S Takahashi, M Colvin, J Toyosawa, M Ishida, T Kagawa, S Kuraoka, Y Aoyama, K Okamoto, I Sakakihara, K Izumikawa, K Yamamoto, S Tanaka, M Matsuura, S Ishikawa, M Wato, T Hasui, T Inaba, Journal of Crohn’s and Colitis, Volume 12, Issue supplement_1, February 2018

Cytapheresis therapy as an additional therapy to oral tacrolimus is effective in patients with severe ulcerative colitis.

)https://academic.oup.com/ecco-jcc/article/12/supplement_1/S328/4808317

Dan Turner ¹, Frank M Ruemmele ², Esther Orlanski-Meyer ¹, Anne M Griffiths ³, Javier Martin de Carpi  et al. J Pediatr Gastroenterol Nutr. 2018 Aug;67(2):257-291. doi: 10.1097/MPG.0000000000002035.

Background: The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of pediatric UC and inflammatory bowel diseases (IBD)-unclassified through detailed recommendations and practice points. Methods: These guidelines are a joint effort of the European Crohn’s and Colitis Organization (ECCO) and the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). An extensive literature search with subsequent evidence appraisal using robust methodology was performed before 2 face-to-face meetings. All 40 included recommendations and 86 practice points were endorsed by 43 experts in Paediatric IBD with at least an 88% consensus rate. Results: These guidelines discuss how to optimize the use of mesalamine (including topical), systemic and locally active steroids, thiopurines and, for more severe disease, biologics. The use of other emerging therapies and the role of surgery are also covered. Algorithms are provided to aid therapeutic decision-making based on clinical assessment and the Paediatric UC Activity Index (PUCAI). Advice on contemporary therapeutic targets incorporating the use of calprotectin and the role of therapeutic drug monitoring are presented, as well as other management considerations around pouchitis, extraintestinal manifestations, nutrition, growth, psychology, and transition. A brief section on disease classification using the PIBD-classes criteria and IBD-unclassified is also part of these guidelines. Conclusions: These guidelines provide a guide to clinicians managing children with UC and IBD-unclassified management to provide modern management strategies while maintaining vigilance around appropriate outcomes and safety issues.

https://pubmed.ncbi.nlm.nih.gov/30044357/

https://www.zora.uzh.ch/id/eprint/165387/

Satoko Yamasaki ¹, Yasuhisa Sakata ², Hisako Yoshida ³, Sinpei Shirai ¹, Yuichiro Tanaka ¹, Ryo Nakano ¹, Takahiro Yukimoto ¹, Nanae Tsuruoka ¹, Ryo Shimoda ¹, Makoto Fukuda ¹, Motoaki Miyazono ¹, Yuji Ikeda ¹, Ryuichi Iwakiri ¹, Keizo Anzai ¹, Kazuma Fujimoto ¹ , Digestion. 2019;100(4):247-253.

Background: Leukocyte removal therapy (LRT) is an effective treatment for active ulcerative colitis (UC). The present study was performed to evaluate the relapse-free period after LRT and identify risk factors for relapse. Methods: In total, 94 patients who underwent first-time LRT for remission of moderate to severe UC from April 2004 to March 2016 were enrolled in the present study. The patients were randomly assigned to one of 2 treatments: leukocytapheresis (LCAP; n = 43) or granulocyte and monocyte/macrophage adsorptive apheresis (GMA; n = 51). The 5-year cumulative relapse-free rate and risk factors for relapse were evaluated. Results: The therapeutic response rate was 82% for GMA and 70% for LCAP without a statistically significant difference. The 5-year relapse-free rate was 34.7% in the LRT group. The 5-year relapse-free rate in patients aged > 40 years was 49.9%, which was significantly higher than that in patients aged ≤40 years (22.9%, p < 0.01). The relapse-free period was longer in the older than younger patients. The relapse-free period was longer in the ≥40- than <40-year-old patients (1,197 vs. 441 days, respectively; p = 0.03). Conclusions: The relapse-free period after LRT was examined in patients with UC, and 34.7% of patients achieved clinical remission within a 5-year period. The risk factor for early relapse after LRT was younger age. In conclusion, LRT might be a therapeutic option for maintenance of remission in patients with UC, especially patients aged ≥40 years.

https://pubmed.ncbi.nlm.nih.gov/30540999/

Esteban Sáez-González ¹, Mariam Aguas ², José M Huguet ³, Pilar Nos ⁴, Belén Beltrán ² , Dig Liver Dis. 2018 Apr;50(4):415-417.

