Portola Pharmaceuticals Research Articles

Trajectories of adherence to extended treatment with direct oral anticoagulants and risks of recurrent venous thromboembolism and major bleeding.

BACKGROUND: Little is known about medication adherence patterns and their association with effectiveness and safety among patients with venous thromboembolism (VTE) receiving direct oral anticoagulant (DOAC) therapy beyond 3-6 months of initial treatment. OBJECTIVE: To examine the associations between adherence trajectories of extended treatment with DOAC and the risks of recurrent VTE and major bleeding among patients with VTE. METHODS: We conducted a retrospective cohort study of patients with incident VTE who completed 6 months of initial anticoagulant treatment and received either DOAC extended therapy or no extended therapy using MarketScan Commercial and Medicare Supplemental databases (2013-2019). We used group-based trajectory models to identify distinct adherence patterns during extended treatment. Using inverse probability treatment weighted Cox proportional hazards models, we examined the association between the adherence trajectories and the risks of recurrent VTE and major bleeding. RESULTS: Among 10,960 patients with extended treatment with DOACs (rivaroxaban, apixaban, dabigatran, edoxaban) and 5,133 patients with no extended treatment, we identified 4 distinct trajectories (consistently high, gradually declining, rapidly declining, and no extended treatment). Compared with the no extended treatment group, the groups with consistently high adherence (hazard ratio = 0.09, 95% CI = 0.05-0.17) and with gradually declining adherence (0.13, 0.03-0.53) showed decreased recurrent VTE risk without increased major bleeding risk (consistently high adherence 1.19, 0.71-1.99; gradually declining adherence 1.96, 0.81-4.70). There was no difference in the risk of recurrent VTE (0.34, 0.10-1.16) for the group with rapidly declining adherence, but this group was associated with increased major bleeding risk (2.65, 1.01-6.92). CONCLUSIONS: Our findings underscore the clinical importance of continuing and remaining adherent to extended DOAC treatment without increased major bleeding risk for patients with VTE. DISCLOSURES: This research was supported by the BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program. The funding source had no role in the design, collection, analysis, or interpretation of the data or the decision to submit the article for publication. Dr Lo-Ciganic reported receiving research funding from Merck Sharp & Dohme Corp. Dr Dietrich reported receiving honorarium for training and education from BMS/Pfizer. Dr DeRemer is a stockholder of Portola Pharmaceuticals and reported receiving personal fees for advisory board meeting from BMS. No other disclosures were reported.

Minimal acceptable functional outcomes according to surrogates and professionals caring for unconscious patients (P3-7.003)

