Patients In Real-world Clinical Practice Research Articles

A phase IV study to evaluate the safety of fruquintinib in Chinese patients in real-world clinical practice.

Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade≥3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.

A Patient Similarity Network (CHDmap) to Predict Outcomes After Congenital Heart Surgery: Development and Validation Study.

Although evidence-based medicine proposes personalized care that considers the best evidence, it still fails to address personal treatment in many real clinical scenarios where the complexity of the situation makes none of the available evidence applicable. "Medicine-based evidence" (MBE), in which big data and machine learning techniques are embraced to derive treatment responses from appropriately matched patients in real-world clinical practice, was proposed. However, many challenges remain in translating this conceptual framework into practice. This study aimed to technically translate the MBE conceptual framework into practice and evaluate its performance in providing general decision support services for outcomes after congenital heart disease (CHD) surgery. Data from 4774 CHD surgeries were collected. A total of 66 indicators and all diagnoses were extracted from each echocardiographic report using natural language processing technology. Combined with some basic clinical and surgical information, the distances between each patient were measured by a series of calculation formulas. Inspired by structure-mapping theory, the fusion of distances between different dimensions can be modulated by clinical experts. In addition to supporting direct analogical reasoning, a machine learning model can be constructed based on similar patients to provide personalized prediction. A user-operable patient similarity network (PSN) of CHD called CHDmap was proposed and developed to provide general decision support services based on the MBE approach. Using 256 CHD cases, CHDmap was evaluated on 2 different types of postoperative prognostic prediction tasks: a binary classification task to predict postoperative complications and a multiple classification task to predict mechanical ventilation duration. A simple poll of the k-most similar patients provided by the PSN can achieve better prediction results than the average performance of 3 clinicians. Constructing logistic regression models for prediction using similar patients obtained from the PSN can further improve the performance of the 2 tasks (best area under the receiver operating characteristic curve=0.810 and 0.926, respectively). With the support of CHDmap, clinicians substantially improved their predictive capabilities. Without individual optimization, CHDmap demonstrates competitive performance compared to clinical experts. In addition, CHDmap has the advantage of enabling clinicians to use their superior cognitive abilities in conjunction with it to make decisions that are sometimes even superior to those made using artificial intelligence models. The MBE approach can be embraced in clinical practice, and its full potential can be realized.

Treatment Patterns and Outcomes in Patients with Multiple Myeloma Who Received Ixazomib and in Patients with Triple-Class Refractory Multiple Myeloma: A Retrospective, Observational, Real-World Historical Database Analysis Study from China

Background: Multiple myeloma (MM) is a fatal, malignant disease of plasma cells characterized by an abnormal proliferation of monoclonal antibodies. China is estimated to have 22,450 newly diagnosed (ND) cases of MM and 17,360 related deaths in 2022. Emerging novel therapies have significantly improved survival in MM, and treatment guidelines have been updated to reflect these advances. Ninlaro® (ixazomib) is the first oral proteasome inhibitor (PI) approved by the US FDA in 2015 and by China's National Medical Products Administration in 2018 (conditionally) for MM patients receiving ≥1 prior therapy owing to its convincing efficacy and well-tolerated safety profile as seen in the landmark Phase III TOURMALINE-MM1 trial and the China Continuation Study. Novel drugs such as PIs, immunomodulatory drugs (IMDs), and anti-CD-38 monoclonal antibodies are the core component of MM treatment and have improved patient outcomes considerably. However, many patients remain refractory to these drugs (triple-class refractory, TCR) and have poor clinical outcomes. There is a lack of real-world evidence characterizing treatment patterns and outcomes of MM patients receiving ixazomib and TCR-MM patients, in China. The objective of this study is to bridge this data gap by providing vital information on the treatment patterns and outcomes, and healthcare resource utilization in Chinese MM patients receiving ixazomib and TCR-MM patients in real-world clinical practice. Study Design and Methods: This study is an ongoing, single-centre, non-interventional, retrospective database analysis study of MM patients identified from the Chinese National Longitudinal Cohort of Haematologic Diseases (NICHE)-MM registry, a historical and ongoing longitudinal data registry of the Institute of Haematology and Blood Diseases Hospital (IHBDH), and representing the top-tier MM care in China. The patients will be divided into two groups. Patients (aged ≥18 years) with a confirmed MM diagnosis receiving all ixazomib-based regimen as 2nd-line and above therapy (RR-MM), or as a 1st-line therapy (ND-MM) will form group one and TCR-MM patients' refractory to at least one IMiD (lenalidomide, pomalidomide or thalidomide), one PI (bortezomib, ixazomib, or carfilzomib) and one anti-CD-38 monoclonal antibody (daratumumab and isatuximab) will form group two. TCR-MM patients receiving ixazomib will be part of both groups. Patients enrolled in clinical trials will be excluded. The data for analysis will be collected from the ixazomib launch date in China (April 12, 2018) and/or the index date of the first patient enrolled in ixazomib Named Patient Program to September 2023 (tentative). Since 2000 till January 2023, the NICHE-MM registry has enrolled 3,329 MM patients of whom 156 patients have received ixazomib. This is the preliminary sample count and the final sample size will be calculated during data cleaning and analysis phases. The primary objective of this study will be to determine 1) treatment patterns and responses by lines of treatments and 2) time-to-event outcomes. The treatment patterns will include treatment name, dosage, type (induction, consolidation, or maintenance), number of cycles, duration and severe adverse event causing hospitalization. The treatment responses will include complete response (CR), stringent CR, partial response (PR), very good PR, minimal response, stable disease, and progressive disease as defined by the International Myeloma Working Group. The overall response rate of the last line of treatment for both study groups will be calculated as composite endpoint. Time-to-event outcomes will include progression-free survival, overall survival, duration of therapy, and time to next line of treatment in ND/RR-MM and TCR-MM patient groups. Secondary objectives will include assessment of patients' demographic, disease and clinical characteristics. Depending on data availability, the exploratory objective will be to determine the healthcare resource utilization and costs incurred by patients in both groups. Subgroup analysis between ND-MM vs. RR-MM or RR-MM patients receiving ixazomib in 2nd-line setting vs. TCR-MM patients receiving ixazomib in >3rd-line setting is also planned. Descriptive statistics will be used for the analyses. Our findings will also help clinicians in making strategic decision about more apt positioning of ixazomib in the treatment algorithm of MM.

