Article

Feasibility and safety of granulocytapheresis in Crohn's disease: A prospective cohort study

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Abstract

This study evaluated the feasibility and safety of granulocytapheresis (GCAP) in inducing and maintaining remission in refractory Crohn's disease. The relationship between the clinical outcomes and the location (ileal or ileocolonic) of disease was also assessed. We evaluated 16 patients with ileal location (group A), 14 with ileocolonic location (group B). The patients underwent five sessions (1 session/wk) of GCAP (Adacolumn(TM)). CDAI was measured at the end of the GCAP, at 6, 9 and 12 months. No major complications were observed. At the end of GCAP, 19 (63.3%) patients showed a clinical remission: 10 (62.5%) in group A versus 9 (64.2%) in group B. At 6 months, 16 (53.3%) of the cases had maintained remission: 9 (56.2%) in group A versus 7 (50.0%) in group B. At 9 months, 13 (43.3%) patients had maintained remission: 7 (43.7%) in group A versus 6 (42.8%) in group B. At 12 months, 12 (40%) patients were still in clinical remission: 7 (43.7%) in group A versus 5 (35.7%) in group B. Risk of relapse was not related to disease location. The procedure was well tolerated and feasible in an important percentage of Crohn's disease patients.

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... Hence, a therapeutic strategy based on a nondrug intervention like GMA may have advantages over drugs, including lack of adverse side effects. Additionally, refractoriness or loss of response now seen in patients receiving anti-TNF-α biologics are unlikely with GMA [7,19,26,27,[31][32][33][34][35][36][37][38][39]. A detailed description of the clinical trials of GMA in adult IBD is not presented in this regular review article because our main focus has been on the outcomes in the pediatric IBD setting (Section 3.4). ...
... In this section, the clinical efficacy and the safety of GMA in the general adult population are briefly reviewed. A large number of studies mostly from Japan [41][42][43][44][45][46][47][48][49][50], and Europe [32,33,[51][52][53][54][55][56][57][58][59][60][61][62], but also from the United States [63][64][65][66][67] have reported on the efficacy and safety of the Adacolumn GMA in patients with IBD, in particular UC. In Japan and in most European Union countries, GMA has been widely applied in clinical practice setting to treat patients with IBD, including patients who are steroid-dependent or steroid-refractory [32]. ...
Article
Introduction: Patients with inflammatory bowel diseases (IBD) require life-long medications, which even if effective have the potential to cause adverse effects as additional morbidity factors. In pediatric patients, drug therapy has more serious limitations, including impaired physical and mental development. A non-drug therapeutic option is believed to be depletion of elevated and activated granulocytes and monocytes known to release inflammatory cytokines, like the CD14+CD16+ monocyte phenotype known to release tumor necrosis factor-α. Areas covered: Granulomonocyteapheresis (GMA) with an Adacolumn as a treatment option for IBD patients has been applied for the past 15 years. This article reviews the argument that GMA is a relevant and effective non-pharmacologic intervention in pediatric IBD setting. Expert Commentary: GMA with an Adacolumn has shown promise in adult, pediatric, and adolescent patients with active IBD. There is evidence of post-GMA immunomodulation in terms of increased regulatory T-cell and B-cell activities. Additionally, patients who respond to GMA may attain a favorable long-term clinical course by avoiding pharmacologicals during an early phase of their active IBD. GMA has a good safety profile, especially in difficult-to-treat and pediatric settings. An additional trial is warranted to assess the efficacy of GMA in the early phase of pediatric IBD to optimize patient selection.
... IA utilizes plasmapheresis to remove immunoglobulin and immune complexes and in cytapheresis, immune cells from the circulation [23]. Accordingly, IA could be successfully applied in patients with severe atopic dermatitis and high total serum IgE levels [24][25][26][27]. An IgE-specific adsorber, called IgEnio, has been developed [28]. ...
