Persistence of ibrutinib-associated hypertension in CLL pts treated in a real-world experience.

7525 Background: Cardiovascular (CV) complications associated with ibrutinib (Ibr) include hypertension (HTN) and atrial fibrillation (AFIB) (incidence 26% and 9%, OBrien, ASH 2016). Unlike clinical trials, Ibr toxicities are the most common reasons for its discontinuation in clinical practice. The incidence of HTN in pts treated with Ibr outside of clinical trial setting and its impact on outcomes is unknown. Methods: Retrospective, cohort study of Ibr-treated CLL pts to estimate HTN incidence. Baseline CLL characteristics and co-morbidities were recorded. Blood pressure (BP) measurements were recorded prior to Ibr and sequentially following exposure at specific time points. CV meds were reviewed during a 12 mo follow-up period. The association between Ibr exposure and BP was tested. Results: 153 consecutive CLL pts treated with Ibr at a dose of 420 mg/day were identified. Med age was 57 yr (range: 34-87), relapsed CLL (69%), follow-up 14.5 mo. CV pre-Ibr characteristics included: smoking hx (49%), HTN (42%), hyperlipidemia (39%), diabetes (17%), CAD (12%), AFIB (6.8%). Proportion of pts on ≥1 anti-HTN med increased from 44% pre-Ibr (20% ≥ 2) to 57% during Ibr (30% ≥ 2). Med pre-Ibr BP was 127/70 mmHg (range 90-182/48-95mmHg). At 1, 3, 6, 9, 12 mo, med BPs were 137/73, 141/75, 143/76, 140/75, 142/77 (7 mo to peak BP). There was a significant association between Ibr exposure and increased BP (p<.01). New HTN was observed in 40% of pts and 36% HTN pts had BP increased above baseline (med baseline 135/70 vs peak 161/80). Incidence of new AFIB was 8.1%. In UV analyses, predictive clinical factors for HTN were not identified. Pre-Ibr HTN (OR 3.0, p .05), CAD (OR 4.3, p .03), prior AFIB event (OR 10.8, p.001), hyperlipidemia (OR 3.4, p.05) were associated with post-Ibr AFIB. Conclusions: In the largest real-world series focused on BP in Ibr treated pts, we demonstrate a clear association between Ibr and HTN. Nearly 40% of pts developed HTN within 12 mo of Ibr exposure (vs. 26% in clinical trials over 5 yr). Despite aggressive management (multiple agents), Ibr associated HTN was persistent. These data underscore the critical need for monitoring and management strategies for HTN and follow-up data on future CV events.

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Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides difficile Infection

Journal of Clinical Medicine ◽

10.3390/jcm10010002 ◽

2020 ◽

Vol 10 (1) ◽

pp. 2

Author(s):

Rosa Escudero-Sánchez ◽

María Ruíz-Ruizgómez ◽

Jorge Fernández-Fradejas ◽

Sergio García Fernández ◽

María Olmedo Samperio ◽

...

Keyword(s):

Clinical Trials ◽

Real World ◽

Recurrence Rates ◽

Factors Associated ◽

Clostridioides Difficile ◽

Multicentre Cohort Study ◽

Clostridioides Difficile Infection ◽

Prevention Of Recurrence ◽

Multicentre Cohort

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.

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LDL-cholesterol change and goal attainment following statin intensity titration among Asians in primary care: a retrospective cohort study

Lipids in Health and Disease ◽

10.1186/s12944-020-01427-z ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Hao Sen Andrew Fang ◽

Qiao Gao ◽

Mong Li Lee ◽

Wynne Hsu ◽

Ngiap Chuan Tan

Keyword(s):

Primary Care ◽

Clinical Trials ◽

Cohort Study ◽

Real World ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Goal Attainment ◽