Patient-Reported Outcomes Among Patients with Triple-Class Refractory Multiple Myeloma in Real-World Clinical Practice: A Prospective, Multi-Site Observational Study

BACKGROUND Several studies have highlighted the poor outcomes observed among patients with relapsed/refractory multiple myeloma (MM), particularly those with triple-class refractory (TCR; refractory to at least one PI, one IMiD, and one anti-CD38 mAb) disease. The aim of this study was to describe the longitudinal changes in quality of life (QOL) and other patient-reported outcomes (PROs) among TCR MM patients in real-world clinical practice who initiate a new line-of-therapy. METHODS A prospective, multi-site observational study of patients with TCR MM was conducted through the Mayo Clinic system. Patients initiating a new post-TCR therapy (defined as the index date) were followed for a 12-month observation period during which PRO surveys were administered for the first 6 months. For patients initiating a CAR-T therapy, a survey assessment was conducted at apheresis, lymphodepletion chemotherapy, and every month after T-cell infusion until Month 6. All other patients received a survey assessment before index and then every month thereafter until Month 6. PRO measures included the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30; including the Global Health Score [GHS]), the EORTC Multiple Myeloma Questionnaire (QLQ-MY20; including the Disease Symptoms [DS] domain score), the EORTC QLQ for Chemotherapy-Induced Peripheral Neuropathy (CIPN20), the EuroQoL-5 Dimensions (EQ-5D), the Patient Global Impression of Severity (PGIS), and the Patient Global Impression of Change (PGIC). Patient surveys were supplemented with retrospective chart reviews conducted 3 months and 12 months following the index date to obtain clinical information. Descriptive data were reported at each timepoint separately for patients who received CAR-T and non-CAR-T index therapies. The study is ongoing and this abstract reflects all patient visit data as of April 2023. RESULTS N=55 patients (60% male, 96% White, mean age 66 years) were included in this interim analysis. The median time interval between becoming TCR and the index date was 3.9 months (interquartile range [IQR]: 1.7, 15.5). Most patients had an ECOG score of 0 or 1 (53% and 38%, respectively) and were R-ISS I or II (36% and 54%, respectively); 53% of patients had high-risk cytogenetics and 20% had extramedullary disease. The median (IQR) number of prior treatment lines was 4 (4.0, 5.5). N=24 patients initiated a CAR-T therapy as their index therapy (equally split between ide-cel and cilta-cel); the remaining N=31 patients predominantly initiated a treatment regimen containing an IMiD (52%), a PI (55%), an anti-CD38 antibody (13%), or an alkylating agent (36%). Among CAR-T patients, QOL and disease-related symptoms worsened from baseline through Month 2-3 (eg, mean GHS was 65.9 at apheresis, 64.9 at lymphodepletion, and 53.3 at Month 2 [higher scores indicate better QOL]; mean DS domain score from the QLQ-MY20 was 24.1 at apheresis, 23.4 at lymphodepletion, and 33.7 at Month 2 [higher scores indicate more symptoms]; see Table 1). These decrements were followed by improvement back to baseline levels and, in some cases, improvement above baseline levels (eg, GHS was 67.9 and 65.0 at Months 4 and 5, respectively; DS was 18.3 and 17.8 at Months 4 and 5), though few patients had sufficient follow up to analyze QOL at later timepoints. Based on the PGIC, 77.8% of patients reported being “a little better” or “much better” as early as Month 1, though this number declined over time. Among non-CAR-T patients, QOL largely plateaued (GHS was 62.2 at baseline and 58.3 at Month 6), though disease symptoms improved over time (DS was 28.6 at baseline and 24.5 at Month 6; pain was 42.3 at baseline and 29.2 at Month 6). Based on the PGIC, 34.7% of patients reported being “a little better” or “much better” at Month 1, which improved to 50% by Month 6. CONCLUSIONS In this interim analysis of an ongoing prospective observational study, QOL and symptom measures generally worsened over the first few months for CAR-T patients in the real-world though improved to baseline levels and beyond at later time points. Patients did, however, directly report improvement in their disease state as early as Month 1 based on the PGIC. Non-CART patients generally showed a QOL plateau with some modest improvement in disease symptoms which was also reflected in their self-reported assessment of disease state improvement based on the PGIC.

