Evelien Bultman

Barrett's oesophagus is characterized by a predominantly humoral inflammatory response

Barretts oesophagus (BO) is thought to be an intermediate step in the progression from reflux oesophagitis (RO) to oesophageal adenocarcinoma. Premalignant conditions that develop in the presence of chronic inflammation are often associated with the development of a more pronounced humoral immune response during progression of the disease. The aim of this study was to determine whether BO is also associated with a more pronounced humoral immune response when compared to RO. Immunohistochemical studies were performed to quantify the mean numbers of Th2 effector cells (plasma cells and mast cells) and Th1 effector cells (macrophages and CD8+ T cells) to detect the antibody classes produced by plasma cells (IgA, IgG, IgM or IgE) and to determine the presence of isolated lymph follicles [segregated B and T cell areas, follicular dendritic cells (CD23) and expression of CXCL13] in 124 oesophageal biopsies from 20 patients with BO and 20 patients with RO. The proportion of Th2 effector cells was higher in BO than in RO, mainly due to higher numbers of plasma cells and mast cells in BO (p < 0.001). Most plasma cells in BO and RO expressed IgG, but several IgE+ plasma cells were detected in BO: these were rare in RO. In line with this, isolated lymph follicles were observed in 4/20 (20%) patients with BO, but not in RO. We therefore conclude that the inflammatory response is skewed towards a more pronounced humoral immune response when RO progresses to BO. It may be that this shift, which is similar to that found in other chronic inflammatory conditions, contributes to an increased cancer risk in BO. Copyright

Predictors of dose escalation of adalimumab in a prospective cohort of Crohn's disease patients.

Background  Adalimumab is effective for the induction and maintenance of remission in Crohn’s disease (CD)‐patients.

Systematic review: steroid withdrawal in anti-TNF-treated patients with inflammatory bowel disease

Aliment Pharmacol Ther 2010; 32: 313–323

Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease

AIM To analyze sex differences in adverse drug reactions (ADR) to the immune suppressive medication in inflammatory bowel disease (IBD) patients. METHODS All IBD patients attending the IBD outpatient clinic of a referral hospital were identified through the electronic diagnosis registration system. The electronic medical records of IBD patients were reviewed and the files of those patients who have used immune suppressive therapy for IBD, i.e., thiopurines, methotrexate, cyclosporine, tacrolimus and anti-tumor necrosis factor agents (anti-TNF); infliximab (IFX), adalimumab (ADA) and/or certolizumab, were further analyzed. The reported ADR to immune suppressive drugs were noted. The general definition of ADR used in clinical practice comprised the occurrence of the ADR in the temporal relationship with its disappearance upon discontinuation of the medication. Patients for whom the required information on drug use and ADR was not available in the electronic medical record and patients with only one registered contact and no further follow-up at the outpatient clinic were excluded. The difference in the incidence and type of ADR between male and female IBD patients were analyzed statistically by χ(2) test. RESULTS In total, 1009 IBD patients were identified in the electronic diagnosis registration system. Out of these 1009 patients, 843 patients were eligible for further analysis. There were 386 males (46%), mean age 42 years (range: 16-87 years) with a mean duration of the disease of 14 years (range: 0-54 years); 578 patients with Crohns disease, 244 with ulcerative colitis and 21 with unclassified colitis. Seventy percent (586 pts) of patients used any kind of immune suppressive agents at a certain point of the disease course, the majority of the patients (546 pts, 65%) used thiopurines, 176 pts (21%) methotrexate, 46 pts (5%) cyclosporine and one patient tacrolimus. One third (240 pts, 28%) of patients were treated with anti-TNF, the majority of patients (227 pts, 27%) used IFX, 99 (12%) used ADA and five patients certolizumab. There were no differences between male and female patients in the use of immune suppressive agents. With regards to ADR, no differences between males and females were observed in the incidence of ADR to thiopurines, methotrexate and cyclosporine. Among 77 pts who developed ADR to one or more anti-TNF agents, significantly more females (54 pts, 39% of all anti-TNF treated women) than males (23 pts, 23% of all anti-TNF treated men) experienced ADR to an anti-TNF agent [P = 0.011; odds ratio (OR) 2.2, 95%CI 1.2-3.8]. The most frequent ADR to both anti-TNF agents, IFX and ADA, were allergic reactions (15% of all IFX users and 7% of all patients treated with ADA) and for both agents a significantly higher rate of allergic reactions in females compared with males was observed. As a result of ADR, 36 patients (15% of all patients using anti-TNF) stopped the treatment, with significantly higher stopping rate among females (27 females, 19% vs 9 males, 9%, P = 0.024). CONCLUSION Treatment with anti-TNF antibodies is accompanied by sexual dimorphic profile of ADR with female patients being more at risk for allergic reactions and subsequent discontinuation of the treatment.

P598 Adalimumab trough levels in a prospective cohort of Crohn's disease patients

managements were similar in all treatment groups. The children remained in the study until recovery from diarrhea but up to a maximum of 7 days. Stool weight and duration of diarrhea were the primary outcomes. Results: Baseline clinical characteristics of the children are comparable between the groups. There is a trend in stool weight reduction in the groups receiving L-isoleucine and L-arginine alone or in combination and the reduction is significant on day 1(data presented in Table ). Also similar trend of reduction of duration of diarrhea was observed in those groups although the reduction was not statistically significant (combined analysis). Conclusion: L-isoleucine and L-arginine supplemented food help recovery by reducing stool weight and duration of diarrhea in children with acute diarrhea. Further large study is warranted to establish the beneficial effect of L-isoleucine and L-arginine supplemented food. Comparison of outcome variable (Data are Median, range

Commentary: BMI and the need for adalimumab dose escalation in Crohn's disease – authors’ reply

We would like to clarify some of the questions raised by Van Assche et al. in response to our recently published article. We believe indeed that a real pharmacokinetic analysis is valuable to exclude confounders and is warranted in further research on this topic. However, our study was directed towards predictive factors before the start of adalimumab, and therefore anti-TNF levels were not included. Furthermore, we would like to note that patients stopped due to adverse events (21, 29%), loss of response (37, 51%), patients’ preferences (13, 18%), or unknown reasons (2, 3%), and no primary nonresponders were included. Of the patients who had dose escalation and were previously exposed to infliximab, 12 regained response 3 months after dose escalation, follow-up data were not available for three patients and in 12 patients, dose escalation was not effective. We agree with Van Assche et al. that further research is warranted.