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Leukocyte adsorption apheresis for the treatment of pyoderma gangrenosum

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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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Nonbiological therapeutic management of ulcerative colitis

Nicolò Mezzina 1Sophia Elizabeth Campbell Davies 2Sandro Ardizzone 1 Expert Opin Pharmacother 2018 Nov;19(16):1747-1757. doi: 10.1080/14656566.2018.1525361. Epub 2018 Sep 27.

Introduction: Treatment of ulcerative colitis (UC) is constantly evolving. In the last two decades, new therapeutic strategies have been implemented by addressing specific disease mechanisms: biological agents against tumor necrosis factor-α and integrins are now widely used, and more agents targeting different pathological pathways are being marketed. Despite these novel therapies, nonbiological drugs are still the mainstay of treatment, especially in mild-to-moderate disease, since a proven safety and tolerability profile is observed. Excellent efficacy both in induction and maintenance of remission is obtained, with a lower cost compared to biological agents. Areas covered: The purpose of this review is to summarize the current knowledge and the latest clinical evidence regarding nonbiological therapies for UC. Expert opinion: Concomitant administration of oral and rectal 5-aminosalicylates acid is more effective in the treatment of UC in remission. Corticosteroids are the treatment of choice in patients with moderately severe or severe UC. The association of azathioprine with biological treatments is more effective than monotherapy. Cyclosporine is an effective drug in severe UC, but its poor management must be considered. Probiotics are very popular; however, evidence on their actual role in UC still must be demonstrated; cytapheresis plays only a niche role at this time.

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Shorter Relapse-Free Period after Leukocyte Removal Therapy in Younger than Older Patients with Ulcerative Colitis

Satoko Yamasaki 1Yasuhisa Sakata 2Hisako Yoshida 3Sinpei Shirai 1Yuichiro Tanaka 1Ryo Nakano 1Takahiro Yukimoto 1Nanae Tsuruoka 1Ryo Shimoda 1Makoto Fukuda 1Motoaki Miyazono 1Yuji Ikeda 1Ryuichi Iwakiri 1Keizo Anzai 1Kazuma Fujimoto 1 , Digestion. 2019;100(4):247-253.

Background: Leukocyte removal therapy (LRT) is an effective treatment for active ulcerative colitis (UC). The present study was performed to evaluate the relapse-free period after LRT and identify risk factors for relapse. Methods: In total, 94 patients who underwent first-time LRT for remission of moderate to severe UC from April 2004 to March 2016 were enrolled in the present study. The patients were randomly assigned to one of 2 treatments: leukocytapheresis (LCAP; n = 43) or granulocyte and monocyte/macrophage adsorptive apheresis (GMA; n = 51). The 5-year cumulative relapse-free rate and risk factors for relapse were evaluated. Results: The therapeutic response rate was 82% for GMA and 70% for LCAP without a statistically significant difference. The 5-year relapse-free rate was 34.7% in the LRT group. The 5-year relapse-free rate in patients aged > 40 years was 49.9%, which was significantly higher than that in patients aged ≤40 years (22.9%, p < 0.01). The relapse-free period was longer in the older than younger patients. The relapse-free period was longer in the ≥40- than <40-year-old patients (1,197 vs. 441 days, respectively; p = 0.03). Conclusions: The relapse-free period after LRT was examined in patients with UC, and 34.7% of patients achieved clinical remission within a 5-year period. The risk factor for early relapse after LRT was younger age. In conclusion, LRT might be a therapeutic option for maintenance of remission in patients with UC, especially patients aged ≥40 years.

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Granulocyte and Monocyte Apheresis for Induction of Remission in Children With New Onset Inflammatory Bowel Colitis.

Helena Rolandsdotter 1 2Michael Eberhardson 1 3Ulrika L Fagerberg 4 5Yigael Finkel 1 2 , J Pediatr Gastroenterol Nutr 2018 Jan;66(1):84-89.

Objective: The aim of the study was to analyze the effect of granulocyte and monocyte apheresis (GMA) with mesalazine for induction of remission in pediatric patients with newly onset chronic inflammatory bowel disease (IBD) colitis. Methods: Thirteen pediatric patients with newly onset extensive IBD colitis were investigated per the ECCO/ESPGHAN IBD protocol. Of these 13, 12 received 10 treatments with Adacolumn (ADA) during a median of 6.25 weeks in combination with low-to-moderate doses of mesalazine, which was continued after apheresis. A control colonoscopy was performed 12 to 16 weeks after GMA treatment. Primary outcomes were mucosal healing (Mayo endoscopic score) and histopathologic grading of biopsies. A secondary outcome was disease activity as measured by the Pediatric Ulcerative Colitis Activity Index. Results: Twelve children (6 girls) with a median age of 14.6 years and a median duration of symptoms at diagnosis of 3.2 months received all planned 10 treatment sessions with ADA. Ten of 12 patients had pancolitis and 2 of 12 extensive colitis. A final diagnosis, however, indicated ulcerative colitis in 10 children and Crohn disease in 2 children. At control colonoscopy, 8 of 12 children were in clinical remission and the Mayo endoscopic score showed significant improvement in 9 of 12 patients (P = 0.006). Complete microscopic remission, according to the Geboes score, was observed in 2 patients. Conclusions: In this small study GMA for induction of remission of newly onset pediatric IBD colitis was effective in 8 of 12 patients. Further controlled studies are warranted to confirm the efficacy of this treatment model.

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