1467. Effects Of Oral Antibiotic Prophylaxis For Surgical Site Infections In Colorectal Surgery: Insights From Real World Data

Abstract Background Surgical site infection (SSI) after colorectal surgery is a significant burden on healthcare costs and patient quality of life. Preventive strategies are very important to working on this problem. In a multicenter randomized controlled trial (RCT) published in Annals of Surgery(2016;263:1085-1091), we reported the efficacy of oral antimicrobial prophylaxis in preventing SSI before colorectal surgery. Since the end of the RCT in 2012, we have applied this prophylaxis in our clinical practice and have experienced a large number of cases. Here, we report the incidence of SSIs when this prophylactic measure is applied in real-world clinical practice. Methods We retrospectively evaluated the incidence of SSI in 1192 patients who underwent elective laparoscopic colorectal resection for colorectal tumors between January 2013 and June 2022. We excluded 24 patients who were unable to receive oral prophylaxis. Antimicrobial prophylaxis consisted of oral kanamycin (1 g) and metronidazole (750 mg) twice on the day before surgery and intravenous cefmetazole (1 g) just before and every 3 hours during surgery. The diagnosis of SSI follows the CDC/NHSN definition. Results Our study included 647 males and 545 females, with a mean age of 69.3 years (IQR 63-77) and BMI of 22.6 kg/m2 (IQR 20.2-24.7). The incidence of SSI in all surgical cases was 61/1192 (5.1%; 95% CI 4.0-6.5). The incidence of SSIs in colon surgery was 16/769 (2.1%; 95% CI 1.3-3.4), and in rectal surgery, 45/400 (11.3%; 95% CI 8.5-14.7). The incidence of Clostridioides difficile colitis, which is regarded as a side effect of oral antimicrobial agents, was low at 6/1192 cases (0.5%; 05%CI 0.2-1.1). In our previous RCT, the incidence of SSI was 21/289 (7.26%) in patients treated with oral antibiotics. In a subanalysis of this trial published in the International Journal of Colorectal Disease(2016;31:1775-1784), the incidence of SSI was 9/188 (4.8%) in colon surgery and 13/103 (13%) in rectal surgery. The incidence of SSIs in the present data was similar to or lower than the incidence of SSIs in well-conditioned patients selected in the RCT. Conclusion Our results suggest that preoperative oral antibiotic prophylaxis in colorectal surgery is an effective method to reduce SSIs in a wide variety of patients in real-world clinical practice. Disclosures All Authors: No reported disclosures

Clinical impact of switching or continuation of apixaban or rivaroxaban among patients with non-valvular atrial fibrillation

Abstract Background Numerous studies have demonstrated varied clinical outcomes with initiation of different direct oral anticoagulants (DOACs) among patients with non-valvular atrial fibrillation (NVAF). Although switching of DOACs either for medical or non-medical reasons occurs among some NVAF patients in real-world clinical practice, there has been a lack of evidence on the clinical outcomes of those switchers. Purpose Assess the risk of stroke/systemic embolism (SE) and major bleeding (MB) among NVAF patients who switched from apixaban therapy to rivaroxaban or switched from rivaroxaban therapy to apixaban. Methods This retrospective study identified NVAF patients who initiated the most commonly used DOACs (apixaban or rivaroxaban) between 01 Jan 2013 and 31 December 2021 using a large US administrative claims database (Optum’s de-identified Clinformatics® Data Mart Database) representing patients in commercial or Medicare Advantage insurance plans. Patients who switched from one DOAC to the other within 30 days before or 90 days after discontinuation of initial DOAC and patients who continued receiving the initial DOAC were included. For switchers, the switch date was the index date. For continuers, a hypothetic index date was randomly assigned based on the distribution of the time from initial DOAC prescription to the switch date in the switchers group. Two final cohorts (switchers and continuers) within apixaban initiators and rivaroxaban initiators were further propensity score matched (PSM) based on pre-index characteristics up to a 1:5 ratio. The risks of stroke/SE and MB after the index date were compared between patients who continued the initial DOAC and patients who switched to the other DOAC. Results There were 167,868 apixaban initiators and 65,888 rivaroxaban initiators. After PSM, 2,884 patients who switched from apixaban to rivaroxaban were matched to 14,296 patients who continued apixaban, and 2,853 patients who switched from rivaroxaban to apixaban were matched to 13,330 patients who continued rivaroxaban. Patient characteristics were balanced between the continuers and switchers for both apixaban and rivaroxaban initiators. Patients who switched from apixaban to rivaroxaban were associated with a higher risk of stroke/SE (Hazard Ratio (HR):1.54, 95% Confidence Interval (CI): 1.06-2.24) and MB (HR: 1.73, 95% CI: 1.40-2.14) than those who continued apixaban. Patients who switched from rivaroxaban to apixaban were associated with a similar risk of stroke/SE (HR:0.75, 95% CI: 0.45-1.24) and a lower risk of MB (HR:0.58, 95%CI: 0.44-0.76) compared to those who continued rivaroxaban. Conclusion Bleeding outcomes associated with switching or continuation of apixaban or rivaroxaban in NVAF patients were consistent with existing evidence supporting a better safety profile for apixaban vs rivaroxaban.

