. Purpose To assess if the diagnostic accuracy of algorithm-based AF detection of 5 smart devices has improved over time. Methods In this prospective study, consecutive patients undergoing electrophysiological procedures in a tertiary referral center were included between April 2021 to May 2023. Each participant received a 12-lead ECG and 5 SL-ECGs with different smart devices (AliveCor KardiaMobile, Apple Watch 6, Fitbit Sense, Samsung Galaxy Watch 3 and Withings ScanWatch). All SW were continuously updated for newest software or firmware as recommend by the manufacturers. The SW rhythm classification was compared to manual cardiologist-based interpretation of SL-ECGs. The change in number of inconclusive SL-ECGs by manufacturer’s algorithm were investigated over time via Cochran-Armitage test for trend and illustrated over time via logistic regression. Results 247 participants were included (30% female, mean age 66.3 [IQR: 57-74] years) resulting in a total of 1’235 SL-ECGs. Among these, 202 SL-ECGs (16%) were labeled as inconclusive by at least one smart-device. Inconclusive rates for individual SW ranged from 15% to 19%. When comparing the first and last quintile of patients in the study period, the inconclusive rates for the KardiaMobile were 14% vs. 6%, for the Apple Watch 14% vs. 6%, for the Fitbit Sense 20% vs. 14%, for the Samsung Galaxy 18% vs. 10% and for the Withings ScanWatch 22% vs. 14%, respectively. When assessed continuously over time, we observed a trend towards fewer inconclusive tracings, without reaching statistical significance (Figure 1). Conclusion Over 26 months, inconclusive tracings of 5 SW didn’t significantly decrease despite frequent software updates in a real-world patient cohort. Larger, long-term cohorts are needed to assess if automated AF detection has significantly improved over time.Figure 1

Early rhythm control in patients with recently diagnosed atrial fibrillation: findings from the GLORIA-AF Registry Phase III

Abstract Background Early rhythm control (ERC) can improve outcomes in select patients with atrial fibrillation (AF) but real-world data are lacking. Purpose To evaluate the effectiveness of ERC in a real-world cohort of AF patients. Methods From the global, prospective GLORIA-AF Phase III Registry, adult patients with recent diagnosis (< 3 months and < 4.5 months in Latin America) of AF and CHA2DS2-VASc score ≥1 were included. ERC was defined as treatment with an antiarrhythmic drug, catheter ablation, or cardioversion at the baseline. Multivariable logistic regression analysis determined the odds of receiving ERC and an oral anticoagulant [OAC] with results reported as adjusted Odds Ratio (aOR) and 95% Confidence Intervals (95%CI). Risk of major outcomes was determined using multiple Cox regression analyses. The primary outcome was a composite of all-cause death and major adverse cardiovascular events (MACE). Secondary outcomes included all-cause death, thromboembolism and major bleeding. Results were reported as adjusted Hazard Ratio (aHR) and 95%CI. Results 21,051 AF patients (age: 70.2±10.3, 45% female) were included. Of these, 6,932 (32.9%) received ERC, while 14,119 (67.1%) did not. Patients receiving ERC were younger with a higher prevalence of paroxysmal AF (62.8% vs. 53.2%) and heart failure (23.1% vs. 21.4%). They were less likely to have prior stroke/transient ischemic attack (TIA), chronic obstructive pulmonary disease (COPD), and they had a lower mean CHA2DS2-VASc score (3.0±1.5 vs. 3.3±1.5). Age ≥75 [aOR: 0.53; 95%CI (0.0.49-0.57)] and age 65-75 [aOR: 0.76; 95%CI (0.70-0.82)] were associated with lower odds of receiving ERC. Those with prior stroke/TIA [aOR: 0.55; 95%CI (0.50-0.61)] and COPD [aOR: 0.82; 95%CI (0.71-0.94)], as well as patients with more sustained form of AF and patients recruited in North America were less likely to receive ERC. Conversely, female sex, higher symptom burden, hypertension and coronary artery disease were associated with higher odds of receiving ERC (Figure 1). Patients who received ERC were more likely to receive OACs [aOR: 1.36; 95%CI (1.25-1.48)]. Survival curve for the primary outcome according to ERC are shown in Figure 2. During a median follow-up of 3.0 [IQR: 2.9-3.1] years, ERC was associated with lower risk of the primary composite outcome (aHR: 0.88, 95% CI:0.80-0.96, p=0.006); Similar results were observed for the secondary outcomes. Conclusions In a real-world population with recently diagnosed AF, clinical risk factors and characteristics were associated with ERC. Patients who received ERC had a reduced risk of major outcomes. These findings suggest that in real-world patients with AF, ERC may provide beneficial effects on long-term outcome.Odds Ratios to be treated with ERC.Survival curve.

