Gerda C Leitner 1, Nina Worel, Harald Vogelsang, Transfus Med Hemother. 2012 Aug;39(4):246-252.
Tag: Steroid-refractory
Scientific corner
Selective granulocyte and monocyte apheresis as a non-pharmacological option for patients with inflammatory bowel disease.
Ulcerative colitis and Crohn’s disease are the two most prevalent inflammatory bowel diseases. In both cases, the medically refractory and steroid-dependent type presents a therapeutic challenge. To help resolve this problem, a mainly Japanese team developed a new therapeutic option. There are two systems, both of which are able to selectively remove the main mediators of the disease, namely the activated pro-inflammatory cytokine-producing granulocytes and monocytes/macrophages, from the patient’s blood circulation (GMA = granulocyte monocyte apheresis). One of the two systems is the Adacolumn( (®) ) (Immunoresearch Laboratories, Takasaki, Japan) consisting of the ADA-monitor and a single-use column, which contains approximately 35,000 cellulose acetate beads. The exact mode of action is not yet sufficiently understood, but however, a modulation of the immune system takes place. As a result, less pro-inflammatory cytokines are released. Furthermore, the production of anti-inflammatory interleukin-1 receptor antagonist is increased, and the apoptosis of granulocytes boosted. The decreased LECAM-1-expression on leukocytes impedes the leukotaxis to the inflamed tissue, and CD10-negative immature granulocytes appear in the peripheral blood. Another effect to be mentioned is the removal of the peripheral dendritic cells and the leachate of regulatory T cells (T-regs). The second system is the Cellsorba( (®) ) FX Filter (Asahi Medical, Tokyo, Japan). The range of efficiency, the indication, and the procedure are very similar to the Adacolumn. Solely the additional removal of lymphocytes can possibly limit the implementation since lymphopenia can increase the risk of autoimmune disease. Both systems provide a low-risk therapy with few adverse reactions. ASFA recommendations for GMA in inflammatory bowel disease are 2B due to the fact that not enough randomized double-blind studies are available to proof the efficacy of this treatment.
Adacolumn / apoptosis / ASFA / CD10- / Cellsorba / Clinical remission / DC / IL1R / immunological effects / LECAM-1(L-selectin) / non-pharmacological / Safety / steroid-dependent / Steroid-refractory / Tregs /
Scientific corner
Predictive factors of clinical response in steroid-refractory ulcerative colitis treated with granulocyte-monocyte apheresis
Valeria D’Ovidio 1, Donatella Meo, Angelo Viscido, Giampaolo Bresci, Piero Vernia, Renzo Caprilli, World J Gastroenterol. 2011 Apr 14;17(14):1831-5.
GMA may be a valid therapeutic option for steroid-dependent ulcerative colitis patients with mild-moderate disease and its clinical efficacy seems to persist for 12 months.
Scientific corner
The Asia-Pacific consensus on ulcerative colitis
Choon Jin Ooi 1, Kwong Ming Fock, Govind K Makharia, Khean Lee Goh, Khoon Lin Ling, Ida Hilmi, Wee Chian Lim, Thia Kelvin, Peter R Gibson, Richard B Gearry, Qin Ouyang, Jose Sollano, Sathaporn Manatsathit, Rungsun Rerknimitr, Shu-Chen Wei, Wai Keung Leung, H Janaka de Silva, Rupert Wl Leong, Asia Pacific Association of Gastroenterology Working Group on Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is increasing in many parts of the Asia-Pacific region. There is a need to improve the awareness of IBD and develop diagnostic and management recommendations relevant to the region. This evidence-based consensus focuses on the definition, epidemiology and management of ulcerative colitis (UC) in Asia. A multi-disciplinary group developed the consensus statements, reviewed the relevant literature, and voted on them anonymously using the Delphi method. The finalized statements were reviewed to determine the level of consensus, evidence quality and strength of recommendation. Infectious colitis must be excluded prior to diagnosing UC. Typical histology and macroscopic extent of the disease seen in the West is found in the Asia-Pacific region. Ulcerative colitis is increasing in many parts of Asia with gender distribution and age of diagnosis similar to the West. Extra-intestinal manifestations including primary sclerosing cholangitis are rarer than in the West. Clinical stratification of disease severity guides management. In Japan, leukocytapheresis is a treatment option. Access to biologic agents remains limited due to high cost and concern over opportunistic infections. The high endemic rates of hepatitis B virus infection require stringent screening before initiating immune-suppressive agents. Vaccination and prophylactic therapies should be initiated on a case-by-case basis and in accordance with local practice. Colorectal cancer complicates chronic colitis. A recent increase in UC is reported in the Asia-Pacific region. These consensus statements aim to improve the recognition of UC and assist clinicians in its management with particular relevance to the region.
asia / consensus / efficacy / gma / GUIDELINES / Leukocytapheresis / procedure / severe / steroid-dependent / steroid-naive / Steroid-refractory / ulcerative colitis /
Scientific corner
13 Apheresis therapy showed its high safety and adequate efficacy for the treatment of patients with ulcerative colitis – the postmarketing surveillance of more than 600 ulcerative colitis patients in Japan
Scientific corner
Clinical trial: five or ten cycles of granulocyte-monocyte apheresis (GMA) show equivalent efficacy and safety in ulcerative colitis
A U Dignass 1, A Eriksson, A Kilander, A Pukitis, J M Rhodes, S Vavricka, Aliment Pharmacol Ther. 2010 Jun;31(12):1286-95.