<h3>Objective:</h3> To determine the minimum level of recovery (LOR) deemed acceptable by surrogate decision makers and healthcare professionals (HCPs) of unconscious patients with intracerebral hemorrhage (ICH). <h3>Background:</h3> Prognosticating recovery of acutely brain-injured patients is imprecise but may be improving with the development of novel technology. Understanding acceptable functional outcomes and factors that influence these thresholds for families and caregivers of patients with neurological injury is critical to ensure effective communication and the delivery of goal-concordant care. <h3>Design/Methods:</h3> We prospectively recruited surrogates and HCPs caring for unconscious patients with ICH. Participants completed a thirteen-item survey that captured data on demographics, education, and religiosity. Respondents selected the minimum LOR they would deem acceptable one-year post-injury. Response options were adapted from the Glasgow Outcome Scale–Extended and ranged from “survival” to “full recovery.” <h3>Results:</h3> A total of 134 participants completed the survey, including 85 HCPs (40 physicians/PAs, 45 RNs) and 49 surrogates. The majority of participants were female (65%) and completed at least some college (93%). HCPs were more likely than surrogates to choose a higher minimum acceptable LOR (median 4 [IQR 3–5] vs 3 [IQR 2.5–5]; OR 4.1, 95%-CI 2.1–8.1, p=0.00008). Among all respondents, participants who identify as Black/African-American were less likely to choose a higher LOR (median 3 [IQR 2–4] vs 4 [IQR 3–5]; OR 0.2, 95%-CI 0.1–0.5, p=0.002). Participants who indicated religion was “the most important part” of their life were less likely to choose a higher LOR (median 3 [IQR 2–3] vs 4 [IQR 3–5]; OR 0.3, 95%-CI 0.1–0.9, p=0.032). In a multivariate model, HCP vs. surrogate status was the only significant predictor; HCPs were more likely than surrogates to choose a higher LOR ([OR 2.2, 95%-CI 1.0–4.6, p=0.048). <h3>Conclusions:</h3> This study highlights the need for HCPs to recognize in goals of care discussions that surrogates find acceptable a lower LOR than do HCPs themselves. <b>Disclosure:</b> Mr. Heinonen has nothing to disclose. Miss Carmona has nothing to disclose. Kevin Doyle has nothing to disclose. Ms. Grobois has nothing to disclose. Miss Kruger has nothing to disclose. Dr. Velazquez has nothing to disclose. Ms. Vrosgou has nothing to disclose. Dr. Shen has nothing to disclose. Mrs. Cespedes has nothing to disclose. Ms. Yazdi has nothing to disclose. Dr. Ghoshal has nothing to disclose. Dr. Roh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Portola Pharmaceuticals. Dr. Agarwal has nothing to disclose. Dr. Park has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurocritical Care. The institution of Dr. Park has received research support from National Institutes of Health. The institution of Dr. Dugdale has received research support from McDonald Agape Foundation. Dr. Dugdale has received publishing royalties from a publication relating to health care. Dr. Dugdale has received publishing royalties from a publication relating to health care. Dr. Dugdale has received personal compensation in the range of $500-$4,999 for serving as a Speaking honoraria for various lectures with Multiple organizations. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Marinus. Dr. Claassen has stock in iCE Neurosystems. The institution of Dr. Claassen has received research support from NINDS. The institution of Dr. Claassen has received research support from McDonnel Foundation. Dr. Claassen has received publishing royalties from a publication relating to health care. Dr. Claassen has received publishing royalties from a publication relating to health care.

Utility and Feasibility of Simulation-based Training in Teaching Concepts of Traumatic Brain Management to Neurology Trainees (P8-2.001)

<h3>Objective:</h3> To assess the feasibility and utility of simulation-based training in teaching concepts surrounding management of traumatic brain injury (TBI). <h3>Background:</h3> Neurology trainees respond to neurological emergencies but often do not have the opportunity to practice implementing their clinical knowledge and communication skills in managing such emergencies outside the clinical setting. <h3>Design/Methods:</h3> We developed a simulation-based training program for neurology residents to practice managing a patient presenting with acute TBI under the direct supervision of an expert in neurocritical care with opportunities for debriefing and feedback. The educational aims of the simulation were to familiarize learners with Brain Trauma Foundation guidelines on the management of TBI and to allow learners to practice closed loop communication in a multidisciplinary team. The simulation involved two learners, one confederate playing the role of emergency room nurse and ICU fellow, and a hired actor who played the role of the patient. Prior to the simulation, learners were given a 10-slide presentation to review relevant topics. A total of 40 minutes was allotted per session; 5 minutes to introduce the scenario, 20 minutes to complete the scenario, and 10 minutes for a debriefing. The effect of the simulation on learner aptitude in managing TBI was assessed via anonymous post-test. <h3>Results:</h3> A total of 8 learners participated in the simulation-based training. We were able to complete all simulation sessions in the allotted 40-minute time frame. On post-test reporting, 7/8 learners felt confident in managing TBI, 8/8 felt their confidence improved with the simulation, and 8/8 endorsed comfort in accessing resources regarding TBI guidelines. <h3>Conclusions:</h3> Teaching TBI management via simulation-based training is feasible and allows trainees to gain experience and comfort managing TBI. <b>Disclosure:</b> Dr. Franzova has nothing to disclose. Dr. Waldrop has nothing to disclose. Dr. Nwankwo has nothing to disclose. Dr. Ader has nothing to disclose. Dr. Bell has nothing to disclose. Dr. Velazquez has nothing to disclose. Dr. Agarwal has nothing to disclose. Dr. Roh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Portola Pharmaceuticals. Dr. Park has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurocritical Care. The institution of Dr. Park has received research support from National Institutes of Health. Sander Connolly has received intellectual property interests from a discovery or technology relating to health care. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Marinus. Dr. Claassen has stock in iCE Neurosystems. The institution of Dr. Claassen has received research support from NINDS. The institution of Dr. Claassen has received research support from McDonnel Foundation. Dr. Claassen has received publishing royalties from a publication relating to health care. Dr. Claassen has received publishing royalties from a publication relating to health care. Dr. Amiel has nothing to disclose. Dr. Ghoshal has nothing to disclose.