Factors associated with early and late Staphylococcus aureus bacteraemia after first cardiac implantable electronic device implantation a Danish nationwide cohort study

Abstract Background Staphylococcus aureus bacteraemia (SAB) is a serious condition with high morbidity and mortality. Patients with a cardiac implantable electronic device (CIED) and SAB carries a risk of up to 50 % for device related infection. Yet, little is known about risk factors for early and late SAB in CIED patients in real-world clinical practice. Purpose We aimed to identify risk factors associated with first-time early and late SAB following de novo CIED implantation among adult Danish patients. Methods Using the Danish Pacemaker and ICD Register, we identified all Danish patients aged 18 to 99 years with a first CIED implantation between 2000 and 2020. The primary outcome of first-time post-CIED implantation SAB was identified from The National Danish Staphylococcus Aureus Bacteriemia Database. Early SAB was defined as SAB ≤ 6 months from CIED implantation. Late SAB was defined as first-time SAB after CIED, occurring > 6 months from CIED implantation. Multivariable Cox regression with backward elimination was used to identify factors associated with increased risk of developing early and late SAB. Age, sex, device type, implantation year, preexisting co-morbidity, procedure related factors and prior surgery (thoracic, abdominal, orthopedic, gynecologic, or urologic) was evaluated. Statistically significant variables were fitted to the final models to obtain hazard ratios with 95% confidence intervals. Results We identified 87,216 patients with first-time CIED implantation within the study period: PM n = 66,151 (75.8%); Implantable Cardioverter Defibrillator (ICD) n = 13,498 (15.5%); Cardiac resynchronization therapy PM (CRT-P) n = 3,491 (4.0 %); Cardiac resynchronization therapy with defibrillator (CRT-D) n = 4,076 (4.7 %). Median age across the population was 75 years (IQR 66-82) and 62.6% were males. Median time to SAB in the early SAB group was 46 days (IQR 18-105) and 2,9 years (IQR 1.5-5.1) in the late SAB group. Post implantation SAB was observed in 1,399 (1.6%) patients; with 363 (25.9%) early SAB events and 1,036 (74.1%) late SAB events. Factors associated with early SAB included previous SAB, renal dialysis, COPD, surgery 1 year prior to CIED implantation, liver disease, diabetes, and congestive heart failure (Figure 1). Male sex, increasing age, previous SAB, congestive heart failure, aortic valve disease, diabetes, renal dialysis, COPD, cancer, liver disease and the use of systemic corticosteroids were associated with an increased risk of late SAB. Conclusions Renal dialysis, previous SAB, diabetes, congestive heart failure, COPD and liver disease were associated with an increased risk of both early and late SAB. Increasing age, male sex, aortic valve disease and cancer were associated with an increased risk of late SAB, while surgery within 1 year prior to CIED implantation was associated with early SAB. Most of the identified factors were non-modifiable and comparable to known risk factors for SAB in non-CIED patients.Figure 1

Safety and effectiveness of oral blonanserin for schizophrenia in adolescents in China: Data from a 12-week post-marketing surveillance

Background and objectivesBlonanserin is a second-generation antipsychotic (SGA)for the treatment of schizophrenia and has been approved for use in Japan, South Korea and China. This analysis aimed to evaluate the effectiveness and safety of blonanserin in Chinese adolescent patients, using data from a post-marketing surveillance of blonanserin started in September 2018. MethodsA 12-week, prospective, multi-center, open-label post-marketing surveillance was conducted. Patients in this analysis were stratified by age. Results78 patients with schizophrenia aged < 18 years were included. The incidence of adverse drug reactions in adolescent patients was 33.3% significantly higher than patients over 40 years old. After 12-week treatment, 8.1% of adolescent patients had a weight gain ≥ 7%, and it was not significantly different from other age groups. Mean Brief Psychiatric Rating Scale (BPRS) total score was significantly reduced at week 12, and the decline of anergia score and thought disturbance score of adolescent patients was significantly greater than in adults. ConclusionsBlonanserin was well tolerated and effective in the treatment of schizophrenia in Chinese adolescent patients in real-world clinical practice. Blonanserin might be a reasonable choice for the treatment of schizophrenia in adolescent patients.

Prevalence, patient characteristics and treatment patterns among SLE-PAH patients in real-world clinical practice: A retrospective analysis of Medical Data Vision Database in Japan.

Real-world evidence regarding prevalence, patient characteristics and treatment patterns for pulmonary arterial hypertension (PAH) related to systemic lupus erythematosus (SLE) in Japan is limited. We conducted a retrospective study analysing Japan's Medical Data Vision (MDV) database from April-2008 to September-2020. Prevalence, incidence, patient characteristics, treatment patterns and use of vasodilators by treatment line were evaluated. Prevalence of PAH was 0.392% in SLE patients (n=114/29,077). Cumulative incidence was 0.53% (3-years (y)) and 0.77% (5y). Of 114 SLE-PAH patients, 49% developed PAH <1 year from SLE diagnosis. SLE-PAH patients were more female (88% vs. 72%), had lower mean age at SLE diagnosis (53y vs. 56y) and more severe SLE (61% vs 25%), versus non-PAH SLE patients. Glucocorticoids (58%) and vasodilators (27%) were preferred first-line monotherapy for SLE-PAH. Glucocorticoids+immunosuppressants (19%) was predominant first-line combination therapy. Endothelin receptor antagonists (40% and 44%) and nitric oxide analogues (31% and 40%) were dominant first- and second-line vasodilators. SLE-PAH patients were more females, younger at diagnosis, had more severe SLE than non-PAH SLE patients. Most were diagnosed <1 year of SLE diagnosis. In Japan's real-world practice, initial treatment goal is SLE management, while vasodilators are preferred in advanced disease, as per MDV database.

