Effectiveness and Safety of Apixaban vs Warfarin in Patients with Venous Thromboembolism with Risk Factors for Bleeding or for Recurrences

Introduction Patients at increased risk of bleeding and recurrent VTE who develop venous thromboembolism (VTE) present challenges for clinical management. This study evaluated the effectiveness and safety of apixaban vs warfarin in patients with VTE who have risk factors for bleeding or recurrences. Methods Adult patients with VTE initiating apixaban or warfarin were identified from five claims databases. Stabilized inverse probability treatment weighting (IPTW) was used to balance characteristics between cohorts for the main analysis. Subgroup interaction analyses were conducted to evaluate treatment effects among patients with and without each of the conditions that increased the risk of bleeding (thrombocytopenia and history of bleed) or recurrent VTE (thrombophilia, chronic liver disease, and immune-mediated disorders). Results A total of 94,333 warfarin and 60,786 apixaban patients with VTE met selection criteria. After IPTW, all patient characteristics were balanced between cohorts. Apixaban (vs warfarin) patients were at lower risk of recurrent VTE (HR [95% confidence interval (CI) 0.72 [0.67–0.78]), major bleeding (MB) (HR [95% CI] 0.70 [0.64–0.76]), and clinically relevant non-major (CRNM) bleeding (HR [95% CI] 0.83 [0.80–0.86]). Subgroup analyses showed generally consistent findings with the overall analysis. For most subgroup analyses, there were no significant interactions between treatment and subgroup strata on VTE, MB and CRNM bleeding. Conclusion Patients with prescription fills for apixaban had lower risk of recurrent VTE, MB, and CRNM bleeding compared with warfarin patients. Treatment effects of apixaban vs warfarin were generally consistent across subgroups of patients at increased risk of bleeding/recurrences

Risk governance: Examining its impact upon bank performance and risk-taking

As policy-makers in the United States contemplate a relaxation of financial regulation, our study contributes to this dialogue by testing the veracity of heightened standards of risk governance activities for US bank holding companies (BHCs). Our study examines evidence relating to the adoption of these standards by BHCs following regulatory intervention. We find that board-level risk appetite practices have a profound association upon BHC performance and tail risk. Our estimates show that BHCs which adopt risk appetite practices exhibit a significant improvement in headline performance and reduced tail risk measures. Our research is relevant to academics by identifying the significance of this risk governance practice which has been introduced by global regulators. For practitioners (including board members, risk managers, policy-makers and regulators), our study validates the efficacy of risk appetite frameworks as the future shape of financial regulation is being actively debated in the US

Patterns of use of systemic therapies among patients with metastatic melanoma: a retrospective claims database analysis in the United States

Objectives: This retrospective analysis of the IMS PharMetrics Plus claims database aimed to describe the current real-world treatment patterns for metastatic melanoma in the USA. Methods: Included patients (aged ≥18 years) had ≥1 prescription for ipilimumab, vemurafenib, temozolomide or dacarbazine between 1 January 2011 and 31 August 2013; diagnosis of melanoma and metastasis before first use (index date); no index drug use prior to the index date; continuous health plan enrollment for ≥6 months before and ≥3 months after index date. Proportion of days covered (PDC) was defined as days exposed to index therapy divided by continuously enrolled days between index date and last prescription date. Results: Overall, 1043 patients were included (median age 57 years, 63% male), of whom 39% received the index drug ipilimumab, 35% vemurafenib, 19% temozolomide and 7% dacarbazine. Mean treatment duration (days) was 174 (vemurafenib), 100 (temozolomide) and 64 (dacarbazine). Mean PDC was 81% (vemurafenib), 67% (temozolomide) and 51% (dacarbazine). For patients receiving ipilimumab, 58% had the full 4 doses, 20% 3 doses, 14% 2 doses and 9% 1 dose only for the first induction course; 4% received re-induction, and none had a second re-induction. Conclusions: This study provides insights into the treatment patterns for metastatic melanoma, including newer agents, in real-world clinical practice

Effectiveness and Safety of Anticoagulants Among Patients with VTE and Common Cancers or Cancers with High VTE Risk - supplementary material

Supplemental Tables 1a – 1b. Additional Characteristics for Patients with Common or High-Risk Cancer (Post-IPTW) </p

The Association between Direct Oral Anticoagulants Prescribing Behavior and Non-Valvular Atrial Fibrillation Outcomes: An Instrumental Variable Analysis of Real-World Data

