Rodolfo Sacco ¹, Tomotaka Tanaka, Takayuki Yamamoto, Giampaolo Bresci, Abbi R Saniabadi, Expert Rev Gastroenterol Hepatol. 2015 Mar;9(3):327-33.

The authors’ view is that in patients with UC, there is an evolving scope for therapeutic opportunity based on taking away the sources of inflammatory cytokines, also considering the favorable safety profile of GMA.

https://pubmed.ncbi.nlm.nih.gov/25160857/

Maurizio Vecchi ¹, Piero Vernia, Gabriele Riegler, Renata D’Incà, Vito Annese, Siro Bagnoli, Clin Exp Gastroenterol. 2013;6:1-7.

Granulocyte-monocyte apheresis is a relatively new therapy that has been proposed, sometimes with controversial results, for the treatment of inflammatory bowel disease, particularly ulcerative colitis. The aim of the present study was to perform a thorough review of the literature on the application of this type of treatment in ulcerative colitis and discuss the results, in order to provide an opinion on its use which is shared by the involved experts. The review of the literature was performed by searching PubMed with appropriate key words. The results obtained suggest that the major role for this treatment at this moment is for those patients with steroid dependency or with major contraindications to use of steroids. However, promising, albeit very preliminary, results have also been observed in steroid-naïve subjects, and this is of particular interest in consideration of the safety profile of this therapeutic method. As such, the Adacolumn may prove useful in specific subgroups of patients. Future phenotypic, genotypic, and molecular characterization of patients with inflammatory bowel disease might prove useful in defining better those subjects who might benefit most from this treatment modality.

https://pubmed.ncbi.nlm.nih.gov/23323022/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541711/pdf/ceg-6-001.pdf

The selective therapeutic apheresis procedures.

J. Clin. Apheresis 28:20–29, 2013  doi:10.1002/jca.21265 

Selective apheresis procedures have been developed to target specific molecules, antibodies, or cellular elements
in a variety of diseases. The advantage of the selective apheresis procedures over conventional therapeutic plasmapheresis is preservation of other essential plasma components such as albumin, immunoglobulins, and clotting
factors. These procedures are more commonly employed in Europe and Japan, and few are available in the
USA. Apheresis procedures discussed in this review include the various technologies available for low-density
lipoprotein (LDL) apheresis, double filtration plasmapheresis (DFPP), cryofiltration, immunoadsorption procedures, adsorption resins that process plasma, extracorporeal photopheresis, and leukocyte apheresis.

https://onlinelibrary.wiley.com/doi/abs/10.1002/jca.21265

Ryoko SHUKUYA,Toshio HASEGAWA,Yusuke NIWA,Keiko OKUMA,Shigaku IKEDA, Journal of dermatology First published: 18 October 2011

In both patients, GCAP resulted in an immediate improvement in skin lesions and fever reduction, without any adverse effects. We suggest that GCAP is an effective therapy for refractory GPP.

https://onlinelibrary.wiley.com/doi/10.1111/j.1346-8138.2011.01279.x

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

Objectives: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC. Methods: This was an open-label, prospective, randomized multicenter study to compare an intensive, two GMA sessions per week, with the routine, one GMA session per week. A total of 163 patients with mild-to-moderately active UC were randomly assigned to routine weekly treatment or intensive treatment. The maximum number of sessions of GMA permitted was 10. However, when patients achieved remission, GMA was discontinued. Remission rate at the end of the study, time to remission, and adverse events were assessed in both groups. Results: Of the 163 patients, 149 were available for efficacy analysis as per protocol, 76 were in weekly GMA, and 73 were in intensive GMA. At the end of the study period, clinical remission was achieved in 41 of 76 patients (54.0%) in weekly GMA and in 52 of 73 patients (71.2%) in intensive GMA (P=0.029). The mean time to remission was 28.1+/-16.9 days in the weekly GMA treatment group and 14.9+/-9.5 days in the intensive GMA group (P<0.0001). Intensive GMA was well tolerated without GMA-related serious adverse side effects. Conclusions: Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients’ morbidity time without increasing the incidence of side effects.

