Impact Of De-escalation Research Articles

Sustained Remission and Outcomes with Abatacept plus Methotrexate Following Stepwise Dose De-escalation in Patients with Early Rheumatoid Arthritis.

One target of rheumatoid arthritis (RA) treatment is to achieve early sustained remission; over the long term, patients in sustained remission have less structural joint damage and physical disability. We evaluated Simplified Disease Activity Index (SDAI) remission with abatacept + methotrexate versus abatacept placebo + methotrexate and impact of de-escalation (DE) in anti-citrullinated protein antibody (ACPA)-positive patients with early RA. The phase IIIb, randomized, AVERT-2 two-stage study (NCT02504268) evaluated weekly abatacept + methotrexate versus abatacept placebo + methotrexate. SDAI remission (≤ 3.3) at week24. Pre-planned exploratory endpoint: maintenance of remission in patients with sustained remission (weeks40 and 52) who, from week56 for 48weeks (DE period), (1) continued combination abatacept + methotrexate, (2) tapered abatacept to every other week (EOW) + methotrexate for 24weeks with subsequent abatacept withdrawal (abatacept placebo + methotrexate), or (3) withdrew methotrexate (abatacept monotherapy). Primary study endpoint was not met: 21.3% (48/225) of patients in the combination and 16.0% (24/150) in the abatacept placebo + methotrexate arm achieved SDAI remission at week24 (p = 0.2359). There were numerical differences favoring combination therapy in clinical assessments, patient-reported outcomes (PROs) and week52 radiographic non-progression. After week56, 147 patients in sustained remission with abatacept + methotrexate were randomized (combination, n = 50; DE/withdrawal, n = 50; abatacept monotherapy, n = 47) and entered DE. At DE week48, SDAI remission (74%) and PRO improvements were mostly maintained with continued combination therapy; lower remission rates were observed with abatacept placebo + methotrexate (48.0%) and with abatacept monotherapy (57.4%). Before withdrawal, de-escalating to abatacept EOW + methotrexate preserved remission. The stringent primary endpoint was not met. However, in patients achieving sustained SDAI remission, numerically more maintained remission with continued abatacept + methotrexate versus abatacept monotherapy or withdrawal. ClinicalTrials.gov identifier, NCT02504268. Video abstract (MP4 62241 KB).

Impact of Extended and Restricted Antibiotic Deescalation on Mortality.

Background: More data are needed about the safety of antibiotic de-escalation in specific clinical situations as a strategy to reduce exposure to broad-spectrum antibiotics. This study aims to compare the survival curve of patient de-escalated (early or late) against those not de-escalated on antibiotics, to determine the association of patient related, clinical related, and pressure sore/device related characteristics on all-cause 30-day mortality and determine the impact of early and late antibiotic de-escalation on 30-day all-cause mortality. Methods: This is a retrospective cohort study on patients in medical ward Hospital Kuala Lumpur, admitted between January 2016 and June 2019. A Kaplan–Meier survival curve and Fleming–Harrington test were used to compare the overall survival rates between early, late, and those not de-escalated on antibiotics while multivariable Cox proportional hazards regression was used to determine prognostic factors associated with mortality and the impact of de-escalation on 30-day all-cause mortality. Results: Overall mortality rates were not significantly different when patients were not de-escalated on extended or restricted antibiotics, compared to those de-escalated early or later (p = 0.760). Variables associated with 30-day all-cause mortality were a Sequential Organ Function Assessment (SOFA) score on the day of antimicrobial stewardship (AMS) intervention and Charlson’s comorbidity score (CCS). After controlling for confounders, early and late antibiotics were not associated with an increased risk of mortality. Conclusion: The results of this study reinforce that restricted or extended antibiotic de-escalation in patients does not significantly affect 30-day all-cause mortality compared to continuation with extended and restricted antibiotics.

De-escalation from ticagrelor to clopidogrel in acute coronary syndrome patients: a systematic review and meta-analysis

De-escalation from ticagrelor to clopidogrel in acute coronary syndrome (ACS) may occur for a variety of reasons, including side effects (bleeding and non-bleeding) and costs. This study sought to assess the prevalence of de-escalation from ticagrelor to clopidogrel and the occurrence of adverse clinical outcomes following de-escalation. We conducted a systematic review of clinical trials and real-world studies in ACS patients treated with ticagrelor. Real-world data on the prevalence of de-escalation during hospitalization or at discharge, after hospital discharge, and during the whole study period were included for meta-analysis. Major adverse cardiovascular events (MACE) and bleeding events occurring after de-escalation were also assessed. A total of 12 studies were eligible for meta-analysis of the prevalence of de-escalation. De-escalation from ticagrelor to clopidogrel therapy occurred with a mean prevalence of 19.8% [95% confidence interval (CI) 11.2–28.4%]. De-escalation occurred more frequently in-hospital or at discharge than after hospital discharge (23.7% vs. 15.8%). For assessment of clinical outcomes, a total of six studies were eligible for meta-analysis. Mean rate of MACE for patients with de-escalation was 2.1% (95% CI 1.1–4.1%) and the rate of major bleeding events was 1.3% (95% CI 0.4–4.5%). In conclusion, de-escalation commonly occurs in real-world practice. Although rates of major cardiovascular and bleeding events in this analysis were generally low, the profile of patients suitable for de-escalation, the impact of de-escalation on adverse clinical outcomes and how this is affected by the timing after index ACS warrants further large-scale investigation.

De-Escalation of Treatment With Oral P2Y12 Receptor Inhibitors: Current Status and Perspectives.

