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Diarrea y colitis inmunomediadas con hallazgos bioquímicos, endoscópicos e histológicos normales: un estudio
Malek Shatila1, Sharada Wali1, Carolina Colli Cruz1
1The University of Texas MD Anderson Cancer Center, Department of Gastroenterology, Hepatology, and Nutrition, Houston, TX (Malek Shatila, Sharada Wali*, Carolina Colli Cruz*, Krishnavathana Varatharajalu, Anusha Shirwaiker Thomas, Yinghong Wang).
Insights
La diarrea y colitis inmunomediadas (DCIM) sin marcadores de inflamación se asocia con inhibidores de PD-1/PD-L1. Estos pacientes experimentan síntomas más leves y menos hospitalizaciones, aunque algunos aún necesitan inmunosupresión.
Área de la Ciencia:
- Oncología; Gastroenterología; Inmunología
Sus antecedentes:
- La diarrea y colitis inmunomediadas (DCIM) pueden ocurrir con los inhibidores de puntos de control.; Un subconjunto de pacientes se presenta con DCIM pero carece de biomarcadores fecales, evidencia endoscópica o histológica de inflamación.; La comprensión del tratamiento y los resultados para este grupo específico de DCIM es limitada.
Objetivo del estudio:
- Describir las características de los pacientes con DCIM sin evidencia de inflamación.; Aclarar el papel de los tratamientos inmunosupresores en el manejo de este subconjunto de DCIM.; Investigar los posibles vínculos entre los inhibidores de PD-1/L1 y esta presentación específica de DCIM.
Principales métodos:
- Estudio retrospectivo unicéntrico.; Criterios de inclusión: pacientes tratados con inhibidores de puntos de control inmunitario que desarrollaron síntomas clínicos de DCIM sin evidencia de inflamación (calprotectina fecal, endoscopia, histología).; Período de estudio: enero de 2010 a febrero de 2024.
Principales resultados:
- El 11,4 % de los pacientes con DCIM (131/1151) no mostraron inflamación.; Estos pacientes tuvieron una mayor exposición a agentes PD-1/L1 y una diarrea menos grave, con menores tasas de hospitalización.; Aproximadamente el 40 % requirió tratamiento inmunosupresor, sin diferencias significativas en los síntomas o la gravedad entre los que lo recibieron y los que no.
Conclusiones:
- Este es el primer estudio sobre DCIM con marcadores de inflamación normales.; La inhibición de PD-1/L1 puede predisponer a esta forma de DCIM, asociada con resultados más leves.; A pesar de la presentación más leve, el tratamiento inmunosupresor a menudo es necesario, y algunos pacientes pueden desarrollar posteriormente inflamación colónica.
Background:
Immune-mediated diarrhea and colitis (IMDC) due to checkpoint inhibition infrequently presents with normal stool biomarkers and no endoscopic or histologic evidence of inflammation. Little is known about the treatment needs and outcomes of this subset of patients. We aimed to describe this entity and clarify the role of immunosuppressive treatments in its management.
Method:
This was a single-center, retrospective study of patients treated with immune checkpoint inhibitors who developed clinical symptoms of IMDC, with no evidence of inflammation based on fecal calprotectin or endoscopic/histologic evaluation, between January 2010 and February 2024.
Results:
Of 1151 patients with IMDC, 131 (11.4%) had no evidence of inflammation. These patients more frequently had PD-1/L1 agent exposure (P=0.019) and presented with less severe diarrhea than patients with evidence of inflammation (P<0.001). This group had a lower rate of hospitalization (P=0.003). Around 40% of patients with no evidence of inflammation required immunosuppressive treatment. There was no difference in clinical symptoms or severity between patients requiring immunosuppression and those who did not.
Conclusions:
Our study is the first to explore IMDC with no elevations in calprotectin and normal endoscopic/histologic findings. We found that PD-1/PD-L1 inhibition may predispose patients to developing this form of IMDC, which is associated with a lower severity of diarrhea, fewer hospitalizations and lower recurrence rates. Many patients still require immunosuppressive treatment, and a small subset later develop colonic inflammation. Future studies are needed to further elucidate the treatment needs and outcomes of this patient population.
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