Association of TNF and FcγRΙΙΙA gene polymorphisms with differential response to infliximab in a Greek cohort of Crohn's disease patients.

BACKGROUND AND AIM: Infliximab (IFX) has revolutionized the treatment of patients with Crohn's disease (CD). However, a significant proportion of patients may fail to respond primarily or lose response over time. The genetic background of a particular individual may partially explain differences in responsiveness to anti-TNFα therapy. The aim of this study was to investigate whether polymorphisms in the promoter region of the TNF and FcγRΙΙΙA gene are associated with response to IFX in patients with CD. METHODS: We investigated the following single nucleotide polymorphisms in the promoter region of the TNF gene (-238 G/A, -308 G/A, and -857 C/T) and the -158 V/F polymorphism in the FcγRΙΙΙA gene in a cohort of 79 adults and 27 children, who were all Greek patients with CD. These polymorphisms were determined using PCR-RFLP or allele-specific PCR. RESULTS: Regarding the 106 patients included in the study, 68 (64.15%) were classified as complete and 25 (23.58%) as partial responders to IFX, while 13 (12.26%) patients were primary non responders. There were no significant differences in the frequencies of the various TNF and FcγRΙΙΙA genotypes among complete, partial responders or primary non responders. CONCLUSION: These results suggest that TNF and FcγRΙΙΙA genotypes did not affect the response to IFX in this cohort of Greek patients with CD.

Safety and efficacy of total-dose infusion of low molecular weight iron dextran for iron deficiency anemia in patients with inflammatory bowel disease.

BACKGROUND: Intravenous iron has been suggested as a safe and effective treatment of anemia complicating inflammatory bowel disease (IBD). Low molecular weight (LMW) iron dextran has the ability to administer the patient's total iron requirement in a single infusion. AIMS: The aim of this study was to assess the safety and efficacy of the total dose of LMW iron dextran infusion for the treatment of iron deficiency in IBD. METHODS: Fifty IBD patients (27 female, 35 Crohn's disease, 15 ulcerative colitis) were included in the study. Mean +/- standard deviation (SD) hemoglobin and ferritin levels before the infusion were 9.88 +/- 1.42 g/dl and 13.9 +/- 10.9 ng/ml, respectively. A 25-mg test dose was followed by infusion of the total dose of LMW iron dextran based on the iron deficit. Several clinical and laboratory parameters were measured before and on week 4 after infusion. RESULTS: Four patients (8%) developed adverse reactions during the test infusion and did not receive the total-dose infusion. Only one patient developed an allergic reaction during the total-dose infusion. In the remaining 45 patients, the mean +/- SD iron dose that was given was 1,075 +/- 269 mg. The mean +/- SD elevation of hematocrit and hemoglobin on week 4 was 4.9 +/- 1.9% and 1.7 +/- 0.8 g/dl, respectively. Hematopoietic response was observed in 23 of 45 patients (51.1%). CONCLUSION: Total parenteral iron replacement with LMW iron dextran is an easy, safe, and effective alternative method for treating iron deficiency anemia in IBD. Harmless adverse reactions may develop in a minority of patients.

A pilot study comparing hydrocortisone premedication to concomitant azathioprine treatment in preventing loss of response to infliximab.

OBJECTIVES: Antibodies to infliximab may lead to loss of response to infliximab (IFX) in Crohn's disease. Azathioprine (AZA) coadministration prevents the formation, whereas hydrocortisone (HC) premedication reduces the levels of antibodies to IFX. This pilot study aims at assessing the efficacy of these strategies to prevent loss of response to IFX. METHODS: Eligible patients had active steroid-dependent luminal Crohn's disease and received IFX (5 mg/kg at weeks 0, 2, and 6 for induction and then scheduled q8 week for remission maintenance). Patients were stratified in a 1 : 1 ratio to oral AZA (2-2.5 mg/kg/day, stratum A) or HC premedication (250 mg intravenously, stratum B). Stratum A included only patients naive to AZA; stratum B included both AZA naive and intolerant patients. Steroids were tapered within 6-8 weeks. Patients were followed up with monthly clinical assessments, laboratory tests, Crohn's Disease Activity Index calculations, adverse-events check up, and adherence to treatment. RESULTS: Overall, 23 patients received IFX/HC and 23 IFX/AZA. There were no differences at baseline in any patient-related or disease-related parameters. Seventeen (74%) patients on IFX/AZA completed the study; six patients were withdrawn for primary nonresponse (one patient), lost response to IFX (two patients), or AZA-related adverse events. Eighteen (78%) patients on IFX/HC completed the study; five patients were withdrawn for primary nonresponse (one patient), loss of response (two patients), or infusion reactions to IFX. No significant differences emerged between strata in clinical remission rates or lost response to IFX. CONCLUSION: This prospective 2-year pilot study has not confirmed superiority of any available strategy to maintain the efficacy of IFX.

Prevalence and axial length of hiatus hernia in patients, with nonerosive reflux disease: a prospective study.

BACKGROUND AND AIMS: The relationship between hiatus hernia and reflux esophagitis is well established. However, there are conflicting reports regarding its effect on the development of nonerosive reflux disease (NERD). Our aim was to investigate the prevalence and axial length of hiatus hernia in patients with NERD, compared with patients with reflux esophagitis, Barrett esophagus, and controls. METHODS: Axial hernia length of the diaphragmatic hiatus was measured prospectively at endoscopy in controls and patients with typical reflux symptoms occurring at least weekly during the last month relieved by antacids. RESULTS: A final diagnosis of hiatus hernia was established in 21.2% of 249 controls, 60.4% of 346 patients with NERD, 78.1% of 251 patients with reflux esophagitis, and 88.2% of 17 patients with Barrett esophagus. Patients aged >59 years were most likely to have a hiatus hernia. There was an increased prevalence in patients with NERD as compared with controls (P<0.0001), and decreased prevalence as compared with those with reflux esophagitis and Barrett esophagus (P<0.0001 and 0.02, respectively). Axial length of hiatus hernia >3 cm was found more frequently in patients with reflux esophagitis and Barrett esophagus as compared with patients with NERD (P<0.0001 and 0.0052, respectively). There was no statistical significant difference between controls and patients with NERD regarding the prevalence of hiatus hernia >3 cm (P=0.0904). CONCLUSIONS: A small (<3 cm) hiatus hernia may contribute to the development of NERD, whereas an axial length >3 cm is associated with a more severe disease.