Targeted immunotherapy approach improves sepsis outcomes

Targeted immunotherapy approach improves sepsis outcomes

Immunotherapy for sepsis is effective when doctors tailor treatment to the state of the patient's immune system. While previous research showed little benefit from immunotherapy in sepsis, a new study shows that a targeted immunotherapy approach improves clinical outcomes. This is reported by a consortium of 33 hospitals in JAMA led by the Radboud University Medical Center and the Hellenic Institute for the Study of Sepsis.

In sepsis, the immune system reacts incorrectly to an infection, which can lead to life-threatening organ failure. Every year, 49 million people worldwide develop sepsis and 11 million die from it. Correcting the impaired immune response seems promising, but a uniform approach has so far brought little success. A new clinical trial shows that a precision medicine-based approach tailored to the patient's immune status actually improves disease severity.

Immune paralysis

This precision approach is based on different forms of sepsis. “In sepsis, the immune system reacts incorrectly to an infection, but this can happen in different ways,” explains Mihai Netea, Professor of Experimental Internal Medicine at Radboudumc and head of the consortium. “The immune system can be overactive or paralyzed.” This depends on the type of microorganism causing the infection, the location of the infection, as well as the immune status and general health of the patient.”

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 worked. In the study, only patients with proven overactive immunity (macrophage activation-like syndrome) or immune paralysis (systemic hyperinflammation) were stratified to receive immunotherapy, a total of 276 patients. For overactive immunity, treatment consisted of a drug that suppresses the immune system, anakinra. Patients with immune paralysis were given a drug that stimulates immunity: interferon-gamma.

Smart selection

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

This study provides the first robust, large-scale evidence that biomarker-driven, targeted selection of sepsis patients for immunotherapy results in 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 Greek Institute for the Study of Sepsis, clinical trial sponsor

The researchers expect their study to provide a boost in the field of immunotherapy for sepsis patients. Netea: “The groups with overactive or paralyzed immunity in this study account for about a quarter of all sepsis cases.” We want to conduct large follow-up studies for them in the near future to further validate our results. In addition, we will now also look for tailor-made immunotherapy for the remaining sepsis patients.”

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