Kazuki Kakimoto ¹, Minoru Matsuura ², Takumi Fukuchi ³, Hitoshi Hongo ⁴, Tsuguhiro Kimura ⁴, Nobuo Aoyama ⁵, Yorihide Okuda ⁶, Kazuki Aomatsu ⁷, Noriko Kamata ⁸, Yoko Yokoyama ⁹, Chiemi Mizuno ¹⁰, Takuya Inoue ¹, Takako Miyazaki ¹, Shiro Nakamura ¹, Kazuhide Higuchi ¹, Hiroshi Nakase ¹¹ , Crohns Colitis 360. 2020 Sep 23;2(4):otaa073.

GMA shows effectiveness in inducing remission in UC patients not receiving steroid.

https://pubmed.ncbi.nlm.nih.gov/34192247/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797742/pdf/otaa073.pdf

Takayuki Yamamoto ¹, Toshiaki Tanaka ², Tadashi Yokoyama ³, Takahiro Shimoyama ¹, Hiroki Ikeuchi ⁴, Motoi Uchino ⁴, Toshiaki Watanabe ⁵ , Therap Adv Gastroenterol. 2017 Feb;10(2):199-206.

GMA has a good safety profile, but its efficacy appears to be limited in the management of chronic refractory pouchitis. However, a large controlled study should be conducted to evaluate the efficacy of GMA therapy in patients with pouchitis at an earlier clinical stage, before the disease has become refractory to conventional medical therapy.

https://pubmed.ncbi.nlm.nih.gov/28203278/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298477/pdf/10.1177_1756283X16679348.pdf

Gianni Imperiali ¹, Arnaldo Amato ¹, Maria Maddalena Terpin ², Ivo Beverina ³, Aurora Bortoli ⁴, Massimo Devani ⁴, Chiara Viganò ⁵,Gastroenterol Res Pract2017;2017:9728324.

Our study shows that a standard course of granulocyte-monocyte apheresis is associated with a 36% steroid-free clinical remission in patients with steroid-dependent, azathioprine-intolerant or resistant moderate ulcerative colitis. Apheresis might represent an alternative to biologic therapy or surgery in this specific subgroup of patients

https://pubmed.ncbi.nlm.nih.gov/29403531/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748298/pdf/GRP2017-9728324.pdf

Atsushi Sakuraba ¹, Toshiro Sato, Yuichi Morohoshi, Katsuyoshi Matsuoka, Susumu Okamoto, Nagamu Inoue, Hiromasa Takaishi, Haruhiko Ogata, Yasushi Iwao, Toshifumi Hibi,Ther Apher Dial. 2012 Jun;16(3):213-8.

The effect of granulocyte and monocyte adsorption apheresis (GMA) on prevention of relapse of ulcerative colitis (UC) is not clear. This was a pilot open-labeled, prospective, randomized, unblinded study to compare the tolerability and efficacy of intermittent GMA (once every 2 weeks) with mercaptopurine to maintain remission of UC. Twenty-one patients with UC, who had achieved remission by induction therapies were randomly assigned to receive either intermittent GMA (N = 10) or oral mercaptopurine (0.5 mg/kg per day; N = 11). The study period was 24 months. The rate of the patients maintaining remission and the incidences of adverse effects were compared between the two groups. At 24 months, seven of 10 patients (70.0%) on intermittent GMA and seven of 11 patients (63.6%, P = 1.00) on oral mercaptopurine were still in remission. Three patients relapsed in each group. One patient taking mercaptopurine, but none receiving intermittent GMA, dropped out because of adverse effects. Intermittent therapy with GMA was well tolerated and a substantial proportion of patients maintained remission. Intermittent GMA therapy in maintaining remission of UC merits further investigation.

https://pubmed.ncbi.nlm.nih.gov/22607563/

Takayuki Yamamoto ¹, Satoru Umegae, Koichi Matsumoto, J Gastroenterol 2011 Aug;46(8):1003-9.

This is the first report on daily GMA in the treatment of patients with UC. Daily GMA was safe and well tolerated without serious AE. Furthermore, daily GMA was associated with rapid improvement of clinical symptoms in patients with moderately active UC. However, controlled trials are warranted to assess a definite efficacy for daily GMA therapy.

https://pubmed.ncbi.nlm.nih.gov/21681409/

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/

Irene Modesto, Daniela Scimeca, Ambrogio Orlando, Mario Cottone, Inflamm Bowel Dis 12 (10), October 2006

We report the results of an open prospective study of LCAP in moderate to severe steroid-dependent UC. LCAP is an effective procedure in obtaining discontinuation of steroids in 36% of patients with UC for at least 3 months. Overall 4 of 11(36%) patients could discontinue steroids within 3 months. No relevant side effects were observed. The procedure was well tolerated. In our series, there was no endoscopic response. Most of the patients obtained a clinical temporary response, but many relapsed

https://pubmed.ncbi.nlm.nih.gov/17012976/

Bresci Giampaolo ¹, Parisi Giuseppe, Bertoni Michele, Mazzoni Alessandro, Scatena Fabrizio, Capria Alfonso, World J Gastroenterol. 2006 Apr 14;12(14):2201-4.

Even if the number of our patients with steroid-refractory IBDs was not big, we can assert that GCAP is well tolerated and effective, especially in the first six months after the treatment, in a significant percentage of cases. The rate of sustained response drops slightly after 6 mo and significantly after 12 mo, however the absence of severe side effects can be a stimulus for further evaluating new schedules of treatment.

https://pubmed.ncbi.nlm.nih.gov/16610021/

[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/

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