Several observational studies have compared apixaban with rivaroxaban in patients with non-valvular atrial fibrillation (NVAF), but these analyses may be confounded by unmeasured characteristics. This study used provider prescribing preference (PPP) as an instrumental variable (IV) to assess the association between prescriber choice of rivaroxaban vs. apixaban and the study outcomes of stroke/systemic embolism (SE), major bleeding, and death in a retrospective cohort of NVAF patients in the US. Initiators of either medication were linked to their prescribers and followed until the first of the study outcome, the end of rivaroxaban/apixaban use, or 365 days after initiation. PPP for each patient was the percent of rivaroxaban initiations issued by the provider for the prior 10 NVAF patients. Cox regression models tested associations between quintiles of PPP and each outcome. A total of 61,155 patients and 1726 providers were included. The IV was a strong predictor of rivaroxaban prescription (OR = 17.9; 95% CI: 16.6, 19.3). There were statistically significant associations between increasing preference for rivaroxaban and rates of major bleeding (ptrend = 0.041) and death (ptrend = 0.031), but not stroke/SE (ptrend = 0.398). This analysis provides evidence of the relative safety of apixaban over rivaroxaban for the risk of major bleeding and death

Effectiveness and safety of anticoagulants among patients with venous thromboembolism and active cancer who also had prior bleed or prior renal disease

Patients with active cancer and venous thromboembolism (VTE) have elevated risk of recurrent VTE (rVTE) and major bleeding (MB). The risk is even higher within those with a prior bleeding event or renal disease. There is a need to understand the risk of rVTE and MB of commonly used anticoagulants among these high-risk patients. VTE patients with active cancer and treated with apixaban, warfarin or low molecular weight heparin (LMWH) within 30 days of VTE were identified from 5 claims databases in the United States. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. Post-IPTW population was stratified by prior bleed or renal disease status. Cox proportional hazards models were used to evaluate interactions between treatment and prior bleed or renal disease on risk of rVTE and MB, with p-value Study criteria were met by 30,586 VTE cancer patients: 35.0% had prior bleed and 29.0% had renal disease. For apixaban, LMWH, and warfarin cohorts, incidence (events per 100 person-years) of MB was higher in patients with prior bleed (17.48 vs 7.58, 25.61 vs 13.11, and 20.38 vs 8.97) or renal disease (15.79 vs 8.71, 22.11 vs 15.90, and 18.49 vs 10.39) vs those without the conditions. Generally, there was no significant interactions between anticoagulant use and prior bleed or renal disease on rVTE and MB (p for interaction >0.1). Incidence of MB was higher among those with prior bleed or renal disease. Effects of apixaban, warfarin, or LMWH were generally consistent regardless of prior bleed or renal disease status.</p

Real-World Effectiveness of Dupilumab in Atopic Dermatitis Patients: Analysis of an Electronic Medical Records Dataset.

IntroductionWhile the efficacy of dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis (AD) has been demonstrated in several clinical trials, patients in such trials may not necessarily reflect the real-world clinical practice setting. This study evaluated the real-world effectiveness of dupilumab in adults with moderate-to-severe AD based on physician global assessment, percent body surface area affected, and patient-reported itch.MethodsFrom Modernizing Medicine's Electronic Medical Assistant dermatology-specific electronic medical records, adults (≥ 18&nbsp;years) were identified with a diagnosis of AD and ≥ 1 dupilumab prescription (index event) between 1 April 2017 and 31 January 2019. Three cohorts were identified based on 3-month pre-index (1) Investigator Global Assessment (IGA) score ≥ 3, (2) an itch severity numerical rating scale (NRS) score ≥ 3, and (3) body surface area (BSA) affected ≥ 10%. Changes from pre-index on the outcome within each cohort were evaluated at 4&nbsp;months post-index. Patients were also stratified for evaluation of outcomes by baseline demographic (sex, age) and prior AD treatments (topical therapy only or no treatment, any systemic therapy).ResultsMore than 70% of the 435 AD patients with baseline IGA score ≥ 3 improved to an IGA score of ≤ 2 at month 4 post-dupilumab initiation, including 42.8% who achieved IGA 0/1 (clear/minimal). Among 112 patients with a pre-index itch severity NRS ≥ 3, scores were reduced from mean (SD) 7.0 (2.4) pre-index to 2.8 (2.8) at month 4 (p &lt; 0.0001); 70.5% of patients had a reduction ≥ 3 points. In the BSA cohort (n = 387), affected BSA was significantly reduced from a pre-index mean (SD) of 39.3% (26.1%) to 16.3% (21.2%) at month 4 (p &lt; 0.0001). Significant improvements in IGA, itch NRS, and BSA were observed regardless of demographic (age and sex) or clinical characteristics such as treatment history (all p &lt; 0.0001 compared with pre-index).ConclusionsConsistent with outcomes observed in clinical trials, patients treated with dupilumab in real-world clinical settings achieved clinically meaningful improvements in severity and extent of AD and severity of itch comparable to those reported in clinical trials at a similar time point