Journal
CRITICAL CARE MEDICINE
Volume 44, Issue 2, Pages 275-281Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCM.0000000000001402
Keywords
anakinra; disseminated intravascular coagulation; hepatobiliary dysfunction; interleukin-1 receptor antagonist; macrophage activation syndrome; multiorgan dysfunction syndrome; sepsis mortality
Categories
Funding
- National Institutes of Health (NIH)
- National Institute of General Medical Sciences (NIGMS)
- MODS/macrophage activation syndrome [MAS]
- Swedish Orphan Biovitrum (SOBI)
- SOBI (clinical trial of anakinra for MAS)
- Archeogen and Ketotek (data and safety monitoring boards)
- Asahi Kasei (clinical coordinating center for their phase 3 trial in sepsis)
- Cardeas (clinical coordinating center for their phase 2 trial in severe pneumonia)
- Arsanis (preclinical study of monoclonal antibodies for blood stream infection)
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available