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Allergic diseases are inflammatory disorders that involve many types of cells and factors, including allergens, immunoglobulin (Ig)E, mast cells, basophils, cytokines and soluble mediators. Among them, IgE plays a vital role in the development of acute allergic reactions and chronic inflammatory allergic diseases, making its control particularly important in the treatment of IgE-mediated allergic diseases. This review provides an overview of the current state of IgE targeted therapy development, focusing on three areas of translational research: IgE neutralization in blood; IgE-effector cell elimination; and IgE⁺ B cell reduction. IgE-targeted medicines such as FDA approved drug Xolair (Omalizumab) represent a promising avenue for treating IgE-mediated allergic diseases given the pernicious role of IgE in disease progression. Additionally, targeted therapy for IgE-mediated allergic diseases may be advanced through cellular treatments, including the modification of effector cells.
... Hitherto, a large number of articles mostly from Ja-pan [65][66][67][68][69][70][71][72][73][74][75][76][77] , and Europe [78][79][80][81][82][83][84][85][86][87][88][89][90][91] , but also from the United States [92][93][94][95][96] have described the efficacy of GMA in patients with IBD. The clinical application of GMA with the Adacolumn began following a pioneering multicentre clinical trial by Shimoyama et al [41] described below under steroid sparing effects of GMA. ...
Article
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Ulcerative colitis and Crohn's disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients' own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients' disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 21(st) century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs.
... In this study, we performed intensive GMAA (twice per week) as an alternative to weekly GMAA as an induction therapy. Previous data on the ratios of the induction of remission in active CD refractory to corticosteroids by weekly GMAA vary (30%-60%) [20][21][22]. Thus, the efficacy of GMAA therapy on active CD patients as an induction therapy has not been established. ...
Article
Full-text available
Background: Early induction with biologics can reduce complications in patients with Crohn's disease (CD) and improve their quality of life. The safety of biologics, however, is uncertain. Granulocyte and monocyte adsorptive apheresis (GMAA) is a natural biologic therapy that selectively removes granulocytes and monocytes/macrophages and has few severe adverse effects. The effects of GMAA on patients with early-diagnosed CD are unclear. We investigated the effects of GMAA combined with thiopurines on patients with early-diagnosed CD. Methods: Twenty-two corticosteroid- and biologic-naïve patients with active early-diagnosed CD were treated with intensive GMAA (twice per week) combined with thiopurines administration. Active early-diagnosed CD was defined as follows: (i) within 2years after diagnosis of CD, (ii) with no history of both surgical treatment and endoscopic dilation therapy, and (iii) Crohn's Disease Activity Index (CDAI) was higher than 200. We investigated the ratios of clinical remission defined as CDAI was less than or equal to 150 at 2, 4, 6 and 52weeks and mucosal healing defined as a Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD) as 0 at 6 and 52weeks. Adverse events were recorded at each visit. Results: The ratios of clinical remission at 2, 4, and 6 weeks were 6 of 22 (27.2%), 12 of 22 (54.5%), and 17 of 22 (77.2%), respectively. At 52 weeks, 18 of 21 patients (81.8%) were in clinical remission. The ratios of mucosal healing at 6 and 52 weeks were 5 of 22 (22.7%) and 11 of 22 (50%), respectively. The difference in the mucosal healing ratio was significant between 6 and 52 weeks (p = 0.044). No serious adverse effects were observed during this study. Conclusions: Combination therapy with intensive GMAA and thiopurines administration rapidly induced high remission in patients with active early-diagnosed CD without serious adverse effect. Mucosal healing was observed in 50.0% of enrolled patients. This combination therapy might be a rational option for patients with early-diagnosed CD.
... By cytapheresis, inflammatory cells (granu-locytes, monocytes, or lymphocytes) or platelets are depleted from the peripheral blood. Cytapheresis has been successfully applied in rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease (7)(8)(9). In dermatology, patients with psoriasis and pyoderma gangrenosum have been successfully subjected to leukocytpheresis (10,11). ...
