A new study reported in JAMA shows that immunotherapy for sepsis can be effective when precisely tailored to a patient’s immune system condition. Although earlier research found limited benefit from generalized immunotherapy, this clinical trial demonstrates that a targeted, precision medicine approach significantly improves disease severity and clinical outcomes. Conducted by a consortium of 33 hospitals led by Radboud University Medical Center and the Hellenic Institute for the Study of Sepsis, the study addresses the challenge of sepsis where an abnormal immune response to infection can cause life-threatening organ failure affecting 49 million people and causing 11 million deaths worldwide each year.

This precision-based approach recognizes that sepsis affects the immune system in different ways, as explained by Mihai Netea, Professor of Experimental Internal Medicine at Radboudumc and consortium leader. In some patients, the immune system becomes excessively active, while in others it is severely suppressed, depending on factors such as the infecting microorganism, infection site, and the patient’s overall immune health. The ImmunoSep consortium, comprising 33 centers across six countries, analyzed patients’ immune responses and selected 276 individuals with clearly defined immune profiles. Those with overactive immunity received the immune-suppressing drug anakinra, while patients with immune paralysis were treated with the immune-stimulating drug interferon-gamma.

Both patient groups receiving immunotherapy showed better outcomes than control groups without such treatment, with faster improvement in organ function within nine days and quicker resolution of infection within 15 days. Notably, patients treated with anakinra experienced threefold better outcomes. According to Evangelos Giamarellos-Bourboulis, Professor of Internal Medicine and Infectious Diseases at the National and Kapodistrian University of Athens and President of the Hellenic Institute for the Study of Sepsis, this study provides the first strong large-scale evidence that biomarker-guided, targeted immunotherapy can meaningfully improve sepsis outcomes. The researchers believe these findings will advance sepsis immunotherapy research, noting that patients with overactive or suppressed immunity account for about 25% of sepsis cases, with further large-scale validation studies planned and efforts underway to develop tailored treatments for the remaining patient groups.

Source: https://www.radboudumc.nl/en/news-items/2025/immunotherapy-works-for-sepsis-thanks-to-smart-patient-selection