Therapeutic sequencing in inflammatory bowel disease: Determining the optimal position of vedolizumab for long-term Crohn's disease control using real-world evidence.

BACKGROUND: Several biologics are available for the treatment of moderate to severe Crohn's disease, but data to optimize their use are scarce. Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking monoclonal antibody that was approved in 2014 for the treatment of moderate to severe Crohn's disease. Based on real-world evidence, a model was developed to examine the effect of VDZ's position in the treatment sequence on clinical outcomes. OBJECTIVE: The aim of this study was to develop a model using real-world data to investigate how the positioning of VDZ in a sequence of biologic therapies for CD affects clinical effectiveness outcomes of quality-adjusted life-years (QALYS), patient-reported disease activity, and surgery rates. METHODS: A semi-Markov sequential model was developed to identify the optimal position of VDZ in a treatment sequence that included corticosteroids (CS), two biologics, and best supportive care (BSC). Using real-world data, three sequences were compared: VDZ as first (position), second, and last biologic (with anti-tumor necrosis factor alpha agents adalimumab (ADA) and infliximab (IFX) and the anti-interleukin-12 and -23 agent ustekinumab (UST) as alternative biologic treatments). Published real-world evidence informed model inputs. Vedolizumab sequences were compared and ranked based on QALYS, patient-reported outcomes from Crohn's disease activity index scores, or proportion of patients undergoing surgery by the 10-year time horizon for model simulation. Sensitivity analyses were used to evaluate the impact of model input uncertainty. RESULTS: Vedolizumab as the first biologic was the optimal position for this treatment according to all criteria, including yielding the highest QALYs (5.09) versus VDZ in second (4.97) and third (4.96) biologic sequence positions in sequences containing CS, anti-TNFα (aggregated data), UST, and BSC; 1780/2000 (89%) probabilistic simulations. In sequences containing ADA, VDZ, and UST biologics, ADA and VDZ in the first-line biologic position yielded QALYs of 5.09 versus 5.07, respectively. Adalimumab as the first biologic was best for clinical remission. CONCLUSIONS: This simulation model using real-world evidence indicates that positioning VDZ or ADA as the first biologic is likely to lead to improved long-term patient outcomes when compared to administering these treatments later or starting with IFX monotherapy.

Economic Evaluation of an N-terminal Pro B-type Natriuretic Peptide-Supported Diagnostic Strategy Among Dyspneic Patients Suspected of Acute Heart Failure in the Emergency Department.

Our objective was to perform an economic evaluation of an N-terminal pro B-type natriuretic peptide (NT-proBNP)-supported diagnostic strategy in dyspneic patients suspected of acute heart failure in the emergency department (ED). A decision-tree model was developed to evaluate clinical outcomes and costs for NT-proBNP-supported assessment compared with clinical assessment alone over 6 months from the United States (US) Medicare perspective. The model considered rule-in/rule-out cutoffs identified in the ICON and ICON-RELOADED studies. Acute heart failure prevalence, diagnostic accuracies, and medical resource use conditional on disease status and test results were derived from ICON-RELOADED. Several assumptions based on previous studies of NT-proBNP acute dyspnea and verified with clinicians were applied to medical resource use and assessed in sensitivity analyses. Compared with clinical assessment alone, NT-proBNP-supported assessment improved overall probability of correct diagnosis by a relative 7% (18% for true-positive and 5% for true-negative). This led to relative reductions in medical resource use in ED and hospital, including fewer initial hospitalizations (-14%), required echocardiograms (-31%), cardiology admissions (-16%), intensive care unit admissions (-12%), ED readmissions (-3%), and hospital readmissions (-22%). NT-proBNP use decreased average inpatient management costs by a relative 10%, yielding cost savings of US$2,337 per patient ED visit. These findings were robust in sensitivity analyses. In conclusion, based on a contemporary trial of patients with acute dyspnea, this analysis reaffirmed that using NT-proBNP as a diagnostic tool may improve the management of patients with dyspnea presenting to EDs and is likely to be cost-saving from the US Medicare perspective.