Article
Immunoadsorption (IA) has been successfully used in a large variety of autoantibody-mediated disorders. In dermatology, IA is increasingly applied as adjuvant treatment for severe and/or refractory autoimmune bullous diseases. These disorders are characterized by autoantibodies against structural proteins of the skin and/or mucous membranes and include, among others, pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid. Autoimmune blistering diseases are associated with a high mortality (pemphigus) or morbidity (bullous pemphigoid) and in particular in pemphigus diseases, treatment is challenging. The pathogenetic role of autoantibodies in most of the immunobullous diseases has been clearly demonstrated, therefore, removal of these autoantibodies is a rational therapeutic approach. IA has been shown to effectively lower the serum autoantibodies and to lead to rapid clinical responses. Most recently, IA has been successfully applied in patients with severe atopic dermatitis and high total serum IgE levels. Here, the different treatment protocols, clinical efficacy, and adverse events are summarized.
... 13 Further, the Adacolumn has CE mark, which allows its clinical application in the European countries. 4,[14][15][16][17] With this background in mind, the present case was treated with daily followed by twice a week GMA. To our knowledge, hitherto, one case of neutrophilic dermatitis has been reported in association with GMA. ...
Article
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Chapter
Inflammatory bowel diseases (IBD) have become a major focus for gastroenterologists worldwide, with the increasing incidence and complexity of cases, which pose therapeutic challenges. Currently available approaches fail in controlling the disease activity in a significant proportion of patients and some of the therapies are associated with significant adverse events. Although new molecules are on the horizon and treatment strategies have been optimized, novel therapeutic tools are much needed in IBD for patients who fail to attain control of the disease. Apheresis is now a common non-pharmacological therapeutic modality used in several pathologies, IBD also. In the current review, we summarize currently available evidence with respect to selective apheresis in IBD.
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In a study of 615 new patients with Crohn's disease consecutively diagnosed at the Cleveland Clinic between 1966 and 1969, 592 patients were observed (mean greater than 13 yr, minimum 7 yr), giving a follow-up rate of 96.3%. The original hypothesis was that initial anatomic involvement (the clinical pattern) bears directly on clinical course and prognosis. Disease sites were as follows: 246 ileocolic, 165 small intestine, and 181 colon/anorectal. Among patients with ileocolic disease, 225 (91.5%) had surgery. For the small intestine pattern, the operative incidence was 65.5%; for the colon/anorectal pattern, it was 58%. Operations were for specific reasons: internal fistula with abscess or intestinal obstruction for ileocolic pattern; intestinal obstruction for small intestine pattern; and severe perianal disease or toxic megacolon for colon/anorectal pattern. Complications among nonoperated patients included perianal fistulas and extraintestinal manifestations. No statistical correlation existed between type and duration of medical treatment and prognosis. Seventy-five deaths occurred (12.8%), 36 of which related directly to Crohn's disease. Even after many years, symptoms continued and quality of life tended to be suboptimal among operated patients. For nonoperated patients, the most favorable quality of life was experienced by those with segmental involvement of the colon or ileum. Poor prognosis correlated with ileocolic disease and presence of sepsis because of an internal fistula.
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Riis, P., Anthonisen, P., Wulff, H. R., Folkenborg, O., Bonnevie, O. & Binder, Vibeke. 1973. The Prophylactic Effect of Salazosulphapyridine in Ulcerative Colitis during Long-Term Treatment. A Double-Blind Trial on Patients Asymptomatic for One Year. Scand. J. Gastroent. 8, 71-74. The present trial is intended to show how long prophylactic treatment with salazosulphapyridine (Salazopyrin®) should be continued in symptom-free patients. The investigation included 27 non-pregnant women and 23 men with ulcerative colitis (aged 15-79 years), all treated non-surgically and having had no symptoms during one year’s treatment with salazosulphapyridine alone. In a double-blind trial about half these patients continued treatment with salazosulphapyridine in their accustomed dosage, while the rest were given placebo. One patient left the trial. Of the remaining 49 patients 13 developed recurrences in the 6-month trial period; 6 of these occurred in the salazosulphapyridine group of 25 patients (24 %) and 7 in the placebo group of 24 patients (29 %). From a statistical analysis it was concluded that: 1) Cessation of salazosulphapyridine treatment gave only a minimal increase in recurrence rate, which may easily have occurred by chance. 2) It is unlikely that the true difference between the recurrence rate after cessation of therapy and the rate during continued treatment is more than 26 %. Cessation of salazosulphapyridine treatment ought to be tried in ulcerative colitis patients who are receiving long-term treatment if they have been symptom-free for one year. About 75 % of the patients will not have symptoms for at least 6 months after cessation of treatment under the given circumstances.