Medications and conditions associated with weight loss in patients prescribed semaglutide based on real-world data.

Approved by the Food and Drug Administration (FDA) in 2017 for diabetes and in 2021 for weight loss, semaglutide has seen widespread use among individuals who aim to lose weight. The aim of this study was to evaluate weight loss and the influence of clinical factors on semaglutide patients in real-world clinical practice. Using data from 10 health systems within the Greater Plains Collaborative (a PCORnet Clinical Research Network), nearly 4000 clinical factors encompassing demographic, diagnosis, and prescription information were extractedfor semaglutide patients. A gradient-boosting, machine-learning classifier was developed for weight-loss prediction and identification of the most impactful factors via SHapley Additive exPlanations (SHAP) value extrapolation. A total of 3555 eligible patients (539 of whom were observed 52 weeks following exposure) from March 2017 to April 2022 were studied. On average, individuals lost 4.44% (male individuals, 3.66%; female individuals, 5.08%) of their initial weight. History of diabetes mellitus diagnosis was associated with less weight loss, whereas prediabetes and linaclotide use were associated with more pronounced weight loss. Weight loss in patients prescribed semaglutide from real-world evidence was strong but attenuated compared with previous clinical trials. Machine-learning analysis of electronic health record data identified factors that warrant further research and consideration when tailoring weight-loss therapy.

Oral Corticosteroid Reduction Between Biologics Initiated and Non-Initiated Patients with Severe Asthma.

The oral corticosteroid (OCS)-sparing effect of several biologics (BIOs) has been shown in clinical trials. To date, no study has evaluated differences in OCS dose reduction between BIO-initiated and BIO-non-initiated patients in real-world clinical practice. We compared dose reductions in maintenance OCS between BIO-initiated and BIO-non-initiated severe asthma patients in a real-world setting. This retrospective cohort study used the data from the Diagnosis Procedure Combination database of Medical Data Vision in Japan. Severe asthma patients with continuous use of OCS were selected from December 2015 to February 2020. The primary endpoint was the proportion reduction in daily maintenance OCS dose from Week 0 to Week 24. Analyses were performed using inverse probability treatment weighting. In total, 2927 patients were included (BIO-initiated: 239 patients, BIO-non-initiated: 2688 patients). Adjusted median (quartile [Q] 1-Q3) proportion reduction in daily maintenance OCS dose at Week 24 from the index date was 25.0% (0.0-100.0%) and 0.0% (0.0-83.3%) in the BIO-initiated and BIO-non-initiated groups, respectively (Hodges-Lehmann estimate [95% confidence interval], 0.0000% [0.0000-0.3365%]). Respective proportions of patients in the BIO-initiated and BIO-non-initiated groups achieving dose reductions from the index date in the daily maintenance OCS dose at Week 24 were >0% reduction, 56.6% and 44.1% (odds ratio [OR] 1.6554); ≥25% reduction, 50.5% and 40.6% (OR 1.4888); ≥50% reduction, 42.8% and 33.7% (OR 1.4714); and 100% reduction, 26.2% and 24.4% (OR 1.1005). Among severe asthma patients, the daily dose of maintenance OCS was reduced with BIO treatment. Although a higher percentage of patients in the BIO-initiated group had an OCS reduction of ≤75% than the BIO-non-initiated group, we found no clear difference in OCS reduction. Our findings will be justified by further research that incorporates a longer observation period and variables excluded from this study. ClinicalTrials.gov (NCT05136547).

AWARE A novel web application to rapidly assess cardiovascular risk in type 2 diabetes mellitus

AimTo describe the development of the AWARE App, a novel web application for the rapid assessment of cardiovascular risk in Type 2 Diabetes Mellitus (T2DM) patients. We also tested the feasibility of using this App in clinical practice.MethodsBased on 2019 European Society of Cardiology/European Association for the Study of Diabetes criteria for cardiovascular risk stratification in T2DM, the AWARE App classifies patients into very high (VHCVR), high (HCVR) and moderate (MCVR) cardiovascular risk categories. In this retrospective clinical study, we employed the App to assess the cardiovascular risk of T2DM patients, while also collecting data about current glycaemic control and pharmacological treatment.Results2243 T2DM consecutive patients were evaluated. 72.2% of the patients were VHCVR, 8.9% were HCVR, 0.8% were MCVR while 18.2% did not fit into any of the risk categories and were classified as “moderate-to-high” (MHCVR). Compared with the other groups, patients with VHCVD were more frequently ≥ 65 years old (68.9%), with a longer disease duration (≥ 10 years [56.8%]), a history of cardiovascular disease (41.4%), organ damage (35.5%) and a higher numbers of cardiovascular risk factors. Patients with MHCVD generally had disease duration < 10 years (96%), younger age (50–60 years [55%]), no history of cardiovascular disease, no organ damage, and 1–2 cardiovascular risk factors (89%). Novel drugs such as Glucagon Like Peptyde 1 Receptor Agonists or Sodium-Glucose Linked Transporter 2 inhibitors were prescribed only to 26.3% of the patients with VHCVR and to 24.7% of those with HCVR. Glycaemic control was unsatisfactory in this patients population (HbA1c 7.5 ± 3.4% [58.7 ± 13.4 mmol/mol]).ConclusionsThe AWARE App proved to be a practical tool for cardiovascular risk stratification of T2DM patients in real-world clinical practice.

