Infliximab Treatment Response in Refractory IBD

Sixty-one patients with active IBD (24 UC, 19 CDc and 18 CDi), refractory to corticosteroids and/or immunosuppression, and a control group of 12 individuals (6 colon and 6 ileum) who underwent endoscopy for screening for polyps were studied. The patients underwent endoscopy with biopsies from diseased bowel (colon for UC and CDc, and ileum for CDi) within a week prior to the first intravenous infusion of 5 mg infliximab per kg body weight. They underwent a second endoscopy with biopsies 4 weeks after the first infliximab infusion in case of a single infusion and at 6 weeks if they received a loading dose of infliximab at weeks 0, 2 and 6. The biopsies were taken at sites of active inflammation but at a distance of ulcerations. In the case of healing at control endoscopy, the biopsies were obtained in the areas where lesions were present before therapy. The endoscopist was not blinded to treatment. Half of the biopsies were immediately snap-frozen in liquid nitrogen and stored at −80°C until RNA isolation and/or immunohistochemistry, except for the biopsies from 1 CDc patient after infliximab treatment which were of poor technical quality. The residual biopsies were fixed in Carnoy's fixative for up to 5 hours and then dehydrated, cleared and paraffin-embedded for histologic examination. The features of chronic intestinal inflammation were scored in haematoxylin-eosin stained slides from the paraffin blocks of each patient using a previously reported scoring system for UC [26] (link) and for CD [8] (link). The pathologists who scored the biopsies (KG and GDH) were blinded to treatment.
The response to infliximab was assessed 4 to 6 weeks after the first infliximab treatment. For UC and CDc, the response to infliximab was defined as a complete mucosal healing with a decrease of at least 3 points on the histological score for CDc [8] (link) and as a decrease to a Mayo endoscopic subscore of 0 or 1 with a decrease to grade 0 or 1 on the histological score for UC [26] (link), [27] (link). Patients who did not achieve this healing were considered non-responders although some of them presented endoscopic and/or histologic improvement. Of the 43 colonic IBD (IBDc) patients, we identified 20 responders (8 UC and 12 CDc) and 23 non-responders (16 UC and 7 CDc). If the same response criteria of CDc were used for CDi, only one patient showed complete endoscopic and histologic healing. Therefore, we had to use less strict response criteria for CDi. Patients with a clear improvement of the ulcerations and a decrease on the histological score [8] (link) were considered responders. Of the 18 CDi patients, we identified 8 (partial) responders and 10 non-responders.
The baseline characteristics of the patients are summarized in table 1.