Real World Data ◽

World Data ◽

Asian Patients

Abstract Background Clinical trials have demonstrated that either initiating or up-titrating a statin dose substantially reduce Low-Density Lipoprotein-Cholesterol (LDL-C) levels. However, statin adherence in actual practice tends to be suboptimal, leading to diminished effectiveness. This study aims to use real-world data to determine the effect on LDL-C levels and LDL-C goal attainment rates, when selected statins are titrated in Asian patients. Methods A retrospective cohort study over a 5-year period, from April 2014 to March 2019 was conducted on a cohort of multi-ethnic adult Asian patients with clinical diagnosis of Dyslipidaemia in a primary care clinic in Singapore. The statins were classified into low-intensity (LI), moderate-intensity (MI) and high-intensity (HI) groups according to the 2018 American College of Cardiology and American Heart Association (ACC/AHA) Blood Cholesterol Guidelines. Patients were grouped into “No statin”, “Non-titrators” and “Titrators” cohorts based on prescribing patterns. For the “Titrators” cohort, the mean percentage change in LDL-C and absolute change in LDL-C goal attainment rates were computed for each permutation of statin intensity titration. Results Among the cohort of 11,499 patients, with a total of 266,762 visits, there were 1962 pairs of LDL-C values associated with a statin titration. Initiation of LI, MI and HI statin resulted in a lowering of LDL-C by 21.6% (95%CI = 18.9–24.3%), 28.9% (95%CI = 25.0–32.7%) and 25.2% (95%CI = 12.8–37.7%) respectively. These were comparatively lower than results from clinical trials (30 to 63%). The change of LDL-C levels due to up-titration, down-titration, and discontinuation were − 12.4% to − 28.9%, + 13.2% to + 24.6%, and + 18.1% to + 32.1% respectively. The improvement in LDL-C goal attainment ranged from 26.5% to 47.1% when statin intensity was up-titrated. Conclusion In this study based on real-world data of Asian patients in primary care, it was shown that although statin titration substantially affected LDL-C levels and LDL-C goal attainment rates, the magnitude was lower than results reported from clinical trials. These results should be taken into consideration and provide further insight to clinicians when making statin adjustment recommendations in order to achieve LDL-C targets in clinical practice, particularly for Asian populations.

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Discordant American Society of Anesthesiologists Physical Status Scoring between Anesthesiologists and Surgeons Is Correlated With Adverse Patient Outcomes: A Retrospective Cohort Study of 46284 Elective Surgical Patients

10.21203/rs.3.rs-590499/v1 ◽

2021 ◽

Author(s):

Charlene Xian Wen Kwa ◽

Jiaqian Cui ◽

Daniel Yan Zheng Lim ◽

Yilin Eileen Sim ◽

Yuhe Ke ◽

...

Keyword(s):

Cohort Study ◽

Patient Outcomes ◽

Real World ◽

Odds Ratio ◽

Retrospective Cohort ◽

Clinical Factors ◽

Physical Status ◽

Asa Score ◽

American Society ◽

American Society Of Anesthesiologists

Abstract BackgroundThe American Society of Anesthesiologists Physical Status Classification (ASA) score is used for communication of patient health status, risk scoring, benchmarking and financial claims. Prior studies using hypothetical scenarios have shown poor concordance of ASA scoring among healthcare providers. However, there is a paucity of concordance studies using real-world data, as well as studies of clinical factors or patient outcomes associated with discordant scoring. The study aims to assess real-world ASA score concordance between surgeons and anesthesiologists, factors surrounding discordance and its impact on patient outcomes. MethodsThis retrospective cohort study was conducted in a tertiary academic medical center on 46284 consecutive patients undergoing elective surgery between January 2017 and December 2019. ASA scores entered by surgeons and anesthesiologists, patient demographics, and post-operative outcomes were collected. We assessed the concordance of preoperative ASA scoring between surgeons and anesthesiologists, clinical factors associated with score discordance, the impact of score discordance on clinically important outcomes, and the discriminative ability of the two scores for 30-day mortality, 1-year mortality, and intensive care unit (ICU) admission. Statistical tests used included Cohen’s weighted 𝜅 score, chi-square test, t-test, unadjusted odds ratios and logistic regression models. ResultsThe ASA score showed moderate concordance (weighted Cohen’s 𝜅 0.53) between surgeons and anesthesiologists. 15098 patients (32.6%) had discordant scores, of which 11985 (79.4%) were scored lower by surgeons. We found significant associations between discordant scores and anesthesiologist-assessed comorbidities, patient age and race. Patients with discordant scores had a higher risk of 30-day mortality (odds ratio 2.00, 95% confidence interval [CI] = 1.52-2.62, p<0.0001), 1-year mortality (odds ratio 1.53, 95% CI = 1.38-1.69, p < 0.0001), and ICU admission >24 hours (odds ratio 1.69, 95% CI = 1.47-1.94, p< 0.0001), and stratified analyses showed a trend towards higher risk when the surgeons’ ASA score was lower. ConclusionsThere is moderate concordance between surgeons and anesthesiologists in assigning the ASA classification. Discordant ASA scores are associated with adverse patient outcomes. Hence, there is a need for improved standardization of ASA scoring and cross-specialty review in ASA-discordant cases.