Clinical impact of ICD implantation in octogenarians: a longitudinal cohort study

Abstract Background The implantation of defibrillators (ICDs) in patients over 80 years old is becoming increasingly common; however, evidence-based data regarding the actual clinical benefit in this population remain limited and contradictory. While age seems not to affect mortality and arrhythmia risk in octogenarians undergoing secondary prevention, the mortality reduction benefit given by ICD implantation for primary prevention appears to decrease with advancing age, likely due to the high number of non-arrhythmic deaths. Purpose This study aims to assess the long-term incidence of ventricular arrhythmias and mortality in a real-world cohort of octogenarian patients undergoing ICD implants. Methods This was an observational, retrospective, longitudinal cohort study. Demographic, clinical, and radiological data were collected for all patients undergoing ICD implantation between 2014 and 2021. Deaths from all causes and significant arrhythmic events (sustained ventricular tachycardias and ventricular fibrillation) detected during routine device controls and remote monitoring were recorded. Then was performed an univariate Kaplan-Meier analysis, stratifying the population by age in relation to the two study endpoints: ventricular arrhythmias and all-cause mortality. Results Out of a total of 700 patients, 512 underwent ICD implantation before the age of 80 (mean age at implantation 64±12), while 188 underwent ICD implantation after the age of 80 (mean age at implantation 82±3.2). No significant differences were found between these two groups in terms of gender (82% vs. 83% male; p 0.12), indication for implantation (74% vs. 75% primary prevention; p 0.79), and the presence of late gadolinium enhancement (LGE) on cardiac MRI (68% vs. 77%; p 0.14). Octogenarians were more frequently affected by ischemic heart disease (54% vs. 65%; p 0.01) and were more frequently treated with Amiodarone (17% vs. 24%; p 0.02). At the end of the average 8-year follow-up, octogenarians had significantly higher all-cause mortality than younger patients (HR=2.35 [1.88-3.16]; p<0.05), with survival curves diverging from 3 years after implantation. However, ventricular arrhythmic events were significantly reduced in octogenarian patients (HR=0.88 [0.87-0.89]; p<0.05). Conclusions In a real-world population of octogenarian patients, the clinical benefit of ICD implantation for primary prevention appears diminished, considering the trade-off between ventricular arrhythmias and mortality, in both ischemic and non-ischemic cardiomyopathy patients.

#2533 Real-world challenges associated with the use of systemic glucocorticoids in a US IgAN cohort

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease and up to 50% of patients progress to kidney failure within 10-20 years. Until early 2022, management of IgAN was primarily focused on supportive care. As outlined in the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, patients at high risk of progressive chronic kidney disease despite maximal supportive care can be considered for a 6-month course of systemic glucocorticoids (SGC), although important risks of toxicity and contraindications must be considered. There is currently limited real-world evidence describing the impact of the use of SGC on treatment‑emergent toxicity and healthcare resource utilization (HCRU) in patients with IgAN. We report the incidence of adverse events (AEs) commonly associated with SGC, as well as HCRU rates and costs, in a real-world cohort of IgAN patients, comparing new initiators of SGC with patients who have never initiated SGC. Method This non-interventional, retrospective cohort study was conducted in the TriNetX Dataworks - United States of America Network, a database of de-identified, patient-level electronic medical records (EMR) of approximately 100 million patients. The cohort was selected from a total of 19, 687 patients with IgAN, identified using proxy ICD‑10 codes N02.8 (recurrent and persistent hematuria with other morphologic changes) or N04.1 (nephrotic syndrome) between January 1, 2011, and May 4, 2022. Eligible patients were required to have: an incident diagnosis of IgAN with the same diagnosis within 30-180 days; at least 12 months of EMR history available prior to and after initial IgAN diagnosis; not experienced kidney failure prior to or on the initial date of IgAN diagnosis; and not received SGC prior to the date of diagnosis. Data assessed included demographic and clinical characteristics, IgAN-directed medications, AEs, and HCRU. To promote balance between cohorts, new initiators of SGC (dexamethasone, prednisone, prednisolone, methylprednisolone) were matched with patients who did not receive SGC using a propensity score (PS) approach based on their characteristics at diagnosis. To avoid immortal-time bias, the index date was set as the time of SGC initiation in patients in the SGC cohort; for the non-SGC cohort, a pseudo-index date was assigned using the same lag from diagnosis to index date as their 1:1 PS-matched patient in the SGC cohort. Differences in the cumulative incidence of individual AEs were analyzed using the chi-square test or Fisher's exact test, and differences in HCRU rates and costs were analyzed using the Kruskal-Wallis test. Results After implementing the PS approach, the final analysis included 802 patients (401 PS-matched pairs), with a mean age of 41.2 years and 55% being male. Median duration of follow-up was 3.5 and 3.1 years for the SGC and non-SGC cohorts, respectively. Of AEs that occurred in at least ten of the 802 patients, patients who received SGC experienced a significantly increased incidence of all AEs except for fractures, new onset of diabetes, and reported onset of glaucoma (Table 1). Patients who received SGC had a 12-fold increased incidence of severe infections requiring hospitalization compared with the non-SGC cohort. Annualized mean HCRU rates and costs were significantly greater across all HCRU types for patients who received SGC vs those who did not receive SGC, including an 8-fold increase in inpatient visits, a 4-fold increase in emergency department admissions, and twice as many ambulatory visits (Fig. 1). Results were consistent when the cohort was restricted to patients with IgAN identified using only the ICD-10 code N02.8 (recurrent and persistent hematuria with other morphologic changes). Conclusion The findings of this real-world analysis demonstrate significant side effects and costs for IgAN patients treated with SGC compared with patients not treated with SGC, underscoring the recommendation in the 2021 KDIGO guidelines to carefully consider treatment-emergent toxicity before treating IgAN patients with SGC.

