Scientific corner

Selective depletion of peripheral granulocyte/monocyte enhances the efficacy of scheduled maintenance infliximab in Crohn’s disease

Ken Fukunaga 1, Yoko Yokoyama, Koji Kamikozuru, Koji Yoshida, Risa Kikuyama, Kazuko Nagase, Shiro Nakamura, Yoshiyuki Takei, Hiroto Miwa, Takayuki Matsumoto, J Clin Apher. 2010;25(4):226-8.

IFX appears to induce and maintain remission of CD, but it may lose its efficacy after repeated administration. GMA is safe and by selectively depleting elevated/activated leukocytes may be a useful adjunct for IFX efficacy.

https://pubmed.ncbi.nlm.nih.gov/20544712/

Scientific corner

An open-label prospective randomized multicenter study of intensive versus weekly granulocyte and monocyte apheresis in active crohn’s disease.

Atsushi Sakuraba 1, Satoshi Motoya, Kenji Watanabe, Masakazu Nishishita, Kazunari Kanke, Toshiyuki Matsui, Yasuo Suzuki, Tadayuki Oshima, Reiko Kunisaki, Takayuki Matsumoto, Hiroyuki Hanai, Ken Fukunaga, Naoki Yoshimura, Toshimi Chiba, Shinsuke Funakoshi, Nobuo Aoyama, Akira Andoh, Hiroshi Nakase, Yohei Mizuta, Ryoichi Suzuki, Taiji Akamatsu, Masahiro Iizuka, Toshifumi Ashida, Toshifumi Hibi, Am J Gastroenterol. 2009 Dec;104(12):2990-5.

Background: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn’s disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD. Methods: In an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level). Results: Of the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 ± 5.3 days in the weekly GMA and 21.7 ± 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/μL to 6950/μL (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern. Conclusions: In this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.

https://pubmed.ncbi.nlm.nih.gov/26585569/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653849/

Scientific corner

Case Report: Combination Therapy With Granulocyte Apheresis and Infliximab for Refractory Crohn’s Disease

P. Gonzalez Carro, F. Perez Roldan, O. Roncero Garcıa Escribano,R. Lafuente, M.L. Legaz Huidobro, and A. Amigo Echenagusıa

Journal of Clinical Apheresis 21: 249–251 (2006)

To our knowledge, no cases of combined therapy with infliximab and granulocyte apheresis have been previously reported. Our results suggest that this combined therapy is a possible alternative to treat CD patients in the event of loss of response to infliximab.

https://onlinelibrary.wiley.com/doi/10.1002/jca.20093

Scientific corner

Granulocyte apheresis for pouchitis with arthritis and pyoderma gangrenosum after restorative proctocolectomy for ulcerative colitis: a case report

Ritsuko Yanaru-Fujisawa, Takayuki Matsumoto, Shotaro Nakamura, Shuji Kochi, Mitsuo Iida, Futoshi Kohda, Minako Hirahashi, Takashi Yao, Ryuichi Case Reports Inflamm Bowel Dis. 2005 Aug;11(8):780 DOI: 10.1097/01.mib.0000172558.39767.b7

Our case and the case of Kanekura et al8 suggest that circulating leukocytes may play an important role in the pathogenesis of PG and that GCAP in combination with corticosteroids may be a promising strategy for intractable PG. Furthermore, as has been the case for active UC, GCAP may be a choice for severe pouchitis. An accumulation of data with respect to the effect of GCAP on pouchitis seems to be warranted.

https://pubmed.ncbi.nlm.nih.gov/16043996/

https://academic.oup.com/ibdjournal/article/11/8/780/4685895

Scientific corner

Immunomodulatory effects of selective leucocytapheresis as a new adjunct to interferon-alpha2b plus ribavirin combination therapy: a prospective study in patients with high plasma HCV viraemia

K Sawada 1, N Masaki, S Hayashi, M Zeniya, T Ishikawa, H Takahashi, K Ohnishi, K Fukunaga, N Hara, T Yamamoto, T Hada, G Toda, J Viral Hepat. 2005 May;12(3):274-82.