We have reported the first case of using GMA in combination with vedolizumab in a patient with active, steroid-dependent UC with an inadequate response to vedolizumab and previous biologic failure to adalimumab and infliximab, achieving remission in the follow-up. It is believed that the primary consequence of GMA therapy is a selective depletion of certain subsets of myeloid leucocytes, the most relevant of which could be the CD14+ CD16+ DR++phenotype, also known as the proinflammatory monocytes.This selective depletion of circulating leucocytes could enhance the reduction of gut trafficking of leucocytes induced by vedolizumab and modify the concentration of proinflammatory cytokines. In this clinical context, GMA therapy could be a safe, on pharmacological treatment that could help to reduce the inflammatory load, thereby enhancing the effect of biologic drugs.

https://pubmed.ncbi.nlm.nih.gov/29397323/

https://www.dldjournalonline.com/article/S1590-8658(18)30138-5/fulltext

Takayuki Yamamoto ¹, Takayuki Iida ², Kentaro Ikeya ², Masaichi Kato ², Ai Matsuura ², Satoshi Tamura ³, Ryosuke Takano ³, Shinya Tani ⁴, Satoshi Osawa ⁴, Ken Sugimoto ³, Takahiro Shimoyama ⁵, Hiroyuki Hanai ² , Clin Transl Gastroenterol 2018 Jul 6;9(7):170.

Objectives: Adsorptive granulomonocytapheresis (GMA) with the Adacolumn has been introduced as a non-pharmacologic treatment for ulcerative colitis (UC). However, a subset of patients who might respond well to GMA needs to be targeted. This study was conducted at three IBD centers to determine factors affecting the efficacy of GMA in patients with moderately-to-severely active UC. 1234567890(); 1234567890(),; 1234567890(); 1234567890(); Methods: From January 2008 to December 2017, a total of 894 active episodes (first attack or relapse) in 593 patients were treated with GMA. Clinical remission was defined as normal stool frequency and no rectal bleeding. Multiple clinical and laboratory parameters at entry were considered for efficacy assessment. Results: Clinical remission was achieved during 422 (47%) of the 894 treatment cases. In the multivariate analysis, predictors for favorable response to GMA were age ≤60 years, UC duration <1 year, Mayo endoscopic subscore 2 (vs. 3), steroid naïve UC, and biologic naïve UC. Clinical remission rate was 70% in patients with four of the five factors, 52% in patients with three factors, 46% in patients with two factors, 39% in patients with one factor, and 18% in patients with none of these factors. Overall, the clinical remission rate was significantly higher in patients with a greater number of the five predictors (P < 0.0001). Conclusions: GMA appeared to be effective in steroid naïve and biologic naïve patients with short duration of UC. Elderly patients (>60 years) and those with severe endoscopic activity did not respond well to GMA. Additional, well designed, prospective, controlled trials should strengthen our findings.

https://pubmed.ncbi.nlm.nih.gov/29977035/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033883/pdf/41424_2018_Article_37.pdf

Tomoyoshi Shibuya ¹, Keiichi Haga ¹, Masato Kamei ¹, Koki Okahara ¹, Shoko Ito ¹, Masahito Takahashi ¹, Osamu Nomura ¹, Takashi Murakami ¹, Masae Makino ¹, Tomohiro Kodani ¹, Dai Ishikawa ¹, Naoto Sakamoto ¹, Taro Osada ¹, Tatsuo Ogihara ¹, Sumio Watanabe ¹, Akihito Nagahara ¹ , Intest Res. 2018 Jul;16(3):484-488.