Percutaneous Coronary Interventions with Sirolimus-Eluting Alex Plus Stents in Patients with or without Diabetes: 4-Year Results.

We characterized the performance, as well as the safety, of a second-generation thin-strut sirolimus-eluting stent with a biodegradable polymer, Alex Plus (Balton, Poland), implanted in patients with type 2 diabetes (DM) with a 4-year follow-up. We defined the primary endpoint as the 48-month rate of major cardiovascular adverse events (MACE), including cardiac death, myocardial infarction (MI), or target lesion revascularization (TLR). The secondary endpoints were all-cause death, cardiac death, MI, and TLR rates at 12, 24, 36, and 48 months. We enrolled 232 patients in whom 282 stents were implanted, including 97 DM and 135 non-DM patients. The mean age of the DM patients was 69.5 ± 10.1 years and females accounted for 30% of the patients. DM patients had higher rates of arterial hypertension (97% vs. 88%, p = 0.016), dyslipidemia (86% vs. 70%, p = 0.005), prior MI (61% vs. 40%, p = 0.002), prior PCI (65% vs. 50%, p = 0.020), and prior CABG (14% vs. 5.9%, p = 0.029). We recorded statistically significant differences for MACE (HR 1.85, 95% CI 1.01-3.41, p = 0.046), cardiac death (HR 4.46, 95% CI 1.44-13.8, p = 0.010), and MI (HR 3.17, 95% CI 1.10-9.12, p = 0.033), but not for TLR, between DM and non-DM patients in terms of the analyzed endpoints at 4 years. Our study showed that Alex Plus was efficient and safe in a contemporary cohort of real-world DM patients undergoing percutaneous revascularization.

Efficacy-effectiveness analysis on survival in a population-based real-world study of BRAF-mutated metastatic colorectal cancer patients treated with encorafenib-cetuximab.

Encorafenib-cetuximab has been approved for pretreated BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients based on efficacy demonstrated in the randomized phase III BEACON trial. The aim of this real-world effectiveness study is to improve knowledge on the generalizability of trial results. This population-based real-world study includes all mCRC patients in the Netherlands treated with encorafenib-cetuximab since approval. Individual patient data and pathology reports were collected. Overall survival (OS) was compared to BEACON and subgroup analyses were conducted for patients who would have been eligible and ineligible for BEACON. 166 patients were included with a median follow-up time of 14.5 months. Median OS was 6.7 months (95% CI:6.0-8.3) and differed from BEACON (9.3 months; 95% CI:8.0-11.3, p-value 0.002). Thirty-six percent of real-world patients would have been ineligible for the BEACON trial. Trial ineligible subgroups with symptomatic brain metastases and WHO performance status ≥2 had the poorest median OS of 5.0 months (95% CI:4.0-NR) and 3.9 months (95% CI:2.4-NR). This real-world cohort of mCRC patients treated with encorafenib-cetuximab showed a clinically relevant efficacy-effectiveness gap for OS. The chance of survival benefit from encorafenib-cetuximab in patients with brain metastases and/or WHO performance status ≥2 is negligible as neither efficacy nor effectiveness has been demonstrated.

Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort

BackgroundComprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling.MethodsSeventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification.ResultsThe overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition.ConclusionsOur study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.

Outcomes of concomitant antiobesity medication use with endoscopic sleeve gastroplasty in clinical US settings

BackgroundTo evaluate the weight loss outcomes of the large US cohort of patients undergoing endoscopic sleeve gastroplasty (ESG) with or without concomitant anti-obesity (AOM) use. MethodsWe performed a retrospective analysis of adult patients who underwent ESG from seven different sites, from January 1, 2020 to November 30, 2022. Percent total body weight loss (%TBWL) and %excess weight loss (%EWL) were calculated based on baseline weight at the procedure. Medication use was considered if the subject received a prescribed AOM during the study period. SPSS (version 29.0) was used for statistical analyses. ResultsA total of 1506 patients were included (1359 (90.2 %) no AOM use and 147 (9.8 %) AOM use). Patients who were on an active AOM at the time of the procedure had a significantly lower TBWL% as compared to patients not on AOMs at 6 months. At the 24-month visit, patients who were prescribed AOMs after the 12-month visit had a significantly higher TBWL% and EWL% as compared to patients who were on active AOM at the time of the procedure. There was no significant difference between classes of medications at any time point, however, patients on a GLP-1RA had a trend towards improved weight loss at 18 and 24 months. ConclusionIn this large, real-world cohort of patients from the United States, data signal that with the use of pharmacotherapy at the appropriate time, patients can achieve optimal results.