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Demographics, Treatment Patterns, Safety, and Real-World Effectiveness in Patients ≥70 Years of Age with Chronic Lymphocytic Leukemia Receiving Bendamustine with or without Rituximab,

Blood ◽

10.1182/blood.v118.21.3914.3914 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3914-3914

Author(s):

Kathryn S. Kolibaba ◽

Avani D. Joshi ◽

James A. Sterchele ◽

Michael Forsyth ◽

Erin Alwon ◽

...

Keyword(s):

Clinical Trials ◽

Chronic Lymphocytic Leukemia ◽

Partial Response ◽

Real World ◽

Progressive Disease ◽

Lymphocytic Leukemia ◽

Social Security Administration ◽

Grade 3

Abstract Abstract 3914 Background Bendamustine is a unique, well-established alkylating agent with multifaceted actions leading to cancer cell death in several hematologic malignancies. In a phase 3 trial in treatment-naïve patients with chronic lymphocytic leukemia (CLL), rates of response and progression-free survival (PFS) were significantly superior to those for chlorambucil [Knauf WU et al. J Clin Oncol 2009;27:4378–84]. In vitro studies have found that the cytotoxic activity of bendamustine against CLL-derived cell lines is synergized by rituximab, an anti-CD20 monoclonal antibody [Demidem A et al. Cancer Biother Radiopharm 1997;12:177–86]. Older patients may demonstrate lower tolerance to chemoimmunotherapy [Foon KA & Hallek MJ. Leukemia 2010;24:500–11], and published clinical data on bendamustine-rituximab in CLL are scarce. Thus, this retrospective study sought to characterize a population of adults ≥70 years old with CLL receiving bendamustine with or without rituximab, describe patterns of care, assess data on real-world effectiveness outside of the controlled environment of clinical trials [Waldthaler C et al. Wien Klin Wochenschr 2011;123:269–275], and assess safety. Methods Records were extracted from US Oncology iKnowMed (iKM) record databases for all outpatients ≥70 years old with CLL (but no other tumor) and more than 1 visit recorded (but not enrolled in clinical trials) who received bendamustine between March 2008 and May 2010. Patients were classified as treatment-naïve or relapsed (including ≥ second-line therapy). To ascertain mortality, the iKM data were supplemented with vital-status data from the Social Security Administration Death Index. The overall response rate (ORR) included complete response (CR), nodal partial response (nPR), and partial response (PR). PFS was time from first bendamustine dose to progressive disease (change in line of therapy), relapse, or death from any cause. Data from patients who did not die, or had no progression and were lost to follow-up were censored. Results Among 91 patients, the mean (SD) initial age at beginning of first therapy was 77.4 (5.6) years, age at diagnosis was 70.3 (6.5) years, and 63.7% were male. Of the 16 (17.6%) treatment-naïve patients, 10 had received bendamustine monotherapy and 6 received bendamustine-rituximab. Of the 75 (82.4%) relapsed patients, 20 had received bendamustine monotherapy and 55 received bendamustine-rituximab. The observed ORR for treatment-naïve patients was 56.3% (n=9; 18.8% CR, 37.5% PR, and 0 nPR); 6.3% had progressive disease. For relapsed patients, the ORR was 58.7% (n=44; 13.3% CR, 44.0% PR, and 1.3% nPR); 24.0% had progressive disease. Among patients with data, median PFS for 16 treatment-naïve patients has not been reached (median follow-up 15.1 months); for 73 relapsed patients, PFS was 18.4 months. Kaplan-Meier estimates for PFS over time for each group are shown in the Figure. No unexpected toxicities were seen. The overall rate of blood/bone marrow toxicities (all grades) was 40.7%; grade 3/4 rates were 18.8% for treatment-naïve patients and 25.3% for relapsed patients. Other grade 3/4 adverse events (AEs) included upper respiratory infection and abdominal pain in the relapsed group as well as rash and sepsis in both groups (n=1 each). The most frequent nonhematologic AEs (≥5%, any grade) were fatigue (33.0%), weight loss (11.0%), infection (9.9%; herpes zoster [n=2]; cryptococcal sepsis, Klebsiella sepsis, and pneumonia [n=1 each]), gastrointestinal (8.8%), fever (8.8%), pulmonary (6.6%), and rash (5.5%). o = data censored. Conclusions In this retrospective chart review of patients ≥70 years old with CLL, bendamustine, either alone or with rituximab, provided meaningful response rates and was generally well tolerated. The length of PFS of both treatment-naïve and relapsed patients was clinically meaningful. This research was sponsored by and conducted in collaboration with Cephalon, Inc., Frazer, PA. Disclosures: Sterchele: Cephalon, Inc.: Employment. Beygi:Cephalon, Inc.: Employment. Kennealey:Cephalon, Inc.: Employment.

