TY - JOUR
T1 - Intestinal fibrosis is associated with lack of response to Infliximab therapy in Crohn's disease
AU - de Bruyn, Jessica R.
AU - Becker, Marte A.
AU - Steenkamer, Jessica
AU - Wildenberg, Manon E.
AU - Meijer, Sybren L.
AU - Buskens, Christianne J.
AU - Bemelman, Willem A.
AU - Löwenberg, Mark
AU - Ponsioen, Cyriel Y.
AU - van den Brink, Gijs R.
AU - D'Haens, Geert R.
PY - 2018
Y1 - 2018
N2 - Overt fibrostenotic disease is a relative contraindication for anti-TNF therapy in Crohn's disease. We hypothesized that subclinical fibrosis may also contribute to an incomplete response to anti-TNF therapy before the onset of symptomatic stenosis. In a previous trial, patients with ileocecal Crohn's disease were randomized to either immediate ileocecal resection or medical treatment with Infliximab. In case of insufficient response to Infliximab, the latter underwent secondary ileocecal resection. We compared specimens from those patients undergoing immediate resection (Infliximab naïve, n = 20) to those who failed Infliximab therapy (n = 20). Infliximab naïve and Infliximab failure patients had similar severity of inflammation when assessed by CRP levels (median 14 vs 9 mg/L) and histology (Geboes-D'Haens-score, median 10 vs 11 points). On immunohistochemistry, collagen-III and fibronectin depositions were increased in patients previously exposed to Infliximab compared to patients naïve to Infliximab. On mRNA level, procollagen peptidase showed significantly more mucosal mRNA expression in Crohn's disease patients who failed Infliximab. Infliximab responders showed no increase of this marker after 4 weeks of successful Infliximab treatment. Failure to Infliximab therapy is associated with subclinical fibrosis in Crohn's disease
AB - Overt fibrostenotic disease is a relative contraindication for anti-TNF therapy in Crohn's disease. We hypothesized that subclinical fibrosis may also contribute to an incomplete response to anti-TNF therapy before the onset of symptomatic stenosis. In a previous trial, patients with ileocecal Crohn's disease were randomized to either immediate ileocecal resection or medical treatment with Infliximab. In case of insufficient response to Infliximab, the latter underwent secondary ileocecal resection. We compared specimens from those patients undergoing immediate resection (Infliximab naïve, n = 20) to those who failed Infliximab therapy (n = 20). Infliximab naïve and Infliximab failure patients had similar severity of inflammation when assessed by CRP levels (median 14 vs 9 mg/L) and histology (Geboes-D'Haens-score, median 10 vs 11 points). On immunohistochemistry, collagen-III and fibronectin depositions were increased in patients previously exposed to Infliximab compared to patients naïve to Infliximab. On mRNA level, procollagen peptidase showed significantly more mucosal mRNA expression in Crohn's disease patients who failed Infliximab. Infliximab responders showed no increase of this marker after 4 weeks of successful Infliximab treatment. Failure to Infliximab therapy is associated with subclinical fibrosis in Crohn's disease
U2 - https://doi.org/10.1371/journal.pone.0190999
DO - https://doi.org/10.1371/journal.pone.0190999
M3 - Article
C2 - 29364909
SN - 1932-6203
VL - 13
SP - e0190999
JO - PLOS ONE
JF - PLOS ONE
IS - 1
ER -