Ethical implications of detecting cognitive motor dissociation early after brain injury (P4-7.005)

<h3>Objective:</h3> To determine the impact of cognitive motor disassociation (CMD) in goals of care (GOC) decisions for surrogate decision makers and healthcare professionals (HCPs) of unconscious patients and assess support for clinical research participation. <h3>Background:</h3> Predictions of recovery from acute disorders of consciousness are imprecise but novel diagnostic tools are emerging. CMD refers to the detection of willful brain activation following motor commands in the absence of behavioral command following as detected by machine learning-supported EEG or MRI analysis. This phenomenon has been identified as a predictor of long-term recovery but acceptance of technology-supported prognostication by surrogates and HCPs remains uncertain. <h3>Design/Methods:</h3> We recruited surrogates and HCPs caring for unconscious patients with intracerebral hemorrhage. All participants completed a thirteen-item survey that captured data on demographics, education, religiosity, support for research participation, and receptiveness to technology-assisted prognostication in decision-making. <h3>Results:</h3> A total of 134 participants completed the survey, including 85 HCPs (40 physicians/PAs, 45 RNs) and 49 surrogates. There were no differences in sex between the two groups (67% of HCPs and 61% of surrogates were female). Surrogates reported stronger religious affiliation with 73% indicating religion was “very important” or “the most important part” of their life vs. 29% of HCPs. Both surrogates (73%) and HCPs (93%) indicated a diagnosis of CMD would help in decision-making. There was broad support for clinical trial participation in surrogates (86%) and HCPs (89%). HCPs were more likely than surrogates to change their goals if CMD could not be detected (OR 5.5, 95%-CI 2.4–12.7, p=0.00005). There was only a trend for a higher chance of HCPs to change their goals if CMD could be detected when compared to surrogates (OR 1.9, 95%-CI 0.9–3.8, p=0.08). <h3>Conclusions:</h3> These results demonstrate acceptance of technology-supported prognostication amongst HCPs and surrogate decision-makers. Targeted education to interpret detection and failure of detection of CMD is needed. <b>Disclosure:</b> Mr. Heinonen has nothing to disclose. Miss Carmona has nothing to disclose. Kevin Doyle has nothing to disclose. Ms. Grobois has nothing to disclose. Miss Kruger has nothing to disclose. Dr. Velazquez has nothing to disclose. Ms. Vrosgou has nothing to disclose. Dr. Shen has nothing to disclose. Mrs. Cespedes has nothing to disclose. Ms. Yazdi has nothing to disclose. Dr. Ghoshal has nothing to disclose. Dr. Roh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Portola Pharmaceuticals. Dr. Agarwal has nothing to disclose. Dr. Park has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurocritical Care. The institution of Dr. Park has received research support from National Institutes of Health. The institution of Dr. Dugdale has received research support from McDonald Agape Foundation. Dr. Dugdale has received publishing royalties from a publication relating to health care. Dr. Dugdale has received publishing royalties from a publication relating to health care. Dr. Dugdale has received personal compensation in the range of $500-$4,999 for serving as a Speaking honoraria for various lectures with Multiple organizations. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Marinus. Dr. Claassen has stock in iCE Neurosystems. The institution of Dr. Claassen has received research support from NINDS. The institution of Dr. Claassen has received research support from McDonnel Foundation. Dr. Claassen has received publishing royalties from a publication relating to health care. Dr. Claassen has received publishing royalties from a publication relating to health care.