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Neutrophil apoptosis leads to macrophage ingestion of intact senescent neutrophils. This may represent a neutrophil removal mechanism that is important both in the control of inflammatory tissue injury and for the normal resolution processes of inflammation. Because apoptosis is likely to be a key control process in cell and tissue homeostasis, a number of inflammatory mediators were tested for their ability to modulate the rate of apoptosis in populations of neutrophils aging in culture. Endotoxic lipopolysaccharide, human recombinant complement factor 5a, and human recombinant granulocyte-macrophage colony-stimulating factor all markedly inhibited the rate of neutrophil apoptosis in a concentration-dependent fashion, without inducing necrosis (as assessed by trypan blue exclusion). This inhibitory effect on the rate of neutrophil apoptosis was shown by morphological criteria and confirmed by gel electrophoresis of extracted DNA. Inhibition of apoptosis of aging neutrophil populations was associated with prolongation of the functional life span of the population as assessed by the ability of neutrophils to spread on glass surfaces, to polarize in response to deliberate stimulation with N-formyl-Met-Leu-Phe (fMLP), and to release the granule enzyme marker myeloperoxidase on fMLP stimulation. These observations show that inflammatory mediators prolong the functional life span of neutrophils through modulation of apoptosis. Further elucidation of these mechanisms will lead to a better understanding of the processes controlling neutrophil residence and function in inflamed tissues and may provide further insights into the molecular mechanisms of apoptosis, which is of widespread importance in tissue biology.
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To define what effect seminal and controlled clinical trials have on practice patterns within a gastroenterological community. To define whether these practice patterns reproduce reported treatment methods and whether results comparable with those reported in such trials are noted within a community practice setting. Mailed surveies, with telephone follow-up, were sent to all members of the Pacific Northwest Gastroenterology Society. Respondents were queried regarding cyclosporin use in the precolectomy chronic ulcerative colitis (CUC) patient. Data collected included patient demographics, disease duration and extent, pre-treatment use of steroids, method, dosage, and duration of cyclosporin therapy, side effects, and short-term and subsequent clinical results. Twenty-one percent of 81 respondents had used cyclosporin for precolectomy CUC, approximately one-half using constant infusion and one-half using parenteral bolus therapy. Side effects attributed to the cyclosporin were noted in eight of 30 patients (27%), and acute colectomy was avoided in 17 patients (57%). Subsequent colectomy was required in an additional nine patients (73% total) within a 6-month follow-up period, a significantly higher colectomy rate than that reported in prospective trials. Potential reasons precluding cyclosporin use within the gastroenterological community may include lack of knowledge about cyclosporin therapy for CUC, lack of opportunity, skepticism, fear of medication side effects, survey sampling error, or treatment philosophy. Potential reasons for failure to duplicate the results reported in controlled trials are more complex but may include inadequate treatment duration the learning curve associated with the use of a new medication, or acceptance of colectomy as the treatment of choice in patients with acutely or chronically debilitating disease.