An Adjusted Treatment Comparison Comparing Amivantamab Versus Real-World Clinical Practice in Europe and the United States for Patients with Advanced Non-Small Cell Lung Cancer with Activating Epidermal Growth Factor Receptor Exon 20 Insertion Mutations.

Patients with advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC) with Exon 20 insertion mutations (Exon20ins) have poor prognoses, exacerbated by a previous lack of specific treatment guidelines and unmet need for targeted therapies. Amivantamab, an EGFR and MET bispecific antibody, demonstrated efficacy and tolerability in patients with advanced EGFR-mutated NSCLC with Exon20ins following platinum-based therapy in CHRYSALIS (NCT02609776; Cohort D+). Since CHRYSALIS was single-arm, individual patient data (IPD)-based adjusted analyses versus similar patients in real-world clinical practice (RWCP) were conducted to generate comparative evidence. RWCP cohorts were derived from seven European and US real-world sources, comprising patients fulfilling CHRYSALIS Cohort D+eligibility criteria. Amivantamab was compared with a basket of RWCP treatments. Differences in prognostic characteristics were adjusted for using inverse probability weighting (IPW; average treatment effect among the treated [ATT]). Balance between cohorts was assessed using standardized mean differences (SMDs). Overall response rate (ORR; investigator- [INV] and independent review committee-assessed [IRC]), overall survival (OS), progression-free survival (PFS; INV and IRC) and time-to-next treatment (TTNT) were compared. Binary and time-to-event endpoints were analyzed using weighted logistic regression and proportional hazards regression, respectively. Pre-adjustment, baseline characteristics were comparable between cohorts. IPW ATT-adjustment improved comparability, giving closely matched characteristics. ORR (INV) was 36.8% for amivantamab versus 17.0% for the adjusted EU+US cohort (response rate ratio [RR]: 2.16). Median OS, PFS (INV) and TTNT were 22.77 versus 12.52months (hazard ratio [HR]: 0.47; p<0.0001), 6.93 versus 4.17months (HR: 0.55; p<0.0001) and 12.42 versus 5.36months (HR: 0.44; p<0.0001) for amivantamab versus the adjusted EU+US cohort, respectively. Results were consistent versus EU- and US-only cohorts, and when using IRC assessment. Adjusted comparisons demonstrated significantly improved outcomes for amivantamab versus RWCP, highlighting the value of amivantamab in addressing unmet need in patients with advanced EGFR Exon20ins NSCLC following platinum-based therapy. CHRYSALIS: NCT02609776.

What predicts the clinical benefits of PARP inhibitors in platinum-sensitive recurrent ovarian cancer: A real-world single-center retrospective cohort study from China.

ObjectiveThis study assessed the real-world application, effectiveness, and safety of olaparib and niraparib as maintenance therapies in patients with platinum-sensitive recurrent ovarian cancer (PSROC) in China and investigated clinical factors associated with prolonged benefits of poly ADP-ribose polymerase (PARP) inhibitors to help guide clinician treatment-decision making in daily practice.MethodsThis real-world single-center retrospective cohort study was conducted at the Shandong Cancer Hospital and Institute. Archival data of consecutive patients diagnosed with PSROC who achieved a complete response (CR) or partial response (PR) after the last platinum-based chemotherapy and treated with olaparib or niraparib as maintenance therapy from August 2018 to September 2021 were collected.ResultsOverall, 106 women were included in the cohort. Seventy-two (68%) patients were treated with olaparib, while 34 (32%) received niraparib; 99.1% of the patients were diagnosed with high-grade serous carcinoma, and 73.6% had FIGO stages III–IV. Approximately 71.7% of the patients had received PARP inhibitors after the second platinum-based line and 44.3% of the patients achieved a CR in their last platinum-based therapy. The median platinum-free interval (PFI) after the penultimate platinum-based therapy was 10 (95% CI: 10–13.6) months. The median PFS was 21 (95% CI: 13–24.5) months and the median CFI was 22 (95% CI: 16–26.5) months. Consistent with the univariate analysis, the multivariate analysis identified three independent factors associated with prolonged progression-free survival (PFS) and chemotherapy-free interval (CFI): breast cancer susceptibility gene (BRCA) mutant type (p = 0.005 and p = 0.003); PFI ≥12 months (p = 0.01 and p = 0.006); and CR to last platinum-based therapy (p = 0.016 and p = 0.019). It was found that there was no appreciable difference in any grade 3–4 hematological AE between patients who received olaparib and niraparib.ConclusionMaintenance treatment with olaparib and niraparib is effective and well tolerated for PSROC patients in real-world clinical practice. Three clinical factors were identified that predicted prolonged survival under maintenance therapy with PARP inhibitors: BRCA mutant type, PFI ≥12 months, and CR to last platinum-based therapy. These findings should be further confirmed with an appropriately powered analysis in studies with larger sample sizes.

Physician behavior and perceptions around genetic biomarker test utilization for the management of newly diagnosed advanced ovarian cancer patients: US physician survey (223)

Physician behavior and perceptions around genetic biomarker test utilization for the management of newly diagnosed advanced ovarian cancer patients: US physician survey (223)

Platelet Doubling After First Decitabine Cycle Predicts Response and Survival of Myelodysplastic Syndrome Patients.

