Ulcerative Colitis: Sieper J

Braun J, Baraliakos X, Listing J, Davis J, van der Heijde D, Haibel H, Rudwaleit M, Sieper J. · Ruhr-University Bochum, Germany. · Arthritis Rheum. · Pubmed #17471540 links to  free full text

Abstract: OBJECTIVE: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are clinically and pathologically linked. Anti-tumor necrosis factor (anti-TNF) agents are efficacious in treating AS, but not all are equally effective in treating IBD (Crohn's disease [CD] and ulcerative colitis [UC]). The purpose our study was to analyze the incidence of flares and new onset of IBD in patients with AS treated with anti-TNF agents. METHODS: Data from 9 trials, 7 placebo-controlled trials and 2 open studies, were analyzed. RESULTS: Data were available on 419 AS patients exposed to etanercept (625 patient-years), 366 exposed to infliximab (618 patient-years), 295 exposed to adalimumab (132 patient-years), and 434 placebo patients (150 patient-years). A history of IBD was reported in 76 of 1,130 patients (6.7%). There were 2 reports of IBD while receiving placebo (1.3 per 100 patient-years), 1 while receiving infliximab, and 3 while receiving adalimumab. Among the 14 IBD cases receiving etanercept (2.2 per 100 patient-years) there were 8 CD and 6 UC cases, significantly different from infliximab (P = 0.01) but not from placebo. Patients with a history of IBD had an IBD flare odds ratio of 18.0 (95% confidence interval [95% CI] 2-154) while taking etanercept and 4.2 (95% CI 0.4-44) while taking adalimumab, in comparison with infliximab. The incidence rates of new onset of IBD showed no significant difference between etanercept (0.8 per 100 patient-years) and placebo (0.5 per 100 patient-years). CONCLUSION: New onset and flare of IBD are infrequent events in AS patients receiving anti-TNF therapy. Infliximab (but not etanercept) largely prevents IBD activity. More data are required for adalimumab. The incidence of new onset of IBD was statistically not different from placebo for all anti-TNF agents.

Niesner U, Albrecht I, Janke M, Doebis C, Loddenkemper C, Lexberg MH, Eulenburg K, Kreher S, Koeck J, Baumgrass R, Bonhagen K, Kamradt T, Enghard P, Humrich JY, Rutz S, Schulze-Topphoff U, Aktas O, Bartfeld S, Radbruch H, Hegazy AN, Löhning M, Baumgart DC, Duchmann R, Rudwaleit M, Häupl T, Gitelman I, Krenn V, Gruen J, Sieper J, Zeitz M, Wiedenmann B, Zipp F, Hamann A, Janitz M, Scheffold A, Burmester GR, Chang HD, Radbruch A. · German Rheumatism Research Center Berlin, 10117 Berlin, Germany. · J Exp Med. · Pubmed #18663125 links to  free full text

Abstract: The basic helix-loop-helix transcriptional repressor twist1, as an antagonist of nuclear factor kappaB (NF-kappaB)-dependent cytokine expression, is involved in the regulation of inflammation-induced immunopathology. We show that twist1 is expressed by activated T helper (Th) 1 effector memory (EM) cells. Induction of twist1 in Th cells depended on NF-kappaB, nuclear factor of activated T cells (NFAT), and interleukin (IL)-12 signaling via signal transducer and activator of transcription (STAT) 4. Expression of twist1 was transient after T cell receptor engagement, and increased upon repeated stimulation of Th1 cells. Imprinting for enhanced twist1 expression was characteristic of repeatedly restimulated EM Th cells, and thus of the pathogenic memory Th cells characteristic of chronic inflammation. Th lymphocytes from the inflamed joint or gut tissue of patients with rheumatic diseases, Crohn's disease or ulcerative colitis expressed high levels of twist1. Expression of twist1 in Th1 lymphocytes limited the expression of the cytokines interferon-gamma, IL-2, and tumor necrosis factor-alpha, and ameliorated Th1-mediated immunopathology in delayed-type hypersensitivity and antigen-induced arthritis.