864-P: Glycemic Control across eGFR Categories with the Dual SGLT1 and 2 Inhibitor Sotagliflozin in SCORED

In cardiovascular (CV) outcome trials (OT) of glucose-lowering medications (GLM) , glycated hemoglobin (A1c) is typically treated according to local standard of care, with aim of glycemic equipoise between the randomized groups. However, in SGLT inhibitor CVOTs, larger A1c reductions are consistently seen in the active therapy vs. placebo (PBO) groups, since the former has access to an additional class of GLM. SCORED was a multicenter, double-blind, placebo-controlled CVOT of the dual SGLT1 and 2 inhibitor sotagliflozin (SOTA) , which may have preserved antihyperglycemic effects even in those with advanced chronic kidney disease (CKD.) We assessed the association between A1c lowering and assignment to SOTA vs. PBO in the overall trial population and across various pre-specified subgroups, including CKD categories. 10,584 type 2 diabetes (T2D) (A1c ≥7%) patients with CKD (eGFR 25-60 mL/min/1.73 m2) and increased CV risk were randomized to SOTA vs. PBO and followed for a median of 15.9 months. We previously reported that the risk for the primary composite outcome of total CV deaths and hospitalizations or urgent visits for heart failure was reduced by 26% in the SOTA group (p&amp;lt;0.001) . In the overall population, from a baseline A1c of 8.7%, the least-squares mean change in A1c was -0.60% with SOTA and -0.17% with placebo (mean difference [95% CI] = -0.42% [-0.47, -0.38]; p&amp;lt;0.0001) . Differences were larger with increasing baseline A1C: &amp;lt;8%: -0.31%; 8-&amp;lt;9%: -0.40%; and ≥9%: -0.57% (all p&amp;lt;0.0001) . The association between SOTA use and A1c lowering vs. placebo was consistent across strata of baseline eGFR, including those with CKD stage 4 (eGFR&amp;gt;45, 30-&amp;lt;45, and &amp;lt;30: -0.47%. -0.38%, and -0.31%, respectively [all p&amp;lt;0.001]) . These results were similarly consistent across age, sex, race/ethnicity, age, and BMI subgroups. In SCORED, SOTA consistently reduced A1c across all pre-specified subgroups, including patients with the lowest baseline eGFR, possibly reflecting SOTA’s dual mechanism of action. Disclosure S.E.Inzucchi: Advisory Panel; Abbott Diagnostics, ESPERION Therapeutics, Inc., vTv Therapeutics, Consultant; Merck &amp; Co., Inc., Pfizer Inc., Other Relationship; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk. J.P.Dwyer: Consultant; Akebia Therapeutics, Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Cincor, Inc, CSL Behring, FibroGen, Inc., Reata Pharmaceuticals, Inc., Sanofi, Tricida, Inc. B.M.Scirica: Consultant; Allergan, Boehringer Ingelheim International GmbH, ESPERION Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Novo Nordisk, Research Support; Better Therapeutics, Eisai Co., Ltd., Merck &amp; Co., Inc., Novo Nordisk, Pfizer Inc., Stock/Shareholder; Heath At Scale. C.J.Bailey: None. P.L.Banks: Employee; Lexicon Pharmaceuticals, Inc. R.Diaz: None. K.K.Ray: Consultant; Abbott, AstraZeneca, Cargene, CSL Behring, Daiichi Sankyo, Eli Lilly and Company, ESPERION Therapeutics, Inc., GlaxoSmithKline plc., Kaleido, Kowa Company, Ltd., New Amsterdam Pharma, Novartis Pharmaceuticals Corporation, Pfizer Inc., Regeneron Pharmaceuticals Inc., Roche Diagnostics, The Medicines Company, Research Support; Amgen Inc., Daiichi Sankyo, Regeneron Pharmaceuticals Inc., Sanofi, Speaker's Bureau; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Medscape, Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi, Viatris Inc., Stock/Shareholder; Cargene, PEMI31. J.A.Udell: Consultant; Boehringer Ingelheim International GmbH, Novartis AG, Sanofi, Other Relationship; GlaxoSmithKline plc., Sanofi, Research Support; Amgen Inc., Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research &amp; Development, LLC. R.D.Lopes: Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Daiichi Sankyo, GlaxoSmithKline plc., Medtronic, Pfizer Inc., Portola Pharmaceuticals, Inc., Other Relationship; Bristol-Myers Squibb Company, Sanofi, Research Support; Medtronic, Pfizer Inc. L.A.Leiter: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; AstraZeneca, Bayer AG, Lexicon Pharmaceuticals, Inc., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Servier Laboratories. P.G.Steg: Advisory Panel; AstraZeneca, Bristol-Myers Squibb Company, Board Member; Novartis AG, Consultant; Amarin Corporation, Amgen Inc., Bayer AG, Idorsia Pharmaceuticals Ltd., Lexicon Pharmaceuticals, Inc., PhaseBio Pharmaceuticals, Inc., Sanofi. D.L.Bhatt: Research Support; Afimmune Limited, Amarin Corporation, Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Chiesi USA, Inc., Lexicon Pharmaceuticals, Inc., Lilly, Novartis AG, Sanofi. Scored investigators: n/a. B.Pitt: Advisory Panel; Merck &amp; Co., Inc., Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Vifor Pharma Funding Sanofi/Lexicon

