K O Arseneau 1, F Cominelli, Dig Liver Dis. 2009 Aug;41(8):551-2.
Tag: digestive
Scientific corner
Leukocytapheresis in ulcerative colitis: a possible alternative to biological therapy?
In summary, selective adsorption of granulocytes and monocytes from the peripheral blood
of patients with active ulcerative colitis using the extracorporal Adacolumn GMA appears to
be an extremely safe treatment modality. Although conflicting results have been reported
regarding the efficacy of Adacolumn GMA, this study by Hibi et al. adds to the existing
literature by providing data from the largest population of ulcerative colitis patients yet to be
studied. If the observed treatment effect of 77.7% is representative of the true response rate,
Adacolumn GMA would be a safe alternative to biological therapies for patients with
refractory ulcerative colitis. In addition, granulocyte fractions could be used to help identify
patients who are most likely to benefit from this procedure
Scientific corner
Decreased numbers of FoxP3-positive and TLR-2-positive cells in intestinal mucosa are associated with improvement in patients with active inflammatory bowel disease following selective leukocyte apheresis
Vladislaw Muratov 1, Ann-Kristin Ulfgren, Marianne Engström, Kerstin Elvin, Ola Winqvist, Robert Löfberg, Joachim Lundahl, J Gastroenterol. 2008;43(4):277-82.
Downregulation of FoxP3 and TLR-2 cells in the colorectal mucosa mirrors both short-and long-term improvement in patients with active IBD responding to GCAP. This observation suggests a potential role of these cells in the pathogenesis of IBD and the induction of immunological tolerance in the mucosa.
Scientific corner
Cytapheresis in Inflammatory Bowel Diseases: Current Evidence and Perspectives
Silvio Danese 1, Erika Angelucci, Tommaso Stefanelli, Paolo Omodei, Carmelo Luigiano, Silvia Finazzi, Nico Pagano, Alessandro Repici, Maurizio Vecchi, Alberto Malesci, Digestion. 2008;77(2):96-107.
Ulcerative colitis and Crohn’s disease are inflammatory bowel diseases with a chronic relapsing course. Management of both conditions is far from being fully satisfactory. For this reason in the last decade a large number of biological therapies, targeting cytokines involved in intestinal inflammation, has been developed with various results in terms of efficacy, safety and costs. Activated granulocytes and monocytes represent the major sources of pro-inflammatory cytokines in the intestinal mucosa, playing a pivotal role in inducing and maintaining intestinal inflammation. Leukocytapheresis using an adsorptive carrier-based system (Adacolumn) or a removal filter column (Cellsorba) has been proposed as a feasible, safe and effective therapy for ulcerative colitis and Crohn’s disease. The objective of this paper is to provide an overview on the current knowledge about mechanisms of action, available clinical data and the possible future perspectives for the use of Adacolumn and Cellsorba in the management of inflammatory bowel diseases.
Scientific corner
Leucocytapheresis for inflammatory bowel disease in the era of biologic therapy
Hiroyuki Hanai 1 , Eur J Gastroenterol Hepatol. 2008 Jul;20(7):596-600.
The development of biologicals such as infliximab to intercept TNF-alpha validates the current perception that certain cytokines are major factors in the immunopathogenesis of inflammatory bowel disease (IBD), ulcerative colitis and Crohn’s disease. Furthermore, major sources of inflammatory cytokines include activated peripheral granulocytes and monocytes (GM), which in patients with IBD are elevated with increased survival time and are found in vast numbers within the inflamed intestinal mucosa. Hence, elevated GM should be appropriate targets of therapy in IBD. Accordingly, in recent years technologies such as the Adacolumn have been developed for selective depletion of elevated GM by extracorporeal adsorption (GMA). Published data show that GMA in patients with steroid-dependent or steroid-refractory IBD is associated with striking efficacy and tapering or discontinuation of steroids, whereas in steroid-naïve patients GMA spared patients from steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse significantly suppressed relapse, thus sparing the patients from the morbidity associated with active IBD. First ulcerative colitis episode, steroid naivety and short disease duration seem to be good predictors of response to GMA and on the basis of our experience, GMA seems to have an excellent safety profile.
Scientific corner
Granulocytapheresis versus methylprednisolone in patients with acute ulcerative colitis: 12-month follow up
Giampaolo Bresci 1, Giuseppe Parisi, Alessandro Mazzoni, Fabrizio Scatena, Alfonso Capria, J Gastroenterol Hepatol. 2008 Nov;23(11):1678-82.
GCAP results were superior to MP for the treatment of UC, even though no statistically significant difference was observed. Side-effects in the GCAP group were significantly lower than in the MP group. This new therapeutic approach seems able to maintain the condition of remission for a longer time after a flare. In fact, the patients who had obtained a remission after a course of CGAP showed fewer relapses during the follow up compared to the patients treated with MP.
Scientific corner
Selective white cell apheresis reduces relapse rates in patients with IBD at significant risk of clinical relapse
Laurence Maiden 1, Ken Takeuchi, Rosie Baur, Ingi Bjarnason, John O’Donohue, Ian Forgacs, Guy Chung-Faye, Jeremy Sanderson, Ingvar Bjarnason, Inflamm Bowel Dis. 2008 Oct;14(10):1413-8.
