Targeted approach of immunotherapy improves sepsis outcomes

Immunotherapy for sepsis is effective when doctors tailor the treatment precisely to the patient's immune system condition. While earlier research showed little benefit of immunotherapy in sepsis, a new study demonstrates that a targeted approach of immunotherapy does improve clinical outcomes. This is reported by a consortium of 33 hospitals in JAMA, led by Radboud university medical center and the Hellenic Institute for the Study of Sepsis.

In sepsis, the immune system responds incorrectly to an infection, which can lead to life-threatening organ failure. Worldwide, 49 million people develop sepsis each year, and 11 million die from it. Adjusting the disrupted immune response seems promising, but a one-size-fits-all approach has so far yielded little success. A new clinical trial shows that a precision medicine-based approach tailored to the patient's immune status does improve disease severity.

Immune paralysis

This precision approach is based on different forms of sepsis. 'The immune system reacts incorrectly to an infection in sepsis, but this can happen in different ways', explains Mihai Netea, professor of Experimental Internal Medicine at Radboudumc and leader of the consortium. 'The immune system can be overly active, or it can become paralyzed. This depends on the type of microorganism causing the infection, the location of the infection, and the patient's immune status and overall health.'

The ImmunoSep consortium, involving 33 centers in six countries, analyzed the functional state of the immune response to determine how the host defense mechanisms of sepsis patients were functioning. Only patients with proven overactive immunity (macrophage activation-like syndrome) or immune paralysis (systemic hyperinflammation) were stratified to receive immunotherapy in the study, 276 patients in total. For overactive immunity, the therapy consisted of a drug that suppresses the immune system, anakinra. Patients with immune paralysis received a drug that stimulates immunity, interferon-gamma.

Smart selection

Both groups fared better than their control groups who did not receive immunotherapy. In the first nine days, the organ dysfunction improved and in the first 15 days, underlying infection resolved sooner. In the anakinra group, patients did three times better.

This study provides the first robust large-scale evidence that biomarker-guided, targeted selection of sepsis patients for immunotherapy leads to clinically meaningful improvement in outcomes."

Evangelos Giamarellos-Bourboulis, professor of Internal Medicine and Infectious Diseases, National and Kapodistrian University of Athens and President of the Hellenic Institute for the Study of Sepsis, clinical trial sponsor

The researchers expect their study to give a boost to the field of immunotherapy for sepsis patients. Netea: 'The groups with overactive or paralyzed immunity in this study represent about a quarter of all sepsis cases. For them, we aim to perform large follow-up studies in the near future to further validate our findings. In addition, we will now also look for tailored immunotherapy for the remaining sepsis patients.'