reported for 4% of placebo and 11.6% of ISIS 2302 subjects (p -0.03); this did not increase (11.1%) for the high AUC subgroup.Allergic manifestations were felt to be treatment related in 2% and led to study withdrawal for 1.5% of ISIS 2302 subjects.The maximum postinfusion aPTF averaged 42 seconds (individual peak 47.4) in the high AUC subgroup, a class effect of phosphorothiorate oligonucleotides, without reported bleeding.This study supports a future evaluation of ISIS 2302 to block ICAM-1 expression at higher dose levels in Crohn s disease.

Background: Histamine exerts a broad range of immediate proinflammatory effects in the body.There is growing evidence that mast cells, histamine and other immunomediators associated with a TH2-response may playa role in the pathogenesis of IBD.This study was designed to investigate whether loratadine (10 mg/die), a non-sedating HI-receptor antagonist, may have a positive effect on the course of Ue.Methods: 16 UC patients (CAl> 4) were randomly assigned to receive either prednisolone/5ASAJloratadine or prednisolone/5ASNplacebo over 6 months.In both groups, a standardized conventional steroid tapering regime (starting with 60 mg/day) over 12-16 weeks was used and the dose of 5ASA (3g/day) kept stable during the study period.Clinical activity, cumulative steroid dose, CRP, urine methylhistamine and orosomucoid were recorded at I, 2, 4 and 6 months.Results: After month 2, clinical activity was found to be slightly lower in the loratadine-treated group than in the placebo group.The most impressive effect of loratadine was seen at the cumulative steroid dose.After 2, 4 and 6 months loratadine-treated patients had clearly lower mean cumulative prednisolone doses (23.2, 26.0 and 28.5mg/kg) than untreated patients (24.9, 33.7 and 40.8 mg/kg).In addition, at the same time points C-reactive protein levels were also lower in treated (0.3, 0.37 and 0.83 mg/dl) than untreated UC-patients (0.78, 1.09 and 1.67mg/dl), whereas urinary methylhistamine and serum orosomucoid levels did not differ from another.No significant side effects were recorded with the use of loratadine.Conclusion: This pilot study shows that low-dose HIreceptor antagonist treatment as adjunctive therapy in UC exhibits a clear steroid-sparing effect.In comparison with steroids and 5ASA, HI-receptor blockage appears to mediate additional anti-inflammatory effects in UC.The beneficial effect of 10 mg loratadine/day in UC treated with conventional drugs needs one to two months treatment and may be further augmented in future trials, when using higher daily antihistamine doses.