Incremented Amyloid-beta values predict mortality during long-term follow-up in patients with acute myocardial infarction, both STEMI and NSTEMI

Abstract Funding Acknowledgements None. Background Both the amyloid-β (Aβ) isoforms, namely Aβ1-40 and Aβ1-42 are implicated in the pathogenesis of Alzheimer’s disease through different mechanisms. While Aβ42 easily forms oligomers in brain, Aβ1-40 is more abundant in circulation where it exerts a pro-inflammatory role. Recently, Aβ1-40 has raised interest in the cardiovascular field for its contribution to atherosclerosis, more specifically through plaque formation and destabilization. However, to date, the prognostic role of Aβ1-40 in patients with acute myocardial infarction (AMI) is limited to NSTEMI. Purpose Since there is a need for better risk stratification of AMI patients, we analyzed the impact of plasma Aβ1-40 on long-term mortality in a cohort of real-world patients with AMI, including STEMI and NSTEMI. Further, we sought to identify predictors for elevated Aβ1-40 levels. Methods Blood samples were obtained from patients hospitalized for AMI and Aβ1-40 levels were evaluated with Human Aβ40 ELISA Kit. The endpoint was all-cause mortality. Results Our population included 1119 consecutive patients, with a mean age of 67 years, 72% male, 2/3 of them had a first ischemic event and 68.4% had STEMI diagnosis. The median plasma Aβ1-40 concentration on admission was 86.9 [54.5-128.9] pg/ml and there was no difference in Aβ1-40 levels between NSTEMI and STEMI (93.6 [61.2-130.9] Vs. 85.3 [52.9-128.7] pg/ml, respectively, p=0.1). At logistic regression multivariate analysis, higher Aβ1-40 levels were predicted by older age, worse left ventricular systolic function, HbA1C > 39 mmol/mol and GFR<60ml/min/m 2 (Fig.1a). From the final multivariable model, a nomogram for prediction of high levels of Aβ1-40 was computed (Fig.1b). One hundred ninety-three patients (17.2%) died, during the median follow-up of 57 [30 - 80] months. Patients who died had significantly higher levels of Aβ1-40 compared to alive patients (113.1 [67.9 – 159.5] Vs. 83.9 [52.5 – 122.6] pg/ml, p<0.01). Higher plasma Aβ1-40 values were associated with increased mortality risk, in both STEMI and NSTEMI (p<0.01) (Fig.2a). Further, at Cox multivariate analysis including the whole population, Aβ1-40 levels were predictive of mortality (HR 1.03, p=0.02), together with older age, higher Il-1β, GFR<60ml/min/m 2 and worse left ventricular systolic function (Fig.2b). The predictive value of our final model was superior to GRACE score for up to 60 months (AUC 0.830 (0.793 – 0.868) Vs 0.797 (0.756 – 0.837), respectively, p=0.03, Fig.2c), after which they were comparable. Conclusions Elevated levels of Aβ1-40 values are independent predictors of long-term mortality in a real-world cohort including both STEMI and NSTEMI patients.

Long-term effectiveness of natalizumab in secondary progressive multiple sclerosis: A propensity-matched study

Treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. We aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). This multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st June 2012 and the 15th May 2018 ​at 33 Italian MS centers contributing to the Italian MS Registry NTZ or IFNb-1b. Confirmed Expanded Disability Status Scale worsening (CEW) and progression independent of relapse (PIRA) were evaluated. In order to correct for non-randomization, a propensity score matching of the groups was performed. Out of 5206 MS patients identified at the time of data extraction, 421 SPMS patients treated with NTZ (224 [53.2%] females, mean age 45.3 ​± ​25.4 years) and 353 with IFNb-1b (133 [37.8%] females, mean age 48.5 ​± ​19.8 years) were enrolled. After applying the matching procedure, 102 patients were retained in the NTZ group and 98 in the IFNb-2b group. The proportion of patients who reached the 48-month 1-point CEW was significantly higher in IFNb-1b compared to NTZ group (58.2% versus 30.4%, p ​= ​0.01). The proportion of patients who developed PIRA at 48 months were significantly higher in IFNb-1b compared to NTZ (72.4% versus 40.2%, p ​= ​0.01). EDSS before treatment initiation and SPMS duration were risk factors for disability progression in terms of PIRA (HR 2.54, 25%CI 1.67–5.7; p ​= ​0.006 and HR 2.04, 25%CI 1.22–3.35; p ​= ​0.01, respectively). Patients treated with IFNb-1b were 1.64 times more to likely to develop PIRA (HR 1.64, 25%CI 1.04–4.87; p ​= ​0.001). Treatment with NTZ in SPMS patients showed more favorable disability outcomes compared to IFNb-1b with beneficial effects over 48 months.