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Risk of arterial (ATE) and venous thromboembolism (VTE) in a population-based cohort of bevacizumab-treated metastatic colorectal cancer (mCRC) patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.545 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 545-545 ◽

Cited By ~ 1

Author(s):

Irene S. Yu ◽

Winson Y. Cheung

Keyword(s):

Clinical Trials ◽

Population Based ◽

Related Effect ◽

Related Factors ◽

Increased Risk ◽

Venous Thromboembolic ◽

Lost To Follow Up ◽

Study Setting ◽

Trial Setting

545 Background: Bevacizumab is associated with both arterial (ATE) and venous thromboembolic (VTE) events, estimated to be </=15% from clinical trials. Our objectives were to 1) characterize the incidence of ATE or VTE among mCRC patients receiving bevacizumab in a non-clinical trial setting; 2) determine patient and treatment-related factors that predispose to an increased risk of ATE or VTE; and 3) explore how thromboembolism is managed and whether bevacizumab is discontinued and/or resumed after an event. Methods: A random sample of mCRC patients diagnosed between 2008 and 2009, referred to 1 of 5 regional cancer centers in British Columbia, and who were offered bevacizumab was reviewed. Summary statistics were used to describe and compare clinical factors between those who experienced an ATE or VTE and those who did not. Results: Of the 200 mCRC patients offered bevacizumab, 10 never received the drug and 12 were lost to follow up. Among the 178 remaining patients, median age was 61 years, 103 (58%) were male, and 121 (85%) had ECOG 0 to 1. A total of 39 patients (28%) experienced at least 1 documented thromboembolic event. Compared to patients who developed a clot, those who did not had similar median age (62 vs 61), gender distribution (23% men and 20% women), ECOG 0 to 1 (84% vs 85%) and body mass index (26.4 vs 25.3). However, the mean number of bevacizumab doses was higher in the group with thromboembolism (12.6 vs 9.0), suggesting a potential dose-related effect. There were a total of 43 VTE and 5 ATE events documented, with 7 of the 39 patients (18%) experiencing more than 1 event. Bevacizumab was held or discontinued in 60% of cases, but it was continued in 25% of the cases; 4% of the events were fatal, and 10% of the VTE/ATE occurred after bevacizumab was stopped. Conclusions: The incidence of ATE and VTE in a non-study setting appears to be higher than that reported in clinical trials. There may be a dose-related effect. Bevacizumab was not consistently held or discontinued in the setting of a VTE or ATE. Development of guidelines for the management of thromboembolism with bevacizumab may be warranted.

