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.
Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective
GMA is the only available therapy for UC directly targeting neutrophils. Two controlled, multicentre, European studies and a number of recent cases series found a potential therapeutic benefit of GMA in different clinical scenarios of UC with a still unmet need for optimal treatment. Moreover, GMA has an excellent safety profile and is perceived as a convenient procedure by patients, making this non-pharmacological therapy a suitable alternative or add-on therapy in UC, particularly for frail or comorbid patients.
Granulocyte and monocyte apheresis as an adjunctive therapy to induce and maintain clinical remission in ulcerative colitis: a systematic review and meta analysis
The results support the hypothesis that patients with active UC have a better chance of clinical remission if GMA is administered as an adjunctive therapy. As regards the frequency of AEs, we found no statistically significant difference between the two groups. With regard to remission maintenance, GMA was identified as an effective alternative therapeutic option
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
S-05-05 Efficacy and safety of cytapheresis in elderly patients with ulcerative colitis (poster)
Remission induction was more challenging in elderly UC patients. However, CAP was safe and effective for remission induction as a non-pharmacological treatment, even in elderly UC patients, after the incorporation of practical measures. Optimized and contrived CAP is still useful as the sole or concomitant treatment.
Refractory Ulcerative Colitis Improved by Scheduled Combination Therapy of Vedolizumab and Granulocyte and Monocyte Adsorptive Apheresis
Masanao Nakamura 1, Takeshi Yamamura 1, Keiko Maeda 2, Tsunaki Sawada 2, Yasuyuki Mizutani 1, Eri Ishikawa 1, Ayako Ohashi 1, Go Kajikawa 1, Kazuhiro Furukawa 1, Eizaburo Ohno 1, Takashi Honda 1, Hiroki Kawashima 1, Masatoshi Ishigami 1, Mitsuhiro Fujishiro 1
Intern Med. 2020 Dec 1;59(23):3009-3014. doi: 10.2169/internalmedicine.5302-20. Epub 2020 Jul 28.
Granulocyte and monocyte adsorptive apheresis (GMA) is occasionally introduced as an alternative combination therapy after loss of response to biologics in ulcerative colitis (UC) patients. However, there have been no reports of the concomitant use of vedolizumab (VDZ) and GMA for the initial induction of UC. A 20-year-old man with refractory UC was admitted for recrudescence. VDZ monotherapy had previously been introduced but was ineffective. Therefore, he received scheduled combination of VDZ and GMA and achieved clinical remission. The combination of two different approaches to inhibit the migration of leukocytes into the inflamed tissue led to satisfactory clinical outcomes.
Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients With Active Ulcerative Colitis (EXPECT Study): A Multicenter Prospective Clinical Trial
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.
Safety and efficacy of single-needle leukocyte apheresis for treatment of ulcerative colitis
Yoichiro Shindo 1, Keiichi Mitsuyama 2, Hiroshi Yamasaki 1 2 3, Tetsuro Imai 4, Shinichiro Yoshioka 1 2, Kotaro Kuwaki 1 2, Ryosuke Yamauchi 1 2, Tetsuhiro Yoshimura 1 2, Toshihiro Araki 1 2, Masaru Morita 1 2, Kozo Tsuruta 1 2, Sayo Yamasaki 1, Kei Fukami 5, Takuji Torimura, Ther Apher Dial 2020 Oct;24(5):503-510.
Single-needle (SN) apheresis may be safe and effective and may reduce patient burden during UC treatment. Nevertheless, further comparative studies are needed.
Apheresis in Inflammatory Bowel Disease: Current Evidence
Daniel Vasile Balaban and Mariana Jinga Crohn’s Disease Recent Advances book, October 15th, 2020 DOI: 10.5772/intechopen.93605
Inflammatory bowel diseases (IBD) have become a major focus for gastroenterologists worldwide, with the increasing incidence and complexity of cases, which pose therapeutic challenges. Currently available approaches fail in controlling the disease activity in a significant proportion of patients and some of the therapies are associated with significant adverse events. Although new molecules are on the horizon and treatment strategies have been optimized, novel therapeutic tools are much needed in IBD for patients who fail to attain control of the disease. Apheresis is now a common non-pharmacological therapeutic modality used in several pathologies, IBD also. In the current review, we summarize currently available evidence with respect to selective apheresis in IBD.
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