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Re-Evaluating Biologic Pharmacotherapies That Target the Host Response during Sepsis
Journal article   Open access   Peer reviewed

Re-Evaluating Biologic Pharmacotherapies That Target the Host Response during Sepsis

Kristopher M. Tuttle, Matthew D. McDonald and Ethan J. Anderson
International journal of molecular sciences, Vol.20(23), p.6049
12/01/2019
DOI: 10.3390/ijms20236049
PMCID: PMC6929091
PMID: 31801287
url
https://doi.org/10.3390/ijms20236049View
Published (Version of record) Open Access

Abstract

Multiple organ dysfunction syndrome (MODS) caused by the systemic inflammatory response during sepsis is responsible for millions of deaths worldwide each year, and despite broad consensus concerning its pathophysiology, no specific or effective therapies exist. Recent efforts to treat and/or prevent MODS have included a variety of biologics, recombinant proteins targeting various components of the host response to the infection (e.g., inflammation, coagulation, etc.) Improvements in molecular biology and pharmaceutical engineering have enabled a wide range of utility for biologics to target various aspects of the systemic inflammatory response. The majority of clinical trials to date have failed to show clinical benefit, but some have demonstrated promising results in certain patient populations. In this review we summarize the underlying rationale and outcome of major clinical trials where biologics have been tested as a pharmacotherapy for MODS in sepsis. A brief description of the study design and overall outcome for each of the major trials are presented. Emphasis is placed on discussing targets and/or trials where promising results were observed. Post hoc analyses of trials where therapy demonstrated harm or additional risk to certain patient subgroups are highlighted, and details are provided about specific trials where more stringent inclusion/exclusion criteria are warranted.
Biochemistry & Molecular Biology Chemistry Chemistry, Multidisciplinary Life Sciences & Biomedicine Physical Sciences Science & Technology

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