Apheresis: A cell-based therapeutic tool for the inflammatory bowel disease
Inflammatory Bowel Disease (IBD) is a hallmark of leukocyte infiltration, followed by the release of cytokines and interleukins. Disease progression to Ulcerative Colitis (UC) or Crohn’s Disease (CD) remained largely incurable. The genetic and environmental factors disrupt enteral bacteria in the gut, which hampers the intestinal repairing capability of damaged mucosa. Commonly practiced pharmacological therapies include 5-aminosalicylic acid with corticosteroids and tumor necrosis factor (TNF)-α. New interventions such as CDP571 and TNF-blocking RDP58 report the loss of patient response. This review discusses the non-pharmacologic selective granulocyte-monocyte-apheresis (GMA) and leukocytapheresis (LCAP) that have been proposed as treatment modalities that reduce mortality. GMA, an extracorporeal vein-to-vein technique, presents a strong safety profile case for its use as a viable therapeutic option compared to GMA’s conventional medication safety profile. GMA reported minimal to no side effects in the pediatric population and pregnant women. Numerous studies report the efficacious nature of GMA in UC patients, whereas data on CD patients is insufficient. Its benefits outweigh the risks and are emerging as a favored non-pharmacological treatment option. On the contrary, LCAP uses a general extracorporeal treatment that entraps leukocytes and suppresses cytokine release. It has been deemed more efficacious than conventional drug treatments, the former causing better disease remission, and maintenance. Patients with UC/CD secondary to complications have responded well to the treatment. Side effects of the procedure have remained mild to moderate, and there is little evidence of any severe adverse event occurring in most age groups. LCAP decreases the dependence on steroids and immunosuppressive therapies for IBD. The review will discuss the role of GMA and LCAP.
Targeting neutrophils in inflammatory bowel disease: revisiting the role of adsorptive granulocyte and monocyte apheresis
Introduction: Inflammatory bowel disease (IBD) is a chronic immune-mediated disease of the gastrointestinal tract comprising Crohn’s disease (CD) and ulcerative colitis (UC). While any part of the digestive tract can be affected in CD, mucosal inflammation in UC is limited to the colon. Differences and similarities between the two conditions are reflected by their pathophysiology. Areas covered: An overview of immunological aspects, pharmacological management, and biomarkers of IBD is provided. The role of adsorptive granulocyte and monocyte apheresis (GMA) is reviewed including its primary and secondary effects on the immune system, as well as clinical studies in IBD (mainly UC), and potential biomarkers for adsorptive GMA. Expert opinion: In UC, adsorptive GMA with Adacolumn (Adacolumn®, JIMRO Co., Ltd. Takasaki, Gunma, Japan) selectively depletes elevated myeloid lineage leukocytes and has a range of beneficial secondary immune effects. Adsorptive GMA is a safe and effective non-pharmacological treatment option for UC. Pilot studies have reported promising results for adsorptive GMA in combination with biological agents, although larger studies are required. Fecal calprotectin concentrations, neutrophil counts in histological samples and/or the neutrophil/lymphocyte ratio in peripheral blood may prove to be useful biomarkers for predicting GMA effectiveness in the future.
An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis
The main goals of Ulcerative Colitis (UC) treatment are to both induce and maintain the clinical and endoscopic remission of disease, reduce the incidence of complications such as dysplasia and colorectal carcinoma and improve quality of life. Although a curative medical treatment for UC has not yet been found, new therapeutic strategies addressing specific pathogenetic mechanisms of disease are emerging. Notwithstanding these novel therapies, non-biological conventional drugs remain a mainstay of treatment. The aim of this review is to summarize current therapeutic strategies used as treatment for ulcerative colitis and to briefly focus on emerging therapeutic strategies, including novel biologic therapies and small molecules. To date, multiple therapeutic approaches can be adopted in UC and the range of available compounds is constantly increasing. In this era, the realization of well-designed comparative clinical trials, as well as the definition of specific therapeutic models, would be strongly suggested in order to achieve personalized management for UC patients. They also presented other non-Pharmacological Therapies for UC including probiotics, cytapheresis and fecal transplantation.
Concomitant granulocyte and monocyte adsorption apheresis accelerates clinical efficacy and mucosal healing of colonic lesions in patients with active Crohn’s disease
S. Yasukawa*, F. Hirai, Y. Takada, Y. Yano Fukuoka University Chikushi , Department of Gastroenterology, Chikushino, Japan
Concomitant GMA not only improved clinical outcome but also benefited treatment of colonic mucosal lesions in
patients with CD who showed resistance to other treatments.
Inflammatory Bowel Disease and Neutrophil–Lymphocyte Ratio: A Systematic Scoping Review
The findings of this systematic scoping review highlight the potential utility of NLR as an adjunctive IBD biomarker with broad applications, including differentiation from non-IBD controls, clinical and endoscopic disease activity differentiation, prediction of loss of response to treatment, and prediction of risk of complications. NLR has promise for guiding therapeutic decision making, specifically for predicting loss of response to IFX. In conclusion, NLR is an emerging IBD biomarker with potential utility at nearly every point in IBD management. As a potential IBD biomarker, NLR is particularly advantageous given that it is minimally invasive, economical, and accessible as it is easily calculated from blood count data routinely and serially monitored in patients with IBD. Additional research is justified to better understand if routine observation of NLR in research and clinical practice could beneficially impact the care of patients with IBD.
PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system
Histological remission is evolving as an important treatment target in UC. We aimed to develop a simple histological index, aligned to endoscopy, correlated with clinical outcomes, and suited to apply to an artificial intelligence (AI) system to evaluate inflammatory activity. Methods: Using a set of 614 biopsies from 307 patients with UC enrolled into a prospective multicentre study, we developed the Paddington International virtual ChromoendoScopy ScOre (PICaSSO) Histologic Remission Index (PHRI). Agreement with multiple other histological indices and validation for inter-reader reproducibility were assessed. Finally, to implement PHRI into a computer-aided diagnosis system, we trained and tested a novel deep learning strategy based on a CNN architecture to detect neutrophils, calculate PHRI and identify active from quiescent UC using a subset of 138 biopsies. Results: PHRI is strongly correlated with endoscopic scores (Mayo Endoscopic Score and UC Endoscopic Index of Severity and PICaSSO) and with clinical outcomes (hospitalisation, colectomy and initiation or changes in medical therapy due to UC flare-up). A PHRI score of 1 could accurately stratify patients’ risk of adverse outcomes (hospitalisation, colectomy and treatment optimisation due to flare-up) within 12 months. Our inter-reader agreement was high (intraclass correlation 0.84). Our preliminary AI algorithm differentiated active from quiescent UC with 78% sensitivity, 91.7% specificity and 86% accuracy. Conclusions: PHRI is a simple histological index in UC, and it exhibits the highest correlation with endoscopic activity and clinical outcomes. A PHRI-based AI system was accurate in predicting histological remission.
S-05-06 Efficacy of Adsorptive Granulocyte/Monocyte Apheresis in Inflammatory Bowel Disease Patients Experiencing Loss of Response to Infliximab (poster)
To our knowledge this is the first report of adding GMA to restore the efficacy of infliximab in patients with LoR. However, the efficacy outcomes following addition of a non-drug GMA to infliximab is potentially very interesting in therapeutic settings and should inspire further studies
Evidence-based clinical practice guidelines for inflammatory bowel disease 2020
Hiroshi Nakase,1,2Motoi Uchino,1Shinichiro Shinzaki,1Minoru Matsuura,1Katsuyoshi Matsuoka,1Taku Kobayashi,1Masayuki Saruta,1Fumihito Hirai,1Keisuke Hata,1Sakiko Hiraoka,1Motohiro Esaki,1Ken Sugimoto,1Toshimitsu Fuji,1Kenji Watanabe,1Shiro Nakamura,1Nagamu Inoue,1Toshiyuki Itoh,1Makoto Naganuma,1Tadakazu Hisamatsu,1Mamoru Watanabe,1Hiroto Miwa,1Nobuyuki Enomoto,1Tooru Shimosegawa,1 and Kazuhiko Koike1 ,J Gastroenterol. 2021; 56(6): 489–526.
Inflammatory bowel disease (IBD) is a general term for chronic or remitting/relapsing inflammatory diseases of the intestinal tract and generally refers to ulcerative colitis (UC) and Crohn’s disease (CD). Since 1950, the number of patients with IBD in Japan has been increasing. The etiology of IBD remains unclear; however, recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development. UC and CD display heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management depends on the understanding and tailoring of evidence-based interventions by physicians. In 2020, seventeen IBD experts of the Japanese Society of Gastroenterology revised the previous guidelines for IBD management published in 2016. This English version was produced and modified based on the existing updated guidelines in Japanese. The Clinical Questions (CQs) of the previous guidelines were completely revised and categorized as follows: Background Questions (BQs), CQs, and Future Research Questions (FRQs). The guideline was composed of a total of 69 questions: 39 BQs, 15 CQs, and 15 FRQs. The overall quality of the evidence for each CQ was determined by assessing it with reference to the Grading of Recommendations Assessment, Development and Evaluation approach, and the strength of the recommendation was determined by the Delphi consensus process. Comprehensive up-to-date guidance for on-site physicians is provided regarding indications for proceeding with the diagnosis and treatment.
Inflammatory Bowel Disease in Japan Is It Similar to or Different from Westerns?
Ulcerative colitis and Crohn’s disease, the most common types of inflammatory bowel disease, are idiopathic, intractable disease characterized by chronic inflammation in the intestine. In recent years, studies elucidating the clinical characteristics of these diseases and basic researches have suggested that the diseases are induced by the immunological abnormalities through the involvement of environmental factors with their predisposition. In Japan, significant progress of basic and epidemiological researches has been developed for these diseases and the clinical guidelines have been established. However, no fundamental treatment for these diseases has been established yet. The current number of patients in Japan continues to increase, with at least 180,000 patients suffering from ulcerative colitis and 40,000 suffering from Crohn’s disease. Thus, further studies are required to understand these diseases and improve medical treatments
Apheresis in Inflammatory Bowel Disease: Current Evidence
Daniel Vasile Balaban, Mariana Jinga, Crohn’s Disease Recent Advances
While leukocyte-derived proinflammatory cytokines have been validated as successful targets in IBD treatment, so should leukocytes themselves be considered as treatment options. As activated leukocytes migrate into the bowel wall and drive the inflammatory cascade in IBD patients, their depletion by apheresis techniques are considered beneficial to control the mucosal inflammation.
Leukapheresis, consisting in either granulomonocyte apheresis or leukocyte apheresis, are cell-based therapies with promising results in some patient categories and with a good safety profile. They have been studied as an alternative in patients with steroid toxicity, dependency or refractoriness, or in the event of contraindications to conventional therapy. Most of the early studies were not controlled, with only a few randomized controlled trials providing quality data on their efficacy. Future studies should be designed to look at selection of IBD patients who benefit most and safely from this non-pharmacological therapy.
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