H. Nakase, M. Matsuura, T. Chibam , https://doi.org/10.1111/j.1365-2036.2010.04552.x

These new data suggest that GMAA might be safe and effective for UC patients positive for CMV because it does not cause CMV reactivation. Because CMV reactivation might affect the clinical outcome of patients with refractory UC,⁵ GMAA could be a promising option for UC patients with CMV infection. A new clinical trial with a larger number of patients is ongoing to evaluate further the effects of GMA on UC patients with CMV infection.

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2036.2010.04552.x

Toshifumi Ashida ¹, Yutaka Kohgo, Akihiro Munakata, Mitsunori Noguchi, Bunei Iizuka, Yutaka Endo, Hiroyuki Hanai, Toshikazu Yoshikawa, Takayuki Matsumoto, Nobuo Aoyama, Toshiyuki Matsui, Keiichi Mitsuyama, Toshifumi Hibi

Transfus Apher Sci 2011 Apr;44(2):113-7. doi: 10.1016/j.transci.2011.01.001.

We conducted a multicenter study to investigate the efficacy of leukocytapheresis (LCAP) without concomitant steroid therapy in active ulcerative colitis (UC) patients. Twenty patients were enrolled. LCAP was performed twice a week for 3 weeks. The results revealed a significant decrease of the Lichtiger’s clinical activity index (CAI) from 11.7±2.6 at baseline to 6.6±4.1 after the therapy. The endoscopic index and serum C-reactive protein levels also decreased significantly after the therapy. Of the 20 patients, 15 (75%) were assessed as responders (CAI≤4 or ΔCAI≥3), and 7 (35%) achieved complete remission (CAI≤4). No serious adverse reactions were encountered. The results suggest that LCAP is an effective and safe option for patients with active UC who had not received systemic steroid treatment.

https://pubmed.ncbi.nlm.nih.gov/21402309/

Kosaku Moribata ¹, Jun Kato, Sae Iimura, Satoshi Yoshida, Naoki Shingaki, Kazuki Ueda, Hisanobu Deguchi, Izumi Inoue, Takao Maekita, Mikitaka Iguchi, Hideyuki Tamai, Masao Ichinose, J Clin Apher. 2011;26(4):225-7.

We report a case of a 16-year-old male who suffered from Crohn’s disease (CD) with esophageal involvement, showing remarkable improvement with granulocyte/monocyte adsorption (GMA). The patient had been diagnosed as ileocolic CD and was treated with 5-aminosalicylate. He was admitted to our hospital with symptoms of fever, diarrhea, and odynophagia. Endoscopic examinations revealed that the exacerbation of ileocolic ulcers, and advent of ulcers in esophagus. Because of the patient’s refusal to receive corticosteroids, immunomodulators, or biologics, he underwent GMA twice a week. After 10 sessions of GMA, he entered remission with significant decrease in clinical activity. In addition, endoscopic examinations showed remarkable improvement of ileocolic ulcers and disappearance of esophageal lesions. No adverse events were observed. GMA could be effective for manifestations of CD in gastrointestinal tract other than ileum or colon.

https://pubmed.ncbi.nlm.nih.gov/21786316/

John K Triantafillidis, Emmanuel Merikas, and Filippos Georgopoulos Drug Des Devel Ther. 2011; 5: 185–210. doi: 10.2147/DDDT.S11290

During the last decade a large number of biological agents against tumor necrosis factor-α (TNF-α), as well as many biochemical substances and molecules specifically for the medical treatment of patients with inflammatory bowel disease (IBD), have been developed. This enormous progress was a consequence of the significant advances in biotechnology along with the increased knowledge of the underlying pathophysiological mechanisms involved in the pathogenesis of IBD. However, conventional therapies remain the cornerstone of treatment for most patients. During recent years conventional and biologic IBD therapies have been optimized. Newer mesalazine formulations with a reduced pill size and only one dose per day demonstrate similar efficacy to older formulations. New corticosteroids retain the efficacy of older corticosteroids while exhibiting a higher safety profile. The role of antibiotics and probiotics has been further clarified. Significant progress in understanding thiopurine metabolism has improved the effective dose along with adjunctive therapies. Quite a large number of substances and therapies, including biologic agents other than TNF-α inhibitors, unfractionated or low-molecular-weight heparin, omega-3 polyunsaturated fatty acids, microbes and microbial products, leukocytapheresis, and other substances under investigation, could offer important benefits to our patients. In this paper we review the established and emerging therapeutic strategies in patients with Crohn’s disease and ulcerative colitis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084301/

M.I wamoto K.Shigetoh H. Maruyama T. Kondo Transfusion and Apheresis Science Volume 43, Supplement, September 2010, Pages S6-S7 doi.: .10.1016/S1473-0502(10)70013-6

https://www.sciencedirect.com/science/article/abs/pii/S1473050210700136

Ken Fukunaga,Yoko Yokoyama,Koji Kamikozuru,Koji Yoshida,Risa Kikuyama,Kazuko Nagase,Shiro Nakamura,Yoshiyuki Takei,Hiroto Miwa,Takayuki Matsumoto