960-P: Multisite Quality Improvement Initiative within the Project ECHO Diabetes Virtual Network

Poor outcomes for people with diabetes have necessitated targeted quality improvement (QI) projects to affect change. Project ECHO Diabetes is a tele-education and tele-mentoring program for community health clinics in California and Florida serving under-resourced patients with diabetes who lack routine access to specialty care. The model provided a unique opportunity to undertake a multi-site QI initiative, where 12 community clinics participated in measuring and improving quality of care. Using a modified-Delphi approach, clinic providers rated various QI measures on their validity and feasibility. A total of 18 measures were selected, and each clinic chose its own measures to track throughout the one-year initiative. The number of measures each clinic focused on ranged from 1 to 9, with a median of 3. Quarterly, clinics met remotely to report performance based on selected measures and discuss their efforts, successes, and setbacks. At the end of the QI year, clinics reported widespread improvements across structural, process, and outcome measures (Table) . Remarkable improvement ideas came from the sharing of best practices during the remote tele-ECHO clinic sessions and the changes made in the data systems used to track important measures. The Project ECHO Diabetes tele-education model has the potential to improve care for people living with diabetes in clinics serving under-resourced communities. Disclosure C.Wang: None. L.Figg: None. C.Anez-zabala: None. E.Sheehan: None. S.C.Westen: None. C.E.Deremer: Research Support; Pfizer-BMS Alliance, Stock/Shareholder; Portola Pharmaceuticals, Inc. A.Bernier: None. W.T.Donahoo: None. A.F.Walker: None. E.Lewit: n/a. C.Clark: None. D.M.Maahs: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Consultant; Aditx Therapeutics, Inc., Biospex. M.J.Haller: Advisory Panel; SAB Biotherapeutics , Consultant; MannKind Corporation, Sanofi. A.Addala: None. R.Lal: Advisory Panel; Provention Bio, Inc., Consultant; Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Deep Valley Labs, Gluroo, Morgan Stanley, Tidepool. N.Cuttriss: Advisory Panel; American Diabetes Association, Board Member; American Youth Understanding Diabetes Abroad , Consultant; Cecelia Health, Leona M. and Harry B. Helmsley Charitable Trust, Med-IQ. L.G.Baer: None. Funding The Leona M. and Harry B. Helmsley Charitable Trust

Early and Late Recurrent Cardiovascular Risk in Patients With Recent Acute Coronary Syndrome: Meta-Analysis and Implications in Trial Design†

Lead Author's Financial Disclosures G.C. has receieved research grant support to the Beth Israel Deaconess Medical Center, Harvard Medical School from Portola Pharmaceuticals, Bayer, Janssen Scientific Affairs, and CSL Beh-ring. Study Funding CSL Behring. Background/Synopsis Despite optimal medical therapy, a substantial residual atherosclerotic risk exists among patients with an acute coronary syndrome (ACS). Objective/Purpose This study aimed to estimate the risk of early and late major adverse cardiovascular events (MACE) and address its implications in trial design. Methods A comprehensive search was performed to collect phase III interventional trials on high-risk ACS patients. Pooled event rates at 90 and 360 days were estimated with meta-analytic approaches by fitting a random-effects model using the DerSimonian-Laird method. Using the log-rank test (n=10,000; 1-sided α=0.025)), the relationship between power and relative risk reduction (RRR) or absolute risk reduction (ARR) was explored for early vs. late MACE endpoint. Results A total of 82,727 high-risk patients with recent ACS from 7 trials were analyzed. Pooled rates of recurrent MACE were 4.1% (95% CI: 3.0% to 5.7%) at 90 days and 8.3% (95% CI: 7.1% to 9.8%) at 360 days. Approximately 49% of events occurred within the first 90 days. To attain 90% statistical power, a lower RRR is required for late MACE (22% vs. 30%), whereas a lower ARR is required for early MACE (1.2% vs. 1.8%). Conclusions The initial 90-day window after an ACS event represents a vulnerable period for recurrent MACE. From a trial design perspective, determining a clinically important benefit by relative vs. absolute risk reduction may influence the choice between early vs. late MACE as the study endpoint. G.C. has receieved research grant support to the Beth Israel Deaconess Medical Center, Harvard Medical School from Portola Pharmaceuticals, Bayer, Janssen Scientific Affairs, and CSL Beh-ring.

