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2016 ; 44
(2
): 275-81
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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
#MMPMID26584195
Shakoory B
; Carcillo JA
; Chatham WW
; Amdur RL
; Zhao H
; Dinarello CA
; Cron RQ
; Opal SM
Crit Care Med
2016[Feb]; 44
(2
): 275-81
PMID26584195
show ga
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.