Abstract PO4-14-11: Findings of clinically significant variants (Tier IA) with OmniSeq INSIGHT ® in a breast cancer cohort of 987 patients

Abstract Background: There were an estimated 2.3 million new breast cancer cases worldwide in 2020, with breast cancer now the most diagnosed type of cancer representing 25% of cancer cases and 17% of cancer deaths (1). The GLOBOCAN Cancer Tomorrow prediction tool estimates that incidence will increase by > 45% by 2040 (2). Optimal treatment for breast cancer is increasingly dependent upon knowing a patient’s somatic and germline genomic alteration status. To highlight the importance of these genomic alterations, we provide an overview of the genomic findings in 987 consecutive breast cancer patients tested in the course of routine clinical care. Methods: Comprehensive Genomic and Immune Profiling (CGIP) was performed on 987 qualified breast cancer samples at a CAP/CLIA and NYS CLEP certified reference laboratory with the OmniSeq INSIGHT ® test (3). OmniSeq INSIGHT ® is a next generation sequencing-based laboratory developed test for the detection of genomic variants, signatures, HLA Class I genotypes, and immune gene expression in formalin-fixed paraffin-embedded (FFPE) tumor tissue. DNA is sequenced to detect small variants in the full exonic coding region of 523 genes, copy number alterations in 59 genes (gains and losses), as well as analysis of microsatellite instability (MSI) and tumor mutational burden (TMB). RNA is sequenced to detect fusions and splice variants in 55 genes, in addition to mRNA expression in 64 immune genes. The resultant information, along with PD-L1 protein expression by immunohistochemistry (IHC), is intended for use by qualified health care professionals in accordance with professional guidelines in oncology for management of patients with solid neoplasms. Tier IA variants include variants with strong clinical significance as per AMP–ASCO–CAP recommendations (4). Results: There were 384 Tier IA variants detected in 370 of 987 breast cancer patients (~37.5%) with 251 in PIK3CA (65.3%), 60 in ERBB2 (15.6%), 46 in BRCA2 (11.9%), 19 in BRCA1 (4.9%), 4 in NTRK3 (1.0%), 1 in NTRK1 (0.26%) and 1 in PALB2 (0.26%) including copy number variations (CNV), gene fusion and single nucleotide variants (SNV). At the individual gene level for Tier IA variants, PIK3CA had 251 SNVs detected, ERBB2 had 55 CNVs, 1 gene fusion and 4 SNVs detected, BRCA2 had 39 SNVs and 8 CNVs detected, BRCA1 had 19 SNVs, NTRK3 had 4 gene fusions, NTRK1 had 1 gene fusion and PALB2 had 1 SNV detected. At the variant class level, there were 63 CNVs, 6 gene fusions and 315 SNVs observed. Conclusions: CGIP for breast cancer patients identified one or more clinically significant Tier IA genomic alterations that directs targeted therapy in ~ 37.5% of patients in a cohort of real world patients tested during the standard course of clinical care. This highlights the need for comprehensive genomic testing in breast cancer patients to drive therapeutic decision making.

Abstract PO5-02-14: Clinical-pathological determinant factors to choose between four or six cycles of adjuvant chemotherapy with docetaxel/cyclophosphamide (TC) in a retrospective real-world cohort of HER2-negative breast cancer patients

