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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.

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Toxic Megacolon: Background, Pathophysiology, Management Challenges and Solutions

Jiten Desai 1Mohamed Elnaggar 2Ahmed A Hanfy 2Rajkumar Doshi 2

Clin Exp Gastroenterol. 2020 May 19;13:203-210. doi: 10.2147/CEG.S200760. eCollection 2020.

Leukocytapheresis (LCAP) is useful in the management of TM

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Leukocyte adsorption apheresis for the treatment of pyoderma gangrenosum

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Leukocytapheresis for rheumatoid arthritis cases that are super-resistant to any class of biological drugs and tofacitinib

Shunsuke Mori Transfusion and Apheresis Science Volume 59, Issue 6, December 2020, 102920 doi: 10.1016/j.transci.2020.102920

Many biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are currently available as treatment options for rheumatoid arthritis (RA), but a subset of RA patients shows inadequate responses to any of these DMARDs. This phenomenon, which we call super-resistance, is becoming a serious concern. In this study, I present two cases of super-resistant RA in which patients failed to respond to treatment with bDMARDs of any class as well as to tsDMARD therapy with tofacitinib. In these cases, leukocytapheresis (LCAP), a treatment that removes overabundant leukocytes from the body, rapidly induced low disease activity and made patients subsequently responsive to previously ineffective DMARDs. My experience with the present cases suggests that LCAP is worth considering as an alternative therapeutic option for the management of RA patients with super-resistance to DMARD therapies.

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Safety and efficacy of single-needle leukocyte apheresis for treatment of ulcerative colitis

Yoichiro Shindo 1Keiichi Mitsuyama 2Hiroshi Yamasaki 1 2 3Tetsuro Imai 4Shinichiro Yoshioka 1 2Kotaro Kuwaki 1 2Ryosuke Yamauchi 1 2Tetsuhiro Yoshimura 1 2Toshihiro Araki 1 2Masaru Morita 1 2Kozo Tsuruta 1 2Sayo Yamasaki 1Kei Fukami 5Takuji 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.

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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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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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GS1-04 The apheresis guidelines for digestive diseases

Kazuaki Inoue, Tomoki Furuya, Yoko Yokoyama

The apheresis guidelines for digestive diseases are divided into the following four fields: acute liver failure (ALF); ascites; acute pancreatitis (AP); inflammatory bowel disease (IBD).

IBD: Ulcerative colitis (UC) and Crohn’s disease (CD) are the major forms of I BD. Although their etiology is still not fully understood, activated leukocytes are significant factors in their exacerbations. In Japan, granulocyte and monocyte apheresis (GMA) and leukocytapheresis (LCAP) are approved for IBD treatment. They are recommended for remission induction in UC
patients with mild-to-moderate activity, whether steroid-resistant or -dependent. Although GMA is recommended for remission induction in colonic type CD refractory to conventional therapy, its efficacy is lower than in UC patients.

poster at ISFA 2019 pag 100-101

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SY3-04 Real-world experiences of cytapheresis therapy for ulcerative colitis; results from large-scale multicenter observational studies

Taku Kobayashi

poster at ISFA 2019 pag 53

There are two types of extracorporeal therapy for treating active ulcerative colitis (UC), granulocyte and monocyte adsorption (GMA) and leukocytapheresis (LCAP). Although Sawada et al reported the efficacy of LCAP by the randomized controlled trial (Sawada K et al. Am J Gastroenterol 2005), the larger sham-controlled multicenter trial of GMA failed to prove its efficacy (Sands BE et al. Gastroenterol 2008). Therefore, evidence to show their efficacy relies more on the real-world data, including the post-marketing surveillance (PMS). The large-scale PMS for LCAP was named as REFINE study, involving 847 patients from 116 medical facilities in Japan (Yokoyama Y, Kobayashi T et al. J Crohn Colitis 2014). Adverse events were seen only in 10.3% and the vast majority were mild. The overall clinical remission rate was 68.9%, and the mucosal healing rate was 62.5%. These results were very consistent with the results from PMS of 697 patients treated with GMA, which also demonstrated its real-world effectiveness and safety (Hibi T et al. Dig Liver Dis 2008). In addition, a retrospective observational study aimed to evaluate the clinical outcome at 1 year and identify risk factors for relapse after LCAP was recently conducted among patients who had achieved remission in the PMS (Kobayashi T et al. J Gastroenterol 2018). The 1-year cumulative relapse free rate was 63.6%. Following LCAP, a high clinical activity and a high leukocyte count were associated with a greater risk of relapse. Intensive LCAP was associated with favorable long-term outcomes in corticosteroidrefractory patients. The response rate of re-treatment upon relapse was as high as 85%. These results on the risks of relapse as well as effectiveness of re-treatment may help to overcome the weakness of cytapheresis therapy in maintaining remission. Results from the clinical trial evaluating the clinical efficacy of intermittent maintenance cytapheresis therapy are also warranted.

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