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Clin Transl Gastroenterol ; 11(9): e00217, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-33094957

RESUMEN

INTRODUCTION: Anti-tumor necrosis factor (TNF) therapy is effective in inducing remission in Crohn's disease in 60% of patients. No serological biomarkers are available, which can predict response to anti-TNF. We aimed to investigate serological markers of collagen turnover reflecting tissue inflammation as predictors of response to anti-TNF. METHODS: In 2 retrospective observational cohorts, markers for matrix metalloproteinase-degraded type III and IV collagens (C3M and C4M, respectively) and for formation of type III and IV collagens (PRO-C3 and PRO-C4, respectively) were measured in serum and compared with standard C-reactive protein in patients with active Crohn's disease who started infliximab (IFX, n = 21) or adalimumab (ADA, n = 21). Disease activity was classified by the Harvey-Bradshaw index (active disease ≥5); response was defined as clinical remission. RESULTS: Seventeen patients (81%) treated with IFX were in remission at week 14; 15 patients (71%) treated with ADA were in remission at week 8. Serum C4M at baseline was increased in nonresponders compared with responders (IFX: 35.0 ± 2.4 vs 23.2 ± 2.6, P = 0.04, ADA: 53.0 ± 3.2 vs 34.1 ± 2.8, P = 0.006). C4M levels at baseline predicted response in both cohorts (IFX: odds ratio 39 [95% confidence interval, 2.4-523.9] P = 0.02, cutoff 35.2 nmol/L; ADA: odds ratio 26 [95% confidence interval, 1.8-332.5], P = 0.01, cutoff 46.9 nmol/L). C-reactive protein was not able to predict response to anti-TNF. DISCUSSION: Response to anti-TNF therapy within the first 14 weeks of treatment can be predicted based on baseline levels of basement membrane marker C4M. This marker could be used as biomarker for response to anti-TNF and could aid in early therapy decision making. Validation in larger well-defined cohorts is needed.


Asunto(s)
Antiinflamatorios/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/farmacología , Adalimumab/uso terapéutico , Adulto , Anciano , Antiinflamatorios/farmacología , Biomarcadores/sangre , Colágeno Tipo IV/sangre , Colágeno Tipo IV/metabolismo , Enfermedad de Crohn/sangre , Enfermedad de Crohn/inmunología , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/inmunología , Matriz Extracelular/patología , Femenino , Humanos , Infliximab/farmacología , Infliximab/uso terapéutico , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Masculino , Metaloproteasas/metabolismo , Persona de Mediana Edad , Proyectos Piloto , Prueba de Estudio Conceptual , Inducción de Remisión/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
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