J. Clin. Apheresis, 2010;25(4):226-8. doi: 10.1002/jca.20242.

Background: This is the first report on a case of Crohn’s disease (CD), who was successfully maintained with a combination of infliximab (IFX) and selective depletion of granulocytes/monocytes by adsorption (GMA). Case: A 33-year-old female with CD activity index (CDAI) 294.2 responded to iv IFX (5mg/kg) administered at weeks 0, 2, and 6 in combination with 3000 mg/day oral 5-aminosalicylic acid (5-ASA; CDAI = 118). Then IFX at 8 week intervals was given as maintenance therapy. Two weeks before the 5th scheduled IFX, the patient worsened with an increase in stool frequency and a rise in CDAI. GMA was administered at weeks 5, 6, and 7 after her 6th iv IFX. Her CDAI decreased from 166.2 to 126.3 and 111.9 before 2nd and 3rd GMA sessions. She received her 7th iv IFX while the CDAI was 83.6. GMA course was repeated before 8th and 9th IFX. The patient remained in stable clinical and endoscopic remission without experiencing any serious side effect. After achieving mucosal healing, the patient decided to cease IFX therapy while continuing with GMA. Conclusions: 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/

https://onlinelibrary.wiley.com/doi/10.1002/jca.20242

Takeshi Tomomasa ¹, Hitoshi Tajiri, Seiichi Kagimoto, Toshiaki Shimizu, Atsushi Yoden, Kosuke Ushijima, Keiichi Uchida, Hiroaki Kaneko, Daiki Abukawa, Mutsuko Konno, Shun-ichi Maisawa, Takao Kohsaka, Akio Kobayashi, Japanese Study Group for Pediatric Ulcerative Colitis J Pediatr Gastroenterol Nutr. 2011 Jul;53(1):34-9. doi: 10.1097/MPG.0b013e31821058bc.

Objective: Leukocytapheresis (LCAP) is a nonpharmacologic therapy that has recently been used to treat ulcerative colitis (UC). This multicenter open-label study prospectively assessed the efficacy and safety of LCAP in pediatric patients with UC. Patients and methods: Twenty-three patients ages 8 to 16 years with moderate (n = 19) to severe (n = 4) steroid-resistant UC were enrolled. One of 2 LCAP columns with different volumes (model EX and the half-volume model EI) was selected, according to body weight. LCAP was performed once per week for 5 consecutive weeks. Clinical and laboratory data were collected at predetermined time points. The primary endpoint was decreased stool frequency/hematochezia score, and secondary endpoints were clinical, laboratory, and endoscopic improvements. Results: The stool frequency/hematochezia score decreased significantly from 4.5 ± 1.2 before treatment to 1.6 ± 1.9 after the fifth treatment. Clinical parameters, including stool frequency, presence of visible blood, abdominal pain, and body temperature, were significantly improved. Fecal calprotectin decreased significantly. Endoscopic findings evaluated using Matts score also improved (P < 0.01). The steroid dose decreased from 1.1 ± 0.4 mg/kg before treatment to 0.8 ± 0.5 mg/kg after treatment. There were no significant differences in changes between the EX and EI columns. The incidence of adverse effects was 61%, although none was serious. The most common adverse effects were decreased hematocrit and hemoglobin concentration. Conclusions: The present study showed that LCAP was well tolerated in children with UC, mostly moderate, and was as effective as in adults. The types of pediatric patients best suited to LCAP remain to be determined.

https://pubmed.ncbi.nlm.nih.gov/21694533/

https://journals.lww.com/jpgn/Fulltext/2011/07000/Leukocytapheresis_in_Pediatric_Patients_With.5.aspx

Brigitte Habermalz ¹, Stefan Sauerland, Dig Dis Sci. 2010 May;55(5):1421-8.

The purpose of this meta-analysis was to determine whether selective adsorptive granulocyte and monocyte apheresis (GMA apheresis) using the Adacolumn device can effectively reduce clinical symptoms and endoscopic signs of inflammation in patients with ulcerative colitis (UC). A comprehensive search for randomized controlled trials (RCTs) published up to May 2008 was performed. Each study’s quality was evaluated, and the data reported in the results were abstracted. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the fixed-effects model. Heterogeneity was quantified statistically and explained by the variation in the trial design. Seven RCTs including 594 patients were found, and six RCTs on active UC contributed to the main analyses. In half of the trials, GMA apheresis was compared to steroids. Only one trial was fully blinded. A response or remission after 6 weeks was achieved more often in patients treated with GMA apheresis (RR 1.42; CI 1.15-1.75). Also, after 12 weeks, GMA apheresis produced significantly higher remission rates (RR 1.41; CI 1.08-1.83), but long-term data were sparse. In the trials that compared GMA apheresis and steroids (n = 220 patients), side effects were much less frequent in the GMA apheresis groups (RR 0.19; CI 0.11-0.34). Homogeneous evidence from seven RCTs shows that GMA apheresis induces a clinical remission in a higher proportion of UC patients as compared to conventional medical therapy.

https://pubmed.ncbi.nlm.nih.gov/19517236/

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/

Javier Martin-Carpi Martín-Carpi, Vicente Varea Journal of Crohn’s and Colitis, Volume 3, Issue 3, September 2009, Pages 216–217, https://doi.org/10.1016/j.crohns.2009.03.003

Treatment of paediatric ulcerative colitis (UC) unresponsive to conventional treatment constitutes a challenge. The finding of new secure, steroid-sparing and long acting treatments for these cases are mandatory. We report our experience with a long-term therapeutic strategy with Adacolumn in a chronically active paediatric UC patient (9 year-old boy) with the aim of achieving stabilization and ameliorating symptoms, permitting a successful switch to AZA monotherapy. These two aspects have been achieved without reappearance of rectal bleeding after oral mesalamine suppression. But the most interesting and promising finding is the confirmation of GMA apheresis effect on mucosal healing after prolonged treatment: maintenance treatment with Adacolumn has been effective in achieving a complete endoscopic and histological remission.

This case shows the utility of prolonged Adacolumn treatment in chronically active UC patients.

https://academic.oup.com/ecco-jcc/article/3/3/216/384285