In patients with an acute coronary syndrome undergoing percutaneous coronary intervention, novel P2Y12 receptor inhibitors, prasugrel and ticagrelor, are proposed as "first-line" antiplatelet agents in the absence of contraindications and up to a year from the index event. However, de-escalation of treatment to clopidogrel occurs with a variable frequency in real-life practice, most commonly due to an increased bleeding potential, more frequent side effects, and a higher cost for the novel agents. Pharmacodynamic studies provide most of the data on guidance for de-escalation. Despite positive messages from recent trials and registries, lack of definitive efficacy or safety results of such a strategy remains an obstacle to suggest de-escalation in a routine basis. Carefully designed studies are likely to improve our understanding of the impact of de-escalation and help to better define its position in current pharmacotherapy.

Impact of De-escalation on Prognosis of Patients With Bacteremia due to Enterobacteriaceae: A Post Hoc Analysis From a Multicenter Prospective Cohort.

More data are needed about the safety of antibiotic de-escalation in specific clinical situations as a strategy to reduce exposure to broad-spectrum antibiotics. The aims of this study were to investigate predictors of de-escalation and its impact on the outcome of patients with bloodstream infection due to Enterobacteriaceae (BSI-E). A post hoc analysis was performed on a prospective, multicenter cohort of patients with BSI-E initially treated with ertapenem or antipseudomonal β-lactams. Logistic regression was used to analyze factors associated with early de-escalation (EDE) and Cox regression for the impact of EDE and late de-escalation (LDE) on 30-day all-cause mortality. A propensity score (PS) for EDE vs no de-escalation (NDE) was calculated. Failure at end of treatment and length of hospital stay were also analyzed. Overall, 516 patients were included. EDE was performed in 241 patients (46%), LDE in 95 (18%), and NDE in 180 (35%). Variables independently associated with a lower probability of EDE were multidrug-resistant isolates (odds ratio [OR], 0.50 [95% confidence interval {CI}, .30-.83]) and nosocomial infection empirically treated with imipenem or meropenem (OR, 0.35 [95% CI, .14-.87]). After controlling for confounders, EDE was not associated with increased risk of mortality; hazard ratios (HR) (95% CIs) were as follows: general model, 0.58 (.25-1.31); model with PS, 0.69 (.29-1.65); and PS-based matched pairs, 0.98 (.76-1.26). LDE was not associated with mortality. De-escalation was not associated with clinical failure or length of hospital stay. De-escalation in patients with monomicrobial bacteremia due to Enterobacteriaceae was not associated with a detrimental impact on clinical outcome.

Abstract WMP89: Stroke Code De-escalation: Safety and Outcomes

Introduction: “Stroke codes” (SCs) facilitate the timely treatment of acute ischemic stroke (AIS) with IV tPA or intra-arterial thrombectomy (IAT), but are inherently resource-intensive and can expose patients to unnecessary and potentially harmful interventions. While all healthcare providers are encouraged to activate SCs, this might lead to low SC-to-treatment-ratios (SCTR). We examined the impact of de-escalation of stroke codes (DSCs) on SCTR. Methods: DSCs were initiated in our institution in January 2015. All DSCs were reviewed for the patient’s eligibility for IV tPA or IAT, and reason for de-escalation. We reviewed all stroke codes 12 months before and after the initiation of this process and compared the SCTR by chi-squared testing. Results: In 2014, prior to DSCs, 253 SCs resulted in 22 AIS interventions (22 IV tPA) for a SCTR of 8.7%. In 2015, 348 SCs were activated with 64 subsequent DSCs (18.4%) and 45 AIS interventions (38 IV tPA, 7 IAT, 7 both), for a SCTR of 15.8%. The improvement in SCTR after introducing DSCs was statistically significant (p=0.012). When restricting the analysis to IV tPA interventions alone, there remained a trend (p=0.068) towards improvement in SCTR. Retrospective chart review did not reveal any DSC cases that resulted in missed opportunity for IV TPA or IAT treatment. No DSCs were due to an acute ICH. Justifications for de-escalations are summarized in figure 1. Conclusions: The introduction of DSCs resulted in a statistically significant absolute improvement in SCTR of 7.1%. Importantly, DSCs did not result in any eligible AIS patient forgoing IV tPA or IAT, nor missed ICH. More research is needed to increase the yield of stroke codes, refine the criteria for both activating and de-escalating them, and quantify the resource and cost implications of such de-escalations.

Bloodstream infections and sepsis in Greece: over-time change of epidemiology and impact of de-escalation on final outcome.

BackgroundChoice of empirically prescribed antimicrobials for sepsis management depends on epidemiological factors. The epidemiology of sepsis in Greece was studied in two large-periods.MethodsSepsis due to bloodstream infections (BSI) from July 2006 until March 2013 was recorded in a multicenter study in 46 departments. Patients were divided into sepsis admitted in the emergencies and hospitalized in the general ward (GW) and sepsis developing after admission in the Intensive Care Unit (ICU). The primary endpoints were the changes of epidemiology and the factors related with BSIs by multidrug-resistant (MDR) pathogens; the secondary endpoint was the impact of de-escalation on antimicrobial therapy.Results754 patients were studied; 378 from 2006–2009 and 376 from 2010–2013. Major differences were recorded between periods in the GW. They involved increase of: sepsis severity; the incidence of underlying diseases; the incidence of polymicrobial infections; the emergence of Klebsiella pneumoniae as a pathogen; and mortality. Factors independently related with BSI by MDR pathogens were chronic hemofiltration, intake of antibiotics the last three months and residence into long-term care facilities. De-escalation in BSIs by fully susceptible Gram-negatives did not affect final outcome. Similar epidemiological differences were not found in the ICU; MDR Gram-negatives predominated in both periods.ConclusionsThe epidemiology of sepsis in Greece differs in the GW and in the ICU. De-escalation in the GW is a safe strategy.