Scientific corner

Targeting neutrophils in inflammatory bowel disease: revisiting the role of adsorptive granulocyte and monocyte apheresis

Giorgos Bamias 1Evanthia Zampeli 2Eugeni Domènech 3 Expert Rev Gastroenterol Hepatol  2022 Jul 19;1-15. doi: 10.1080/17474124.2022.2100759.

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.

https://pubmed.ncbi.nlm.nih.gov/35833363/

https://www.tandfonline.com/doi/epub/10.1080/17474124.2022.2100759?needAccess=true

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Treatment of Inflammatory Bowel Disease: A Comprehensive Review

Zhaobei Cai 1 2Shu Wang 3Jiannan Li 1 Front Med (Lausanne)  2021 Dec 20;8:765474. doi: 10.3389/fmed.2021.765474. eCollection 2021.

Inflammatory bowel disease (IBD), as a global disease, has attracted much research interest. Constant research has led to a better understanding of the disease condition and further promoted its management. We here reviewed the conventional and the novel drugs and therapies, as well as the potential ones, which have shown promise in preclinical studies and are likely to be effective future therapies. The conventional treatments aim at controlling symptoms through pharmacotherapy, including aminosalicylates, corticosteroids, immunomodulators, and biologics, with other general measures and/or surgical resection if necessary. However, a considerable fraction of patients do not respond to available treatments or lose response, which calls for new therapeutic strategies. Diverse therapeutic options are emerging, involving small molecules, apheresis therapy, improved intestinal microecology, cell therapy, and exosome therapy. In addition, patient education partly upgrades the efficacy of IBD treatment. Recent advances in the management of IBD have led to a paradigm shift in the treatment goals, from targeting symptom-free daily life to shooting for mucosal healing. In this review, the latest progress in IBD treatment is summarized to understand the advantages, pitfalls, and research prospects of different drugs and therapies and to provide a basis for the clinical decision and further research of IBD.

https://pubmed.ncbi.nlm.nih.gov/34988090/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720971/

Scientific corner

The combined efficacy of adalimumab with GMA method on the treatment of ulcerative colitis and repair of intestinal mucosal lesion

Ailing Song, Hai Jiang, Liang Guo, Shanshan Wu, Am J Transl Res 2021;13(5):5156-5164

Objectives: The study discussed and analyzed the combined efficacy of adalimumab with granulocyte and monocyte adsorption apheresis (GMA) method on patients with ulcerative colitis (UC) and the repair of intestinal mucosal lesion. Methods: 60 UC patients in moderate-to-severe active phase that hospitalized from January 2017 to March 2020 were chosen and randomly classified into observation group (n=30) and control group (n=30). The control-group patients received GMA treatment, and the observation-group patients received combination therapy of GMA and adalimumab. The therapeutic efficacy, laboratory indicators, changes of serum inflammatory factors, and intestinal mucosal barrier impairment in two sets of participants were compared. Results: The comprehensive effective rate of clinical treatment was remarkably higher in observation group than that in control group (P<0.05). CRP and ESR of the two groups in post- treatment were notably lower than those before treatment (P<0.05), while Hb and ALB in post-treatment increased significantly than in pre-intervention (P<0.05); CRP in observation group after treatment was remarkably lower than that in control group (P<0.05), while no significant difference was noticed in ESR, ALB and Hb between the two groups (P>0.05). The serum inflammatory factors in observation group in post-treatment were significantly lower than those in the control group (P<0.05). The scores of PCT, DAO and intestinal mucosa in two sets of participants in post-treatment were dramatically lower than those in pre-treatment (P<0.05), and the scores in observation group after treatment were notably lower than those in the control group (P<0.05). Conclusions: The combined efficacy of adalimumab with GMA on UC patients can improve the clinical curative efficacy, effectively reduce the inflammatory factors, which is beneficial to the repair of intestinal mucosal barrier function, and worthy of clinical application.

https://pubmed.ncbi.nlm.nih.gov/34150104/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205815/pdf/ajtr0013-5156.pdf

Scientific corner

Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective

Eugeni DomènechJoan-Ramon GrífolsAyesha Akbar, and Axel U Dignass World J Gastroenterol. 2021 Mar 14; 27(10): 908–918.

