TAKAFUMI ANDO, OSAMU WATANABE, RYUICHI FURUTA, OSAMU MAEDA, YUJI NISHIO,
TSUYOSHI NISHIWAKI, KENJI INA, KAZUO KUSUGAMI AND HIDEMI GOTO Digestive Endoscopy (2005) 17, 153–158
Tag: gma
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Predictors of a response to cyclosporine or leukocyte removal therapy in patients with refractory ulcerative colitis
Introduction: Despite decades of clinical experience in optimizing the induction and maintenance of remission in patients with ulcerative colitis (UC), some patients remain refractory to conventional medical treatment while, in others, the effectiveness of drugs is limited by side-effects. We investigated factors predictive of the efficacy of cyclosporine and leukocyte removal therapy in patients with intractable UC. Methods: Forty-five patients with moderate to severe UC who were refractory to corticosteroid therapy were enrolled. Twenty-six patients were treated with cyclosporine and 19 by leukocyte removal therapy. Disease activity index (DAI) score assessment, and colonoscopic and histological examinations were done before and at 10, 20 and 40 days after the initiation of treatment. A clinical response to treatment was defined as a decrease in DAI score of 3 points or more at 40 days. Results: Responder ratio did not significantly differ between the cyclosporine (65.6%) and leukocyte removal therapy (63.2%) groups. Factors predictive of a response to cyclosporine therapy were fever (≥ 38.0∞C), anemia and large mucosal ulceration. In contrast, mucosal bleeding and poor extensibility of the intestinal lumen were predictive of a poor response to cyclosporine. No significant differences in any clinical or endoscopic parameter predictive of a response to leukocyte removal therapy were identified. Conclusions: Intravenous cyclosporine may be effective in patients who have severe steroid-refractory UC, and leukocyte removal therapy may be useful in patients with moderate active UC predicted to be refractive to cyclosporine.
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Leukocytapheresis (LCAP) for Management
of Fulminant Ulcerative Colitis with
Toxic Megacolon
Dig Dis Sci 2005 Apr;50(4):767-73. doi: 10.1007/s10620-005-2571-3.
Leukocytapheresis (LCAP) is a method of therapeutic apheresis to remove patients’ peripheral leukocytes by extracorporeal circulation. Previous studies showed that LCAP for the treatment of ulcerative colitis (UC) was more effective and had fewer adverse effects compared to high-dose steroid therapy. However, there are no reports on the application of LCAP for UC patients with toxic megacolon (TM). This study reports the effectiveness and safety of LCAP in treating patients with severe or fulminant UC with TM. Six patients were enrolled in this study and LCAP sessions were performed three times per week for 2 weeks, followed by four further times in the next 4 weeks. After completion of therapy, four patients improved in TM and went into the remission stage of UC. The average Rachmilewitz clinical activity index of these four patients improved from 19.5 to 1. The remaining two patients had to undergo colectomy, however, the symptoms had been mitigated by LCAP and the operations were completed without any problems. These results suggest that LCAP is an additional effective and safe option for TM management in preventing colectomy or for bridging to a safer operation.
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Safety and efficacy of extracorporeal granulocyte and monocyte adsorption apheresis in patients with severe persistent bronchial asthma
Tamotsu Ishizuka 1, Tadayoshi Kawata, Yasuo Shimizu, Mitsuyoshi Utsugi, Katsuaki Endou, Takeshi Hisada, Kunio Dobashi, Tsugio Nakazawa, Masatomo Mori
Inflammation. 2005 Feb;29(1):9-16. doi: 10.1007/s10753-006-8963-5.
The Adacolumn is an adsorptive-type extracorporeal device, which is filled with cellulose diacetate beads that selectively adsorb granulocytes and monocytes. Patients with severe persistent asthma experience highly variable continuous symptoms and severe exacerbations in spite of medication based on inhaled glucocorticosteroids. Granulocyte and monocyte adsorption apheresis using extracorporeal circulation through the Adacolumn was performed in nine patients with severe persistent asthma. The extracorporeal circulation through the Adacolumn was performed once a week for 5 weeks. We were able to perform this therapy without any severe adverse effects in all patients, although one patient complained of general fatigue just after the circulations. In six of the nine patients, the increase in peak expiratory flow (PEF) was more than 50 mL/min. The average increase in morning PEF was 23.3% while that in the evening PEF was 26.4% after the therapy. This therapy was not harmful for patients with severe persistent asthma. A placebo-controlled study will be desired to evaluate the efficacy of this nonpharmacological strategy accurately.