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Trial in Progress: Real-World Safety and Effectiveness of Brentuximab Vedotin in Adults with CD30+ Lymphoma in China

Blood ◽

10.1182/blood-2021-149031 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4552-4552

Author(s):

Pengpeng Xu ◽

Mingci Cai ◽

Wendy Zhang ◽

Wei Li Zhao

Keyword(s):

Clinical Trials ◽

Clinical Practice ◽

Informed Consent ◽

Survival Rate ◽

Real World ◽

Brentuximab Vedotin ◽

Routine Clinical Practice ◽

Inclusion Criteria ◽

Real World Data

Abstract Background: Clinical trials have demonstrated the effectiveness of the CD30-targeted antibody-drug conjugate brentuximab vedotin (BV) for the treatment of classical Hodgkin lymphoma (HL) and non-Hodgkin lymphoma(e.g. ALCL, PTCL-NOS, AITL, CTCL and etc.). While clinical trials are critical for establishing efficacy, collection of real-world data outside of the controlled trial setting is important to evaluate how interventions are applied and assess the effectiveness of new treatments in routine clinical practice. Inclusion criteria are often rather restrictive compared with the patient populations seen by physicians in daily practice. There are limited real-world data related to treatment with BV in China. Our study aims to obtain timely real-world knowledge in terms of safety and effectiveness of BV in CD30+ lymphoma patients in China. Study Design and Methods: The study (NCT04837222) is a real-world, prospective, multicenter study to evaluate the safety and effectiveness of BV in patients with CD30+ lymphoma in China. Consecutive CD30+ lymphoma patients treated with BV as a part of standard clinical practice will be enrolled. Key inclusion criteria includes adult patients undergoing treatment with BV or to be received with BV, patient/legal guardian must be able to read, understand, and sign the Informed Consent Form, CD30+ lymphoma by INV (any CD30 expression). Exclusion criteria includes patient who currently participates in or with plan to participate in any interventional clinical trial, any other reason that, in the investigator's opinion, makes the patient unsuitable to participate in this study. As CD30+ lymphoma is not a common disease and the affordability of novel treatment is limited, 1000 patients with CD30+ lymphoma will be recruited from almost 30 hematology centers. The physician will determine the treatment regimen, as well as the frequency of laboratory and clinical assessment according to her/his routine practice. All patients will be followed up per routine clinical practice and data will be documented at baseline/3/6/9/12/18/24 months unless withdrawal of Informed Consent, death or loss of follow-up, whichever comes first. Loss to follow-up will be minimized through active contact with participating patients thereafter to ensure almost all clinically relevant outcomes will be captured. The primary endpoint is serious adverse events. Secondary endpoints include adverse events, adverse drug reaction, dose adjustment, characteristics of patients receiving BV, use of BV, number of BV cycles administered, disease characteristics, time to next treatment, overall response rate, duration of response, progression free survival rate, overall survival rate, quality of life and cost-effectiveness ratio. Descriptive analysis will be performed for data analysis. Disclosures Zhang: Takeda Pharmaceuticals: Current Employment.

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Straightforward Transition to Bay 81-8973 Prophylaxis in Patients with Hemophilia A: Prospective Real-World Data from the Taurus Non-Interventional Study Show That Number of Infusions per Week Is Maintained or Reduced

Blood ◽

10.1182/blood-2018-99-116622 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5045-5045

Author(s):

Michael Wang ◽

Beng Fuh ◽

Philip Maes ◽

Maria Eva Mingot-Castellano ◽

Rubén Berrueco ◽

...

Keyword(s):

