poster at ISFA 2019 pag 155

We retrospectively investigated the efficacy and safety of Granulocyte and Monocyte Adsorptive Apheresis (GMA) therapy between 15 elderly patients vs. 19 non-elderly patients with ulcerative colitis. While the remission rates and response rates in non-elderly patients were 33.3% and 94.4%, these rates were 40.0% and 93.3% in elderly patients. There were no significant differences in the 1-year relapse-free rates between elderly and non-elderly patients (71.4% and 50.0%, respectively, P=0.453). These results suggest that GMA therapy is an efficient and safe treatment in elderly patients with ulcerative colitis.

http://www.atalacia.com/isfa/data/abstract.pdf

poster at ISFA 2019 pag 155

Clinical factors correlated with early relapse of ulcerative colitis (UC) after granulocytemonocyte adsorption (GMA) were investigated. The data from 61 UC patients treated by a
series of 10 sessions of GMA were collected retrospectively. UC was relapsed in 14 patients
(23%) within 24 weeks after GMA. Compared with non-relapse group, relapse group had
significantly higher value of Seo index (SI) evaluated before and after GMA treatment.
Binomial logistic regression analysis showed that SI was significantly correlated with UC
relapse. Relapse rate was significantly different between groups divided according to SI. Seo
index may associated with early relapse of UC.

http://www.atalacia.com/isfa/data/abstract.pdf

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

http://www.atalacia.com/isfa/data/abstract.pdf

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.

http://www.atalacia.com/isfa/data/abstract.pdf

Anand Padmanabhan ¹, Laura Connelly-Smith ², Nicole Aqui ³, Rasheed A Balogun ⁴, Reinhard Klingel ⁵, Erin Meyer ⁶, Huy P Pham ⁷, Jennifer Schneiderman ⁸, Volker Witt ⁹, Yanyun Wu ¹⁰, Nicole D Zantek ¹¹, Nancy M Dunbar ¹², Guest Editor Joseph Schwartz ¹³ , J Clin Apher. 2019 Jun;34(3):171-354.

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Eighth Edition of the JCA Special Issue continues to maintain this methodology and rigor in order to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Eighth Edition, like its predecessor, continues to apply the category and grading system definitions in fact sheets. The general layout and concept of a fact sheet that was introduced in the Fourth Edition, has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease entity or medical condition. The Eighth Edition comprises 84 fact sheets for relevant diseases and medical conditions, with 157 graded and categorized indications and/or TA modalities. The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.

https://pubmed.ncbi.nlm.nih.gov/31180581/

Elena Borrego García ¹, María Peña Ortega ², Alicia Martín-Lagos Maldonado ³ , Rev Esp Enferm Dig. 2019 Nov;111(11):889.

Ulcerative proctitis (UP) is often involved in the diagnosis of inflammatory bowel disease (IBD). The increase of leukocytes and pro-inflammatory factors in peripheral blood and in the active forms, as well as the infiltration of neutrophils and monocytes/macrophages in the intestinal mucosa is known to occur in this entity. This infiltration of cells damages the mucosa due to the liberation of proteases, oxidation radicals and cytokines, among others. Apheresis techniques such as leukocyte apheresis may be used among the different therapeutic options such as steroids, sulfasalazine, 5-aminosalicylic, tacrolimus, azathioprine, cyclosporine, mycophenolate and biological agents.

https://pubmed.ncbi.nlm.nih.gov/31595764/

S Rong ¹, W J Yuan, Zhonghua Yi Xue Za Zhi. 2019 Jan 8;99(2):84-87.

https://pubmed.ncbi.nlm.nih.gov/30669744/

Chie Kurihara, Toshihide Ohmori, Hirotaka Furuhashi, Kenichi Inaba, Nao Sugihara, Yoshinori Hanawa, Gastroenterology 2019 156 (6) Suppl. S-1146