This study represents a new approach to the treatment of IBD by targeting a group of asymptomatic patients for treatment who are at significant risk of relapse based on high fecal calprotectin concentrations. Selective leukocytapheresis significantly reduced the number of, and increased the time to, clinical relapse in these patients without serious side effects.
Scientific corner
Granulocytapheresis in the treatment of patients with active ulcerative colitis
Giampaolo Bresci 1 , Expert Rev Gastroenterol Hepatol. 2008 Oct;2(5):639-43.
In recent years, considering the role of inflammatory processes and the involvement of the immune system in ulcerative colitis, granulocytapheresis, a technique for removing circulating leukocytes and preventing their migration into the intestinal mucosa, has been proposed for the treatment of acute ulcerative colitis. Initially introduced for the treatment of patients who did not respond to conventional therapy only, this new therapy may become a useful and safe method to induce clinical remission in patients with acute disease. This article will review the clinical applications and issues concerning the use of granulocytapheresis in ulcerative colitis.
Scientific corner
Regulatory T cells in patients with inflammatory bowel diseases treated with adacolumn granulocytapheresis
Emilio Cuadrado 1, Marta Alonso, Maria-Dolores de Juan, Pilar Echaniz, Juan-Ignacio Arenas, World J Gastroenterol. 2008 Mar 14;14(10):1521-7.
The clinical efficacy of GMA on IBD and related extra intestinal manifestations was associated with an expansion of circulating CD4+ CD25+ Tregs and higher expression of FoxP3 in CD4+ T cells. Accordingly, an elevated CD4+ CD25+ FoxP3 may be a valuable index of remission in patients with IBD and other chronic relapsing-remitting inflammatory conditions during treatment with GMA.
Scientific corner
The logics of leukocytapheresis as a natural biological therapy for inflammatory bowel disease
Takanori Kanai 1, Toshifumi Hibi, Mamoru Watanabe, Expert Opin Biol Ther. 2006 May;6(5):453-66.
Ulcerative colitis (UC) and Crohn’s disease (CD) are debilitating idiopathic inflammatory bowel diseases (IBDs) with symptoms that impair ability to function and quality of life. The aetiology of IBD is inadequately understood and, therefore, drug therapy has been empirical instead of based on sound understanding of the disease mechanisms. This has been a major factor for poor drug efficacy and treatment-related side effects that often add to disease complications. The development of biologicals, notably infliximab, to block TNF-alpha reflects some progress, but there is major concern about their side effects and lack of long-term safety and efficacy profiles. However, IBD by its very nature is exacerbated and perpetuated by inflammatory cytokines, including TNF-alpha, IL-6 and IL-12, for which activated peripheral blood lymphocytes, monocytes/macrophages and granulocytes are major sources. Hence, activated leukocytes should be appropriate targets of therapy. At present, three strategies are available for removing excess and activated leukocytes by leukocytapheresis: centrifugation, Adacolumn and Cellsorba. Centrifugation can deplete lymphocytes or total leukocytes, whereas Adacolumn selectively adsorbs granulocytes and monocytes together with a smaller fraction of lymphocytes (FcgammaR- and complement receptor-bearing leukocytes), and Cellsorba non-selectively removes all three major leukocyte populations. Efficacy has ranged from ‘none’ to an impressive 93% together with excellent safety profiles and downmodulation of inflammation factors. Furthermore, leukocytapheresis has shown strong drug-sparing effects and reduced the number of patients requiring colectomy or exposure to unsafe immunosuppressants, such as cyclosporin A. Leukocytapheresis removes from the body cells that contribute to IBD and, therefore, unlike drugs, it is not expected to induce dependency or refractoriness.
Scientific corner
Selective leukocyte apheresis for the treatment of inflammatory bowel disease
Maria T Abreu 1, Scott Plevy, Bruce E Sands, Robert Weinstein, J Clin Gastroenterol. Nov-Dec 2007;41(10):874-88.
The etiology of inflammatory bowel disease (IBD) is not completely understood, thus current therapies have been empirical and directed at treating symptoms rather than addressing the cause. In IBD, the overexpression of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, leads to a persistent intestinal inflammatory response that damages the intestinal mucosa. Recent advances in pharmacologic therapies that target specific cytokines, chemokines, and adhesion molecules have proved successful in alleviating symptoms for some patients. There are 2 selective adsorption apheresis devices that remove leukocytes from whole blood, which are currently available in Japan and Europe-the Cellsorba leukocytapheresis column and the Adacolumn adsorptive extracorporeal granulocyte/monocyte apheresis device. The purported mechanisms of action of these devices have been extensively reviewed and are believed to exert an immunomodulatory and/or anti-inflammatory effect on patients with systemic inflammatory disease.The clinical trials presented here indicate that selective leukocyte apheresis effectively removes activated granulocytes and monocytes/macrophages from peripheral blood while maintaining an excellent safety profile. Despite these findings, large controlled trials of selective leukocyte apheresis in the treatment of IBD are needed to determine the true efficacy of this approach.
chemokines / Crohn's disease / cytokines / digestive / gma / IBD / immunomodulation / Leukocytapheresis / Safety / ulcerative colitis /
Contact UsFor more information
Contact Us