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Gastroenterology ; 155(4): 1008-1011.e8, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29981298

RESUMEN

Golimumab, a tumor necrosis factor antagonist, is an effective treatment for patients with moderate-to-severe ulcerative colitis (UC); however, more than 50% of initial responders lose their response to the drug within the first year of therapy. A gene expression signature identified in colon biopsies collected before treatment was associated with response to infliximab, and was subsequently refined to associate with mucosal healing in response to golimumab. We performed a phase 2a open-label study of 103 golimumab-treated patients with moderate-to-severe UC to test whether the baseline gene expression signature could be used to predict which patients would achieve mucosal healing, clinical response, and clinical remission at weeks 6 and 30 of treatment. The gene expression signature identified patients who went on to achieve mucosal healing at treatment week 6 with an area under the receiver operating characteristic curve (AUCROC) of 0.688 (P = .002) and at week 30 with an AUCROC of 0.671 (P = .006). The signature identified patients with mucosal healing with 87% sensitivity, but only 34% specificity, limiting its clinical utility. The baseline gene expression signature did not identify patients who went on to achieve clinical remission or clinical response with statistical significance. Further studies are needed to identify biomarkers that can be used to predict which patients with UC will respond to treatment with anti-tumor necrosis factor agents. ClinicalTrials.gov no: NCT01988961.


Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/genética , Colon/efectos de los fármacos , Fármacos Gastrointestinales/uso terapéutico , Perfilación de la Expresión Génica/métodos , Mucosa Intestinal/efectos de los fármacos , Transcriptoma , Antiinflamatorios/efectos adversos , Antiinflamatorios/farmacocinética , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Área Bajo la Curva , Toma de Decisiones Clínicas , Colitis Ulcerosa/sangre , Colitis Ulcerosa/diagnóstico , Colon/metabolismo , Colon/patología , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/farmacocinética , Marcadores Genéticos , Humanos , Mediadores de Inflamación/sangre , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Farmacogenética , Medicina de Precisión , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Inducción de Remisión , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Cicatrización de Heridas/efectos de los fármacos
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