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Development and Validation of a Clinical Risk Score to Predict Immune-mediated Liver Injury Caused by Sintilimab:
Caiyun Zheng1,2, Shunmin Huang1,3, Meimei Lin1
1Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Background And Aims:
Immune-mediated liver injury is a fatal side effect of sintilimab. This study aimed to shed light on the associated risk factors and characteristics of this adverse event.
Methods:
The clinical records of 772 patients treated with sintilimab were retrospectively reviewed to investigate risk factors associated with sintilimab immune-related hepatotoxicity, as well as its incidence and outcome. The Roussel Uclaf Causality Assessment Method was used to identify cases of sintilimab-induced hepatotoxicity. Furthermore, logistic regressions were performed to compare the clinical and bloodwork characteristics of patients with and without immune-mediated liver injury caused by checkpoint inhibitors.
Results:
Of the 585 patients included in the study, 71 (12.1%) developed liver injury during sintilimab use. The median RUCAM score with interquartile range was 7 (6, 8). Hypoproteinemia, dyslipidemia, and the presence of thyroid peroxidase antibodies were risk factors for sintilimab-related hepatotoxicity. A nomogram model was constructed for sintilimab-induced immune-mediated liver injury based on these risk factors, which had a C-index value of 0.713 and a good calibration curve. When applied to patients with grade ≥3 and ≥4 sintilimab-induced immune-mediated liver injury, it achieved C-index values of 0.752 and 0.811, respectively. The nomogram model also showed a good prediction potential in patients ≥65 years and males. Six of the patients with sintilimab-related hepatotoxicity showed improved liver function upon treatment with steroids.
Conclusions:
This study demonstrated that hypoproteinemia, dyslipidemia, and the presence of thyroid peroxidase antibodies were clinically feasible prognostic biomarkers to predict liver injury in patients treated with sintilimab.
