19 research outputs found
Rate and predictors of mucosal healing in patients with inflammatory bowel disease treated with anti-TNF-alpha antibodies.
No full textMucosal healing (MH) is an important treatment goal in patients with inflammatory bowel disease (IBD), but factors predicting MH under medical therapy are largely unknown. In this study, we aimed to characterize predictive factors for MH in anti-TNF-alpha antibody-treated IBD patients.We retrospectively analyzed 248 IBD patients (61.3% CD, 38.7% UC) treated with anti-TNF-alpha antibodies (infliximab and/or adalimumab) for MH, defined as macroscopic absence of inflammatory lesions (Mayo endoscopy score 0 or SES-CD score 0) in colonoscopies which were analyzed before and after initiation of an anti-TNF-alpha antibody treatment.In patients treated with only one anti-TNF-alpha antibody ("TNF1 group", n = 202), 56 patients (27.7%) achieved complete MH at follow-up colonoscopy (median overall follow-up time: 63 months). In a second cohort (n = 46), which comprised patients who were consecutively treated with two anti-TNF-alpha antibodies ("TNF2 group"), 13 patients (28.3%) achieved complete MH (median overall follow-up time: 64.5 months). Compared to patients without MH, CRP values at follow-up colonoscopy were significantly lower in patients with MH (TNF1 group: p = 8.35×10-5; TNF2 group: p = 0.002). Multivariate analyses confirmed CRP at follow-up colonoscopy as predictor for MH in the TNF1 group (p = 0.012). Overall need for surgery was lower in patients with MH (TNF1 group: p = 0.01; TNF2 group: p = 0.03).We identified low serum CRP level at follow-up colonoscopy as predictor for MH, while MH was an excellent negative predictor for the need for surgery
Multivariate analysis for outcome MH in the TNF2 group (n = 46).
No full text<p>Multivariate analysis for outcome MH in the TNF2 group (n = 46).</p
Demographic and clinical characteristics of the study cohorts (n = 248).
No full text<p>Demographic and clinical characteristics of the study cohorts (n = 248).</p
Demographic and clinical characteristics of the TNF2 group (n = 46) regarding MH.
No full text<p>Demographic and clinical characteristics of the TNF2 group (n = 46) regarding MH.</p
CRP values at follow-up colonoscopy (TNF1 group).
No full text<p>At follow-up colonoscopy, CRP values were significantly lower in patients with MH compared to patients without MH (*p = 8.34E-05).</p
Multivariate analysis for outcome MH in the TNF1 group (n = 202).
No full text<p>Multivariate analysis for outcome MH in the TNF1 group (n = 202).</p
Rates of mucosal healing in both groups.
No full text<p>In the TNF1 group, 146 patients (72.3%) had no MH, while 56 patients (27.7%) had MH. In the TNF2 group, 13 patients (28.6%) patients had MH, while 33 patients (71.4%) had no MH at follow-up colonoscopy.</p
Head-to-head study of oxelumab and adalimumab in a mouse model of ulcerative colitis based on NOD/Scid IL2Rγnull mice reconstituted with human peripheral blood mononuclear cells
No full textThis study's aim was to demonstrate that the combination of patient immune profiling and testing in a humanized mouse model of ulcerative colitis (UC) might lead to patient stratification for treatment with oxelumab. First, immunological profiles of UC patients and non-UC donors were analyzed for CD4+ T cells expressing OX40 (CD134; also known as TNFRSF4) and CD14+ monocytes expressing OX40L (CD252; also known as TNFSF4) by flow cytometric analysis. A significant difference was observed between the groups for CD14+ OX40L+ (UC: n=11, 85.44±21.17, mean±s.d.; non-UC: n=5, 30.7±34.92; P=0.02), whereas no significant difference was detected for CD4+ OX40+. CD14+ OX40L+ monocytes were correlated significantly with T helper 1 and 2 cells. Second, NOD/Scid IL2Rγ null mice were reconstituted with peripheral blood mononuclear cells from UC donors exhibiting elevated levels of OX40L, and the efficacy of oxelumab was compared with that of adalimumab. The clinical, colon and histological scores and the serum concentrations of IL-6, IL-1β and glutamic acid were assessed. Treatment with oxelumab or adalimumab resulted in significantly reduced clinical, colon and histological scores, reduced serum concentrations of IL-6 and reduced frequencies of splenic human effector memory T cells and switched B cells. Comparison of the efficacy of adalimumab and oxelumab by orthogonal partial least squares discrimination analysis revealed that oxelumab was slightly superior to adalimumab; however, elevated serum concentrations of glutamic acid suggested ongoing inflammation. These results suggest that oxelumab addresses the pro-inflammatory arm of inflammation while promoting the remodeling arm and that patients exhibiting elevated levels of OX40L might benefit from treatment with oxelumab
Kaplan-Mayer estimate for surgery-free time intervals in the TNF2 group over the follow-up time.
No full text<p>During the follow-up time, no patient with MH underwent surgery as compared to 10 patients without MH (logrank p = 0.03).</p
Demographic and clinical characteristics of the TNF1 group (n = 202) regarding MH.
No full text<p>Demographic and clinical characteristics of the TNF1 group (n = 202) regarding MH.</p