Article
The efficacy of sulphasalazine and mesalazine in preventing relapse in patients with ulcerative colitis is well known. It is less clear how long such maintenance should be continued, and if the duration of disease remission is a factor that affects the risk of recurrence. To determine whether the duration of disease remission affects the relapse rate, by comparing the efficacy of a delayed-release mesalazine (Asacol, Bracco S.p.A., Milan, Italy) against placebo in patients with ulcerative colitis with short- and long-duration of disease remission. 112 patients (66 male, 46 female, mean age 35 years), with intermittent chronic ulcerative colitis in clinical, endoscopic and histological remission with sulphasalazine or mesalazine for at least 1 year, were included in the study. Assuming that a lower duration of remission might be associated with a higher relapse rate, the patients were stratified according to the length of their disease remission, prior to randomization into Group A (Asacol 26, placebo 35) in remission from 1 to 2 years, or Group B (Asacol 28, placebo 23) in remission for over 2 years, median 4 years. Patients were treated daily with oral Asacol 1.2 g vs. placebo, for a follow-up period of 1 year. We employed an intention-to-treat analysis. In Group A, whilst no difference was found between the two treatments after 6 months, mesalazine was significantly more effective than placebo in preventing relapse at 12 months [Asacol 6/26 (23%), placebo 17/35 (49%), P = 0.035, 95% Cl: 48-2.3%]. In contrast, in Group B no statistically significant difference was observed between the two treatments, either at 6 or 12 months [Asacol 5/28 (18%), placebo 6/23 (26%), P = 0.35, 95% Cl: 31-14%] of follow-up. Patients in group B were older, and had the disease and remission duration for longer, than those in Group A. Mesalazine prophylaxis is necessary for the prevention of relapse by patients with ulcerative colitis in remission for less than 2 years, but this study casts doubt over whether continuous maintenance treatment is necessary in patients with prolonged clinical, endoscopic and histological remission, who are at very low risk of relapse.
Article
A large number of physicians have indicated that patients with inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) respond to current apheresis technology treatment. However, the mechanism of the apheresis procedure is undefined for patients with IBD. IBD appears to be caused by a complex of interactions from the genes, environment, and the immune system; therefore, the immune system plays a crucial role in the inflammatory responses. In this process, lots of interactions occur simultaneously, and they cross relate with each other. This review paper briefly discusses the etiology and pathogenesis of IBD and attempts to elucidate the mechanism that occurs after apheresis treatment.
Article
This review covers the use of steroids in the treatment of both ulcerative colitis and Crohn's disease. It looks at controlled trials and uncontrolled trials as to the benefits of this agent in both inducing and maintaining remission. The review also stresses the high incidence of toxicity with prolonged use of steroids and the fact that controlled trials have clearly shown that steroids do not maintain remission in either disorder. Alternatives to initiating steroids in mild to moderately active ulcerative colitis and Crohn's disease are presented. The use of steroids in fistulizing versus nonfistulizing Crohn's is also covered. Finally, there is a review of data and discussion of the role of antibiotics, immunosuppressives, and combination therapy for both ulcerative colitis and Crohn's disease. The expectation is that the reader will consider alternatives to initiating and maintaining steroids for prolonged periods of time in the treatment of inflammatory bowel disease.
Article
Delayed neutrophil apoptosis is a feature of persistent acute inflammation. Neutrophil-mediated damage has been shown to be associated with the development of inflammatory bowel disease (IBD). Persistence of these cells both at the colonic site and circulation may further contribute to IBD. The aims of this study were to determine whether neutrophils isolated from IBD patients delay apoptosis and to investigate possible mechanisms involved in this delay. We studied 20 patients with IBD, 13 with Crohn's disease, and 7 with ulcerative colitis, all of whom were undergoing intestinal resection for symptomatic disease. Seventeen patients undergoing elective resection of colon cancer acted as operative controls. Systemic, mesenteric arterial, and mesenteric venous blood was harvested. Neutrophils isolated from patients with IBD showed decreased spontaneous apoptosis compared to cancer patients. Mesenteric venous serum of IBD patients contributed to this delay, which contained higher concentrations of interleukin-8 (IL-8). Pro-caspase 3 expression was also reduced in IBD neutrophils, which may contribute to decreased spontaneous and Fas antibody-induced apoptosis. Neutrophil apoptosis may be altered in Crohn's disease and ulcerative colitis through release of anti-apoptotic cytokines and altered caspase expression. The alterations in cell death mechanisms may lead to persistence of the inflammatory response associated with IBD.