Background: Granulocyte and monocyte adsorptive apheresis (GMA) is non-pharmacological therapy which selective depletion of activated granulocytes and monocytes/macrophages from peripheral blood. GMA is effective and safe as induction therapy in ulcerative colitis (UC) of moderate to severe patients, and commonly used in Asia and north Europe. However, therapeutic mechanism of GMA, especially its effect on mucosal healing, has not been well characterized. Since moderate to severe patients with UC sometimes become fulminant, it is important to select an appropriate induction therapy. GMA treatment efficacy is reported about 60% patients respond, whereas, there is not useful parameter that predicts GMA therapeutic efficacy before treatment. In this study, we attempted to identify predictive factors of clinical response to GMA treatment in UC patients. Methods: Thirty-two active UC patients (Mayo score ^ 5 and Mayo endoscopic score ^ 2) and 10 non-IBD control subjects were enrolled in this study. All UC patients received 10 or 11 times of GMA, and colonoscopies were applied before the first GMA and after the last GMA. Control subjects underwent colonoscopies for screening of colon cancer. Assessment of disease activity and colonic mucosal healing were determined based on Mayo score. Inflammation-related molecules mRNA expressions were determined by quantitative RT-PCR using biopsy specimen of colonic mucosa. ROC curves analysis was used to assess sensitivity and specificity in prediction of GMA therapeutic efficacy. Results: GMA treatment efficacy is 11 patients (34.4%) achieved clinical remission, 17 patients (53.1%) were response and 4 patients (12.5%) were non-response. Mucosal healing was observed in 18 patients (56.3%) and it was not observed in 14 patients (43.7%). Baseline characteristics were not significantly different according to GMA efficacy. Before the first GMA session, the clinical remission group showed significantly higher expressions of TNFα, MAdCAM-1 and MIP-1β mRNA than those of the non-response group (P <0.05). Patients in the response group who highly expressed these mRNA achieved mucosal healing. In the mucosal healing group, the mRNA levels of TNFα, IL-1β, IL-8, MIP-1β, TGFβ and IL-10 were significantly higher than those in the non-mucosal healing group (P <0.05). TNFα and MIP-1β had 0.83 and 0.79 of area under the curve with 83.3% and 66.7% sensitivity, 71.4% and 100% specificity, 78.9% and 100%positive predictive value, and 76.9% and 70.0% negative predictive value, respectively, for prediction of mucosal healing. Conclusion: Mucosal expression of TNFα and MIP-1β mRNA before treatment in the remission group and the mucosal healing group was significantly higher than non-responder to GMA treatment. We propose that measuring of these molecules’ expression is useful to expect GMA therapeutic efficacy in patients with UC.

https://www.gastrojournal.org/action/doSearch?text1=granulocyte+and+monocyte+apheresis+&field1=AllField&AfterYear=2018&BeforeYear=2021&pageSize=50&startPage=&SeriesKey=ygast

Satoshi Motoya ¹, Hiroki Tanaka ², Tomoyoshi Shibuya ³, Taro Osada ⁴, Takayuki Yamamoto ⁵, Hitoshi Hongo ⁶, Chiemi Mizuno ⁷, Daisuke Saito ⁸, Nobuo Aoyama ⁹, Toshihisa Kobayashi ¹⁰, Hiroaki Ito ¹¹, Satoshi Tanida ¹², Masanori Nojima ¹³, Seiichiro Kokuma ¹⁴, Eiji Hosoi ¹⁴ , BMC Gastroenterol 2019 Nov 21;19(1):196.

Background: The available information on granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease (IBD) under special situations remains unclear. We conducted a retrospective, multicentre cohort study to evaluate the safety and effectiveness of GMA in patients with IBD under special situations.

Methods: This study included patients with ulcerative colitis (UC) or Crohn’s disease who had at least one special situation feature and who had received GMA between November 2013 and March 2017. The incidence of adverse events (AEs) was compared in relation to the special situation, and patient background factors related to an AE were identified. For patients with UC, clinical remission was defined as a partial Mayo score of ≤2.

Results: A total of 437 patients were included in this study. The incidence of AEs among the elderly patients (11.2%) was similar in all patients (11.4%), whereas the incidences of AEs in patients on multiple immunosuppressant medications (15.2%), patients with anaemia (18.1%) and paediatric/adolescent patients (18.9%) were higher than that in all patients (11.4%). In multivariate analysis, anaemia and concomitant immunosuppressant medications were independently associated with the incidence of AEs. Clinical remission was achieved in 46.4% of the patients with UC.

Conclusions: The incidence of AEs in the elderly patients was not higher than that in all patients, whereas the incidence of AE was higher in patients with anaemia and those on multiple immunosuppressant medications than that in all patients. GMA is a safe treatment option in elderly patients with IBD.

https://pubmed.ncbi.nlm.nih.gov/31752695/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873503/pdf/12876_2019_Article_1110.pdf

Abbi R Saniabadi ¹, Tomotaka Tanaka ², Takayuki Yamamoto ³, Wolfgang Kruis ⁴, Rodolfo Sacco ⁵ , J Clin Apher 2019 Feb;34(1):51-60. 

Accordingly, for responder patients, GMA fulfills a desire to be treated without drugs.

https://pubmed.ncbi.nlm.nih.gov/30407662/