Clinical Trials ◽

Real World ◽

Hemophilia A ◽

Weekly Dose ◽

Real World Data ◽

World Data ◽

Real World Setting ◽

Patient Reported ◽

Dosing Frequency

Abstract BACKGROUND: BAY 81-8973 (Kovaltry®, Bayer) is an unmodified full-length recombinant FVIII indicated for prophylaxis and treatment of bleeds in patients with hemophilia A; BAY 81-8973 was launched in 2016 and has since accumulated 6765 patient-years of exposure. The TAURUS study (NCT02830477) was established to investigate BAY 81-8973 prophylaxis dosing regimens chosen in clinical practice and confirm the established safety and efficacy results from the LEOPOLD clinical trials in a real world setting. OBJECTIVES: To analyse the proportion of patients on specific BAY 81-8973 prophylaxis regimens, bleeds, and patient-reported outcomes at baseline and most recent follow-up. METHODS: TAURUS is an international, open label, prospective, non-interventional, single arm study with a target recruitment of 350 previously treated patients with hemophilia A of all ages with moderate or severe hemophilia A (≤ 5% FVIII:C) with ≥ 50 exposure days to any FVIII product who have been switched to prophylaxis with BAY 81-8973. At baseline, physicians document clinical information including age, BMI, severity of hemophilia, number of target joints, prior treatment regimen, bleed history, inhibitor history, and reason for choosing a specific prophylaxis regimen. Patients/caregivers reported bleeds in ongoing patient diaries, and completed questionnaires on treatment satisfaction (HEMOSAT) and adherence (VERITAS-PRO) at baseline and follow-up. A scheduled interim analysis (30% of patients recruited) was conducted with data collected up to 2 July 2018. RESULTS: At the cut-off, 160 enrolled patients were included in the baseline analysis set, of whom 89 had ≥ 6 months of follow-up data available (median observation period 201 days), 33% of whom had completed one year of the study. Median (range) patient age was 22 (2‒69) years, time since diagnosis was 15 (0.5‒64) years, and most patients (76/89, 85%) had baseline FVIII level of <1%. Treatment assignments are shown in the table. All patients had received pre-study prophylaxis, for a median of 15 years, with 66% of patients using rFVIII-FS as their most recent FVIII treatment prior to BAY 81-8973. Most (91%) had been treated with BAY 81-8973 for <3 months prior to study entry. Pre-study, 72% of patients were treated ≥3 times per week (xW). At baseline, most patients (59%) were assigned treatment ≥3xW (every day, 1%; every other day, 16%; 3xW, 41%). The majority remained on their previous regimen (78% on ≤2xW and 97% on ≥3xW); any changes were mainly a reduction in frequency on BAY 81-8973 vs previous treatment (22%), with only 2% increasing frequency on BAY 81-8973. At last follow up, most patients remained on the same regimen: 60% on ≥3xW (≥ every other day, 17%; 3xW, 42%). Most patients (92%) did not alter their dosing frequency. Of the 8% who changed dosing frequency, the majority (6 patients) changed from ≥3xW to ≤2xW; 1 patient changed from ≤2xW to ≥3xW. The median prescribed weekly dose was 52 IU/kg (64 IU/kg for ≥3xW and 43 IU/kg for ≤2xW) on study, slightly lower than those with previous product: 56 IU/Kg overall, 64 IU/kg for ≥3xW and 50 IU/kg for ≤2xW. Median (Q1; Q3) patient diary-reported annualized joint bleed rates were 1.5 (0.0; 5.3), 1.2 (0.0; 5.3) and 1.4 (0.0; 6.1); for ≤2xW, ≥3xW, and all patients, respectively. HEMO-SAT and VERITAS-PRO data will be presented in the poster. No recruited patients developed inhibitors with BAY 81-8973. CONCLUSIONS: These real-world data from 89 patients show that the range of dosing options available for BAY 81-8973 allowed the majority of patients to become established quickly on this treatment upon switching. In the few instances where patients changed dosing frequency either upon switching to BAY 81-8973 or once established on treatment, most moved to less frequent treatment. Joint bleeding rates confirm and extend findings from the clinical trials and speak to effective bleeding prophylaxis with BAY 81-8973 in a real-world setting. Therefore, BAY 81-8973 treatment may be successfully individualized according to patient need and disease characteristics. Disclosures Wang: Terumo BCT: Other: CPC Clinical Research; CSL Behring: Consultancy; Bayer, Bioverative, Novo Nordisk, Octapharma, Shire, Genentech, Biomarain, Pfizer, CSL Behring, HEMA Biologics, Daiichi Sankyo: Research Funding; Bayer: Consultancy; Bayer, Novo Nordisk, Octapharma, Genentech, HEMA Biologics, Shire, CSL Behring: Honoraria; Novo Nordisk: Consultancy. Maes:Bayer: Honoraria. Rauchensteiner:Bayer: Employment.

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P431 Teduglutide use and nutritional outcomes in short bowel syndrome with intestinal failure: a real-world claims database analysis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.555 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S433-S434

Author(s):

D Micic ◽

J Jiang ◽

L Chen ◽

T Fan ◽

F Mu ◽

...

