ImmunoSep Trial Published in JAMA: Precision Immunotherapy Improves Outcomes in Sepsis
The ImmunoSep trial, published in JAMA and representing the core of the project, demonstrates that precision immunotherapy tailored to a patient’s immune status can significantly improve outcomes for people with sepsis compared to standard care.
Why Precision Matters in Sepsis
The ImmunoSep randomized clinical trial used immune biomarkers to guide treatment selection, addressing the fact that sepsis does not affect all patients in the same way. Some patients experience excessive inflammation, while others develop immune suppression. Matching therapy to these immune profiles led to markedly better results.
Improved Organ Function and Immune Recovery
By day nine of treatment, 35.1% of patients receiving precision immunotherapy showed clinically meaningful improvement in organ function, compared to 17.9% in the placebo group. These benefits persisted through day 15 (39.7% vs. 23.4%).
Patients receiving biomarker-guided therapy also experienced:
- Faster reversal of immune dysfunction (78.0% vs. 48.5%)
- Better infection resolution, supporting improved immune control
Targeted Treatments Showed Clear Benefit
Two immune-specific interventions were tested, both proving effective when used in the appropriate patient group:
- Anakinra, for patients with excessive immune activation, led to organ function improvement in 48.0% of patients versus 17.4% with placebo.
- Interferon-gamma, for patients with immune suppression, improved outcomes in 32.1% of patients compared to 18.0% receiving placebo.
Project Conclusion: Advancing Precision Medicine in Sepsis Care
The ImmunoSep trial provides robust evidence that a precision medicine approach can substantially improve sepsis care. By using biomarkers to guide immunotherapy, clinicians can reduce organ dysfunction, restore immune balance more rapidly, and improve infection outcomes.
As the final milestone of the project, these results mark a successful transition from hypothesis to high-quality clinical evidence. ImmunoSep delivers a strong proof of concept for biomarker-guided immunotherapy in sepsis and establishes a solid foundation for future phase III trials and broader clinical implementation.
Publication
Giamarellos-Bourboulis EJ, Kotsaki A, Kotsamidi I, et al.
Precision Immunotherapy to Improve Sepsis Outcomes: The ImmunoSep Randomized Clinical Trial. JAMA, published online December 8, 2025.
Find the journal article here