Abstract Introduction: The long-term severe adverse events associated with anthracyclines, including irreversible cardiotoxicity, myelodysplastic syndromes, and therapy-related leukemias, led researchers to question the risk-benefit of anthracycline-based chemotherapy regimens, especially for patients without axillary lymph node involvement, leading to an increasing trend to omit anthracyclines in adjuvant treatment. Docetaxel plus cyclophosphamide (TC) has replaced doxorubicin plus cyclophosphamide (AC) for lower-risk patients that need adjuvant chemotherapy. However, the optimal number of cycles of adjuvant in patients with node-positive or node-negative breast cancer is currently unknown. Methods: We performed a retrospective cohort study of patients with HER2-negative breast cancer, stage I to III, that received adjuvant docetaxel and cyclophosphamide (TC) for four or six cycles, treated from January 2010 to December 2021. Patients were included from four cancer institutions, both private and public, located in the South, Southeast, and Northeast of Brazil. Objectives: To investigate the clinical-pathological characteristics and survival of earlystage HER2-negative breast cancer patients who received four (TC4) or six cycles (TC6) of adjuvant docetaxel and cyclophosphamide (TC). Results: We collected data from six hundred and ninety-eight patients, 98.7% were female with an average age of 52 years, 51.9% were postmenopausal, 14.6% BRCA gene mutation, 66% had some comorbidity, and only 8.4% were not candidates for anthracyclines. Two hundred and twenty-five patients had public and 473 private health insurance. About 13.2% of the patients were hormone receptor negative (HR-) and 86.8% hormone receptor positive (HR+), 57.4% breast-conserving surgery and 77.7% sentinel lymph node (SL). Five hundred sixty-four (80.8%) patients received TC4 and 134 (19.2%) TC6. We observed that patients who received TC 6 had unfavorable prognostic factors such as: (TC4 vs TC6) previous breast cancer (8.7% vs 16.3%) (p=0.002), invasive ductal carcinoma (IDC) (73.4 vs 86.7%) (p=0.009), histological grade 3 (HG3) (34.9 vs 42.9%) (p= 0,085) conservative surgery (59.4% vs 53%) (p=0144), SL (80.9% vs 62.2%) (p =0.001), Lymph node positive (15% vs 42.3%) (p=0.001), pathological stage II (37.5% vs 50%) (p=0.001).Treatment completion rates were 96.5% and 84.3% for TC4 and TC6, respectively (p=0,02). The incidence of grade 3 or higher toxicity with TC6 (14% vs 21.1%; p= 0,043). Febrile neutropenia was observed in 6.7% of both groups. Grade 3 or higher neuropathy was most common with TC6 (2.2% vs 10.3%; p=0,163). Permanent treatment discontinuation was more frequent in the TC6 group (3.4% vs. 9.8%; p=0,004), as well as late toxicity (3.4% vs. 9.2%; p=0,004). Ninety-four percent of the patients completed the proposed cycles of chemotherapy, 72% received adjuvant radiotherapy and 85.4% received adjuvant hormone therapy, with 42% of these receiving an aromatase inhibitor for 5 years. The median follow-up of the entire cohort was 61 months. There was no difference in the 5-year DFS (77.5% vs. 64.7%; p=0.159) or the 5-year OS (89.5% vs. 70.5%; p= 0,06) between patients treated with TC4 and TC6. Conclusion: TC6 was commonly used for patients with unfavorable prognostic factors as history of previous breast cancer, (IDC), HG III, lymph node positive and stage II. Patients who received TC6 had less chance of completing the treatment and more severe toxicity, especially late peripheral neuropathy. There was no difference in DFS or OS. Citation Format: Mila Kraychete, Marcelle Cesca, Guilherme Almeida, Leonardo Santana, Luciana Leite, Solange M. Sanches, Vladmir Cordeiro de Lima, Rafaela Pirolli, Rafael Manea, Felipe Kaneta, Jean Coutinho, Lucas Vian, Waires Zeviani, Marcio Reis, Luciana Landeiro, Clarissa Mathias, Geila Nunez, Tamara Santana, Monique Tavares. Clinical-pathological determinant factors to choose between four or six cycles of adjuvant chemotherapy with docetaxel/cyclophosphamide (TC) in a retrospective real-world cohort of HER2-negative breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-14.

Abstract PS11-01: Brain metastases in metastatic breast cancer: prevalence per line of treatment and cumulative incidence in a cohort of 18075 real-world patients