Article
Reactive oxygen species, released by phagocytes, are involved in tissue injury in inflammatory bowel diseases. The aim of our study was to evaluate peripheral neutrophil function in patients with ulcerative colitis (N = 66) and Crohn's disease (N = 62) with respect to disease activity and extent, using chemiluminometry after three stimuli. Twenty-seven healthy subjects were enrolled as controls. Neutrophils from ulcerative colitis and Crohn's disease patients had a significantly higher response than those from controls following phorbol myristate acetate (86.6 +/- 6.5, 173.8 +/- 11.9, 167.5 +/- 12.2 mV, P < 0.0001), formyl-methionyl-leucyl-phenylalanine (39.5 +/- 3.4, 41.3 +/- 2.7, 58.6 +/- 4.7 mV, P < 0.001), and zymosan (142.6 +/- 10.4, 223.7 +/- 8.9, 231.2 +/- 9.5 mV, P < 0.0001) administration. The increased response was observed during both active disease and remission. The highest chemiluminescence values were found in patients with active ulcerative pancolitis and ileal Crohn's disease. The activation of circulating neutrophils may indicate persistent intestinal inflammation or may be triggered by luminal factors even in the absence of symptoms.
Article
With the extensive use of mesalamine, the natural history of ulcerative colitis is probably changed. To evaluate the relapse rate and the duration of remission in patients with ulcerative colitis on maintenance treatment with mesalamine. Enrolled in the study were 95 patients divided into 4 groups according to macroscopic location of the disease and treated with the same therapy starting from the date of enrolment. Patients in all 4 groups were followed-up until relapse occurred. The disease activity was evaluated by the Clinical Activity Index and Endoscopic Index. Patients suitable for recruitment showed a Clinical Activity Index and Endoscopic Index lower than 6 and 4, respectively. The patients with ulcerative pancolitis or left-sided colitis were treated with 1.6 g/day while the cases with proctosigmoiditis or proctitis were treated with 5-acetylsalicylic acid enemas 4 g/day Each patient was evaluated with clinical and endoscopic assessment at a 6-month interval. Relapse was defined as an increase in Clinical Activity Index and Endoscopic Index, of more than 6 and 4, respectively. Five patients dropped-out. All enrolled patients showed a clinical and/or endoscopic relapse within 10 years, the majority 2 or 3 years after diagnosis: pancolitis and left-sided colitis within 2-3 years and patients with distal colitis within 9-10 years. A relapse was observed in most cases within 3 years, and in all recruited patients within a space of ten years. The extent of the disease in the colon is an important prognostic factor, as patients with distal colitis showed a lesser tendency to relapse.
Article
The recent development of effective and safe devices to remove leukocytes selectively from circulating blood has facilitated the application of leukocytapheresis for the treatment of inflammatory bowel disease (IBD). Successful results of preliminary trials of leukocytapheresis for IBD led to several nationwide multicenter clinical trials in Japan. As a result, five or six consecutive leukocytaphereses, which were undergone weekly, improved both symptoms and endoscopic findings in approximately 60%-80% of patients with ulcerative colitis (UC). In Japan, leukocytapheresis is now considered to be one of the standard treatments for UC patients with refractory disease to avoid surgery. Here, the current status of indications and mechanisms of action on UC are analyzed by reviewing the results of Japanese multicicenter trials, and the possible application for Crohn's disease is also discussed.
Article
Apheresis has been recognized both economically and therapeutically as a novel approach for the treatment of inflammatory diseases, and certain others, which respond poorly to drug therapy. This report is about Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device with a volume of 335 mL, filled with about 220 g of cellulose acetate beads of 2 mm diameter as the column adsorptive carriers. Pre- and post-column leukocyte counts have shown that the carriers adsorb about 65% of granulocytes, 55% of monocytes and 2% of lymphocytes from the blood in the column. Additionally, after apheresis, there is a marked decrease in inflammatory cytokines (TNF-alpha, IL-1beta, IL-6 and IL-8) produced by blood leukocytes, together with down-modulation of L-selectin and the chemokine receptor CXCR3. Adacolumn has been used to treat patients with rheumatoid arthritis, ulcerative colitis and HIV infection. Typical apheresis sessions have been 4-10, at a frequency of one or two sessions per week. Treatment of patients with Adacolumn has been associated with very promising efficacy and safety data. Accordingly, in Japan, Adacolumn has been approved by the Ministry of Health for the treatment of ulcerative colitia. Furthermore, Adacolumn met the required quality and safety standards for medical devices and received an EC certification (CE-mark) from TUV in 1999. However, although Adacolumn carriers are very efficient in depleting excess and activated granulocytes and monocytes/macrophages, the clinical efficacy associated with Adacolumn apheresis cannot be fully explained on the basis of reducing granulocytes and monocytes per se. Hence, a long lasting effect on inflammatory cytokine generation, chemokine activities or immunomodulation is likely, but the precise mechanisms involved are not fully understood yet.