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Treating ulcerative colitis without medications “Look Mom, no drugs!”
Gastroenterology2005 Vol. 128; Iss. 1 DOI:10.1053/j.gastro.2004.11.024
Clinical response rates in uncontrolled inflammatory bowel disease studies have commonly run in the 30%–50% range; as a result, early uncontrolled trials need validation from adequately blinded randomized trials before widespread application of such novel therapies. Although the long-term maintenance data from this study (60% at 8 months) is encouraging, further studies of the optimal interval for repeating apheresis for reinduction of remission or maintenance arealso in order. The potential for apheresis-based therapies as either a stand-alone strategy or in combination with other proven therapies in
the treatment of inflammatory bowel diseases also needs to be further elucidated. The promise of “no medications” for effective therapy in the treatment of ulcerative colitis is enticing, and perhaps a step closer, but clearly needs to be substantiated by larger controlled trials.
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[Granulocyte and monocyte adsorption apheresis in Korean conventional treatment-refractory patients with active ulcerative colitis: a prospective open-label multicenter study]
[Article in Korean ]Hyo Jong Kim 1, Joo Sung Kim, Dong Soo Han, Suk-Kyun Yang, Ki Baik Hahm, Woo In Lee, Seog-Woon Kwon, Jai Hyun Choi, Won Ho Kim, Kyu Yong Choi, In Sung Song Korean J Gastroenterol 2005 Jan;45(1):34-44. PMID: 15665566
Background/aims: In chronic inflammatory conditions such as ulcerative colitis (UC), the migration of granulocytes and monocytes/macrophages from the circulation into the colonic mucosa is especially important in maintaining inflammation. The aim of this trial was to assess safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with moderate-to-severe UC refractory to conventional drug therapies. Methods: Twenty-seven patients with moderate (55.6%) to severe (44.4%) active UC refractory to conventional drug therapies who had no changes in their conventional therapy regimen in the past two weeks before the recruitment were enrolled in an open-label trial. Concomitant medications were allowed, and steroids were tapered down according to the clinical activity during the course. We used an adsorptive type extracorporeal column (Adacolumn; JIMRO, Takasaki, Japan), which selectively adsorb granulocytes and monocytes. Patients took five apheresis sessions, each with 60 minutes duration for 5 consecutive weeks. The primary efficacy variables were clinical disease activity, short inflammatory bowel disease questionnaire (SIBDQ), C-reactive protein (CRP), and endoscopic scores. These variables were scored at regular intervals, and analyzed at week 7 on an intention-to-treat (ITT) principles. Results: At 7 weeks, 70.4% of patients showed overall improvement. Clinical disease activity (p < 0.0001), endoscopic score (p < 0.001), and the quality of life as assessed by SIBDQ (p < 0.0001) were significantly improved after the therapy. In 56.3% of concomitant steroid users, tapering down or discontinuation of steroids was possible. Treatment was well tolerated, and no severe adverse events were observed. Conclusions: Adacolumn was very efficacious in patients with moderate-to-severe active UC refractory to conventional drug therapy, but further assessment is needed.
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Adsorptive granulocyte and monocyte apheresis for refractory Crohn’s disease: an open multicenter prospective study
Yoshihiro Fukuda 1, Toshiyuki Matsui, Yasuo Suzuki, Kazunari Kanke, Takayuki Matsumoto, Masakazu Takazoe, Takayuki Matsumoto, Satoshi Motoya, Terasu Honma, Koji Sawada, Tsuneyoshi Yao, Takashi Shimoyama, Toshifumi Hibi, J Gastroenterol
. 2004 Dec;39(12):1158-64. doi: 10.1007/s00535-004-1465-z.
GCAP could be effective for inducing remission and improving quality of life in patients with active CD that is refractory to conventional therapy.
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Granulocyte adsorptive apheresis for leg ulcers complicated by rheumatoid arthritis: a report on three successfully treated cases
Shinya Mori MD,Masakazu Nagashima MD,Kazuhiro Yoshida MD,Kouji Yoshino MD,Mikako Aoki MD,Seiji Kawana MD,Ichiro Hirata BSc,Abby Saniabadi PhD, Shinichi Yoshino MD, International journal of Dermatology First published: 06 April 2004
GMA, which depletes activated neutrophils and monocytes/macrophages, appears to be effective for inflammatory skin ulcers which do not respond to conventional medications.