Phase 2a Study of the Dual SYK/JAK Inhibitor Cerdulatinib (ALXN2075) As Monotherapy or in Combination with Rituximab in Patients with Relapsed/Refractory Follicular Lymphoma

Phase 2a Study of the Dual SYK/JAK Inhibitor Cerdulatinib (ALXN2075) As Monotherapy or in Combination with Rituximab in Patients with Relapsed/Refractory Follicular Lymphoma

Final Results from a Phase 2 Study of Tipifarnib in Subjects with Relapsed or Refractory Peripheral T-Cell Lymphoma

Final Results from a Phase 2 Study of Tipifarnib in Subjects with Relapsed or Refractory Peripheral T-Cell Lymphoma

Phase 2a Study of the Dual SYK/JAK Inhibitor Cerdulatinib (ALXN2075) As Monotherapy in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma

Phase 2a Study of the Dual SYK/JAK Inhibitor Cerdulatinib (ALXN2075) As Monotherapy in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma

Favorable Outcomes of Patients with Limited-Stage Ocular Adnexal DLBCL Treated in the Rituximab Era: Long-Term Follow-up of a Single Center Experience

Favorable Outcomes of Patients with Limited-Stage Ocular Adnexal DLBCL Treated in the Rituximab Era: Long-Term Follow-up of a Single Center Experience

Adherence Trajectories of Extended Direct-Acting Oral Anticoagulants and Risk of Recurrent Venous Thromboembolism and Major Bleeding: A Retrospective Cohort Study

▪Introduction: The optimal duration of extended oral anticoagulant treatment for patients with venous thromboembolism (VTE) beyond the initial 3 to 6 months of the treatment remains undetermined. Group-based trajectory modeling (GBTM) is a data-driven method that can categorize patients with similar longitudinal adherence patterns over time into distinct subgroups. This study identified distinct patient subgroups with similar adherence trajectories of extended treatment of direct-acting oral anticoagulants (DOACs), and then examined the association between adherence trajectories and the risk of recurrent VTE and major bleeding among patients with VTE.Methods: We identified patients ≥18 years with a diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) from inpatient claims using 2013-2019 Truven Commercial and Medicare Supplemental database. Patients were included if they initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6 months of therapy-defined as ≥83% proportion days covered (PDC) with oral anticoagulants during the initial 6-month treatment period, and had extended treatment with any DOACs or no extended therapy. Based on the monthly PDC as the DOAC adherence measure, we used GBTM to identify DOAC adherence trajectories during 6 months of the extended treatment. The final trajectory model was chosen by assessing the Bayesian information criteria, Nagin's criteria, and having at least 10% of patients in each trajectory group for improving clinical utility. We compared recurrent VTE and major bleeding among adherence trajectory subgroups. Patients were followed up from the initiation of the extended treatment until the occurrence of the study outcomes, discontinuation of DOACs, switching to warfarin, end of study period, or end of enrollment, whichever occurred first. Cox proportional hazard modeling with inverse probability treatment weighting (IPTW) was used to obtain hazard ratios (HR) and 95% confidence intervals (95% CI).Results: The study cohort (mean age=58.7 years and 51.1% males) consisted of 10,960 patients with extended treatment of DOACs (4,294 apixaban, 6,409 rivaroxaban, 238 dabigatran, and 19 edoxaban users) with a mean treatment duration of 7.7 months and 5,133 patients with no extended treatment following completion of an initial 6 months of anticoagulant treatment. The final GBTM models identified four distinct adherence trajectories for extended therapy including (1) patients with consistent adherence (group 1, 40.7%), (2) patients with gradually declining adherence (group 2, 14.3%), (3) patients with rapidly declining adherence (group 3, 13.1%), and (4) patients with no extended treatment (reference group, 31.9%) (Figure 1). The incidence rates of recurrent VTE were 18.6, 46.9, 84.1, and 160.7 per 10,000 person-years, and those of major bleeding were 61.0, 125.1, 168.3, and 48.7 per 10,000 person-years in group 1, group 2, group 3, and the reference group, respectively. After IPTW, demographics and clinical characteristics (e.g., HAS-BLED bleeding risk score, provoked VTE) were comparable across the four trajectory groups with <0.1 of the standardized mean difference for each pairwise comparison. Compared to the reference group, group 1 (HR=0.09, 95% CI=0.05-0.17) and group 2 (HR=0.16, 95% CI=0.04-0.58) had decreased risk of recurrent VTE without increasing risk of major bleeding (HR=1.26, 95% CI=0.76-2.10 in group 1, HR=2.28, 95% CI=0.96-5.36 in group 2). There was no difference in the risk of recurrent VTE (HR=0.32, 95% CI=0.09-1.16) in group 3 but they had an increased risk of major bleeding (HR=2.69, 95% CI=1.00-7.23). The findings were consistent across different types of DOACs, suggesting a class effect of DOACs as extended therapy.Conclusions: We identified 4 distinct trajectories of DOAC adherence during the 6 months of extended therapy among patients who completed 6 months of initial treatment. Compared to no extended treatment, persistent use of DOACs during extended treatment was associated with a lower risk of recurrent VTE without increasing major bleeding risk, whereas a rapid decline in adherence was associated with an increased risk of major bleeding with no difference in the risk of recurrence. Our findings provide evidence on the benefits of continuing and being adherent to extended anticoagulant treatment in patients with VTE without increasing the risk of major bleeding. [Display omitted] DisclosuresKang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Jones: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Lo-Ciganic: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding; MERCK: Research Funding. DeRemer: BMS advisory board attendee: Honoraria; Portola Pharmaceuticals: Current equity holder in publicly-traded company; BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Dietrich: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Huang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Murphy: North American Thrombosis Foundation: Honoraria. Park: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding.

