Scientific corner

Comparison of adsorption efficiency of leukocytes in single needle GMA with or without PSL treatment in patients with active ulcerative colitis

Yuki Noguchi 1Keiji Shimazu 2Teruhiko Totani 1Kazumasa Komura 3Atsuo Tanaka 2

Transfus Apher Sci  2022 Sep 22;103581. doi: 10.1016/j.transci.2022.103581. Online ahead of print.

Granulocyte monocyte adsorption (GMA) is considered one of the modalities for the remission induction of ulcerative colitis (UC). We previously reported that single-needle GMA (SN-GMA) could simplify the GMA. In the present study, the efficiency of SNGMA was examined according to the administration of corticosteroids (PSL) in UC patients. Blood sample were taken at proximal and distal side of the column during the SN-GMA treatment. Disease activity score (partial Mayo score: pMayo score) before and after the SN-GMA was investigated. The data of 18 patients with active UC (11 and 7 patients with PSL naïve and PSL use groups, respectively) treated with SN-GMA was analyzed. The mean pMayo score before the GMA treatment was comparable between the PSL naïve group (p = 0.26), whereas the score after the GMA treatment was significantly lower in PSL naïve group (0.8 + 0.6) than in PSL use group (3.0 + 2.1) (p = 0.04). Patients achieving the clinical remission were more observed in the PSL naive group (90.9%) than in the PSL use group (42.9%) (p = 0.047). The adsorption efficiency in the PSL naïve and PSL use groups were as follows: leukocytes (34.45 ± 7.43% vs 23.14 ± 7.56%: p = 0.008), granulocytes (41.74 ± 10.07% vs 27.99 ± 15.11%: p = 0.04), monocytes (32.59 ± 24.07% vs 33.16 ± 24.18%: p = 0.95), and lymphocytes (-1.87 ± 18.17% vs -3.79 ± 22.52%: p = 0.84), with a significant difference of the absorption efficiency in leukocytes and granulocytes. These data collectively indicate that the SN-GMA can be applied for the remission induction to active UC patients with a higher clinical remission rate in PSL naïve patients compared to PSL use patients.

https://pubmed.ncbi.nlm.nih.gov/36167614/

Scientific corner

Use of granulocyte and monocyte adsorption apheresis in dermatology (Review)

Laura Gnesotto 1Guido Mioso 1Mauro Alaibac 1

Exp Ther Med 2022 Jun 24;24(2):536. doi: 10.3892/etm.2022.11463. eCollection 2022 Aug. DOI: 10.3892/etm.2022.11463

Adsorptive granulocyte and monocyte apheresis (GMA) is an extracorporeal treatment that selectively removes activated myeloid lineage leukocytes from peripheral blood. This technique consists of a column with cellulose acetate beads as absorptive leukocytapheresis carriers, and was initially used to treat ulcerative colitis. A literature search was conducted to extract recently published studies about the clinical efficacy of GMA in patients with different skin disorders, reporting information on demographics, clinical symptoms, treatment and clinical course. Dermatological diseases, in which GMA has been performed, include generalized pustular psoriasis, pyoderma gangrenosum, palmoplantar pustular psoriasis, Behcet’s disease, Sweet’s syndrome, adult-onset Still’s disease, impetigo herpetiformis, reactive arthritis, acne and hidradenitis suppurativa syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus. In most patients, GMA was started after the failure of conventional therapeutic options and it was helpful in the majority of cases. Based on the information summarized, GMA could be considered a valid non-pharmacological treatment option for patients with several dermatological conditions, which are difficult to treat with other pharmacological preparations.

 PASH syndrome; cutaneous allergic vasculitis; granulocyte and monocyte apheresis; neutrophilic dermatoses; reactive arthritis; systemic lupus erythematosus.

https://pubmed.ncbi.nlm.nih.gov/35837066/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257973/

Scientific corner

Apheresis: A cell-based therapeutic tool for the inflammatory bowel disease

Farah Yasmin 1Hala Najeeb 1Unaiza Naeem 1Abdul Moeed 1Thoyaja Koritala 2Salim Surani 3 4

World J Clin Cases  2022 Jul 26;10(21):7195-7208. doi: 10.12998/wjcc.v10.i21.7195.

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.

https://pubmed.ncbi.nlm.nih.gov/36158031/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353887/

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

Scientific corner

An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis

Francesca Ferretti 1Rosanna Cannatelli 1Maria Camilla Monico 1Giovanni Maconi 1Sandro Ardizzone 

J Clin Med  2022 Apr 20;11(9):2302. doi: 10.3390/jcm11092302.

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.

https://pubmed.ncbi.nlm.nih.gov/35566428/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104748/

Scientific corner

Granulocyte and monocyte apheresis therapy for patients with active ulcerative colitis associated with COVID-19: a case report

Miki Koroku 1Teppei Omori 1Harutaka Kambayashi 1Shun Murasugi 1Tomoko Kuriyama 1Yuichi Ikarashi 1Maria Yonezawa 1Ken Arimura 2Kazunori Karasawa 3Norio Hanafusa 4Masatoshi Kawana 5Katsutoshi Tokushige 

Intest Res 2022 Jan;20(1):150-155. doi: 10.5217/ir.2020.00148. Epub 2021 Mar 12

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now a pandemic. Although several treatment guidelines have been proposed for patients who have both inflammatory bowel disease and COVID-19, immunosuppressive therapy is essentially not recommended, and the treatment options are limited. Even in the COVID-19 pandemic, adjuvant adsorptive granulocyte and monocyte apheresis may safely bring ulcerative colitis (UC) into remission by removing activated myeloid cells without the use of immunosuppressive therapy. Our patient was a 25-year-old Japanese male with UC and COVID-19. This is the first case report of the induction of UC remission with granulocyte and monocyte apheresis treatment for active UC associated with COVID-19.

https://pubmed.ncbi.nlm.nih.gov/33902268/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831771/

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

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

S-05-05 Efficacy and safety of cytapheresis in elderly patients with ulcerative colitis (poster)

ISFA-EIFA-2021

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.

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

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