Abstract BACKGROUND Historic data suggest that incidence of brain metastasis (BM) is relatively distributed over time in HER2-positive (HER2+) breast cancer (BC), occurs early in triple negative BC (TNBC), and occurs late in hormone receptor-positive (HR+) metastatic BC (mBC). However, the timing of BM relative to line of therapy has not been well described. We describe the prevalence per line of therapy and cumulative incidence of BM in a large real-world cohort of patients (pts) with mBC, by BC subtype and line of therapy. METHODS This analysis used data from the longitudinal US Flatiron Health de-identified database, which provides unstructured and structured electronic health record-derived data from >2.6 million pts with cancer in ~800 unique sites of care. Eligible pts had initiated a first line of treatment (index data) for mBC up to March 1, 2021, to allow for ≥2 years potential follow-up time. Baseline characteristics were assessed, and pts categorized by HER2 and HR status: 1) HR+, HER2+; 2) HR+, HER2–, 3) HR–, HER2+ and 4) TNBC (i.e., negative for HR and HER2). For the last two categories, HER2-low subsets were defined based on immunohistochemistry results (1+, 2+, or equivocal). Lines of therapy were derived using both treatment regimens and progression data. The primary outcome was the first diagnosis of BM. The prevalence of BM was evaluated by subtype, at the index date, and by the line of therapy. The cumulative incidence function (CIF) of BM was used to estimate the risk of BM in pts free of BM at the index date, and death was treated as a competing event. RESULTS Overall, 18075 pts were included (HR+, HER2+: 3062 pts [16.9%]; HR–, HER2+: 902 pts [5.0%]; HR+, HER2–: 12331 pts [68.2%] [HR+, HER2-low: 7062 (39.1%)]; TNBC: 1780 pts [9.8%] [HR–, HER2-low: 725 pts (4.0%)]). Median age at the index date was 64 years (interquartile range: 54, 73) and 10271pts (56.8%) had visceral metastasis. In total, 5951 pts (32.9%) had de novo disease, 12090 (66.9%) had recurrent disease, and 34 (0.2%) did not have available data for mBC type. The table shows the number of pts by line of therapy, prevalence of BM, and cumulative incidence of BM from the index date. Of the included pts, 1306 (7.2%) had a BM at the index date; the CIF was run on the remaining 16973 pts. Overall, 2248 pts (13.2%) had an incident BM event during follow-up (HR+, HER2+: 578 events; HR–, HER2+: 237 events; HR+, HER2–: 1119 events [HR+, HER2-low: 619 events]; TNBC: 314 events [HR–, HER2-low: 124 events]), 9314 had a competing event, and 5411 were censored. By fourth-line therapy, the prevalence of BM was 26.1% in HR+, HER2+; 37.1% in HR–, HER2+; 24.7% in TNBC (HR–, HER2-low: 27.9%); but remained low at 7.2% in HR+, HER2– (HR+, HER2-low: 9.4%). The cumulative incidence of BM at 60 months was 23% in HR+, HER2+, 34% in HR–, HER2+, 10% in HR+, HER2–, and, 22% in TNBC. Overall, the HER2-low subsets had BM prevalence and cumulative incidence that were very close to those that were HER2–. CONCLUSIONS This large analysis of real-world data demonstrates that the prevalence of BM across pts with mBC differs by tumor subtype and by line of therapy. Conversely, HER2-low status may have limited impact. The cumulative incidence of BM was highest in the HR–, HER2+ and TNBC subgroups, and lowest in the HR+, HER2– subgroup; despite this, due to the high proportion of HER2–, HR+ mBC cases, the HR+, HER2– group represented the largest number of BM events. These data emphasize the need for clinical and biologic predictors of BM and for strategies to prevent their onset, and provide information on the impact of BM inclusion and exclusion criteria in clinical trials for pts with mBC. Number of patients by line of therapy, prevalence of BM, and cumulative incidence of BM from the index date BM, brain metastasis; HR, hormone receptor, pts, patients; TNBC, triple negative breast cancer. Citation Format: Sarah Sammons, Jose Leone, Thibaut Sanglier, Peter Lambert, Filippo Montemurro, Raf Poppe, Eleonora Restuccia, Sara Tolaney, Nancy Lin. Brain metastases in metastatic breast cancer: prevalence per line of treatment and cumulative incidence in a cohort of 18075 real-world patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS11-01.

Determinants of radiographic progression in early psoriatic arthritis: insights from a real-world cohort

ObjectivePersistent articular inflammation in psoriatic arthritis (PsA) is associated with radiographic damage. Despite advances in diagnosis and therapy, radiographic structural damage remains prevalent in PsA. To elucidate this topic, we...

Quality of Life Improvements with Biologic Initiation Among Subspecialist-Treated US Patients with Severe Asthma.

Patients living with severe asthma (SA) experience multiple health-related quality of life (HRQoL) impairments. This study examined HRQoL changes after biologic treatment initiation among a large, real-world cohort of patients with SA. CHRONICLE is an ongoing observational study of subspecialist-treated adults with SA who receive biologics or maintenance systemic corticosteroids or are uncontrolled on high-dosage inhaled corticosteroids with additional controllers. Patients enrolled February 2018-February 2023 were asked to complete the St. George's Respiratory Questionnaire (SGRQ) every 6 months (total score range of 0-100 [0=best possible health], meaningful change threshold is a 4-unit reduction in the total score). Changes in SGRQ responses from 6 months before initiation to 12 to 18 months after initiation were summarized. A total of 76 patients completed the SGRQ 0 to 6 months before and 12 to 18 months after biologic initiation. The mean (SD) SGRQ total score decreased from 52.2 (20.6) to 41.9 (23.8), with improvement across the symptoms (-14.5), activity (-11.0), and impacts (-8.3) components. For specific impairments reported by ≥50% of patients before biologic initiation, fewer reported each impairment after biologic initiation; the largest reductions were for "Questions about what activities usually make you feel short of breath these days [Walking outside on level ground]" (67% to 43%), "Questions about other effects that your respiratory problems may have on you these days [I feel that I am not in control of my respiratory problems]" (55% to 34%), and "Questions about your cough and shortness of breath these days [My coughing or breathing disturbs my sleep]" (63% to 45%). In this real-world cohort of adults with SA, biologic initiation was associated with meaningful improvements in asthma-related HRQoL. These data provide further insight into the burden SA places on patients and the benefits of biologic treatment.

Long-term Outcome of Risankizumab in Crohn’s Disease: a Real-world GETAID Study

IntroductionThe aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with CD. Patients and MethodsFrom May 2021 to August 2023, all consecutive CD patients treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index (HBI) <5) at 52 weeks. ResultsOf the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 (10.0-18.1) months. The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174, 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174, 20.9%) were hospitalized and 22 (22/174, 12.6%) required intestinal resection. Fifty-one (29%) patients had an adverse event including 26 (15%) serious adverse events (CD flare, n=17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed. ConclusionThis is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. Half of the patients achieved steroid-free clinical remission after one year, and the safety profile was consistent with the literature.