Impact of Choice of Platinum-Based Salvage Therapy on CNS Relapse in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Impact of Choice of Platinum-Based Salvage Therapy on CNS Relapse in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

High-Grade B-Cell Lymphoma, Not Otherwise Specified (HGBL, NOS): Characteristics, Treatment, and Outcomes from 17 Academic US Centers

High-Grade B-Cell Lymphoma, Not Otherwise Specified (HGBL, NOS): Characteristics, Treatment, and Outcomes from 17 Academic US Centers

Safety and Efficacy of Third Generation CD20 Targeted CAR-T (MB-106) for Treatment of Relapsed/Refractory B-NHL and CLL

Safety and Efficacy of Third Generation CD20 Targeted CAR-T (MB-106) for Treatment of Relapsed/Refractory B-NHL and CLL

Clinical Outcomes and CNS Relapse Risk in Patients with Primary Cutaneous DLBCL, Leg Type Treated in the Rituximab Era: Long-Term Follow-up of a Single-Center Experience

Clinical Outcomes and CNS Relapse Risk in Patients with Primary Cutaneous DLBCL, Leg Type Treated in the Rituximab Era: Long-Term Follow-up of a Single-Center Experience

Safety and Efficacy of Acalabrutinib Plus Venetoclax and Rituximab in Patients with Treatment-Naïve (TN) Mantle Cell Lymphoma (MCL)

Safety and Efficacy of Acalabrutinib Plus Venetoclax and Rituximab in Patients with Treatment-Naïve (TN) Mantle Cell Lymphoma (MCL)

Comparative Effectiveness and Safety of Extended Anticoagulant Therapy Among Medicare Beneficiaries with Venous Thromboembolism

