Effect of Intravenous Interferon β-1a on Death and Days Free From Mechanical Ventilation Among Patients With Moderate to Severe Acute Respiratory Distress Syndrome

Abstract

; for the INTEREST Study Group IMPORTANCE Acute respiratory distress syndrome (ARDS) is associated with high mortality. Interferon (IFN) β-1a may prevent the underlying event of vascular leakage. OBJECTIVE To determine the efficacy and adverse events of IFN-β-1a in patients with moderate to severe ARDS. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, double-blind, parallel-group trial conducted at 74 intensive care units in 8 European countries (December 2015-December 2017) that included 301 adults with moderate to severe ARDS according to the Berlin definition. The radiological and partial pressure of oxygen, arterial (PaO 2)/fraction of inspired oxygen (FIO 2) criteria for ARDS had to be met within a 24-hour period, and the administration of the first dose of the study drug had to occur within 48 hours of the diagnosis of ARDS. The last patient visit was on March 6, 2018. INTERVENTIONS Patients were randomized to receive an intravenous injection of 10 μg of IFN-β-1a (144 patients) or placebo (152 patients) once daily for 6 days. MAIN OUTCOMES AND MEASURES The primary outcome was a score combining death and number of ventilator-free days at day 28 (score ranged from −1 for death to 27 if the patient was off ventilator on the first day). There were 16 secondary outcomes, including 28-day mortality, which were tested hierarchically to control type I error. RESULTS Among 301 patients who were randomized (mean age, 58 years; 103 women [34.2%]), 296 (98.3%) completed the trial and were included in the primary analysis. At 28 days, the median composite score of death and number of ventilator-free days at day 28 was 10 days (interquartile range, −1 to 20) in the IFN-β-1a group and 8.5 days (interquartile range, 0 to 20) in the placebo group (P = .82). There was no significant difference in 28-day mortality between the IFN-β-1a vs placebo groups (26.4% vs 23.0%; difference, 3.4% [95% CI, −8.1% to 14.8%]; P = .53). Seventy-four patients (25.0%) experienced adverse events considered to be related to treatment during the study (41 patients [28.5%] in the IFN-β-1a group and 33 [21.7%] in the placebo group). CONCLUSIONS AND RELEVANCE Among adults with moderate or severe ARDS, intravenous IFN-β-1a administered for 6 days, compared with placebo, resulted in no significant difference in a composite score that included death and number of ventilator-free days over 28 days. These results do not support the use of IFN-β-1a in the management of ARDS.

Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)

“…76-2.57). In a recent RCT (INTEREST trial), the use of recombinant interferon β1b (rIFN β1ba) did not reduce mortality in ARDS patients, but in the subgroup of patients receiving corticosteroids, rIFN β1ba use was associated with increased mortality (OR, 2.53, 95% CI 1.12-5.72) [147]. The only direct evidence comes from a retrospective cohort study of 201 patients with COVID-19 pneumonia.…”

Type 1 interferons as a potential treatment against COVID-19

“…This process explains why clinical data indicate a reduction of vascular leakage in acute respiratory distress syndrome (ARDS) with IFNβ1a treatment (Bellingan et al, 2014). However, this effect is insufficient to decrease ARDS mortality (Ranieri et al, 2020). It has been suggested from in vivo studies in mice that the timing of IFN-I administration plays a crucial role: positive effects were observed if IFN-I was administered shortly after infection, but IFN-I failed to inhibit viral replication and had side-effects when administered later (Channappanavar et al, 2019).…”

Interferon-β-1a for patients with moderate to severe acute respiratory distress syndrome: a systematic review and meta-analysis of randomized trials

“…We found 2 clinical trials that met our inclusion criteria. 6,16 This was based on identifying initially a total of 160 citations: 15 in the MED-LINE database, 133 in the EMBASE database, and 12 in the Cochrane Central Register of Controlled Trials. Full texts of 3 studies were screened and 2 trials were retained for the final systematic review (for the Preferred Reporting Items for Systematic Reviews and Meta -Analyses 17 flow diagram, see FIGURE 1).…”