Although the effect of decitabine on myelodysplastic syndrome (MDS) has been demonstrated, merely a proportion of patients respond to therapy, and no well-recognized predictors have been identified. This study was conducted to investigate the effectiveness of decitabine in real-world clinical practice, and determine the predictive factors of response and overall survival (OS) in MDS patients. Clinical and pathological data were collected from 94 patients and analyzed. These patients were reclassified according to the 2016 World Health Organization classification criteria, and restratified by International Prognostic Scoring System prognostic scores. The response evaluation was performed according to the 2006 modified International Working Group response criteria. In this study, 62% of patients responded to decitabine. Among these patients, 15 patients (16%) obtained complete remission (CR), 15 patients (16%) obtained marrow CR with hematologic improvement (HI), 20 patients (21%) obtained marrow CR without HI, and 8 patients (9%) only obtained HI, and no patient botained partial remission. The OS of the responders was significantly longer than that of non-responders (67 months vs. 7 months, P<0.001). The OS in patients with and without platelet doubling was significantly different in both the low/intermediate and high/very high risk groups (P=0.0398 and P=0.0330). The multivariate analysis revealed that platelet doubling after the first decitabine cycle is an independent predictor of response and OS in MDS patients (P=0.002 and P=0.008). Decitabine is effective for treating MDS patients in real-world clinical practice. Furthermore, platelet doubling after the first decitabine cycle can be used as a predictor of response and survival in MDS patients.

Medicine-Based Evidence in Congenital Heart Disease: How Artificial Intelligence Can Guide Treatment Decisions for Individual Patients.

Built on the foundation of the randomized controlled trial (RCT), Evidence Based Medicine (EBM) is at its best when optimizing outcomes for homogeneous cohorts of patients like those participating in an RCT. Its weakness is a failure to resolve a clinical quandary: patients appear for care individually, each may differ in important ways from an RCT cohort, and the physician will wonder each time if following EBM will provide best guidance for this unique patient. In an effort to overcome this weakness, and promote higher quality care through a more personalized approach, a new framework has been proposed: Medicine-Based Evidence (MBE). In this approach, big data and deep learning techniques are embraced to interrogate treatment responses among patients in real-world clinical practice. Such statistical models are then integrated with mechanistic disease models to construct a “digital twin,” which serves as the real-time digital counterpart of a patient. MBE is thereby capable of dynamically modeling the effects of various treatment decisions in the context of an individual's specific characteristics. In this article, we discuss how MBE could benefit patients with congenital heart disease, a field where RCTs are difficult to conduct and often fail to provide definitive solutions because of a small number of subjects, their clinical complexity, and heterogeneity. We will also highlight the challenges that must be addressed before MBE can be embraced in clinical practice and its full potential can be realized.

An Observational Study of Fostamatinib As Second Line Therapy in Adult Patients with Immune Thrombocytopenia (ITP) in Real-World Clinical Practice

Background: In immune thrombocytopenia (ITP), autoantibody-bound platelets are targeted for phagocytosis by Fcγ-receptors on macrophages in a spleen tyrosine kinase (SYK)-dependent signaling pathway. Fostamatinib is a potent oral SYK inhibitor that demonstrated efficacy for the treatment of ITP in two phase 3 randomized, placebo-controlled, double-blind studies and long-term durable responses in the phase 3 open-label extension study. In these studies, 146 patients with ITP were treated with fostamatinib, and 54% had a platelet response (platelet count ≥50,000/µL), which was maintained over a median of 86% of treatment days. These studies led to approval of fostamatinib in the US, Europe, and Canada as a therapy for chronic ITP in adult patients who have had an insufficient response to a prior treatment. Further, a post-hoc analysis showed that, in those who received fostamatinib as second-line therapy (following steroids ± immunoglobulins), 78% achieved a platelet response, which was maintained over a median of 83% of treatment days. 1 Adverse events (AEs) were reported in 72% of second-line patients and 86% of all patients, and common AEs were similar between second-line patients and the total patient population. 1, 2 Bleeding events were reported in 24% of second-line patients vs. 41% of all patients. The results of the post hoc analysis underscored the necessity for further evaluation of fostamatinib as a second-line therapy for ITP.We are conducting a multi-center, prospective, observational, two cohort study of fostamatinib as second-line therapy for the management of ITP in adult patients who have an insufficient response to prior steroids ± immunoglobulins.Aim: This study will evaluate clinical outcomes and safety of fostamatinib as second-line therapy for ITP in adult patients in real-world clinical practice. Patients will also be assessed for quality of life and utilization of health care resources during the study.Methods: The study (FORTE; NCT04904276; O-FOSTA-901) is being conducted at 10 sites across the US and will enroll 45 patients with ITP into 2 cohorts (see Figure). The study is registered at https://clinicaltrials.gov/ct2/show/NCT04904276. The study aims to enroll adult patients with a confirmed diagnosis of ITP and an inadequate response to prior steroids ± immunoglobulins. Patients who have received any prior ITP treatment other than steroids or immunoglobulins will be excluded. Patients who will initiate fostamatinib as second-line therapy at study entry will be enrolled into Cohort 1; patients currently receiving fostamatinib as second-line therapy with the intent to continue treatment will be enrolled in Cohort 2 (historical platelet counts will be retrospectively collected). Patients will be treated by their clinician at the clinician's discretion (not pre-specified by a study protocol).Primary outcome measures will include platelet count over time, duration of platelet count elevation, use of ITP rescue medication, changes in dosing, use of concomitant ITP medications, incidence of serious and ITP-related AEs, and quality of life. Quality of life assessments will utilize the SF-36v2 and ITP-PAQ. All data will be collected at regularly scheduled clinic visits according to the clinician's normal practice for 12 months or until fostamatinib is discontinued.Summary: This ongoing observational study of adult patients with ITP will enable further characterization of the risk/benefit profile of fostamatinib as a second-line treatment for ITP and will provide insight on how clinicians manage ITP in a real-world setting without the constraints of a clinical trial protocol.

