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Cited by 871Sepsis Diagnosis and TreatmentAutoimmune and Inflammatory Disorders ResearchInflammation biomarkers and pathways

The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index.

Interleukin-1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of Macrophage Activation Syndrome: Reanalysis of a Prior Phase III Trial*

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Shakoory, Bita, Carcillo, Joseph A., Chatham, W. Winn, Amdur, Richard L., Zhao, Huaqing, Dinarello, Charles A., Cron, Randall Q., Opal, Steven M.·2016·Critical Care Medicine
DOI 10.1097/ccm.0000000000001402PMC PMC5378312
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Abstract

OBJECTIVE: To determine the efficacy of anakinra (recombinant interleukin-1 receptor antagonist) in improving 28-day survival in sepsis patients with features of macrophage activation syndrome. Despite equivocal results in sepsis trials, anakinra is effective in treating macrophage activation syndrome, a similar entity with fever, disseminated intravascular coagulation, hepatobiliary dysfunction, cytopenias, and hyperferritinemia. Hence, sepsis patients with macrophage activation syndrome features may benefit from interleukin-1 receptor blockade. DESIGN: Reanalysis of deidentified data from the phase III randomized interleukin-1 receptor antagonist trial in severe sepsis. SETTING: Multicenter study recruiting through 91 centers from 11 countries in Europe and North America. PATIENTS: Sepsis patients with multiorgan dysfunction syndrome and/or shock (original study) were regrouped based on the presence or the absence of concurrent hepatobiliary dysfunction and disseminated intravascular coagulation as features of macrophage activation syndrome. The non-hepatobiliary dysfunction/disseminated intravascular coagulation group included patients with only hepatobiliary dysfunction, only disseminated intravascular coagulation, or neither. INTERVENTION: Treatment with anakinra or placebo. MEASUREMENTS AND MAIN RESULTS: Main outcome was 28-day mortality. Descriptive and comparative statistics were performed. Data were available for 763 adults from the original study cohort, randomized to receive either anakinra or placebo. Concurrent hepatobiliary dysfunction/disseminated intravascular coagulation was noted in 43 patients (5.6% of total; 18-75 years old; 47% women). The 28-day survival was similar in both anakinra and placebo-treated non-hepatobiliary dysfunction/disseminated intravascular coagulation patients (71.4% vs 70.8%; p = 0.88). Treatment with anakinra was associated with significant improvement in the 28-day survival rate in hepatobiliary dysfunction/disseminated intravascular coagulation patients (65.4% anakinra vs 35.3% placebo), with hazard ratio for death 0.28 (0.11-0.71; p = 0.0071) for the treatment group in Cox regression. CONCLUSIONS: In this subgroup analysis, interleukin-1 receptor blockade was associated with significant improvement in survival of patients with sepsis and concurrent hepatobiliary dysfunction/disseminated intravascular coagulation. A prospective randomized trial using features of macrophage activation syndrome for mortality risk stratification should be undertaken to confirm the role of interleukin-1 blockage.

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Research works printed but not linked: 4

  1. Emmenegger, 2005, Swiss Med Wkly, 135, 299
  2. Behrens, 2007, J Rheumatol, 34, 1133
  3. Behrens, 2006, J Rheumatol, 33, 2081
  4. Marti-Carvajal, 2012, Cochrane Database Syst Rev, 12, CD004388

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Metadata

Authors
Shakoory, B., Carcillo, J. A., Chatham, W. W., Amdur, R. L., Zhao, H., Dinarello, C. A., Cron, R. Q., & Opal, S. M.
Affiliations
  • George Washington University (US)
  • University of Pittsburgh Medical Center (US)
  • University of Alabama at Birmingham (US)
  • Temple University (US)
  • University of Colorado Anschutz (US)
  • Brown University (US)
ORCID
Venue
Critical Care Medicine
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2016-02
Volume
44
Issue
2
Pages
275-281
ISSN
0090-3493 (ISSN-L)
DOI
10.1097/ccm.0000000000001402
PMC
PMC5378312
OpenAlex
W2177407033
Cited by
867
References
48
Citations by year
2026: 66 · 2025: 64 · 2024: 68 · 2023: 76 · 2022: 87 · 2021: 141 · 2020: 226 · 2019: 43 · 2018: 36 · 2017: 42 · 2016: 15
FWCI
24.58
Type
journal article
Language
en
Open access
Locations
  • Critical Care Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of General Medical Sciences (R01GM108618)
Topics
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords
sepsis, anakinra, interleukin-1 receptor antagonist, interleukin-1 blockade, 28-day mortality, hepatobiliary dysfunction, disseminated intravascular coagulation, multiple organ failure, septic shock, subgroup analysis, hyperferritinemia, cytokine storm
MeSH terms
Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Biliary Tract Diseases, Disseminated Intravascular Coagulation, Double-Blind Method, Female, Humans, Liver Diseases, Male, Middle Aged, Multiple Organ Failure, Respiratory Distress Syndrome, Sex Factors, Shock, Septic, Receptors, Interleukin-1, Sepsis, APACHE, Interleukin 1 Receptor Antagonist Protein, Macrophage Activation Syndrome, Young Adult, Acute Kidney Injury

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