▪Introduction: Approximately 30% of patients with venous thromboembolism (VTE) experience a recurrence within 10 years of the initial event with their recurrence risk peaking during the first 6-12 months. Two large randomized clinical trials AMPLIFY-EXT and PADIS-PE reported that extended treatment with apixaban and warfarin beyond 6 months of initial treatment reduced recurrent VTE without increasing the rate of major bleeding compared to placebo, respectively. Little is known about real-world effectiveness and safety of extended oral anticoagulation beyond 6 months of initial treatment for Medicare beneficiaries with VTE, despite the fact that VTE disproportionately affects the elderly. We assessed the effectiveness and safety of extended use of apixaban and warfarin beyond 6 months of initial treatment for prevention of recurrent VTE and adverse major bleeding events among Medicare beneficiaries with newly diagnosed VTE.Methods: A retrospective cohort study using 2014-2018 Medicare data (5% samples in 2014-2016 and 15% samples of Medicare beneficiaries in 2017-2018) was conducted for patients aged ≥18 years with a diagnosis of deep vein thrombosis or pulmonary embolism ascertained from inpatient claims. Patients were included if they initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6 months of therapy defined as ≥83% proportion days covered with oral anticoagulants during the initial 6-month period, and received extended treatment with either apixaban or warfarin or no extended therapy. We compared the risks of recurrent VTE and major bleeding between apixaban, warfarin, and no treatment groups. To adjust for differences in baseline characteristics and clinical factors (e.g., HAS-BLED score, active cancer, and provoked VTE) between groups, we used the stabilized inverse probability treatment weighting (IPTW) method. Follow-up continued until the occurrence of the first event, switch to the comparator, disenrollment, death, or end of the study period. Multivariable Cox proportional hazards modeling with IPTW was used to obtain adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI).Results: The study cohort (mean age=74 ±12 years, 40% male, 76% White) consisted of 2,315 users of extended apixaban treatment (83% with 5 mg twice a day and 17% with 2.5 mg twice a day; mean duration=6.2 months), 2,757 users of extended warfarin treatment (mean duration=8.2 months), and 2,328 patients with no extended treatment following completion of an initial 6 months of anticoagulant treatment. The incidence rates of recurrent VTE were 0.42, 1.73, and 1.72 per 100 person-years, and those of major bleeding were 2.28, 3.62, and 1.43 per 100 person-years in the apixaban, warfarin, and no treatment groups, respectively (Table 1). Compared to no extended treatment, the use of apixaban was associated with an 80% decreased risk of recurrent VTE (aHR=0.19, 95%CI=0.06-0.55) without increasing the risk of major bleeding (aHR=1.19, 95%CI=0.65-2.19); the use of warfarin did not lower the risk of recurrent VTE (aHR=0.75, 95%CI=0.42-1.37) but increased the risk of major bleeding (aHR=1.92, 95%CI=1.13-3.25). Compared to the use of warfarin, the use of apixaban was associated with a decreased risk of recurrent VTE (aHR=0.26, 95% CI=0.09-0.76) and no difference in major bleeding risk (aHR=0.61, 95%CI=0.36-1.06). These findings remained consistent in subgroup (e.g., patients with provoked vs. unprovoked VTE, patients with active cancer vs. those without, and patients with chronic kidney diseases vs. those without) and sensitivity analyses (e.g., ≥92% proportion days covered with oral anticoagulants during the initial 6-month period).Conclusions: Compared to no extended therapy, extended anticoagulation with apixaban was associated with a reduced risk of recurrent VTE without increasing the risk of major bleeding, whereas warfarin did not lower risk of recurrent VTE but increased the risk of major bleeding among Medicare beneficiaries with VTE. In the head-to-head comparison, the use of apixaban was more effective than warfarin in preventing recurrent VTE, without increasing the risk of major bleeding events. Our findings suggest that apixaban is an effective and safer option for extended treatment of VTE when compared to warfarin or no treatment among Medicare beneficiaries with VTE. [Display omitted] DisclosuresPark: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Kang: BMS/Pfizer Alliance American Thrombosis InvestigatorInitiated Research Program: Research Funding. Huang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Lo-Ciganic: MERCK: Research Funding; BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Dietrich: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Murphy: North American Thrombosis Foundation: Honoraria. DeRemer: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding; Portola Pharmaceuticals: Current equity holder in publicly-traded company; BMS advisory board attendee: Honoraria.

Concurrent Pembrolizumab with AVD for Untreated Classical Hodgkin Lymphoma

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Oral Ixazomib in Untreated Follicular Lymphoma Permits COVID-19 Vaccine Response and Its Efficacy Is Associated with Clinical Factors and Gene Expression Signatures

Oral Ixazomib in Untreated Follicular Lymphoma Permits COVID-19 Vaccine Response and Its Efficacy Is Associated with Clinical Factors and Gene Expression Signatures