OA41 Exploring patterns of patient engagement with electronic patient reported outcome measures in inflammatory arthritis using latent class growth modelling

Abstract Background/Aims Routine collection of electronic patient reported outcome measures (ePROMs) can facilitate dynamic disease activity monitoring in patients with inflammatory arthritis (IA). In a real-world cohort of patients with IA, we describe patient characteristics associated with ever engaging with ePROMs, evaluate whether there are distinct groups of patients with similar engagement trajectories over time and identify patient characteristics associated with these groups. Methods We conducted a prospective observational study based on routinely collected data from a remote monitoring platform (RMP) at Guy’s and St Thomas’ NHS Foundation Trust in London, UK, between 18 December 2018 and 15 August 2022. Patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) were sent text message requests to complete 4-weekly disease specific PROMs. A patient was defined as an engager if they completed at least one PROM episode during the study period of 68 weeks. Logistic regression (LR) was used to identify associations between baseline characteristics and any PROM engagement. Latent class growth modelling (LCGM) was used to determine PROM engagement trajectories, with multinomial LR exploring baseline characteristic associations with latent trajectory class membership. Results Of 1,203 patients on RMP in the study period, 1,129 met the inclusion criteria, of which 91.5% (95% CI 89.7% - 93.0%) completed at least one PROM. Mean age was 49 years and 64% were female. 60% had RA, 24.4% had PsA and 15.7% had AxSpA. Overall engagement was relatively high throughout, with continued engagement &amp;gt;60% over the remaining 68 weeks. Older patients (adj OR 0.98, 95% CI 0.96 - 0.99), those from more deprived areas (adj OR 0.80, 95% CI 0.68 - 0.96) and those who attended &amp;lt;80% of their outpatient visits in the preceding 3 years (adj OR 0.48, 95% CI 0.26 - 0.89) were less likely to complete a PROM. Four latent trajectory classes were identified: consistent engagers (38.1%), high-variable engagers (24.3%), low-variable engagers (19.5%) and never &amp; dis-engagers (18.1%), with a mean (SD) overall response rate per class of 96.5% (7.1), 74.1% (12.1), 35.6% (13.8) and 7.5% (12.0) respectively. Compared to the consistent engager class, the two variable engager classes were significantly more likely to be younger at baseline, whilst the never &amp; dis-engager class was more likely to be from a deprived area. Having an IA type of PsA and previous clinic non-attendance was associated with membership of the three lower engaging classes. Conclusion We have described key patient characteristics that influence engagement with ePROMs in a real-world cohort of patients with IA, and patterns of engagement over time. Overall engagement was very high with &amp;gt;90% of patients enrolled engaging with PROM completion. There is still scepticism among clinicians about remote monitoring’s ability to work, and our findings should be reassuring: patients do engage with ePROMs over time. Disclosure N. Arumalla: None. Z. Yang: None. S. Norton: None. M. Crooks: None. A. Khan: None. R. Fitzgerald: None. R. Gilligan: None. E. Lindberg: None. T. Tabibi: None. Y.L. Man: None. S. Subesinghe: None. J.B. Galloway: Consultancies; Abbvie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Pfizer, Novartis, Roche, Sanofi, Sobi, UCB. Honoraria; Abbvie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Pfizer, Novartis, Roche, Sanofi, Sobi, UCB. T. Garrood: Shareholder/stock ownership; Serac healthcare. Honoraria; Abbvie, UCB. Grants/research support; Versus Arthritis, Pfizer, Gilead, Guy's and St Thomas' Charity, NHSX. Other; Fresnius-Kabi.

Renal cell carcinoma histologic subtypes exhibit distinct transcriptional profiles.

Molecular profiling of clear cell renal cell carcinoma (ccRCC) tumors of patients in a clinical trial has identified distinct transcriptomic signatures with predictive value, yet data in non-clear cell variants (nccRCC) are lacking. We examined the transcriptional profiles of RCC tumors representing key molecular pathways, from a multi-institutional, real-world patient cohort, including ccRCC and centrally reviewed nccRCC samples. ccRCC had increased angiogenesis signature scores compared with the heterogeneous group of nccRCC tumors, while cell cycle, fatty acid oxidation/AMPK signaling, and fatty acid synthesis/pentose phosphate signature scores were increased in one or more nccRCC subtypes. Among both ccRCC and nccRCC tumors, T effector scores statistically correlated with increased immune cell infiltration and were more commonly associated with immunotherapy-related markers (PD-L1+/TMBhi/MSIhi). In conclusion, this study provides evidence of differential gene transcriptional profiles among ccRCC versus nccRCC tumors, providing insights for optimizing personalized and histology-specific therapeutic strategies for patients with advanced RCC.