Our experience indicates that GMA, as a non-drug therapeutic intervention with a favorable safety profile, plus tacrolimus might be a relevant treatment option for patients with active IBD during pregnancy. A future study of a large cohort of pregnant patients should strengthen our findings.

https://pubmed.ncbi.nlm.nih.gov/30090048/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077305/pdf/ir-16-484.pdf

Violeta Balbas-Martinez ^1 2, Leire Ruiz-Cerdá ^1 2, Itziar Irurzun-Arana ^1 2, Ignacio González-García ¹, An Vermeulen ^3 4, José David Gómez-Mantilla ¹, Iñaki F Trocóniz ^1 2 , PLoS One. 2018 Mar 7;13(3):e0192949. doi

In this article, we propose a logic model for Inflammatory Bowel Disease (IBD) which consists of 43 nodes and 298 qualitative interactions. The model presented is able to describe the pathogenic mechanisms of the disorder and qualitatively describes the characteristic chronic inflammation. A perturbation analysis performed on the IBD network indicates that the model is robust. Also, as described in clinical trials, a simulation of anti-TNFα, anti-IL2 and Granulocyte and Monocyte Apheresis showed a decrease in the Metalloproteinases node (MMPs), which means a decrease in tissue damage. In contrast, as clinical trials have demonstrated, a simulation of anti-IL17 and anti-IFNγ or IL10 overexpression therapy did not show any major change in MMPs expression, as corresponds to a failed therapy. The model proved to be a promising in silico tool for the evaluation of potential therapeutic targets, the identification of new IBD biomarkers, the integration of IBD polymorphisms to anticipate responders and non-responders and can be reduced and transformed in quantitative model/s.

https://pubmed.ncbi.nlm.nih.gov/29513758/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841748/pdf/pone.0192949.pdf

Takahiro Shimoyama ¹, Takayuki Yamamoto ², Satoru Umegae ¹, Koichi Matsumoto ¹ , BMC Gastroenterol. 2018 Aug 1;18(1):120.

Our findings indicate that FC is a relevant biomarker, which is convenient to measure for assessing endoscopic activity and predicting relapse in patients who achieve remission following a course of GMA therapy.

https://pubmed.ncbi.nlm.nih.gov/30068300/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090982/pdf/12876_2018_Article_853.pdf

Osamu Nomura ¹, Taro Osada ¹, Tomoyoshi Shibuya ¹, Dai Ishikawa ¹, Keiichi Haga ¹, Tomohiro Kodani ¹, Naoto Sakamoto ¹, Tatsuo Ogihara ¹, Ken Yamaji ², Sumio Watanabe ¹ , J Clin Apher 2018 Feb;33(1):21-28.

In this retrospective efficacy evaluation, cytapheresis was effective as remission induction therapy with steroid sparing effect and desirable safety profile. Further, patients with EN or PG responded favorably to cytapheresis.

https://pubmed.ncbi.nlm.nih.gov/28581039/

Helena Rolandsdotter ^1 2, Michael Eberhardson ^1 3, Ulrika L Fagerberg ^4 5, Yigael Finkel ^1 2 , J Pediatr Gastroenterol Nutr 2018 Jan;66(1):84-89.

Objective: The aim of the study was to analyze the effect of granulocyte and monocyte apheresis (GMA) with mesalazine for induction of remission in pediatric patients with newly onset chronic inflammatory bowel disease (IBD) colitis. Methods: Thirteen pediatric patients with newly onset extensive IBD colitis were investigated per the ECCO/ESPGHAN IBD protocol. Of these 13, 12 received 10 treatments with Adacolumn (ADA) during a median of 6.25 weeks in combination with low-to-moderate doses of mesalazine, which was continued after apheresis. A control colonoscopy was performed 12 to 16 weeks after GMA treatment. Primary outcomes were mucosal healing (Mayo endoscopic score) and histopathologic grading of biopsies. A secondary outcome was disease activity as measured by the Pediatric Ulcerative Colitis Activity Index. Results: Twelve children (6 girls) with a median age of 14.6 years and a median duration of symptoms at diagnosis of 3.2 months received all planned 10 treatment sessions with ADA. Ten of 12 patients had pancolitis and 2 of 12 extensive colitis. A final diagnosis, however, indicated ulcerative colitis in 10 children and Crohn disease in 2 children. At control colonoscopy, 8 of 12 children were in clinical remission and the Mayo endoscopic score showed significant improvement in 9 of 12 patients (P = 0.006). Complete microscopic remission, according to the Geboes score, was observed in 2 patients. Conclusions: In this small study GMA for induction of remission of newly onset pediatric IBD colitis was effective in 8 of 12 patients. Further controlled studies are warranted to confirm the efficacy of this treatment model.

https://pubmed.ncbi.nlm.nih.gov/28604509/