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.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968132/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968132/pdf/WJG-27-908.pdf

Scientific corner

Pyoderma gangrenosum with primary sclerosing cholangitis-associated colitis successfully treated with concomitant granulocyte and monocyte adsorption apheresis with corticosteroids

Munenori Kawai 1Chiharu Kawanami 2Akihisa Fukuda 3Hiroshi Seno 3 Clin J Gastroenterol. 2021 Jun 8. doi: 10.1007/s12328-021-01460-0. Online ahead of print

Together with previous reports, concomitant GMA therapy with corticosteroids may be an effective treatment for PG.

https://pubmed.ncbi.nlm.nih.gov/34101129/

Scientific corner

Granulocyte and monocyte apheresis as an adjunctive therapy to induce and maintain clinical remission in ulcerative colitis: a systematic review and meta analysis

Szabolcs KissDávid NémethPéter Hegyi Mária Földi Zsolt SzakácsBálint Erőss Benedek Tinusz Péter Jenő HegyiPatrícia Sarlós Hussain Alizadeh, BMJ Open 2021 May 19;11(5):e042374.

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

https://pubmed.ncbi.nlm.nih.gov/34011580/

e042374.full.pdf (bmj.com)

Scientific corner

S-05-06 Efficacy of Adsorptive Granulocyte/Monocyte Apheresis in Inflammatory Bowel Disease Patients Experiencing Loss of Response to Infliximab (poster)

ISFA-E-ISFA 2021

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

https://www.eventclass.org/contxt_eisfa2021/online-program/session?s=S-05

Scientific corner

Refractory Ulcerative Colitis Improved by Scheduled Combination Therapy of Vedolizumab and Granulocyte and Monocyte Adsorptive Apheresis

Masanao Nakamura 1Takeshi Yamamura 1Keiko Maeda 2Tsunaki Sawada 2Yasuyuki Mizutani 1Eri Ishikawa 1Ayako Ohashi 1Go Kajikawa 1Kazuhiro Furukawa 1Eizaburo Ohno 1Takashi Honda 1Hiroki Kawashima 1Masatoshi Ishigami 1Mitsuhiro 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.

https://pubmed.ncbi.nlm.nih.gov/32727993/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759717/

Scientific corner

Rapidly Progressing Aseptic Abscesses in a Patient with Ulcerative Colitis

Yoshiharu Yamaguchi 1Marie Nakagawa 1Shoko Nakagawa 1Kazuhiro Nagao 1Satoshi Inoue 1Tomoya Sugiyama 1Shinya Izawa 1Yasutaka Hijikata 1Masahide Ebi 1Yasushi Funaki 1Naotaka Ogasawara 1Makoto Sasaki 1Kunio Kasugai 1 Intern Med  2021 Mar 1;60(5):725-730. doi: 10.2169/internalmedicine.5733-20. Epub 2020 Sep 30.

Aseptic abscesses (AAs) are extraintestinal manifestations of inflammatory bowel disease (IBD). IBD-associated AAs are rare in Japan. We treated a 45-year-old man with ulcerative colitis (UC)-associated AAs. During remission, multiple progressive abscesses were detected in the spleen; he underwent splenectomy because an infectious disease was suspected. Although his condition improved temporarily after splenectomy, a large liver abscess was noted, and a diagnosis of UC-associated AAs was made. Granulocytapheresis (GCAP) and infliximab (IFX) administration resolved the abscess. This is the first reported case of UC-associated AAs in a Japanese patient treated by splenectomy, GCAP, and IFX.

https://pubmed.ncbi.nlm.nih.gov/32999240/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990631/

Scientific corner

Adsorptive Granulocyte and Monocyte Apheresis Is Effective in Ulcerative Colitis Patients Both with and without Concomitant Prednisolone

Keiji Matsuda 1 2Kohei Ohno 1Yuka Okada 1Takahiro Yagi 1Mitsuo Tsukamoto 1Yoshihisa Fukushima 1Atsushi Horiuchi 1Ryu Shimada 1 2Tsuyoshi Ozawa 1 2Tamuro Hayama 1 2Takeshi Tsuchiya 1 2Junko Tamura 1Hisae Iinuma 1Keijiro Nozawa 1 2Hitoshi Aoyagi 2 3Akari Isono 2 3Koichiro Abe 2 3Shinya Kodashima 2 3Takatsugu Yamamoto 2 3Yoshitaka Kawasaki 4Yoshifuru Tamura 4Yuko Sasajima 5Fukuo Kondo 5Yojiro Hashiguchi 1 2 , Inflamm Intest Dis, 2020 Feb;5(1):36-41.

The effect of GMA with concomitant PSL (Prednisolone) and that of GMA without PSL were not different, and GMA was effective irrespective of PSL administration. The present study showed that GMA had efficacy and led many UC patients treated by PSL to be steroid free with no safety concern in the real world, although there is the possibility of recruitment bias due to the retrospective nature of the study.

https://pubmed.ncbi.nlm.nih.gov/32232053/

https://www.karger.com/Article/Pdf/505484

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