)https://pubmed.ncbi.nlm.nih.gov/19724269/

David Schwartz ¹, John R Ferguson, Curr Med Res Opin . 2007 Nov;23(11):2715-28.

Background: A broad range of pharmacologic therapies are available to treat active inflammatory bowel disease (IBD), including 5-aminosalicylate preparations, corticosteroids, and immunosuppressants (e.g., azathio prine/6-mercaptopurine [AZA/6-MP] or methotrexate). Although these therapies are effective, up to 60% of patients are refractory or intolerant. Biologic therapies, such as the anti-TNF agent infliximab, offer promise but are not without controversy; despite many positive reports, steroid-refractory patients are less likely than other individuals to respond to infliximab. Effective, long-term therapies that do not add to the adverse-effects burden in patients with IBD are needed. Of these, granulocyte/monocyte apheresis (GMA) is one promising approach.

Scope: PubMed and relevant congresses databases were searched using the terms ‘granulocyte/monocyte apheresis,’ ‘GMA,’ ‘leukocytapheresis,’ ‘Adacolumn,’ and ‘Cellsorba.’ These studies were further selected to include only those focusing on IBD. A time frame of 2000-2006 was used.

Findings: Data from open-label trials show that patients with moderate-to-severe IBD refractory to conventional pharmacologic treatment achieved clinical response and/or remission after treatment with GMA. Furthermore, recent small open-label trials of GMA show increased rates of induction and maintenance of response/remission in steroid-naïve IBD patients.

Conclusions: The remission rates seen in these open-label clinical trials of GMA are consistent with those of currently available pharmacologic therapies for IBD. However, the majority of these trials enrolled only small numbers of patients, were largely open-label, and were of limited duration. These data must be confirmed in well-controlled, large-scale clinical trials

https://pubmed.ncbi.nlm.nih.gov/17894921/

Katsuya Hiraishi ¹, Yuji Takeda, Noriyuki Shiobara, Hiromu Shibusawa, Fumie Jimma, Nobuhito Kashiwagi, Abby R Saniabadi, Masakazu Adachi, Ther Apher Dial. 2003 Jun;7(3):334-40.

Granulocyte and monocyte adsorptive apheresis (GMA) using a column filled with cellulose acetate (CA) beads (carriers) has been associated with a significant clinical efficacy in patients with rheumatoid arthritis and ulcerative colitis. To obtain further understanding on the mechanisms of disease modification by cellulose acetate-carrier-based GMA, in the present study, we investigated the mechanisms of granulocyte and monocyte adhesion to CA beads following exposure of human peripheral blood to the carriers at 37 degrees C for up to 60 min under controlled conditions. Cellulose acetate beads selectively adsorbed granulocytes, monocytes. CD19+ (B cells) and CD56+ (NK cells) lymphocyte subpopulations. The granulocyte and monocyte adsorption was inhibited by heat-inactivated plasma and EDTA, indicating that the adsorption was plasma protein (immunoglobulin, complement) and calcium dependent. Accordingly, granulocyte and monocyte adsorption was markedly enhanced by coating the carriers with IgG. Similarly, C3b was adsorbed onto the CA beads as a marker of complement activation. The results indicated that IgG and active complement fragments mediated leukocyte adhesion to CA beads via the FcgammaR and/or leukocyte complement receptor like CR3. Additionally, CA beads induced loss of expression of TNF receptors on CD16- granulocytes and CD14+ monocytes, but not on CD3+ lymphocytes In conclusion, CA beads might be an appropriate biomaterial for inducing extracorporeal immunomodulation as a treatment for auto-immune diseases which are associated with pathological leukocyte activity.

https://pubmed.ncbi.nlm.nih.gov/12924609/

Abby R Saniabadi ¹, Hiroyuki Hanai, Ken Takeuchi, Kazuo Umemura, Mitsuyoshi Nakashima, Taro Adachi, Chikako Shima, Ingvar Bjarnason, Robert Lofberg, Ther Apher Dial. 2003 Feb;7(1):48-59.

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.

https://pubmed.ncbi.nlm.nih.gov/12921115/