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Adsorptive Monocyte-granulocytapheresis (M-GCAP) for refractory Crohn’s disease
Takeshi Kusaka 1, Ken Fukunaga, Kunio Ohnishi, Tadashi Kosaka, Toshihiko Tomita, Yoko Yokoyama, Koji Sawada, Yoshihiro Fukuda, Hiroto Miwa, Takayuki Matsumoto
Six patients with active Crohn’s disease (CD) unresponsive to conventional medications (CM) were treated with Monocyte-granulocytapheresis (M-GCAP). CD patients who scored 200-400 points in Crohn’s disease activity index (CDAI) in spite of receiving CM, including enteral nutrition, for at least 2 weeks were enrolled in our double series trial. Each series had 5 weekly M-GCAP and 2 follow-up weeks, and each M-GCAP treated 1,800 ml of patient’s peripheral blood. After the 1st series, patients who decreased more than 50 points on the CDAI were deemed responders and enrolled in the second series. Patients with a CDAI score less than 150 points were considered in remission. The patients’ quality of life was evaluated using an index (IBDQ) before and after the 1st series. The CDAI was significantly decreased comparing before and after the 1st series (258.2 +/- 36.2 vs. 166.5 +/- 16.6; P < 0.02). 50% of patients (3/6) responded to the therapy, and one case (16.7%) could be induced to remission. Significant removal was revealed only for white blood cells (25.6 +/- 16.9%; P < 0.05), especially granulocytes (29.5 +/- 22.5%; P < 0.05). A statistically significant improvement of IBDQ was revealed in the responders’ group (162.3 +/- 17.2 vs. 189.3 +/- 11.5; P < 0.03). M-GCAP could be an effective adjunctive therapy for active CD patients unresponsive to CM allowing them to maintain a high QOL. However, it might be difficult to improve patients who could not be induced to remission after the 1st series by applying another series.
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Leucocytapheresis for ulcerative colitis
P.M. Irving, D.S. Rampton
Digestive and Liver Disease 36 (2004) 799–802
we discuss the theory behind using leucocytapheresis to treat IBD, its different forms, the way in which these remove leucocytes, and the indications, efficacy, safety, and possible future role of leucocytapheresis.
if randomised controlled trials confirm its safety and efficacy in steroid-refractory colitis, it would be tempting to compare leucocytapheresis with cyclosporin rescue therapy in that it can be used on an out-patient basis and, unlike cyclosporin, is not yet reported to have serious side-effects. Furthermore, in patients refractory to aminosalicylates, leucocytapheresis could conceivably have a place as maintenance therapy. Azathioprine and 6-mercaptopurine are not always effective and have rare
but serious side-effects; leucocytapheresis, at least in theory, might be an attractive alternative.
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Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study
E Domènech 1, J Hinojosa, M Esteve-Comas, F Gomollón, J M Herrera, G Bastida, A Obrador, R Ruiz, C Saro, M A Gassull, Spanish Group for the Study of Crohn’s Disease and Ulcerative Colitis (GETECCU)
Background: Uncontrolled studies suggest that granulocyteaphaeresis might be useful in the management of active ulcerative colitis. Aim: To assess the efficacy of granulocyteaphaeresis treatment in active steroid-dependent inflammatory bowel disease. Methods: We conducted a multicentre, prospective, open, pilot study in patients with steroid-dependent inflammatory bowel disease. All patients were started on 60 mg/day of prednisone; after 1 week, a five-session programme of granulocyteaphaeresis (once per week) was started. The steroid dose was tapered weekly if there was clinical improvement. Remission was defined as an inactive clinical activity index together with complete withdrawal of steroids at week 6. The patients were followed up for at least 6 months or until disease relapse. Results: Twenty-six patients (14 ulcerative colitis, 12 Crohn’s disease) were included. More than a half had been previously treated with immunomodulators. Remission was achieved in 62 and 70% of ulcerative colitis and Crohn’s disease, respectively. During a median follow-up of 12.6 months, six of eight ulcerative colitis patients maintained their clinical remission; however, only one Crohn’s disease patient remained in remission after the first 6 months of follow-up. Conclusions: Granulocyteaphaeresis is a safe treatment option in inflammatory bowel disease. A five-session programme of granulocyteaphaeresis seems to be efficient in the treatment of steroid-dependent ulcerative colitis, but not in Crohn’s disease.
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