Takayuki Matsumoto 1, Ken Fukunaga, Koji Kamikozuru, Katsutoshi Tozawa, Yoko Yokoyama, Takeshi Kusaka, Kunio Onishi, Hiroto Miwa, Shiro Nakamura, Transfus Med Hemother. 2008;35(1):18-23.
Tag: Crohn's disease
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Cytapheresis as a Non-Pharmacological Therapy for Inflammatory Bowel Disease.
Although inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic recurrent disease with unknown etiology. Recent immunological studies suggest close relation to autoimmune status featured by antibodies against colonic epithelial cells. For patients with IBD, 5-aminosalycilates are often used in case of mild disease, and corticosteroids are standard therapy for moderate-to-severe disease. However, we often encounter patients who are resistant to or dependent of conventional therapy, which are likely to lead to future problems in quality of life due to adverse effects of drugs used, especially corticosteroids. Extracorporeal leukocyte removal therapy (cytapheresis) is one of the adjunctive therapies for IBD patients refractory to steroids. By removing circulating activated leukocytes, especially granulocytes and lymphocytes, impaired immune response is suppressed. In the present article recently published studies are reviewed in order to reflect the current state of the art in the use of cytapheresis for treating IBD, especially UC and CD. Although there are only few randomized controlled trials, clinical experience so far suggests that cytapheresis has superior efficiency than conventional therapies in steroid-resistant moderate-to-severe UC. Moreover, cytapheresis features its safety characteristic compared with other conventional medications for severe UC, cytapheresis is regarded as safe treatment regimen.
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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.
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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.
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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.
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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.
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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.
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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 /
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Granulocytapheresis in inflammatory bowel disease Efficacy of an induction plus maintenance sessions protocol at 32 weeks
F J Fernández Pérez 1, F Rodríguez, C de Sola, N Fernández Moreno, F Vera, R Rivera, A Sánchez Cantos, Rev Esp Enferm Dig. 2007 Nov;99(11):628-35.
Introduction: Granulocytapheresis (GCAP) eliminates activated granulocytes-monocytes from peripheral blood, thus modifying the circulating pool of leukocytes and reducing intestinal inflammation. Objective: To evaluate the efficacy of GCAP in inflammatory bowel disease (IBD) using an induction and maintenance protocol. Material and method: A retrospective study including patients with active corticosteroid-dependent or refractory IBD. Induction included 5 sessions in ulcerative colitis (UC) and 7 sessions in Crohn’s disease (CD); one monthly session was used thereafter until week 32. Clinical activity indices and use of corticosteroids were monitored. Results: Eighteen patients were included (10 with UC, 8 with CD), 10 of them dependent on and 8 refractory to corticosteroids. Fourteen of them were refractory and a further 4 were intolerant to immunosuppressants (IS). Induction was not completed in 2 UC (severe relapses) and 1 CD (side-effects) patients. One UC and 3 CD patients withdrew during maintenance. Among patients who completed induction, response or remission was achieved in 87.5% of UC cases (2 and 5 patients) and 71.4% of CD cases (1 and 4 patients), respectively. At week 32 response-remission rates reached 75% in CU (3 and 3 patients) and 42.8% in CD (1 and 2 patients) cases, respectively. Corticosteroid withdrawal was possible in 14.2% of CD and in 62.5% of UC patients (25% in remission and 37.5% with response). There were two major side effects (thrombophlebitis and syncope). No colectomies were performed for UC patients who completed GCAP induction after a mean follow-up of 97.6 weeks (range: 72-128). Conclusions: Both UC and CD respond well to GCAP induction. At 32 weeks UC patients maintain similar response-remission rates (87.5 vs. 75%), whereas almost one-third of CD patients lose response. Granulocytapheresis is an alternative, steroid-sparing treatment modality to induce and maintain remission in UC, while good patient selection and a maintenance protocol not well defined yet are needed for CD.
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Therapeutic leukocytapheresis for inflammatory bowel disease
Abbi R.Saniabadi, HiroyukiHanai, KenFukunaga, KojiSawada, ChikakoShima, IngvarBjarnason, RobertLofberg, https://doi.org/10.1016/j.transci.2007.08.003
The inference that granulocytes and monocytes/macrophages (GM) are part of the immunopathogenesis of inflammatory bowel disease (IBD) and hence should be targets of therapy stems from observations of elevated, and activated GM in patients with IBD. The Adacolumn can selectively deplete GM by adsorption (GMA) and in patients with IBD. GMA has been associated with significant clinical efficacy together with sustained suppression of inflammatory cytokine profiles. Additionally, GMA depleted proinflammatory CD14+CD16+ monocytes and was followed by an increase in CD4+ T lymphocytes including the regulatory CD4+CD25high+Foxp3 phenotype. Hence, GMA could be a non-pharmacologic therapy for IBD with potential to spare steroids and other unsafe pharmacologic preparations.
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Granulocytapheresis: Old procedures, new solution
M P Martínez Montiel, Rev Esp Enferm Dig. 2007 Nov;99(11):623-7.
To conclude, granulocytapheresis is a well-tolerated immunomodulating therapy with few side effects and good results in the management of corticoid-dependent or resistant UC, naïve patients, and pediatric subjects; it could be even considered during pregnancy. Results are less clear in CD. Some aspects remain to be elucidated, including session number and duration, and a potential maintenance regimen. Pharmacoeconomics studies are necessary to find the proper place for this technique within
IBD treatment algorithms. Therapy strategies will likely be developed in the future that will combine GMCAP with immunosuppressants and/or biological therapies
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