This prospective study comparing apheresis regimens in ulcerative colitis demonstrates that 5 treatments were not inferior to 10 treatments in steroid-refractory or -dependent ulcerative colitis.
Scientific corner
Emerging drugs for the treatment of ulcerative colitis
Luca Pastorelli 1, Theresa T Pizarro, Fabio Cominelli, Maurizio Vecchi Expert Opin Emerg Drugs. 2009 Sep;14(3):505-21. doi: 10.1517/14728210903146882.
Background: Ulcerative colitis (UC) is a chronic, relapsing inflammatory disorder of the colon for which the etiology is currently unknown. At present, strategies to treat UC are primarily targeted to control inflammation during active phases of disease as well as maintain remission during quiescence. As such, several unmet needs in the treatment of UC still remain. In recent years, basic research has led to the recognition of several key factors in the pathogenesis of UC, translating into the development of several novel therapeutic agents. Objective: The aim of this study is to review emerging therapies that may advance the treatment and improve the overall care of UC patients. Methods: An extensive literature search on published manuscripts and meeting proceedings has been performed to provide a comprehensive review of future drug therapies to treat UC. Results/conclusion: The translational application of new discoveries in the basic understanding of UC pathogenesis is continuing and critical for the development of novel treatment strategies. Design of novel biologic therapies to treat UC has the challenge of addressing potential safety issues, while more traditional drugs should be further developed to facilitate patient compliance to treat this chronic, debilitating disease.
Scientific corner
Clinical, endoscopic and histological remission in paediatric chronically active ulcerative colitis after prolonged treatment with selective granulocyte–monocyte adsorptive apheresis
Javier Martin-Carpi Martín-Carpi, Vicente Varea Journal of Crohn’s and Colitis, Volume 3, Issue 3, September 2009, Pages 216–217, https://doi.org/10.1016/j.crohns.2009.03.003
Treatment of paediatric ulcerative colitis (UC) unresponsive to conventional treatment constitutes a challenge. The finding of new secure, steroid-sparing and long acting treatments for these cases are mandatory. We report our experience with a long-term therapeutic strategy with Adacolumn in a chronically active paediatric UC patient (9 year-old boy) with the aim of achieving stabilization and ameliorating symptoms, permitting a successful switch to AZA monotherapy. These two aspects have been achieved without reappearance of rectal bleeding after oral mesalamine suppression. But the most interesting and promising finding is the confirmation of GMA apheresis effect on mucosal healing after prolonged treatment: maintenance treatment with Adacolumn has been effective in achieving a complete endoscopic and histological remission.
This case shows the utility of prolonged Adacolumn treatment in chronically active UC patients.
Scientific corner
Cytapheresis in patients with severe ulcerative colitis after failure of intravenous corticosteroid: a long-term retrospective cohort study
Ken Fukunaga 1, Kazuko Nagase, Takeshi Kusaka, Nobuyuki Hida, Yoshio Ohda, Koji Yoshida, Katsuyuki Tozawa, Koji Kamikozuru, M Iimuro, Shiro Nakamura, Hiroto Miwa, Takayuki Matsumoto, Gut Liver. 2009 Mar;3(1):41-7. doi: 10.5009/gnl.2009.3.1.41
This study suggest that CAP is an effective therapy in patients who are refractory to conventional medications including iv corticosteroid. Increased remission rates should be expected in refractory patients with moderately severe UC.
Scientific corner
Leukocytapheresis for the treatment of IBD
Fridrik Thor Sigurbjörnsson & Ingvar Bjarnason, Nature Clinical Practice Gastroenterology & Hepatology volume 5, pages509–516 (2008)
Leukocytapheresis is a controversial nonpharmacologic treatment for IBD, in which white blood cells–the effector cells of the inflammatory process–are mechanically removed from the circulation. Current controversy centers on the uncontrolled nature of the leukocytapheresis trials performed and their use of different outcome measures in patient groups that have very variable disease activity and severity. Nonetheless, the efficacy data obtained are generally quite consistent: an excellent response (remission >80%) has been achieved in corticosteroid-naïve patients with ulcerative colitis and an average remission rate of more than 50% has been achieved in patients who have steroid-dependent or refractory ulcerative colitis. Interestingly, the largest randomized, double-blind, sham-controlled study of granulocyte-monocyte apheresis in patients with moderate to severe ulcerative colitis failed to demonstrate efficacy for the induction of clinical remission or response. Regardless, leukocytapheresis seems to be remarkably safe. The precise positioning of leukocytapheresis in the treatment of ulcerative colitis is uncertain at present and will vary according to geography and patient preference for a safe, nonpharmacologic treatment. Further efficacy studies are required to assess what the optimal number and frequency of treatments is, in addition to the need for head-to-head comparisons with established drugs.
Enthusiasm for the use of leukocytapheresis in the treatment of patients with IBD (mainly ulcerative colitis) is fueled by the lack of serious adverse effects and tempered by the lack of conventional placebo-controlled data or head-to-head comparisons with potential competitors
Leukocytapheresis induces clinical remission in more than 80% of corticosteroid-naïve patients who have ulcerative colitis
Average remission rates are in excess of 50% in patients with moderate or severe ulcerative colitis and in patients with corticosteroid-dependent or corticosteroid-resistant ulcerative colitis
Data in Crohn’s disease are sparse and further studies are required
Leukocyte apheresis clearly has potential use in patients with ulcerative colitis, but to decide its precise positioning in treatment algorithms will require targeted studies
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.
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