Abbi R. Saniabadi, Hiroyuki Hanai, Yasuo Suzuki, Toshihide Ohmori, Koji Sawada, Naoki Yoshimura, Yasushi Saito, Yuji Takeda, Kazuo Umemura, Kazunao Kondo, Yasuhiko Ikeda, Ken Fukunaga, Mitsuyoshi Nakashima, Alberto Beretta, Ingvar Bjarnason, Robert Lofberg, https://doi.org/10.1002/jca.20046

In conclusion, selective depletion of myeloid cells appears to induce anti-inflammatory effects and represents a non-pharmacological treatment for patients with active IBD. The treatment has a clear drug-sparing role. Changes in blood levels of inflammatory and anti-inflammatory factors are thought to contribute to the efficacy of this procedure.

https://onlinelibrary.wiley.com/doi/abs/10.1002/jca.20046

Russell D Cohen, Gastroenterology. 2005 Jan;128(1):235-6.

https://pubmed.ncbi.nlm.nih.gov/15633142/

Steven J Brown, Thomas Ullman, David B Sachar, J Clin Gastroenterol. Nov-Dec 2005;39(10):845-6.

https://pubmed.ncbi.nlm.nih.gov/16208106/

Akira Andoh,Tomoyuki Tsujikawa,Osamu Inatomi,Yasuyuki Deguchi,Kazunori Hata,Katsuyuki Kitoh,Masaya Sasaki,Keiichi Mitsuyama,Yoshihide Fujiyama Therap Apher Dial(2005) 9, 2; 23-127, https://doi.org/10.1111/j.1774-9987.2005.00229.x

To elucidate the molecular mechanisms involved in the therapeutic effects of granulocyte/monocyte adsorption apheresis, changes were investigated in the cytokine responses of peripheral blood mononuclear cells (PBMC) before and after granulocyte/monocyte adsorptive apheresis in ulcerative colitis (UC) patients. Four patients with active UC were enrolled. All patients responded to granulocyte/monocyte adsorptive apheresis. A total of 20 sessions of four patients were analyzed. Peripheral blood mononuclear cells were isolated from peripheral venous blood within 5min before and after each session of granulocyte/monocyte adsorptive apheresis. The cells were stimulated with interleukin (IL)-1β and tumor necrosis factor (TNF)-α for 24h, and the secreted IL-8 and IL-6 levels were determined by enzyme-linked immunosorbent assay (ELISA). IL-1β-induced IL-8 and IL-6 secretion was significantly decreased after granulocyte/monocyte adsorptive apheresis. TNF-α-induced IL-8 secretion was also significantly decreased after apheresis, but there was no significant difference in TNF-α-induced IL-6 secretion (P = 0.052). In conclusion, granulocyte/monocyte adsorptive apheresis down-regulates the IL-1β- and TNF-α-induced inflammatory responses in PBMC. The induction of hyporesponsiveness to pro-inflammatory cytokines may be an important factor mediating the clinical effects of granulocyte/macrophage adsorptive apheresis in UC patients.

https://pubmed.ncbi.nlm.nih.gov/15828923/

https://onlinelibrary.wiley.com/doi/10.1111/j.1774-9987.2005.00229.x

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

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.

Koji Sawada ¹, Akimitsu Egashira, Kunio Ohnishi, Ken Fukunaga, Takeshi Kusaka, Takashi Shimoyama

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.

https://pubmed.ncbi.nlm.nih.gov/15844716/

Russell D. Cohen

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.

https://booksc.eu/book/20696837/914ad3

[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.

https://pubmed.ncbi.nlm.nih.gov/15665566/

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.

https://pubmed.ncbi.nlm.nih.gov/15646424/

https://linkinghub.elsevier.com/retrieve/pii/S1590-8658(04)00361-5

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)

Aliment Pharmacol Ther. 2004 Dec;20(11-12):1347-52. doi: 10.1111/j.1365-2036.2004.02288.x.

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.

https://pubmed.ncbi.nlm.nih.gov/15606397/

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2036.2004.02288.x