In conclusion, enhanced efficacy of IFN/RBV following GMA might be attributed to a more efficient immune function and a renewed IFN signaling towards HCV.

https://pubmed.ncbi.nlm.nih.gov/15850468/

Scientific corner

Adacolumn for selective leukocytapheresis as a non-pharmacological treatment for patients with disorders of the immune system: An adjunct or an alternative to drug therapy?

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

Scientific corner

Granulocyte, macrophage, monocyte apheresis for refractory ulcerative proctitis

Purushothaman Premchand 1, Ken Takeuchi, Ingvar Bjarnason Eur J Gastroenterol Hepatol 2004 Sep;16(9):943-5. doi: 10.1097/00042737-200409000-00023.

Refractory ulcerative colitis that fails conventional intense medical treatment often leads to colectomy. Although ciclosporin and infliximab may avert colectomy in certain cases, these treatments come with substantial toxicity and may only act as a bridge to avert emergency surgery. Granulocyte monocyte/macrophage adsorption apheresis is a new treatment and has shown efficacy for refractory colitis in up to 80% of cases in a Japanese study and is apparently only associated with negligible side effects. We report a case of severe refractory proctitis destined for colectomy effectively treated with granulocyte monocyte/macrophage adsorption apheresis. After two of five sessions the patient achieved full clinical remission, which has been sustained with the addition of azathioprine for more than 1 year.

https://pubmed.ncbi.nlm.nih.gov/15316424/

Scientific corner

Experience with granulocytapheresis in Crohn’s disease

Cuenca, F & Paredes, J & Mendoza, J & Cruz, D & Herrero, A & Díaz-Rubio, M.Revista española de enfermedades digestivas : organo oficial de la Sociedad Española de Patología Digestiva .2004,96. 501-3, 504. DOI:10.4321/S1130-01082004000700007.

Objective: To describe our experience with granulocyte apheresis to induce remission in patients with active Crohn’s disease refractory to conventional treatment. We summarize the results previously obtained with this technique.

Conclusions: Granulocyte apheresis is a safe and well tolerated therapeutic modality that can be a valid therapeutic alternative in the induction of remission in inflammatory bowel disease, although controlled clinical trials must be conducted to define long-term efficacy, as well as to establish “optimal patient” selection, re-treatment interval, and number of sessions.

https://pubmed.ncbi.nlm.nih.gov/15283632/

Scientific corner

The present status and the recent development of the treatment for inflammatory bowel diseases: desirable effect of extracorporeal immunomodulation

Masakazu Takazoe 1, Torao Tanaka, Kenji Kondo, Toshiki Ichimori, Toshio Shinoda Ther Apher 2002 Aug;6(4):305-11. doi: 10.1046/j.1526-0968.2002.00445.x.

The immunological and genetic pathogeneses of inflammatory bowel disease (IBD) have been well elucidated in the recent years. The pharmacologic treatment of IBDs accordingly becomes to focus upon the individual pathologic step (targeting therapy), whereas the therapeutic action is not yet a pinpoint one. It has been known recently that new drugs such as biological immunomodulating agents and anti-inflammatory cytokines have better short-term effects in some respects than the conventional drugs, and they might alter the treatment strategy of IBDs in the near future. The limitation of pharmacologic treatments mainly results from adverse effects of the drugs, i.e. infection susceptibility, oncogenesis, teratogenesis and so forth. The extracorporeal therapy such as leukocytapheresis and photopheresis is reportedly effective for IBDs probably through immunomodulation such as decrease in circulating activated T-lymphocytes and activated granulocytes that play a central role in the pathogenesis of IBD. It can be said that these extracorporeal treatment methods have advantage of rapid action and lack of serious adverse effects to drug therapy.

https://pubmed.ncbi.nlm.nih.gov/12164801/

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