JAMA
Precision immunotherapy improves early organ function in sepsis
In the randomized, double-blind ImmunoSep trial (NCT04990232) conducted in six countries, 276 adults with sepsis and either macrophage activation–like syndrome or sepsis-induced immunoparalysis received standard care plus precision immunotherapy or placebo. Patients with hyperinflammation received IV anakinra; those with immunoparalysis received SC interferon gamma. By day 9, 35.1% of the precision immunotherapy group achieved a ≥1.4-point reduction in SOFA score vs. 17.9% in the placebo group (difference, 17.2%; P = 0.002). Mortality at 28 days wasn't significantly different. Serious adverse events occurred in 88.8% of patients, with anemia more common in the anakinra group and hemorrhage in the interferon gamma group.
Clinical takeaway: Biomarker-guided immunotherapy improved early organ dysfunction in sepsis, but mortality benefit remains uncertain.
Source:
Giamarellos-Bourboulis EJ, et al; ImmunoSep Study Group. (2025, December 8). JAMA. Precision Immunotherapy to Improve Sepsis Outcomes: The ImmunoSep Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/41359996/