EFFECTIVENESS OF THE COMBINATION OF TRIMETAZIDINE AND BISOPROLOL IN PATIENTS WITH ANGINA PECTORIS: A POST-HOC ANALYSIS OF CHOICE-2 STUDY

Objective: Objectives. To evaluate the effectiveness of the combination of trimetazidine (TMZ) and bisoprolol in angina patients in real-world clinical practice. Design and method: Methods. This is a post-hoc analysis of CHOICE II, a Russian, multicenter, 6-month, open-label, prospective observational study that assessed the effect of adding TMZ modified release 35 mg bid to antianginal treatment. 896 patients with persistent symptomatic stable angina were included in CHOICE-II, of whom 221 receiving TMZ -bisoprolol were included in the post-hoc analysis. Patients took TMZ 35 mg bid for the entire study duration. There was no optimization of other antianginal drugs. Results: Results. The mean age of patients was 64.8 ± 8.9 years. 52.0% were female. 91.9% had hypertension. Mean heart rate was 71.9 ± 9.6 beats per minute. At baseline patients had stable angina, mostly with CCS Class II (65.6%) or Class III (30.8%). Both angina frequency and short-acting nitrate (SAN) use decreased significantly on TMZ-bisoprolol from baseline to month 6 from 6.2 ± 5.3 to 1.5 ± 1.9 attacks/week and from 5.5 ± 4.4 to 1.0 ± 1.4 SAN/week, respectively (P &lt; 0.001 for both). Exercise capacity also improved: angina-free walking distance significantly increased (from 308 ± 207 to 497 ± 253 meters, P &lt; 0.001), as well as the number of flight of stairs until angina (from 2.9 ± 2.0 to 4.5 ± 2.3, P &lt; 0.001). At 6 months, the number of patients presenting dyspnea decreased from 169 (76.5%) to 87 (39.4%). % of patients with CCS Class I angina increased more than 10-fold during the treatment period (from 2.3% to 27.6%) while % of patients with CCS Class III angina decreased 3-fold (from 30.8% to 10.0%). After 6 months of treatment, mean systolic and diastolic blood pressure decreased by 13.4 ± 13.1 and 6.7 ± 9.4 mm Hg staying within normal ranges, respectively. 3 patients (1.4%) prematurely discontinued the study treatment combination. Conclusions: Conclusion. This analysis supported the antianginal effectiveness of TMZ-bisoprolol in real-life clinical practice.

Patient and disease characteristics of the first 500 patients with pulmonary arterial hypertension treated with selexipag in real-world settings from SPHERE

Selexipag is a selective oral prostacyclin receptor agonist indicated for pulmonary arterial hypertension (PAH) treatment. SelexiPag: tHe usErs dRug rEgistry (SPHERE) (NCT03278002) is collecting data from selexipag-treated patients in real-world clinical practice to elucidate and describe the clinical characteristics, outcomes, and dosing/titration regimens of patients treated with selexipag in routine clinical practice. SPHERE is a United States (US)-based, ongoing, multicenter, prospective observational study (target N = 800). This study enrolls patients who are either newly initiated on selexipag (≤60 days before enrollment) or were previously receiving selexipag with documentation of dose titration at study enrollment. Data collection for the study occurs at routine clinic visits. In this paper, we report on the first 500 patients enrolled. Median follow-up was 17.8 months; 77.6% of patients completed the planned 18 months follow-up, and 22.4% discontinued early from the study. At diagnosis, 94.8% of patients had PAH (World Health Organization [WHO] Group 1), most commonly idiopathic (49.2%) and connective tissue disease associated (26.4%). Most patients (72.4%) initiated selexipag more than 60 days before enrollment. At initiation, 31.0% of patients had WHO functional class (FC) II disease, and 49.6% had WHO FC II or III disease. In addition, 55.0% of patients were receiving double therapy (most commonly an endothelin receptor antagonist plus phosphodiesterase type 5 inhibitor [42.3%]), whereas 30.6% were receiving monotherapy. Despite most patients already receiving PAH-specific therapy, at selexipag initiation, 67.2% (336 of 500) were at intermediate risk, and 9.6% (48 of 500) were at high risk of 1-year mortality. Risk scores remained stable in ∼55% of patients and improved in ∼20% at the end of the study. In total, 72.2% of patients had at least 1 adverse event (AE), and 37.6% reported a serious AE. The median selexipag maintenance dose was 1,200 µg twice daily (interquartile range: 800-1,600 µg twice daily). Real-world, US-based patients with PAH initiating selexipag typically have WHO FC II/III disease and are at intermediate risk, despite receiving PAH-specific treatment. Selexipag was prescribed as part of a combination regimen in most patients. The study identified no unexpected adverse effects.