Keyword(s):

Sensitivity Analysis ◽

Clinical Trials ◽

Short Bowel Syndrome ◽

Real World ◽

Index Date ◽

Intestinal Failure ◽

Sensitivity Analyses ◽

Future Research ◽

Short Bowel

Abstract Background Teduglutide (TED) is a glucagon-like peptide 2 analogue approved for the treatment of patients with short bowel syndrome (SBS) requiring parenteral support (PS). SBS is a rare condition resulting from a reduced absorptive surface area of the small intestine, most commonly due to inflammatory bowel disease (IBD). Patients with SBS with intestinal failure (SBS-IF) remain dependent on PS to maintain adequate calorie, fluid, electrolyte and micronutrient stability. In phase 3 clinical trials, TED reduced PS requirements in patients with SBS-IF. This study aimed to assess PS use and discontinuation rates among patients with SBS on TED using real-world data. Methods This retrospective cohort study of adults with SBS-IF (≥18 years) with ≥1 TED pharmacy claim(s) used the US-based administrative healthcare claims IBM MarketScan database (2009–2019). The first TED claim was defined as the index date. Patients required ≥6 months of continuous enrolment prior to index date (baseline period) and no history of malignancy. Primary analysis was conducted during the follow-up period (index date to earliest of continuous enrolment end or 2 years post-index). A sensitivity analysis was also conducted among the cohort during the TED utilization period (index date to the earliest of continuous enrolment end or TED discontinuation). Patients required PS use during both baseline and follow-up/TED utilization periods (primary and sensitivity analyses). PS discontinuation was defined as a PS utilization gap of ≥30 days. A generalized estimating equation linear regression model evaluated if PS use (days/week) changed significantly from baseline to selected time points post-index. Results Of 110 identified patients with SBS-IF, mean age was 53.4 (SD 13.2) years and 77 (70%) were women. Included were 51 (46%) patients with Crohn’s disease and 20 (18%) with ulcerative colitis. The main comorbidities were renal disease (23%) and liver disease (15%). PS frequency was 4.6 (2.5), 3.3 (2.9), 2.9 (3.0) and 3.6 (3.0) days/week at baseline and months 6 (p<0.0001), 12 (p<0.0001), and 24 (p=0.0267), respectively. PS discontinuation increased over time to 34.4%, 46.7% and 65.2% at 3, 6, and 12 months, respectively. The sensitivity analysis demonstrated similar rates of PS use and discontinuation. Conclusion In this real-world study of adults with SBS-IF, including >50% with IBD, TED was associated with PS reductions comparable to those achieved in clinical trials and higher PS discontinuation rates even when using a conservative analysis approach. Future research will be required to determine individual predictive factors of PS discontinuation.

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A methodology for the extraction and analysis of real-world radiographic and electronic medical record data to reconstruct treatment arms of historical prostate cancer clinical trials.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.5033 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 5033-5033

Author(s):