Article
6-Mercaptopurine and azathioprine have become important therapeutic options for patients with inflammatory bowel disease (IBD). Although accumulating data in the literature have supported the use of these immunomodulators in the management of IBD, marked variation exists in the pattern of clinical practice regarding azathioprine or 6-mercaptopurine therapy in patients with IBD. This article provides a critical review of the data on the clinical efficacy and toxicities of 6-mercaptopurine and azathioprine in the management of IBD. Emerging literature on the potential application of pharmacogenetic testing and metabolite monitoring are also discussed.
Article
Corticosteroid therapy of ulcerative colitis (UC) is associated with frequent adverse side effects and poor quality of life. Recently, adsorptive granulocyte and monocyte/macrophage apheresis has shown efficacy in patients with severe steroid refractory UC. The objective of this study was to investigate if, instead of corticosteroids, adsorptive leukocytapheresis has efficacy as the first-line therapy for steroid-naïve patients with active UC. Twenty patients, aged 15-49 years, with a mean clinical activity index (CAI) of 8.6 were recruited. Adsorptive leukocytapheresis was done with Adacolumn, which contains cellulose acetate beads as adsorptive carriers for granulocytes and monocytes (FcgammaR and complement receptors expressing leukocytes). Each patient received 6 to 10 leukocytapheresis sessions of 60-min duration, at 2 sessions/week. Efficacy was assessed 1 week after the last session. Post treatment, the mean CAI was 3.0 (P = 0001), and 17 of 20 patients (85%) were in remission. There were significant falls in C-reactive protein (P = 0.0003), total white cell counts (P = 0.003), neutrophils (P = 0.0029), and monocytes (P = 0.0038), an increase in lymphocytes (P = 0.001), and increases in the blood levels of soluble TNF-alpha receptors I (P = 0.0007) and II (P = 0.0045) in the column outflow (blood return to the patients). Further, at 8 months, 60% of patients had maintained their remission. No severe side effects were reported. In conclusion, adsorptive leukocytapheresis should reduce corticosteroid therapy in patients with moderate UC; cases with early-stage active disease may benefit most.
Article
In recent years, investigators have readdressed the complex issues involved in the classification of inflammatory bowel diseases. In 2003, a Working Party of investigators with an interest in the issues involved in disease subclassification was formed with the aim of summarising recent developments in disease classification and establishing an integrated clinical, molecular, and serological classification of inflammatory bowel disease. The results of the Working Party were reported at the 2005 Montreal World Congress of Gastroenterology. Here we highlight the key issues that have emerged from discussions of the Montreal Working Party and the relevance to clinical practice and research activities.
Editorial: 5ASA therapy for active Crohn's disease old friends, old data and new conclusion
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Fregan BG. Editorial: 5ASA therapy for active Crohn's disease old friends, old data and new conclusion. Clin Gastroenterol Hepatol 2004;2:376—8. G. Bresci et al.
British Society of Gastroenterology. Guidelines for the management of inflam-matory bowel disease in adults
  • Carter Mj Lobo
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Carter MJ, Lobo AJ, Travis SP. IBD Section. British Society of Gastroenterology. Guidelines for the management of inflam-matory bowel disease in adults. Gut 2004; 53(Suppl. 5):V1-16.
Inflammatory bowel disease-insights into pathogenesis and future therapeutic tar-get
  • Gordon Jn
  • Di Sabatino
  • Macdonald
Gordon JN, Di Sabatino, MacDonald T. Inflammatory bowel disease-insights into pathogenesis and future therapeutic tar-get. In: Bianchi Porro G, editor. IBD Year Book. 2005. p. 19—38.
Inflammatory bowel disease-insights into pathogenesis and future therapeutic target
  • Gordon