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.
Treatment of Inflammatory Bowel Disease: A Comprehensive Review
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.
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.
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.
Pyoderma gangrenosum with primary sclerosing cholangitis-associated colitis successfully treated with concomitant granulocyte and monocyte adsorption apheresis with corticosteroids
Together with previous reports, concomitant GMA therapy with corticosteroids may be an effective treatment for PG.
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
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.
Rapidly Progressing Aseptic Abscesses in a Patient with Ulcerative Colitis
Yoshiharu Yamaguchi 1, Marie Nakagawa 1, Shoko Nakagawa 1, Kazuhiro Nagao 1, Satoshi Inoue 1, Tomoya Sugiyama 1, Shinya Izawa 1, Yasutaka Hijikata 1, Masahide Ebi 1, Yasushi Funaki 1, Naotaka Ogasawara 1, Makoto Sasaki 1, Kunio 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.
Adsorptive Granulocyte and Monocyte Apheresis Is Effective in Ulcerative Colitis Patients Both with and without Concomitant Prednisolone
Keiji Matsuda 1 2, Kohei Ohno 1, Yuka Okada 1, Takahiro Yagi 1, Mitsuo Tsukamoto 1, Yoshihisa Fukushima 1, Atsushi Horiuchi 1, Ryu Shimada 1 2, Tsuyoshi Ozawa 1 2, Tamuro Hayama 1 2, Takeshi Tsuchiya 1 2, Junko Tamura 1, Hisae Iinuma 1, Keijiro Nozawa 1 2, Hitoshi Aoyagi 2 3, Akari Isono 2 3, Koichiro Abe 2 3, Shinya Kodashima 2 3, Takatsugu Yamamoto 2 3, Yoshitaka Kawasaki 4, Yoshifuru Tamura 4, Yuko Sasajima 5, Fukuo Kondo 5, Yojiro 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.
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