William David Lindsay ◽

Christopher A. Ahern ◽

Aaron Kamauu ◽

Robert Wilder ◽

Karen Chagin ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Trial ◽

Clinical Trials ◽

Real World ◽

Castration Resistant Prostate Cancer ◽

Efficacy Evaluation ◽

Real World Data ◽

Trial Treatment ◽

Picture Archiving And Communication

5033 Background: Real-world evidence (RWE), including synthetic comparator arms created from historical real-world data (RWD), has the potential to support the safety and efficacy evaluation of new medical products. However, many available RWD sources lack the details necessary to reliably identify patients comparable to clinical trial cohorts or to assess essential oncologic efficacy endpoints. This project demonstrates the ability to extract and analyze RWD to identify patients matching eligibility criteria to four historical clinical trials in metastatic castration-resistant prostate cancer (mCRPC), and calculate outcome measures. Methods: A total of 5,741 patients treated for prostate cancer at multiple institutions (2010-2020) were analyzed in two cohorts using data extracted from the EMR, Tumor Registry, Oncology Information System, and Picture Archiving and Communication System. Of 3,486 patients with prostate cancer in Cohort 1, 422 mCRPC patients were identified: those treated with ADT who achieved castration-level testosterone ( < 50 ng/dL), had evidence of metastatic disease, and exhibited rising PSA (PCWG2). These patients were further matched to four historical clinical trial treatment arms (COU-AA-301: 49, COU-AA-302: 143, AFFIRM: 30, PREVAIL: 79), based on prior chemotherapy and receipt of Abiraterone or Enzalutamide. Overall survival (OS) and time to skeletal related events (SRE) (pathological fracture, spinal compression, surgery to bone, and radiotherapy to bone) were calculated based on diagnosis and procedure codes using the Kaplan-Meier (KM) Estimator. Of 2,255 patients with prostate cancer in Cohort 2, 101 patients received Abiraterone or Enzalutamide and 59 patients had sufficient baseline and follow-up imaging to be scored. Radiographic progression-free survival (rPFS) was calculated from the start of treatment to the time of progression (RECIST 1.1) or loss to follow-up using the KM estimator. Results: In Cohort 1, median OS was 37.7 months (95% CI: 31.5-NR), and median time to SRE was 17.9 months (13.5-22.6). Median OS per patient cohort matched to historical trial treatment arm was COU-AA-301: 23.7 months (10.7-NR), COU-AA-302: 45.9 months (34.9-NR), AFFIRM: 35.3 months (6.34-NR), PREVAIL: 41.5 months (21.9-NR). In Cohort 2, median rPFS was 37.2 months (13.3-NR). Conclusions: The methodology employed in this analysis not only successfully identified a cohort of RWD patients similar to clinical trial-defined patients, but also curated sufficiently reliable data to calculate essential endpoints (e.g., rPFS). At scale, this methodology can be used to generate RWE, including synthetic comparator arms to support clinical trials with radiographic endpoints.

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Abstract 17109: Real World Assessment of Atrial Fibrillation and Other Arrhythmias After Cryptogenic Stroke

Circulation ◽

10.1161/circ.142.suppl_3.17109 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Naga Venkata K Pothineni ◽

Uyanga Batnyam ◽

Jeffrey Arkles ◽

John Bullinga ◽

Brett L CUCCHIARA ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Trials ◽

Real World ◽

Cryptogenic Stroke ◽

Premature Ventricular Contractions ◽

Entire Cohort ◽

Detection Algorithms ◽

Term Monitoring

Introduction: Long-term monitoring for atrial fibrillation (AF) is recommended in patients, who have experienced a cryptogenic stroke (CS). Clinical trials have identified AF in ~30% of patients after 3 years of continuous monitoring with insertable cardiac monitors (ICMs). Hypothesis: In a real-world analysis from a large academic healthcare system, we sought to evaluate a CS population with ICMs and a) determine the yield of AF and subsequent initiation of anticoagulation; and b) identify the presence of other arrhythmias. Methods: We evaluated all CS patients who had received an ICM between October 2014 and April 2020. We manually reviewed all stored electrocardiograms that were automatically labeled as AF by the ICM and adjudicated them as either a) AF or b) other cardiac arrhythmia including premature atrial contractions (PAC), premature ventricular contractions (PVC), supraventricular tachycardia (SVT), or nonsustained ventricular tachycardia (NSVT). Results: A total of 84 CS patients with ICMs were included: 51% men, mean age 63 years, and mean CHA 2 DS 2 -VASc 4.1. Over a median follow-up duration of 15.7 months, there were 34 patients (40% of the cohort) who did not have any AF alerts. In the remaining 50 patients, there were 960 stored electrograms that were adjudicated. Only 154 recordings from 16 patients (19% of the entire cohort) were adjudicated as AF. Oral anticoagulation was initiated in all these patients with adjudicated AF. The remaining tracings, which had been automatically categorized by the ICM as AF alerts, represented 34 patients (40% of the cohort). These patients had other arrhythmias including frequent PACs or PVCs, SVT, or NSVT. Conclusions: Compared to clinical trials, our real-world assessment suggests that the yield of AF following CS is lower - approximately 20%. Our findings highlight the importance for reviewing device tracings given the high rates of false positive for AF. Further research to refine AF detection algorithms in ICMs is needed.

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